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Objective: Propose a framework for developing and evaluating Total Worker Health ® (TWH) education and training efforts by implementing institutions. Methods: This is a review of TWH information from symposia, workshops, academic offerings, and publications, along with a review of education and training development and evaluation resources applicable across various disciplines. Results: Examples of knowledge, skills, and abilities (KSAs) are provided for each TWH core competency, and a framework for developing and evaluating a TWH competency-based education or training program. Conclusions: The proposed set of KSAs and framework for developing and evaluating TWH education or training programs may inform future pilot testing of KSAs and framework by implementing institutions and help standardize practices across the discipline. Academic, business, community, labor, and government stakeholders are encouraged to provide further input to assist in its maturation and uptake. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets. Methods: We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis. Results: The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption. Conclusions: These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, several therapeutic advances have been made in clear cell renal cell carcinoma (ccRCC) resulting in novel treatment regimens of increased effectiveness. These advances are largely due to breakthroughs in technologies, particularly in transcriptomics, such as single-cell RNA sequencing (scRNA-seq). Using this technology, we have gained a deeper understanding of the biology of ccRCC and revealed various cell populations and their interactions in disease progression. While localized ccRCC patients have shown promising responses to treatment, however, patients with advanced or metastatic disease remain a therapeutic challenge. To address this gap, recent studies have utilized scRNA-seq to investigate both primary and metastatic ccRCC in search of promising therapeutic targets. This review aims to summarize the current state of knowledge in the field, highlight available treatment options and underscore the critical steps needed to improve survival rates, especially for metastatic ccRCC patients. Over the past two decades, significant progress has been made in the treatment of clear cell renal cell carcinoma (ccRCC), with a shift towards adopting new treatment approaches ranging from monotherapy to triple-combination therapy. This progress has been spearheaded by fundamental technological advancements that have allowed a deeper understanding of the various biological components of this cancer. In particular, the rapid commercialization of transcriptomics technologies, such as single-cell RNA-sequencing (scRNA-seq) methodologies, has played a crucial role in accelerating this understanding. Through precise measurements facilitated by these technologies, the research community has successfully identified and characterized diverse tumor, immune, and stromal cell populations, uncovering their interactions and pathways involved in disease progression. In localized ccRCC, patients have shown impressive response rates to treatment. However, despite the emerging findings and new knowledge provided in the field, there are still patients that do not respond to treatment, especially in advanced disease stages. One of the key challenges lies in the limited study of ccRCC metastases compared to localized cases. This knowledge gap may contribute to the relatively low survival rates and response rates observed in patients with metastatic ccRCC. To bridge this gap, we here delve into recent research utilizing scRNA-seq technologies in both primary and metastatic ccRCC. The goal of this review is to shed light on the current state of knowledge in the field, present existing treatment options, and emphasize the crucial steps needed to improve survival rates, particularly in cases of metastatic ccRCC. [ABSTRACT FROM AUTHOR]

• Few studies have examined the change process in written exposure therapy for PTSD. • We examined outcome predictors in two PTSD treatments using trauma narratives. • In written exposure therapy, healthy, balanced beliefs predicted better outcome. • In cognitive processing therapy, avoidance and cognitive factors predicted outcome. • Narratives can provide useful information for examining predictors of outcome. Written exposure therapy (WET) is a brief, five-session treatment for posttraumatic stress disorder (PTSD) that aims to improve access to care. WET has been demonstrated to be an efficacious PTSD treatment with lower rates of dropout and noninferior PTSD symptom outcome compared to cognitive processing therapy (CPT), a 12-session, gold-standard treatment. To identify predictors of treatment outcome in both WET and CPT, the current study examined the content of participants' written narratives. Participants were 123 adults with PTSD who were randomly assigned to receive WET (n = 61) or CPT (n = 62). The Change and Growth Experiences Scale (CHANGE) coding system was used to code all available narratives in both treatment conditions for variables hypothesized to be relevant to therapeutic change. Linear regression analyses revealed that in WET, higher average levels of accommodated (healthy, balanced) beliefs and an increase in accommodated beliefs from the first to the final impact statement predicted better PTSD symptom outcome at 12 weeks postrandomization. In CPT, higher average levels of overgeneralized and accommodated beliefs and lower levels of avoidance expressed in the narratives predicted better PTSD outcome. There were no significant predictors of outcome in analyses of change from the first to final impact statement in CPT. These findings add to research identifying predictors of change in WET and CPT by highlighting the importance of low avoidance in CPT and of trauma-related cognitions in both CPT and WET, even though WET is a brief written intervention that does not explicitly target cognitive change. [ABSTRACT FROM AUTHOR]

