Changes in Personality and Well-Being Across Adulthood: Riding the Self-Esteem Rollercoaster

Personality factors have long been implicated in how individuals manage and cope with circumstances to maintain well-being and health across the lifespan (Lazarus & Folkman, 1984; Mroczek & Spiro, 2007; Wrosch & Scheier, 2003). However, personality factors have also been shown to change over time in both situational and normative contexts (Caspi & Roberts, 1999; Crocker & Wolfe, 2006; Robins et al., 2002; Roberts, Walton & Virchtbauer, 2006). These changes in personality can provide important information about how individuals adapt to and navigate life events and challenges. We investigate self-esteem as a personality factor that changes across the lifespan and identify age-related differences in the impact of self-esteem levels and changes on indices of well-being. This line of research combines personality and lifespan developmental literature to address the question whether levels of and changes in self-esteem can predict well-being and whether there are age-related effects as self-esteem changes across the lifespan. The present dissertation had three main goals: 1) To examine the impact of self-esteem changes and levels across the adult lifespan; 2) to examine changes in self-esteem in different ways – intraindividual changes in self-esteem, normative changes in self-esteem and experimental changes in self-esteem; 3) to investigate the moderating role of self-esteem changes. In order to address these goals, data was collected to examine within-person changes in self-esteem among older adults, data from Statistics Canada was analyzed to examine normative changes in self-esteem, and finally an intervention study was developed to examine experimental changes in self-esteem among young and older adults, and data on psychological and emotional well-being were collected. Three manuscripts were then written based on this data and are included as part of this dissertation. The first manuscript examined the potential moderating role of self-esteem on older adults’ perceived stress and regret intensity, over 10 years in a sample of 167 community dwelling older adults. This study examined the within-person associations between older adults’ perceived stress and regret intensity, and the moderating role of levels of, and within-person changes in, self-esteem. Within-person results indicated that older adults reported higher levels of regret intensity when they reported higher than their average levels of perceived stress, and that within-person increases of self-esteem, but not between-person levels, moderated this association. The results suggest that within-person changes in self-esteem may be more important than individual differences of self-esteem in protecting older adults from experiencing greater regret intensity under stressful circumstances. The second manuscript, revised and re-submitted for publication in Social Science and Medicine, examines normative changes in self-esteem across the adult lifespan in a 16-year longitudinal sample of 14,117 adults from the National Population Health Survey (NPHS). The study examines whether changes in self-esteem and chronic disease exert reciprocal effects on subsequent changes in self-esteem and chronic disease, and whether individuals’ age would moderate these associations. The findings from this paper suggest that there are reciprocal age-related associations between changes in self-esteem and chronic disease. Only among young adults, but not middle-aged or older adults, initial decline in self-esteem predicted subsequent increases in chronic disease, and initial increases in chronic disease predicted subsequent declines in self-esteem. The results from this study highlight that adverse changes in both self-esteem and physical health may be particularly problematic for young adults, and have comparably less impact among middle-aged and older adults. The third and final manuscript included in this dissertation attempted to improve young and older adults’ self-esteem through a brief writing intervention. The study examines whether self-esteem can be improved, whether baseline levels of self-esteem and naturally occurring changes in self-esteem play an adaptive role in mitigating consequences of stress, and predict psychological and emotional well-being, and whether these associations are moderated by age. The study examines 106 young and older adults, randomized into control and intervention groups, who were asked to engage in three consecutive days of writing. All participants completed an in-lab stress task, and cortisol data were also examined. The results of the study suggest that our writing intervention did not work. In addition, the results suggest that high levels of self-esteem and naturally occurring increases in self-esteem (and not experimental changes), predicted positive outcomes, only for older, but not younger, adults. Consistent with previous research, our results highlight age differences in the association between self-esteem and psychological and emotional well-being, which may also suggest that future self-esteem interventions could be more tailored to each specific age group

SBE13, a newly identified inhibitor of inactive polo-like kinase 1

Poster presentation at 5th German Conference on Cheminformatics: 23. CIC-Workshop Goslar, Germany. 8-10 November 2009 Protein kinases are important targets for drug development. The almost identical protein folding of kinases and the common co-substrate ATP leads to the problem of inhibitor selectivity. Type II inhibitors, targeting the inactive conformation of kinases, occupy a hydrophobic pocket with less conserved surrounding amino acids. Human polo-like kinase 1 (Plk1) represents a promising target for approaches to identify new therapeutic agents. Plk1 belongs to a family of highly conserved serine/threonine kinases, and is a key player in mitosis, where it modulates the spindle checkpoint at metaphase/anaphase transition. Plk1 is over-expressed in all today analyzed human tumors of different origin and serves as a negative prognostic marker in cancer patients. The newly identified inhibitor, SBE13, a vanillin derivative, targets Plk1 in its inactive conformation. This leads to selectivity within the Plk family and towards Aurora A. This selectivity can be explained by docking studies of SBE13 into the binding pocket of homology models of Plk1, Plk2 and Plk3 in their inactive conformation. SBE13 showed anti-proliferative effects in cancer cell lines of different origins with EC50 values between 5 microM and 39 microM and induced apoptosis. Increasing concentrations of SBE13 result in increasing amounts of cells in G2/M phase 13 hours after double thymidin block of HeLa cells. The kinase activity of Plk1 was inhibited with an IC50 of 200 pM. Taken together, we could show that carefully designed structure-based virtual screening is well-suited to identify selective type II kinase inhibitors targeting Plk1 as potential anti-cancer therapeutics

