Forgiveness and psychological adjustment following interpersonal transgressions: A longitudinal analysis

Forgiveness is often assumed to be adaptive for psychological adjustment following interpersonal transgressions. Three hundred and forty seven individuals who had experienced a recent interpersonal transgression were surveyed on four occasions over the course of six weeks. Forgiveness was assessed with scales measuring interpersonal avoidance and revenge motivation and psychological adjustment was assessed with scales measuring depression and rumination. Latent growth curve analyses showed that intraindividual changes in forgiveness were positively correlated with changes in adjustment. Latent difference score analyses indicated that adjustment predicted subsequent change in forgiveness, but that forgiveness did not predict subsequent change in adjustment. The results suggest that adjustment facilitates forgiveness, but not that forgiveness facilitates adjustment.

Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study

BACKGROUND Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. DESIGN Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. METHODS Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring. RESULTS POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5 and US$20 and detection limits between 1000 and 10,000 copies/ml, the ICER of POC-VL was US$4010-US$9230 compared with clinical and US$5960-US$25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US$2450-US$5830 and US$2230-US$10380. In Scenario C, the ICER ranged between US$960 and US$2500 compared with clinical monitoring and between cost-saving and US$2460 compared with CD4 monitoring. CONCLUSION The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and assuming that failure of first-line ART is reduced due to targeted adherence counselling.

Comparing growth trajectories of risk behaviors from late adolescence through young adulthood: An accelerated design

Risk behaviors such as substance use or deviance are often limited to the early stages of the life course. Whereas the onset of risk behavior is well studied, less is currently known about the decline and timing of cessation of risk behaviors of different domains during young adulthood. Prevalence and longitudinal developmental patterning of alcohol use, drinking to the point of drunkenness, smoking, cannabis use, deviance, and HIV-related sexual risk behavior were compared in a Swiss community sample (N = 2,843). Using a longitudinal cohort-sequential approach to link multiple assessments with 3 waves of data for each individual, the studied period spanned the ages of 16 to 29 years. Although smoking had a higher prevalence, both smoking and drinking up to the point of drunkenness followed an inverted U-shaped curve. Alcohol consumption was also best described by a quadratic model, though largely stable at a high level through the late 20s. Sexual risk behavior increased slowly from age 16 to age 22 and then remained largely stable. In contrast, cannabis use and deviance linearly declined from age 16 to age 29. Young men were at higher risk for all behaviors than were young women, but apart from deviance, patterning over time was similar for both sexes. Results about the timing of increase and decline as well as differences between risk behaviors may inform tailored prevention programs during the transition from late adolescence to adulthood.

Cardiomyocyte growth and sarcomerogenesis at the intercalated disc

Cardiomyocytes grow during heart maturation or disease-related cardiac remodeling. We present evidence that the intercalated disc (ID) is integral to both longitudinal and lateral growth: increases in width are accommodated by lateral extension of the plicate tread regions and increases in length by sarcomere insertion within the ID. At the margin between myofibril and the folded membrane of the ID lies a transitional junction through which the thin filaments from the last sarcomere run to the ID membrane and it has been suggested that this junction acts as a proto Z-disc for sarcomere addition. In support of this hypothesis, we have investigated the ultrastructure of the ID in mouse hearts from control and dilated cardiomyopathy (DCM) models, the MLP-null and a cardiac-specific β-catenin mutant, cΔex3, as well as in human left ventricle from normal and DCM samples. We find that the ID amplitude can vary tenfold from 0.2 μm up to a maximum of ~2 μm allowing gradual expansion during heart growth. At the greatest amplitude, equivalent to a sarcomere length, A-bands and thick filaments are found within the ID membrane loops together with a Z-disc, which develops at the transitional junction position. Here, also, the tops of the membrane folds, which are rich in αII spectrin, become enlarged and associated with junctional sarcoplasmic reticulum. Systematically larger ID amplitudes are found in DCM samples. Other morphological differences between mouse DCM and normal hearts suggest that sarcomere inclusion is compromised in the diseased hearts.