We evaluated neuropathological consequences of fetal ZIKV exposure in rhesus monkeys, a translatable animal model for human neural development, by carrying out quantitative neuroanatomical analyses of the nearly full-term brains of fetuses infected with ZIKV and procedure-matched controls. For each animal, a complete cerebral hemisphere was evaluated using immunohistochemical (IHC) and neuroanatomical techniques to detect virus, identify affected cell types, and evaluate gross neuroanatomical abnormalities. IHC staining revealed the presence of ZIKV in the frontal lobe, which contained activated microglia and showed increased apoptosis of immature neurons. ZIKV-infected animals exhibited macrostructural changes within the visual pathway. Regional differences tracked with the developmental timing of the brain, suggesting inflammatory processes related to viral infiltration swept through the cortex, followed by a wave of cell death resulting in morphological changes. These findings may help explain why some infants born with normal sized heads during the ZIKV epidemic manifest developmental challenges as they age. [ABSTRACT FROM AUTHOR]

Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) is an effective treatment for children impacted by trauma, and non-offending caregivers play an important role in this treatment. This study aims to identify correlates of four caregiver variables that have been identified as predictors of child outcomes in TF-CBT: support, cognitive-emotional processing, avoidance, and blame/criticism. Audio recorded sessions were coded from a community effectiveness trial of TF-CBT that included 71 child-caregiver dyads participating in the trauma narration and processing phase of treatment. Regression analyses were conducted to examine caregiver trauma history and child baseline symptoms (internalizing, externalizing, and posttraumatic stress disorder [PTSD] symptoms) as predictors of caregiver behavior during the trauma processing sessions. Caregivers who reported exposure to more trauma types exhibited more in-session avoidance and also processing during the trauma processing phase of treatment. Child symptoms at baseline did not predict caregiver in-session behaviors. Bivariate correlations were used to investigate concurrent associations between mean levels of in-session caregiver behaviors and in-session child distress (negative emotion, hopelessness, negative behaviors). More caregiver blame/criticism was associated with more in-session child distress on all three measures. Caregiver avoidance was associated with more child negative emotion and hopelessness. Findings may help identify therapeutic targets when working with caregivers to promote change and enhance TF-CBT outcomes. [ABSTRACT FROM AUTHOR]

Background: Little is known about effects of COVID-19 lockdown on psychosocial factors, health and lifestyle in older adults, particularly those aged over 80 years, despite the risks posed by COVID-19 to this age group. Methods: Lothian Birth Cohort 1936 members, residing mostly in Edinburgh and the surrounding Lothians regions in Scotland, mean age 84 years (SD = 0.3), responded to an online questionnaire in May 2020 (n = 190). We examined responses (experience and knowledge of COVID-19; adherence to guidance; impact on day-to-day living; social contact; self-reported physical and mental health; loneliness; and lifestyle) and relationships between previously-measured characteristics and questionnaire outcomes. Results: Four respondents experienced COVID-19; most had good COVID-19 knowledge (94.7%) and found guidance easy to understand (86.3%). There were modest declines in self-reported physical and mental health, and 48.2% did less physical activity. In multivariable regression models, adherence to guidance by leaving the house less often associated with less professional occupational class (OR = 0.71, 95%CI 0.51–0.98) and poorer self-rated general health (OR = 0.62, 95%CI 0.42–0.92). Increased internet use associated with female sex (OR = 2.32, 95%CI 1.12–4.86) and higher general cognitive ability (OR = 1.53, 95%CI 1.03–2.33). Loneliness associated with living alone (OR = 0.15, 95%CI 0.07–0.31) and greater anxiety symptoms (OR = 1.76, 95%CI 0.45–1.24). COVID-19 related stress associated with lower emotional stability scores (OR = 0.40, 95%CI 0.24–0.62). Decreased physical activity associated with less professional occupational class (OR = 1.43, 95%CI 1.04–1.96), and lower general cognitive ability (OR = 0.679, 95%CI 0.491–0.931). Conclusions: Characteristics including cognitive function, occupational class, self-rated health, anxiety, and emotional stability, may be related to risk of poorer lockdown-related psychosocial and physical outcomes. [ABSTRACT FROM AUTHOR]

