Modulation of nociceptive withdrawal reflexes evoked by single and repeated nociceptive stimuli in conscious dogs by low-dose acepromazine

OBJECTIVES: To investigate the modulation of the nociceptive withdrawal reflex (NWR) and temporal summation (TS) by low-dose acepromazine (ACP) in conscious dogs. To assess the short- and long-term stability of the reflex thresholds. STUDY DESIGN: Randomized, blinded, placebo-controlled cross-over experimental study. ANIMALS: Eight adult male Beagles. METHODS: The NWR was elicited using single transcutaneous electrical stimulation of the ulnar nerve. Repeated stimuli (10 pulses, 5 Hz) were applied to evoke TS. The responses of the deltoideus muscle were recorded and quantified by surface electromyography and the behavioural reactions were scored. Each dog received 0.01 mg kg(-1) ACP or an equal volume saline intravenously (IV) at 1 week intervals. Measurements were performed before (baseline) and 20, 60 and 100 minutes after drug administration. Sedation was scored before drug administration and then at 10 minutes intervals. Data were analyzed with Friedman repeated measures analysis of variance on ranks and Wilcoxon signed rank tests. RESULTS: Acepromazine resulted in a mild tranquilization becoming obvious at 20 minutes and peaking 30 minutes after injection. Single (I(t)) and repeated stimuli (TS(t)) threshold intensities, NWR and TS characteristics and behavioural responses were not affected by the ACP at any time point. Both I(t) and TS(t) were stable over time. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, 0.01 mg kg(-1) ACP IV had no modulatory action on the NWR evoked by single or repeated stimuli, suggesting no antinociceptive activity on phasic nociceptive stimuli. The evidence of the stability of the NWR thresholds supports the use of the model as an objective tool to investigate nociception in conscious dogs. A low dose of ACP administered as the sole drug, can be used to facilitate the recordings in anxious subjects without altering the validity of this model.

Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner

BACKGROUND & AIMS Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. METHODS We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. RESULTS The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P = .020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE.

Time courses and quantitative analysis of atrial fibrillation episode number and duration after circular plus linear left atrial lesions: trigger elimination or substrate modification: early or delayed cure?

OBJECTIVES We sought to analyze the time course of atrial fibrillation (AF) episodes before and after circular plus linear left atrial ablation and the percentage of patients with complete freedom from AF after ablation by using serial seven-day electrocardiograms (ECGs). BACKGROUND The curative treatment of AF targets the pathophysiological corner stones of AF (i.e., the initiating triggers and/or the perpetuation of AF). The pathophysiological complexity of both may not result in an "all-or-nothing" response but may modify number and duration of AF episodes. METHODS In patients with highly symptomatic AF, circular plus linear ablation lesions were placed around the left and right pulmonary veins, between the two circles, and from the left circle to the mitral annulus using the electroanatomic mapping system. Repetitive continuous 7-day ECGs administered before and after catheter ablation were used for rhythm follow-up. RESULTS In 100 patients with paroxysmal (n = 80) and persistent (n = 20) AF, relative duration of time spent in AF significantly decreased over time (35 +/- 37% before ablation, 26 +/- 41% directly after ablation, and 10 +/- 22% after 12 months). Freedom from AF stepwise increased in patients with paroxysmal AF and after 12 months measured at 88% or 74% depending on whether 24-h ECG or 7-day ECG was used. Complete pulmonary vein isolation was demonstrated in <20% of the circular lesions. CONCLUSIONS The results obtained in patients with AF treated with circular plus linear left atrial lesions strongly indicate that substrate modification is the main underlying pathophysiologic mechanism and that it results in a delayed cure instead of an immediate cure.

Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival: a cohort study

Background Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004–2010, and described subsequent mortality and predictors of these. Methods Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient’s last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient’s death, 1st February 2010 or 6 months after the patient’s last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression. Results Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin’s lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004–2010 in this large observational cohort. Conclusions The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC.

Psychoendocrine validation of a short measure for assessment of perceived stress management skills in different non-clinical populations