Vulnerability and Growth. Developmental dynamics and differential effects of the loss of an intimate partner in the second half of life. IP 12: Study outline and first results

This working report gives an overview of the Individual Project 12 “Vulnerability and growth. Developmental dynamics and differential effects of the loss of an intimate partner in the second half of life” of the Swiss National Centre of Competence in Research LIVES led by Pasqualina Perrig-Chiello, University of Bern. This longitudinal and interdisciplinary project aims at examining vulnerability and personal growth after a critical life event, namely the break-up of a long-term intimate relationship in the second half of life, be it due to divorce or due to bereavement. In this report we present details about the rationale, the main research questions, the hypotheses and the methods of the study. Special attention is given to the methodological approach. The authors give a first sample description and report on the validity of the data by comparing the sample with Swiss Labour Force Survey and Swiss Health Survey data.

Challenge stressors: longitudinal effects on self attitudes, work attitudes, and health.

Recent research suggests that some stressors (i.e. hindrance stressors) have mainly negative consequences, whereas others (i.e. challenge stressors) can simultaneously have positive and negative consequences (e.g., LePine et al., 2005). Although a number of studies have dealt with potential outcomes of challenge stressors, some criteria have received only limited attention (e.g., positive self-attitudes; cf. Widmer et al., 2012), and some have been neglected altogether (i.e., physical health outcomes). Furthermore, while sophisticated methods – such as meta-analyses (e.g., LePine et al., 2005), diary studies (Ohly & Fritz, 2010), and multi-source analyses (Wallace et al., 2009) – have been applied to the framework, there are no longitudinal studies. We report results from a longitudinal study containing three waves, with two time-lags of one month each (N = 393). We analyzed relationships between challenge stressors and work attitudes (e.g. job satisfaction), self attitudes (e.g. self-esteem), and health indicators (e.g. sleep quality) using cross-lagged SEM. We expected positive effects of challenge stressors to appear only when their negative variance is controlled (e.g. by including hindrance stressors as a suppressor variable; cf. Cavanaugh et al., 2000). As the positive aspects of challenge stressors relate to self-affirming experiences, we also expected positive effects to be especially strong for self attitudes. Regarding work attitudes, the only significant paths found were from work attitudes to challenge stressors over both time lags. Regarding health, there was a significant cross-sectional association at time 1, which was negative, as expected. Longitudinally, a positive path from challenge stressors to health for both time lags was found only when hindrances stressors were controlled, confirming the expected suppressor effect. Hindrance stressors had a negative effect on health. For self-attitudes, there was a positive cross-sectional association at time one. In addition, a positive effect on self attitudes was found longitudinally for both time lags, but only when hindrance stressors were controlled. Additional analyses showed that the positive longitudinal effect on health was mediated by self attitudes. Although the lack of associations with work attitudes was surprising, our results indicate that challenge stressors contain aspects that provide an opportunity to develop self-esteem through demanding work situations, thereby contributing to personal growth and thriving at the workplace. They also confirm the ambiguous nature of challenge stressors, as, with one exception, positive effects were found only when hindrance stressors were controlled (cf. Widmer et al., 2012). Finally, our results confirm the importance of self-related attitudes in the stress process.

Self-esteem development across the life span: A longitudinal study with a large sample from Germany

The authors examined the development of self-esteem across the life span. Data came from a German longitudinal study with 3 assessments across 4 years of a sample of 2,509 individuals ages 14 to 89 years. The self-esteem measure used showed strong measurement invariance across assessments and birth cohorts. Latent growth curve analyses indicated that self-esteem follows a quadratic trajectory across the life span, increasing during adolescence, young adulthood, and middle adulthood, reaching a peak at age 60 years, and then declining in old age. No cohort effects on average levels of self-esteem or on the shape of the trajectory were found. Moreover, the trajectory did not differ across gender, level of education, or for individuals who had lived continuously in West versus East Germany (i.e., the 2 parts of Germany that had been separate states from 1949 to 1990). However, the results suggested that employment status, household income, and satisfaction in the domains of work, relationships, and health contribute to a more positive life span trajectory of self-esteem. The findings have significant implications, because they call attention to developmental stages in which individuals may be vulnerable because of low self-esteem (such as adolescence and old age) and to factors that predict successful versus problematic developmental trajectories.