This article aims to evaluate a hearing loss intervention versus an aging education intervention on activity engagement in the Aging and Cognitive Health Evaluation in Elders pilot (ACHIEVE-P). Forty adults (70–84 years) with hearing loss recruited from the Atherosclerosis Risk in Communities Study and de novo participated. Participants were randomized 1:1 to a best practices hearing intervention or a successful aging intervention. Hearing was measured with pure-tone audiometry. The Community Healthy Activities Model Program for Seniors questionnaire measured self-reported time engaging in activities at baseline and 6-month follow-up. At baseline, greater hearing loss was associated with reduced time per week on mental activities (−3.0 hours per 10 dB of hearing loss, 95% confidence interval: −5.8, −0.2). Mental activity engagement increased (mean: +1.3 hours, SD = 6.6) for the hearing intervention group but decreased (mean: −1.1 hours, SD = 4.8) for the aging education group (Cohen's d : 0.41). Hearing loss may be associated with reduced engagement in mental activities. Whether hearing loss treatment impacts activity will be studied in the full-scale ACHIEVE trial. [ABSTRACT FROM AUTHOR]

Recent clinical research suggests that facilitating psychological flexibility and emotional processing and decreasing rumination and avoidance are important tasks of treatment for disorders characterized by entrenched patterns of psychopathology, such as major depressive disorder. The current study examined these processes as predictors of treatment outcomes in a subsample of depressed adult patients (n = 49) who had not fully responded to antidepressant medication and were randomized to receive cognitive–behavioral therapy (CBT). Target variables were coded from session recordings at baseline and in the vicinity of two therapeutic transition points: a sudden gain (improvement) and a transient spike in depression symptoms, or at similar periods for those without such transitions. Results indicated that psychological flexibility during the pre-sudden gain period predicted less depression at 12-month follow-up, beyond baseline symptoms and other co-occurring processes. Interaction analyses revealed that when flexibility was low during the post-spike period, avoidance and rumination predicted higher depressive symptoms, whereas emotional processing predicted lower symptoms at the 12-month follow-up. When flexibility was high, none of these variables were associated with outcome. Together, these findings highlight psychological flexibility as a key therapeutic target in CBT for treatment-resistant depression and might have implications for relapse prevention. [ABSTRACT FROM AUTHOR]

Cancer vaccine development has proven challenging with the exception of some virally induced cancers for which prophylactic vaccines exist. Currently, there is only one FDA approved vaccine for the treatment of prostate cancer and as such prostate cancer continues to present a significant unmet medical need. In this study, we examine the effectiveness of a therapeutic cancer vaccine that combines the ISCOMATRIX™ adjuvant (ISCOMATRIX) with the Toll-like receptor 3 agonist, polyinosinic–polycytidylic acid (Poly I:C), and Flt3L, FMS-like tyrosine kinase 3 ligand. We employed the TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) model of prostate cancer and the self-protein mPAP (prostatic acid phosphatase) as the tumor antigen. ISCOMATRIX™–mPAP–Poly I:C–Flt3L was delivered in a therapeutic prime-boost regime that was consistently able to achieve complete tumor regression in 60% of animals treated and these tumor-free animals were protected upon rechallenge. Investigations into the underlying immunological mechanisms contributing to the effectiveness of this vaccine identified that both innate and adaptive responses are elicited and required. NK cells, CD4+ T cells and interferon-γ were all found to be critical for tumor control while tumor infiltrating CD8+ T cells became disabled by an immunosuppressive microenvironment. There is potential for broader application of this cancer vaccine, as we have been able to demonstrate effectiveness in two additional cancer models; melanoma (B16-OVA) and a model of B cell lymphoma (Eµ-myc-GFP-OVA). [ABSTRACT FROM AUTHOR]