BACKGROUND: We investigated the psychometric properties of a short questionnaire for combined assessment of different perceived stress management skills in the general population and tested whether scores relate to physiological stress reactivity. METHODS: For psychometric evaluation, we determined the factor structure of the questionnaire and investigated its measurement invariance in the participant groups and over time in three different independent samples representing the general population (total N=332). Reliability was tested by estimating test-retest reliability, internal consistency, and item reliabilities. We examined convergent and criterion validity using selected criterion variables. For endocrine validation, 35 healthy non-smoking and medication-free men in a laboratory study and 35 male and female employees in a workplace study underwent an acute standardized psychosocial stress task. We assessed stress management skills and measured salivary cortisol before and several times up to 60 min (workplace study) and 120 min (laboratory study) after stress. Potential confounders were controlled. RESULTS: The factor structure of the questionnaire consists of five scales reflecting acceptably distinct stress management skills such as cognitive strategies, use of social support, relaxation strategies, anger regulation, and perception of bodily tension. This factor structure was stable across participant groups and over time. Internal consistencies, item reliabilities, and test-retest reliabilities met established statistical requirements. Convergent and criterion validity were also established. In both endocrine validation studies, higher stress management skills were independently associated with lower cortisol stress reactivity (p's<.029). CONCLUSIONS: Our findings suggest that the questionnaire has good psychometric properties and that it relates to subjective psychological and objective physiological stress indicators. Therefore, the instrument seems a suitable measure for differential assessment of stress management skills in the general population.

A new methodological approach for studying intergenerational mobility with an application to Swiss data

Despite the widespread interest in the topic and a vast international literature, very little is known about the development of intergenerational mobility in Switzerland. Based on a new harmonized database for Switzerland (comprising various surveys such as different waves of the ISSP, EVS, and the ESS), we provide a systematic account of changes in the link between social origin and destination over time (covering birth cohorts from around 1935 to 1980). We analyze effects of parental education and class on own educational achievement and social class for both men and women, using a refined variant of the methodological approach proposed by Jann and Combet (2012). The approach is based on the concept of proportional reduction of error (PRE) and features a number of advantages over more traditional approaches. For example, it provides smooth estimates of changes in social mobility that have a clear interpretation and it can easily incorporate control variables and multiple dimensions of parental characteristics. To evaluate the validity of our approach, we employ the oft-used log-multiplicative layer effect (a.k.a Unidiff) model (Xie 1992, Erikson and Goldthorpe 1992) as a benchmark. Results indicate that our approach performs well and produces qualitatively similar findings as Xie's model. For both men and women, effects of social origin initially decreased, but then, towards the end of the observation period, increased again. This u-shaped pattern, which can be observed with respect to both education and class, appears to be more pronounced for women than for men.

Intergenerational Mobility in Switzerland. A Comparison of Methodological Approaches

Despite the widespread interest in the topic and a vast international literature, only little is known about the development of intergenerational mobility in Switzerland. Based on a new harmonized database for Switzerland (comprising various surveys such as different waves of the ISSP, EVS, or the ESS), we provide a systematic account of changes in the link between social origin and destination over time (covering birth cohorts from 1940 through 1980). We analyze effects of parental education and class on own educational achievement and social class for both men and women, using a refined variant of the methodological approach proposed by Jann and Combet (2012). The approach is based on the concept of proportional reduction of error (PRE) and features a number of advantages over more traditional approaches. For example, it provides smooth estimates of changes in social mobility that have a clear interpretation and it can easily incorporate control variables and multiple dimensions of parental characteristics. To evaluate the validity of our approach, we employ the oft-used log-multiplicative layer effect model (Xie 1992) as a benchmark. Results indicate that our approach performs well and produces qualitatively similar findings as Xie’s model. For men, effects of social origin have been stable over the observed period. For women, however, social mobility significantly decreased among younger cohorts, mostly due to expanding female education and labor force participation. Jann, Ben, Benita Combet (2012). Zur Entwicklung der intergenerationalen Mobilität in der Schweiz (On the Development of Intergenerational Mobility in Switzerland). Swiss Journal of Sociology 38(2): 177-199. Xie, Yu (1992). The Log-Multiplicative Layer Effect Model for Comparing Mobility Tables. American Sociological Review 57(3): 380-395.

Paleoclimate data-model comparison and the role of climate forcings over the past 1500 years

The past 1500 years provide a valuable opportunity to study the response of the climate system to external forcings. However, the integration of paleoclimate proxies with climate modeling is critical to improving the understanding of climate dynamics. In this paper, a climate system model and proxy records are therefore used to study the role of natural and anthropogenic forcings in driving the global climate. The inverse and forward approaches to paleoclimate data–model comparison are applied, and sources of uncertainty are identified and discussed. In the first of two case studies, the climate model simulations are compared with multiproxy temperature reconstructions. Robust solar and volcanic signals are detected in Southern Hemisphere temperatures, with a possible volcanic signal detected in the Northern Hemisphere. The anthropogenic signal dominates during the industrial period. It is also found that seasonal and geographical biases may cause multiproxy reconstructions to overestimate the magnitude of the long-term preindustrial cooling trend. In the second case study, the model simulations are compared with a coral δ18O record from the central Pacific Ocean. It is found that greenhouse gases, solar irradiance, and volcanic eruptions all influence the mean state of the central Pacific, but there is no evidence that natural or anthropogenic forcings have any systematic impact on El Niño–Southern Oscillation. The proxy climate relationship is found to change over time, challenging the assumption of stationarity that underlies the interpretation of paleoclimate proxies. These case studies demonstrate the value of paleoclimate data–model comparison but also highlight the limitations of current techniques and demonstrate the need to develop alternative approaches.