Self-esteem development from age 14 to 30 years: A longitudinal study

We examined the development of self-esteem in adolescence and young adulthood. Data came from the Young Adults section of the National Longitudinal Survey of Youth, which includes 8 assessments across a 14-year period of a national probability sample of 7,100 individuals age 14 to 30 years. Latent growth curve analyses indicated that self-esteem increases during adolescence and continues to increase more slowly in young adulthood. Women and men did not differ in their self-esteem trajectories. In adolescence, Hispanics had lower self-esteem than Blacks and Whites, but the self-esteem of Hispanics subsequently increased more strongly, so that at age 30 Blacks and Hispanics had higher self-esteem than Whites. At each age, emotionally stable, extraverted, and conscientious individuals experienced higher self-esteem than emotionally unstable, introverted, and less conscientious individuals. Moreover, at each age, high sense of mastery, low risk taking, and better health predicted higher self-esteem. Finally, the results suggest that normative increase in sense of mastery accounts for a large proportion of the normative increase in self-esteem.

Self-esteem development from young adulthood to old age: A cohort-sequential longitudinal study

The authors examined the development of self-esteem from young adulthood to old age. Data came from the Americans’ Changing Lives study, which includes 4 assessments across a 16-year period of a nationally representative sample of 3,617 individuals aged 25 years to 104 years. Latent growth curve analyses indicated that self-esteem follows a quadratic trajectory across the adult life span, increasing during young and middle adulthood, reaching a peak at about age 60 years, and then declining in old age. No cohort differences in the self-esteem trajectory were found. Women had lower self-esteem than did men in young adulthood, but their trajectories converged in old age. Whites and Blacks had similar trajectories in young and middle adulthood, but the self-esteem of Blacks declined more sharply in old age than did the self-esteem of Whites. More educated individuals had higher self-esteem than did less educated individuals, but their trajectories were similar. Moreover, the results suggested that changes in socioeconomic status and physical health account for the decline in self-esteem that occurs in old age.

Development of a Tumour Growth Inhibition Model to Elucidate the Effects of Ritonavir on Intratumoural Metabolism and Anti-tumour Effect of Docetaxel in a Mouse Model for Hereditary Breast Cancer

In a mouse tumour model for hereditary breast cancer, we previously explored the anti-cancer effects of docetaxel, ritonavir and the combination of both and studied the effect of ritonavir on the intratumoural concentration of docetaxel. The objective of the current study was to apply pharmacokinetic (PK)-pharmacodynamic (PD) modelling on this previous study to further elucidate and quantify the effects of docetaxel when co-administered with ritonavir. PK models of docetaxel and ritonavir in plasma and in tumour were developed. The effect of ritonavir on docetaxel concentration in the systemic circulation of Cyp3a knock-out mice and in the implanted tumour (with inherent Cyp3a expression) was studied, respectively. Subsequently, we designed a tumour growth inhibition model that included the inhibitory effects of both docetaxel and ritonavir. Ritonavir decreased docetaxel systemic clearance with 8% (relative standard error 0.4%) in the co-treated group compared to that in the docetaxel only-treated group. The docetaxel concentration in tumour tissues was significantly increased by ritonavir with mean area under the concentration-time curve 2.5-fold higher when combined with ritonavir. Observed tumour volume profiles in mice could be properly described by the PK/PD model. In the co-treated group, the enhanced anti-tumour effect was mainly due to increased docetaxel tumour concentration; however, we demonstrated a small but significant anti-tumour effect of ritonavir addition (p value <0.001). In conclusion, we showed that the increased anti-tumour effect observed when docetaxel is combined with ritonavir is mainly caused by enhanced docetaxel tumour concentration and to a minor extent by a direct anti-tumour effect of ritonavir.