Dropout rates in trauma-focused treatments for adult posttraumatic stress disorder (PTSD) are high. Most research has focused on demographic and pretreatment predictors of dropout, but findings have been inconsistent. We examined predictors of dropout in cognitive processing therapy (CPT) by coding the content of trauma narratives written in early sessions of CPT. Data are from a randomized controlled noninferiority trial of CPT and written exposure therapy (WET) in which CPT showed significantly higher dropout rates than WET (39.7% CPT vs. 6.4% WET). Participants were 51 adults with a primary diagnosis of PTSD who were receiving CPT and completed at least one of three narratives in the early sessions of CPT. Sixteen (31%) in this subsample were classified as dropouts and 35 as completers. An additional 9 participants dropped out but could not be included because they did not complete any narratives. Of the 11 participants who provided a reason for dropout, 82% reported that CPT was too distressing. The CHANGE coding system was used to code narratives for pathological trauma responses (cognitions, emotions, physiological responses) and maladaptive modes of processing (avoidance, ruminative processing, overgeneralization), each on a scale from 0 (absent) to 3 (high). Binary logistic regressions showed that, averaging across all available narratives, more negative emotions described during or around the time of the trauma predicted less dropout. More ruminative processing in the present time frame predicted lower rates of dropout, whereas more overgeneralized beliefs predicted higher rates. In the first impact statement alone, more negative emotions in the present time frame predicted lower dropout rates, but when emotional reactions had a physiological impact, dropout was higher. These findings suggest clinicians might attend to clients' written trauma narratives in CPT in order to identify indicators of dropout risk and to help increase engagement. [ABSTRACT FROM AUTHOR]

Background: A growing body of research highlights the limitations of traditional methods for studying the process of change in psychotherapy. The science of complex systems offers a useful paradigm for studying patterns of psychopathology and the development of more functional patterns in psychotherapy. Some basic principles of change are presented from subdisciplines of complexity science that are particularly relevant to psychotherapy: dynamical systems theory, synergetics, and network theory. Two early warning signs of system transition that have been identified across sciences (critical fluctuations and critical slowing) are also described. The network destabilization and transition (NDT) model of therapeutic change is presented as a conceptual framework to import these principles to psychotherapy research and to suggest future research directions.Discussion: A complex systems approach has a number of implications for psychotherapy research. We describe important design considerations, targets for research, and analytic tools that can be used to conduct this type of research.Conclusions: A complex systems approach to psychotherapy research is both viable and necessary to more fully capture the dynamics of human change processes. Research to date suggests that the process of change in psychotherapy can be nonlinear and that periods of increased variability and critical slowing might be early warning signals of transition in psychotherapy, as they are in other systems in nature. Psychotherapy research has been limited by small samples and infrequent assessment, but ambulatory and electronic methods now allow researchers to more fully realize the potential of concepts and methods from complexity science. [ABSTRACT FROM AUTHOR]

[Correction Notice: An Erratum for this article was reported online in Psychology and Aging on Mar 5 2020 (see record 2020-16850-001). This article should have been published under the terms of the Creative Commons Attribution License (CC BY 3.0). Therefore, the article was amended to list the authors as copyright holders, and information about the terms of the CC BY 3.0 was added to the author note. In addition, the article is now open access. All versions of this article have been corrected.] It is unclear how scores on self-report resilience scales relate to key ageing-related domains in older age and if they truly measure resilience. We examined antecedents and outcomes of age-76 Brief Resilience Scale (BRS) scores in participants of the Lothian Birth Cohort 1936 (n = 655). We found bivariate associations between age-76 BRS scores and ageing-relevant antecedent variables measured at least 3 years earlier, from domains of cognitive ability, physical fitness, and wellbeing and, additionally, sociodemographics and personality (absolute r's from .082 to .49). Biological health variables were not associated with BRS scores. Age-73 cognitive ability (largest β = 0.14), physical fitness (largest β = 0.084), and wellbeing variables (largest β = 0.26) made positive independent contributions to age-76 BRS scores in multivariate models. In a conservative model including all variables as covariates, corrected for multiple comparisons, only emotional stability (neuroticism) significantly independently contributed to BRS score (β = 0.33). An exploratory backward elimination model indicated more wellbeing and personality associates of BRS scores (βs from .087 to .32). We used latent difference score modeling to assess outcomes of BRS scores; we examined associations between age-76 BRS and change in latent factors of age-related domains between age 76 and 79. Whereas BRS scores were related cross-sectionally to levels of latent cognitive ability (r = .19), physical fitness (r = .20), and wellbeing (r = .60) factors, they were not related to declines in these domains. The independence of the BRS construct from established wellbeing and personality factors is unclear. (PsycInfo Database Record (c) 2020 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