Drivers of collaboration to mitigate climate change: An illustration of Swiss climate policy over 15 years

Climate change mitigation policy is driven by scientific knowledge and involves actors from the international, national and local decision-making levels. This multi-level and cross-sectoral context requires collaborative management when designing mitigation solutions over time and space. But collaboration in general policymaking settings, and particularly in the complex domain of climate mitigation, is not an easy task. This paper addresses the question of what drives collaboration among collective actors involved in climate mitigation policy. We wish to investigate whether common beliefs or power structures influence collaboration among actors. We adopt a longitudinal approach to grasp differences between the early and more advanced stages of mitigation policy design. We use survey data to investigate actors’ collaboration, beliefs and power, and apply a Stochastic Actor-oriented Model for network dynamics to three subsequent networks in Swiss climate policy between 1995 and 2012. Results show that common beliefs among actors, as well as formal power structures, have a higher impact on collaboration relations than perceived power structures. Furthermore, those effects hold true for decision-making about initial mitigation strategies, but less so for the implementation of those measures.

Multi-proxy summer and winter precipitation reconstruction for southern Africa over the last 200 years

This study presents the first consolidation of palaeoclimate proxy records from multiple archives to develop statistical rainfall reconstructions for southern Africa covering the last two centuries. State-of-the-art ensemble reconstructions reveal multi-decadal rainfall variability in the summer and winter rainfall zones. A decrease in precipitation amount over time is identified in the summer rainfall zone. No significant change in precipitation amount occurred in the winter rainfall zone, but rainfall variability has increased over time. Generally synchronous rainfall fluctuations between the two zones are identified on decadal scales, with common wet (dry) periods reconstructed around 1890 (1930). A strong relationship between seasonal rainfall and sea surface temperatures (SSTs) in the surrounding oceans is confirmed. Coherence among decadal-scale fluctuations of southern African rainfall, regional SST, SSTs in the Pacific Ocean and rainfall in south-eastern Australia suggest SST-rainfall teleconnections across the southern hemisphere. Temporal breakdowns of the SST-rainfall relationship in the southern African regions and the connection between the two rainfall zones are observed, for example during the 1950s. Our results confirm the complex interplay between large-scale teleconnections, regional SSTs and local effects in modulating multi-decadal southern African rainfall variability over long timescales.

Time Heals Some Wounds: Psychological Adjustment To Marital Breakup

Marital breakup is among the most incisive stressors in adult life. While the negative effects of divorce on well-being are well documented in research literature, the large interindividual differences in psychological adaptation to this critical life event over time are still not well understood. Particularly the question, whether marital breakup represents a temporary crisis or rather a chronic strain is still controversially discussed. Against this empirical and theoretical background the aim of this study is to investigate the psychological adaptation (depression, perceived stress and life satisfaction) to marital breakup in a sample of 289 middle aged persons (M = 50.2 years) who were partnered at least 10 years (M = 23. 5 years). We compared two groups: one with a separation within the last 12 months (58 women, 25 men), another with a separation within the last 2-5 years (97 women, 38 men). A group of 441 age-matched married people served as control group. Findings from group comparison reveal that time passed since separation is indeed associated with better psychological adaptation (lower depression and perceived stress rates). Results from regression analyses show that differences in psychological adaptation are a function of neuroticism, resilience, new partnership and time passed since separation. These results provide support for the crisis approach and offer important insights into the process of adaptation to marital breakup, which in can be used for counselling.

Relationship between onset-to-door time and door-to-thrombolysis time: a pooled analysis of 10 dedicated stroke centers