Self-esteem Change and Diurnal Cortisol Secretion in Older Adulthood

Research suggests that self-esteem can decline in older adulthood. This process could remove a buffer that normally protects individuals against distress-related changes in cortisol secretion. We examined this possibility by testing whether change in self- esteem would predict alterations in cortisol secretion, particularly among older adults who reported high levels of depressive symptoms or perceived stress. 147 older adults (Aged 60+) completed three days of diurnal cortisol measurements at three different time points, namely every two years over a total period of four years. Measures of self-esteem, depressive symptoms, and perceived stress were assessed at T1 and T2. Potential demographic and health-related confounds were measured at baseline (partnership status, SES, mortality risk index, and medication). Linear regression models indicated that a decline in self-esteem from T1 to T2 predicted elevated cortisol output (AUCG) from T2 to T3, F (1, 137) = 8.09, ? = -.25, R2 = .05, p = .005. Interaction analyses revealed that this association was particularly strong among participants who experienced higher T1 or T2 levels of depressive symptoms or perceived stress, +1 SD: ?s = -.34 to -.51, ps .43. Declines in self-esteem represent a mechanism that contributes to higher levels of diurnal cortisol secretion if older adults experience psychological distress. Increases in self-esteem, by contrast, can ameliorate older adults� cortisol regulation in stressful circumstances

A randomised clinical trial comparing outcomes of a single digit volar plate injury : buddy loops versus dorsal thermoplastic orthosis in a neutral position : study protocol

Background Volar plate injuries are a common hand injury and complications associated with this injury such as a fixed flexion deformity, persistent pain and oedema can have a significant impact on a person’s function. The literature reports these injuries are treated using various splinting materials such as thermoplastic, in varying degrees of proximal interphalangeal joint flexion or buddy loops. Despite volar plate injuries being reported as common, optimal non-surgical treatment of these injuries remains unclear. This study aims to investigate whether a dorsal blocking orthosis in a neutral position (00) is more effective than buddy loops for a volar plate injury to the proximal interphalangeal joint in preventing a fixed flexion deformity, reducing pain, managing oedema, and promoting function. Methods This study is a single-centre, prospective parallel-group, single blinded (assessor), randomised clinical trial. Patients between 18–65 years, who have sustained a volar plate injury to a single digit, have adequate cognitive functioning and give written informed consent will be invited to participate in this study. Patients will be randomised to either the control group where they will be fitted with buddy loops and commence early active motion exercises or the experimental group where they will receive a dorsal thermoplastic orthosis in a neutral position and commence early active motion exercises. The primary outcome measure is passive proximal interphalangeal joint extension and secondary outcome measures include passive range of motion, total passive motion, active range of motion, total active motion, grip strength, oedema, pain, function and adherence to treatment. Assessments will be completed until 8 weeks following commencement of treatment. The sample size calculation indicates that 23 patients is required in each group. With an expected dropout rate of 25% a total of 32 patients will be enrolled in each group. Discussion This study will assist in trying to improve treatment of volar plate injuries and assist in reducing complications associated with volar plate injuries, potentially reducing the need for prolonged hand therapy. Trial registration This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622001425785p). Ethical approval has been granted by the South Eastern Sydney Local Health District ethical committee (2022/ETH01697)

Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer’s disease

The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment of Alzheimer’s disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer’s disease treatment pipeline. Based on limited published clinical trial data to date, regulators, payors and physicians will need to assess their efficacy, clinical effectiveness and safety, as well as cost and accessibility. We propose that attention to three important questions related to treatment efficacy, clinical effectiveness and safety should guide evidence-based consideration of this important class of drugs. These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a representative clinical population of people with Alzheimer’s disease? and (3) Do the data convincingly demonstrate disease course modification, suggesting that increasing clinical benefits beyond the duration of the trials are likely? We suggest specific approaches to interpreting trial results for these drugs and highlight important areas of uncertainty where additional data and a cautious interpretation of existing results is warranted. Safe, effective and accessible treatments for Alzheimer’s disease are eagerly awaited by millions of patients and their caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying Alzheimer’s disease treatments, rigorous and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based appraisal of these drugs by regulators, payors, physicians and patients

Exploring asymmetric substructures of the outer disk based on the conjugate angle of the radial action