Objective: The sudden gain (SG; large symptom improvements in one between-session interval) has been identified as a consistent predictor of better outcomes at posttreatment and over follow-up in cognitive–behavioral therapy (CBT) for depression. Other defined trajectories of symptom change in CBT, including linear (consistent changes in depression), log-linear (symptom change concentrated in early or late sessions), one-step (substantial change in depression symptoms between two adjacent sessions), and cubic (symptom decrease, increase, and decrease), also predict better treatment outcomes. Method: We explored whether these patterns of symptom change occurred and predicted outcome in a sample of 156 adults with treatment-resistant depression who participated in a randomized controlled trial of CBT as an adjunct to pharmacotherapy (Wiles et al., 2013). Depression symptoms were assessed weekly with the Beck Depression Inventory-II. Results: Multilevel modeling revealed that both SGs and having a defined trajectory predicted lower depression severity at 6- and 12-month follow-up, even controlling for baseline depression symptoms, early slopes of change, and symptom variability. Conclusions: These findings highlight the importance of examining longitudinal data and the robustness of the sudden gain pattern. They further suggest that having a defined symptom trajectory might confer its own advantages in predicting depression outcomes. Clinicians could use weekly depression scores to identify these key patterns of change to guide treatment decisions. This research identified patterns of depression symptom change during treatment that predicted better 6- and 12-month outcomes in a sample receiving cognitive–behavioral therapy and pharmacotherapy for treatment-resistant depression. These key patterns, which included sudden gains (large symptom improvement from one session to the next) and defined trajectories (consistent patterns of change), could be identified directly in clinical practice, especially with the use of weekly symptom monitoring systems and algorithms. [ABSTRACT FROM AUTHOR]

The Plasmodium falciparum ATPase PfATP4is the target of a diverse range of antimalarial compounds, including the clinical drug candidate cipargamin. PfATP4 was originally annotated as a Ca2+ transporter, but recent evidence suggests that it is a Na+ efflux pump, extruding Na+ in exchange for H+. Here we demonstrate that ATP4 proteins belong to a clade of P-type ATPases that are restricted to apicomplexans and their closest relatives. We employed a variety of genetic and physiological approaches to investigate the ATP4 protein of the apicomplexan Toxoplasma gondii, TgATP4. We show that TgATP4 is a plasma membrane protein. Knockdown of TgATP4 had no effect on resting pH or Ca2+ but rendered parasites unable to regulate their cytosolic Na+ concentration ([Na+]cyt). PfATP4 inhibitors caused an increase in [Na+]cyt and a cytosolic alkalinization in WT but not TgATP4 knockdown parasites. Parasites in which TgATP4 was knocked down or disrupted exhibited a growth defect, attributable to reduced viability of extracellular parasites. Parasites in which TgATP4 had been disrupted showed reduced virulence in mice. These results provide evidence for ATP4 proteins playing a key conserved role in Na+ regulation in apicomplexan parasites. [ABSTRACT FROM AUTHOR]