BACKGROUND AND PURPOSE Inverse relationship between onset-to-door time (ODT) and door-to-needle time (DNT) in stroke thrombolysis was reported from various registries. We analyzed this relationship and other determinants of DNT in dedicated stroke centers. METHODS Prospectively collected data of consecutive ischemic stroke patients from 10 centers who received IV thrombolysis within 4.5 hours from symptom onset were merged (n=7106). DNT was analyzed as a function of demographic and prehospital variables using regression analyses, and change over time was considered. RESULTS In 6348 eligible patients with known treatment delays, median DNT was 42 minutes and kept decreasing steeply every year (P<0.001). Median DNT of 55 minutes was observed in patients with ODT ≤30 minutes, whereas it declined for patients presenting within the last 30 minutes of the 3-hour time window (median, 33 minutes) and of the 4.5-hour time window (20 minutes). For ODT within the first 30 minutes of the extended time window (181-210 minutes), DNT increased to 42 minutes. DNT was stable for ODT for 30 to 150 minutes (40-45 minutes). We found a weak inverse overall correlation between ODT and DNT (R(2)=-0.12; P<0.001), but it was strong in patients treated between 3 and 4.5 hours (R(2)=-0.75; P<0.001). ODT was independently inversely associated with DNT (P<0.001) in regression analysis. Octogenarians and women tended to have longer DNT. CONCLUSIONS DNT was decreasing steeply over the last years in dedicated stroke centers; however, significant oscillations of in-hospital treatment delays occurred at both ends of the time window. This suggests that further improvements can be achieved, particularly in the elderly.

Time-Series Panel Analysis (TSPA): Multivariate Modeling of Temporal Associations in Psychotherapy Process.

Objective: Processes occurring in the course of psychotherapy are characterized by the simple fact that they unfold in time and that the multiple factors engaged in change processes vary highly between individuals (idiographic phenomena). Previous research, however, has neglected the temporal perspective by its traditional focus on static phenomena, which were mainly assessed at the group level (nomothetic phenomena). To support a temporal approach, the authors introduce time-series panel analysis (TSPA), a statistical methodology explicitly focusing on the quantification of temporal, session-to-session aspects of change in psychotherapy. TSPA-models are initially built at the level of individuals and are subsequently aggregated at the group level, thus allowing the exploration of prototypical models. Method: TSPA is based on vector auto-regression (VAR), an extension of univariate auto-regression models to multivariate time-series data. The application of TSPA is demonstrated in a sample of 87 outpatient psychotherapy patients who were monitored by postsession questionnaires. Prototypical mechanisms of change were derived from the aggregation of individual multivariate models of psychotherapy process. In a 2nd step, the associations between mechanisms of change (TSPA) and pre- to postsymptom change were explored. Results: TSPA allowed a prototypical process pattern to be identified, where patient's alliance and self-efficacy were linked by a temporal feedback-loop. Furthermore, therapist's stability over time in both mastery and clarification interventions was positively associated with better outcomes. Conclusions: TSPA is a statistical tool that sheds new light on temporal mechanisms of change. Through this approach, clinicians may gain insight into prototypical patterns of change in psychotherapy.

The VEINES-QOL/Sym questionnaire is a reliable and valid disease-specific quality of life measure for deep vein thrombosis in elderly patients.

PURPOSE To prospectively evaluate the psychometric properties of the Venous Insufficiency Epidemiological and Economic Study (VEINES-QOL/Sym) questionnaire, an instrument to measure disease-specific quality of life and symptoms in elderly patients with deep vein thrombosis (DVT), and to validate a German version of the questionnaire. METHODS In a prospective multicenter cohort study of patients aged ≥ 65 years with acute venous thromboembolism, we used standard psychometric tests and criteria to evaluate the reliability, validity, and responsiveness of the VEINES-QOL/Sym in patients with acute symptomatic DVT. We also performed an exploratory factor analysis. RESULTS Overall, 352 French- and German-speaking patients were enrolled (response rate of 87 %). Both language versions of the VEINES-QOL/Sym showed good acceptability (missing data, floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations), validity (convergent, discriminant, known-groups differences), and responsiveness to clinical change over time in elderly patients with DVT. The exploratory factor analysis of the VEINES-QOL/Sym suggested three underlying dimensions: limitations in daily activities, DVT-related symptoms, and psychological impact. CONCLUSIONS The VEINES-QOL/Sym questionnaire is a practical, reliable, valid, and responsive instrument to measure quality of life and symptoms in elderly patients with DVT and can be used with confidence in prospective studies to measure outcomes in such patients.

Vocational Interests and Career Goals: Development and Relations to Personality and Middle Adolescence

Cross-sectional research implies a close relation of vocation interests, goals, and traits, yet little is known about their reciprocal development over time. This longitudinal study examined development of Things/People (T/P) and Data/Ideas (D/I) vocational interests and career goals in relation to Big Five personality traits among 292 Swiss adolescents with a cross-lagged panel design with two measurement points over 1 year from seventh to eighth grade. Interests and goals were significantly related within time and showed significant interactions across time. Traits related significantly and equally to interests and goals within time and predicted their development across time except for T/P goals. Goals and interests possessed incremental validity above traits in affecting each other. Implications include the need to account for dynamic processes in the development of goals and interests and their systematic relation to traits in theory and practice.