We use the conjugate angle of radial action ($\theta_R$), the best representation of the orbital phase, to explore the "mid-plane, north branch, south branch" and "Monoceros area" disk structures that were previously revealed in the LAMOST K giants (Xu et al. 2020). The former three substructures, identified by their 3D kinematical distributions, have been shown to be projections of the phase space spiral (resulting from nonequilibrium phase mixing). In this work, we find that all of these substructures associated with the phase spiral show high aggregation in conjugate angle phase space, indicating that the clumping in conjugate angle space is a feature of ongoing, incomplete phase mixing. We do not find the $Z-V_Z$ phase spiral located in the "Monoceros area", but we do find a very highly concentrated substructure in the quadrant of conjugate angle space with the orbital phase from the apocenter to the guiding radius. The existence of the clump in conjugate angle space provides a complementary way to connect the "Monoceros area" with the direct response to a perturbation from a significant gravitationally interactive event. Using test particle simulations, we show that these features are analogous to disturbances caused by the impact of the last passage of the Sagittarius dwarf spheroidal galaxy.Comment: 53pages, 35 figures, 4 Tables, ApJ accepte

An E. coli-produced single-chain variable fragment (scFv) targeting hepatitis B virus surface protein potently inhibited virion secretion

Hepatitis B virus (HBV) envelopes as well as empty subviral particles carry in their lipid membranes the small (S), middle (M), and large (L) surface proteins, collectively known as hepatitis B surface antigen (HBsAg). Due to their common S domain all three proteins share a surface-exposed hydrophilic antigenic loop (AGL) with a complex disulfide bridge-dependent structure. The AGL is critical for HBV infectivity and virion secretion, and thus represents a major target for neutralizing antibodies. Previously, a human monoclonal antibody (mAb) targeting a conformational epitope in the AGL, IgG12, exhibited 1000-fold higher neutralizing activity than hepatitis B immune globulin (HBIG). Here we designed a single-chain variable fragment (scFv) homolog of IgG12, G12-scFv, which could be efficiently produced in soluble form in the cytoplasm of E. coli SHuffle cells. Independent in vitro assays verified specific binding of G12-scFv to a conformational S epitope shared with IgG12. Despite 20-fold lower affinity, G12-scFv but not an irrelevant scFv potently neutralized HBV infection of susceptible hepatoma cells (IC50=1.8nM). Strikingly, low concentrations of G12-scFv blocked virion secretion from HBV producing cells (IC50=1.25nM) without disturbing intracellular viral replication, whereas extracellular HBsAg was reduced only at >100-fold higher though still nontoxic concentration. The inhibitory effects correlated with S binding specificity and presumably also G12-scFv internalization into cells. Together these data suggest G12-scFv as a highly specific yet easily accessible novel tool for basic, diagnostic, and possibly future therapeutic applications

Comparison of mitotic cell death by chromosome fragmentation to premature chromosome condensation

Mitotic cell death is an important form of cell death, particularly in cancer. Chromosome fragmentation is a major form of mitotic cell death which is identifiable during common cytogenetic analysis by its unique phenotype of progressively degraded chromosomes. This morphology however, can appear similar to the morphology of premature chromosome condensation (PCC) and thus, PCC has been at times confused with chromosome fragmentation. In this analysis the phenomena of chromosome fragmentation and PCC are reviewed and their similarities and differences are discussed in order to facilitate differentiation of the similar morphologies. Furthermore, chromosome pulverization, which has been used almost synonymously with PCC, is re-examined. Interestingly, many past reports of chromosome pulverization are identified here as chromosome fragmentation and not PCC. These reports describe broad ranging mechanisms of pulverization induction and agree with recent evidence showing chromosome fragmentation is a cellular response to stress. Finally, biological aspects of chromosome fragmentation are discussed, including its application as one form of non-clonal chromosome aberration (NCCA), the driving force of cancer evolution

Self-esteem change and diurnal cortisol secretion in older adulthood

Objective: Research suggests that self-esteem can decline in older adulthood. This process could remove a buffer that normally protects individuals against distress-related changes in cortisol secretion. We examined this possibility by testing whether change in self-esteem would predict alterations in cortisol secretion, particularly among older adults who reported high levels of depressive symptoms or perceived stress. Methods: 147 older adults (Aged 60+) completed three days of diurnal cortisol measurements at three different time points, namely every two years over a total period of four years. Measures of self-esteem, depressive symptoms, and perceived stress were assessed at T1 and T2. Potential demographic and health-related confounds were measured at baseline (partnership status, SES, mortality risk index, and medication). Results: Linear regression models indicated that a decline in self-esteem from T1 to T2 predicted elevated cortisol output (AUCG) from T2 to T3, F (1, 137) = 8.09, β = -.25, R2 = .05, p = .005. Interaction analyses revealed that this association was particularly strong among participants who experienced higher T1 or T2 levels of depressive symptoms or perceived stress, +1 SD: βs = -.34 to -.51, ps .43. Conclusions: Declines in self-esteem represent a mechanism that contributes to higher levels of diurnal cortisol secretion if older adults experience psychological distress. Increases in self-esteem, by contrast, can ameliorate older adults’ cortisol regulation in stressful circumstances

Developing and assessing the feasibility of a home-based preexposure prophylaxis monitoring and support program

We piloted PrEP@Home, a preexposure prophylaxis system of remote laboratory and behavioral monitoring designed to replace routine quarterly follow-up visits with home care to reduce the patient and provider burden. The system was highly acceptable and in-demand for future use, and more than one-third of participants reported greater likelihood of persisting in care if available