Abstract Oxytocin (OT) elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates and humans by reducing food intake and increasing energy expenditure. In addition to being important in the regulation of energy balance, OT is involved in social behaviors including parent-infant bonds, friendships, and pair bonds. However, the impact of social context on susceptibility to diet-induced obesity (DIO) and feeding behavior (including food sharing) has not been investigated in a rodent model that forms strong social bonds (i.e. prairie vole). Our goals were to determine in Prairie voles (Microtus ochrogaster) whether i) social context impacts susceptibility to DIO and ii) chronic intranasal OT reverses DIO. Voles were housed in divided cages with holes in the divider and paired with a same-sex animal with either the same food [high fat diet (HFD)/HFD, [low fat diet (LFD; chow)/chow], or the opposite food (HFD/chow or chow/HFD) for 19 weeks. HFD-fed voles pair-housed with voles maintained on the HFD demonstrated increased weight relative to pair-housed voles that were both maintained on chow. The study was repeated to determine the impact of social context on DIO susceptibility and body composition when animals are maintained on purified sugar-sweetened HFD and LFD to enhance palatability. As before, we found that voles demonstrated higher weight gain on the HFD/HFD housing paradigm, in part, through increased energy intake and the weight gain was a consequence of an increase in fat mass. However, HFD-fed animals housed with LFD-fed animals (and vice versa) showed intermediate patterns of weight gain and evidence of food sharing. Of translational importance is the finding that chronic intranasal OT appeared to reduce weight gain in DIO voles through a decrease in fat mass with no reduction in lean body mass. These effects were associated with transient reductions in food intake and increased food sharing. These findings identify a role of social context in the pathogenesis of DIO and indicate that chronic intranasal OT treatment reduces weight gain and body fat mass in DIO prairie voles, in part, by reducing food intake. Highlights • Social context influences susceptibility to diet-induced obesity in prairie voles • Intranasal OT reduces weight gain in diet-induced obese prairie voles • Intranasal OT reduces weight gain through a selective decrease in fat mass [ABSTRACT FROM AUTHOR]

Abstract The broader implications of hearing loss for the health and functioning of older adults have begun to be demonstrated in epidemiologic studies. These research findings on the association between hearing loss and poorer health outcomes have formed the foundation for national initiatives on hearing loss and public health. These national initiatives range from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) clinical trial to the recent passage of the bipartisan Over-The-Counter Hearing Aid Act. Utilizing population health research methodologies to study hearing loss can provide the foundation for initiating top-down approaches to increase the adoption and accessibility of hearing care for older Americans with hearing loss. Highlights • Epidemiologic studies have informed national initiatives to address hearing care. • National initiatives are transforming how hearing loss is addressed. • Policy changes could enhance adoption of hearing aids and improve hearing care access. [ABSTRACT FROM AUTHOR]

Objective Premature dropout is a significant concern in trauma-focused psychotherapy for youth. Previous studies have primarily examined pre-treatment demographic and symptom-related predictors of dropout, but few consistent findings have been reported. The current study examined demographic, symptom, and in-session process variables as predictors of dropout from Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for youth. Method Participants were a diverse sample of Medicaid-eligible youth (ages 7–17; n = 108) and their nonoffending caregivers ( n  = 86), who received TF-CBT through an effectiveness study in a community setting. In-session process variables were coded from audio-recorded sessions, and these and pre-treatment demographic variables and symptom levels were examined as predictors of dropout prior to receiving an adequate dose of TF-CBT (<7 sessions). Twenty-nine children were classified as dropouts and 79 as completers. Results Binary logistic regression analyses revealed that higher levels of child and caregiver avoidance expressed during early sessions, as well as greater relationship difficulties between the child and therapist, predicted dropout. Those children who were in foster care during treatment were less likely to drop out than children living with parents or relatives. No other demographic or symptom-related factors predicted dropout. Conclusions These findings highlight the importance of addressing avoidance and therapeutic relationship difficulties in early sessions of TF-CBT to help reduce dropout, and they have implications for improving efforts to disseminate evidence-based trauma-focused treatments. [ABSTRACT FROM AUTHOR]

The inorganic core of the iron storage protein, ferritin, is recognized as being analogous to the poorly crystalline iron mineral, ferrihydrite (Fh). Fh is also abundant in soils where it is central to the redox cycling of particular soil contaminants and trace elements. In geochemical circles, it is recognized that Fh can undergo Fe(II)-catalyzed transformation to form more crystalline iron minerals, vastly altering the reactivity of the iron oxide and, in some cases, the redox poise of the system. Of relevance to both geochemical and biological systems, we investigate here if the naturally occurring reducing agent, ascorbate, can effect such an Fe(II)-catalyzed transformation of Fh at 25 °C and circumneutral pH. The transformation of ferrihydrite to possible secondary Fe(III) mineralization products was quantified using Fourier transform infrared (FTIR) spectroscopy, with supporting data obtained using X-ray absorbance spectroscopy (XAS) and X-ray diffraction (XRD). Whilst the amount of Fe(II) formed in the presence of ascorbate has resulted in Fh transformation in previous studies, no transformation of Fh to more crystalline Fe(III) (oxyhydr)oxides was observed in this study. Further experiments indicated this was due to the ability of ascorbate to inhibit the formation of goethite, lepidocrocite and magnetite. The manner in which ascorbate associated with Fh was investigated using FTIR and total organic carbon (TOC) analysis. The majority of ascorbate was found to adsorb to the Fh surface under anoxic conditions but, under oxic conditions, ascorbate was initially adsorbed then became incorporated within the Fe(III) (oxyhydr)oxide structure (i.e., co-precipitated) over time. [ABSTRACT FROM AUTHOR]