Dissolution-Precipitation in Porous Media: Experiments and Modelling

The evolution of porosity due to dissolution/precipitation processes of minerals and the associated change of transport parameters are of major interest for natural geological environments and engineered underground structures. We designed a reproducible and fast to conduct 2D experiment, which is flexible enough to investigate several process couplings implemented in the numerical code OpenGeosys-GEM (OGS-GEM). We investigated advective-diffusive transport of solutes, effect of liquid phase density on advective transport, and kinetically controlled dissolution/precipitation reactions causing porosity changes. In addition, the system allowed to investigate the influence of microscopic (pore scale) processes on macroscopic (continuum scale) transport. A Plexiglas tank of dimension 10 × 10 cm was filled with a 1 cm thick reactive layer consisting of a bimodal grain size distribution of celestite (SrSO4) crystals, sandwiched between two layers of sand. A barium chloride solution was injected into the tank causing an asymmetric flow field to develop. As the barium chloride reached the celestite region, dissolution of celestite was initiated and barite precipitated. Due to the higher molar volume of barite, its precipitation caused a porosity decrease and thus also a decrease in the permeability of the porous medium. The change of flow in space and time was observed via injection of conservative tracers and analysis of effluents. In addition, an extensive post-mortem analysis of the reacted medium was conducted. We could successfully model the flow (with and without fluid density effects) and the transport of conservative tracers with a (continuum scale) reactive transport model. The prediction of the reactive experiments initially failed. Only the inclusion of information from post-mortem analysis gave a satisfactory match for the case where the flow field changed due to dissolution/precipitation reactions. We concentrated on the refinement of post-mortem analysis and the investigation of the dissolution/precipitation mechanisms at the pore scale. Our analytical techniques combined scanning electron microscopy (SEM) and synchrotron X-ray micro-diffraction/micro-fluorescence performed at the XAS beamline (Swiss Light Source). The newly formed phases include an epitaxial growth of barite micro-crystals on large celestite crystals (epitaxial growth) and a nano-crystalline barite phase (resulting from the dissolution of small celestite crystals) with residues of celestite crystals in the pore interstices. Classical nucleation theory, using well-established and estimated parameters describing barite precipitation, was applied to explain the mineralogical changes occurring in our system. Our pore scale investigation showed limits of the continuum scale reactive transport model. Although kinetic effects were implemented by fixing two distinct rates for the dissolution of large and small celestite crystals, instantaneous precipitation of barite was assumed as soon as oversaturation occurred. Precipitation kinetics, passivation of large celestite crystals and metastability of supersaturated solutions, i.e. the conditions under which nucleation cannot occur despite high supersaturation, were neglected. These results will be used to develop a pore scale model that describes precipitation and dissolution of crystals at the pore scale for various transport and chemical conditions. Pore scale modelling can be used to parameterize constitutive equations to introduce pore-scale corrections into macroscopic (continuum) reactive transport models. Microscopic understanding of the system is fundamental for modelling from the pore to the continuum scale.

The enduring effects of psychodynamic treatments vis-à-vis alternative treatments: A multilevel longitudinal meta-analysis

Although evidence suggests that the benefits of psychodynamic treatments are sustained over time, presently it is unclear whether these sustained benefits are superior to non-psychodynamic treatments. Additionally, the extant literature comparing the sustained benefits of psychodynamic treatments compared to alternative treatments is limited with methodological shortcomings. The purpose of the current study was to conduct a rigorous test of the growth of the benefits of psychodynamic treatments relative to alternative treatments across distinct domains of change (i.e., all outcome measures, targeted outcome measures, non-targeted outcome measures, and personality outcome measures). To do so, the study employed strict inclusion criteria to identify randomized clinical trials that directly compared at least one bona fide psychodynamic treatment and one bona fide non-psychodynamic treatment. Hierarchical linear modeling (Raudenbush, Bryk, Cheong, Congdon, & du Toit, 2011) was used to longitudinally model the impact of psychodynamic treatments compared to non-psychodynamic treatments at post-treatment and to compare the growth (i.e., slope) of effects beyond treatment completion. Findings from the present meta-analysis indicated that psychodynamic treatments and non-psychodynamic treatments were equally efficacious at post-treatment and at follow-up for combined outcomes (k=20), targeted outcomes (k=19), non-targeted outcomes (k=17), and personality outcomes (k=6). Clinical implications, directions for future research, and limitations are discussed.