Iron (oxyhydr)oxides are widespread in natural and engineered systems, potent adsorbents of contaminants and a source of energy for iron-reducing bacteria. Microbial reduction of iron (oxyhydr)oxides results in the formation of Fe(II) which can induce the transformation of these iron minerals, typically from less crystalline to more crystalline forms, affecting the biogeochemical cycling of iron and the behavior of any species adsorbed to the iron (oxyhydr)oxides. Factors influencing the transformation rate of the poorly crystalline iron (oxyhydr)oxide, ferrihydrite, to more crystalline forms in the presence of the iron reducing bacterium Shewanella oneidensis MR-1 are investigated under controlled laboratory conditions in this work. In particular, the amount of Fe(II) produced increased the transformation rate while increasing concentrations of the electron donor, lactate, decreased the rate. Using kinetic parameters determined from abiotic controls, the results of transformation experiments in the presence of Shewanella oneidensis were modeled with this exercise revealing that less goethite and more lepidocrocite formed than expected. Conversely, studies using the Shewanella exudate only, containing biogenic Fe(II), displayed rates of transformation that were satisfactorily modeled using these abiotic control kinetic parameters. This result suggests that the physical presence of the microbes is pivotal to the reduction in ferrihydrite transformation rate observed in the biotic experiments relative to the analogous abiotic controls. [ABSTRACT FROM AUTHOR]

The reduction potential of Fe(II)-Fe(III) (oxyhydr)oxide systems provides an important control on the biogeochemical cycling of redox-sensitive elements such as carbon and nitrogen as well as trace metals and organic contaminants in natural systems. As such, an in-depth understanding of the factors controlling the reduction potential of such systems is critical to predicting the likely transformation, transport and fate of these species in natural and perturbed environments. In this study the mineralogy and reduction potential of ferrihydrite suspensions at pH 6.50 and pH 7.00 were determined over the course of their Fe(II)-catalyzed transformation to lepidocrocite and goethite using X-ray absorption spectroscopy and mediated electrochemical approaches. The measured reduction potentials were compared to those of analogous Fe(II)-Fe(III) (oxyhydr)oxide suspensions reacted for 5 min containing pure ferrihydrite (Fh), lepidocrocite (L) and goethite (Gt). The reduction potentials of the pure Fe(II)-Fe(III) (oxyhydr)oxide suspensions were, respectively, +47.5, −13.5 and −122.3 mV vs. SHE at pH 6.5, and −22.9, −84.1 and −189.7 mV vs. SHE at pH 7. These values are in good agreement with reduction potentials calculated using the Nernst equation and reported thermodynamic solubility products indicating that these suspensions had reached equilibrium within 5 min. The reduction potential of the pH 6.50 Fe(II)-ferrihydrite suspension decreased from +47.4 mV to –126.4 mV over a week, and from −20.1 mV to −188.4 mV (all vs. SHE) after 24 h at pH 7. The changes in reduction potential over time matched well to those calculated from the relative proportion of each pure Fe(III) (oxyhydr)oxide present suggesting that Fe 3+ activity was influenced by the mix of iron oxides present rather than the most insoluble solid species. Finally, evidence is provided that adsorbed Fe(II) has the capacity to reduce a significantly larger fraction of a reducible species than the aqueous Fe(II) species with which it is in equilibrium. As an Fe(III) (oxyhydr)oxide suspension in equilibrium with aqueous and adsorbed Fe(II) species possesses a single, unique reduction potential, this suggests that adsorbed Fe(II) is a more facile reductant than aqueous Fe(II). [ABSTRACT FROM AUTHOR]

In this study, temporal changes in the redox properties of three 0.5 g/L smectite suspensions were investigated -- a montmorillonite (MAu-1) and two nontronites (NAu-1 and NAu-2) in the presence of I mM aqueous Fe(11) at pH 7.8. X-ray absorption spectroscopy revealed that the amount of Fe(II) added quantitatively transformed into chloride-green rust (CI-GR) within 5 min and persisted over 18 days. Over the same time, the reduction potential of all three suspensions increased by 50 to 150 mV to equilibrate at approximately -100 mV vs SHE. The reduction of a model organic contaminant, 4-chloronitrobenzene (4-CINB), also became increasingly slower over time with virtually no 4-CINB reduction being observed after 18 days. There was a strong correlation between reduction potential and the quantity of 4-CINB reduced by MAu-1, although other factors were likely involved in the decreased redox reactivity observed in the nontronites. It is hypothesized that the temporal increase in reduction potential results from clay mineral dissolution resulting in increased Fe(III) contents in the CI-GR These results demonstrate that long-term studies are recommended to accurately predict contaminant management strategies. [ABSTRACT FROM AUTHOR]

Objectives The decisions made by officials have a direct bearing on the outcomes of competitive sport contests. In an exploratory study, we examine the interrelationships between the decisions made by elite netball umpires, the potential contextual and environmental influences (e.g., crowd size), and the umpires' dispositional tendencies – specifically, their propensity to deliberate and ruminate on their decisions. Design/Method Filmed footage from 60 England Netball Superleague matches was coded using performance analysis software. We measured the number of decisions made overall, and for home and away teams; league position; competition round; match quarter; and crowd size. Additionally, 10 umpires who officiated in the matches completed the Decision-Specific Reinvestment Scale (DSRS). Results Regression analyses predicted that as home teams' league position improved the number of decisions against away teams increased. A model comprising competition round and average league position of both teams predicted the number of decisions made in matches, but neither variable emerged as a significant predictor. The umpire analyses revealed that greater crowd size was associated with an increase in decisions against away teams. The Decision Rumination factor was strongly negatively related to the number of decisions in Quarters 1 and 3, this relationship was driven by fewer decisions against home teams by umpires who exhibited higher Rumination subscale scores. Conclusions These findings strengthen our understanding of contextual, environmental, and dispositional influences on umpires' decision-making behaviour. The tendency to ruminate upon decisions may explain the changes in decision behaviour in relation to the home team advantage effect. [ABSTRACT FROM AUTHOR]

Maintaining good cognitive function is important for successful aging, and it has been suggested recently that having and optimistic outlook may also be valuable. However few have studied the relationship between cognitive ability and dispositional optimism and pessimism in older age. It is unclear whether associations found previously between cognitive ability and pessimism in older age, are evident across the life course, and are consistent at different points in older age. In the present study we examined associations between dispositional optimism and pessimism measured in the eighth and ninth decade of life and childhood and older age cognitive ability, and lifetime change in cognitive ability. Participants were two independent narrow-age samples of older individuals with mean ages about 73 ( n = 847) and 87 ( n = 220) years from the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921), respectively. Higher cognitive ability in childhood and older-age, and healthier cognitive change across the lifetime were associated with lower pessimism in older age: age-11 IQ (LBC1936: β = − 0.17, p < 0.001; LBC1921: β = − 0.29, p = 0.001), older-age IQ (LBC1936: β = − 0.18, p < 0.001; LBC1921: β = − 0.27, p < 0.001), cognitive change (LBC1936: β = − 0.06, p < 0.04; LBC1921: β = − 0.15, p = 0.05). Cognitive ability was not significantly associated with optimism in bivariate analyses, and after adjustment for covariates had only small associations with optimism and only in the LBC1936. The results are consistent with differential associations between cognitive functions and optimism and pessimism, and indicate that their associations with cognitive ability are similar in the eighth and ninth decades of life. [ABSTRACT FROM AUTHOR]

Although there is substantial evidence to support the efficacy of cognitive-behavioral treatments (CBT) for posttraumatic stress disorder (PTSD), there is some debate about how these treatments have their effects. Modern learning theory and cognitive and emotional processing theories highlight the importance of reducing avoidance, facilitating the constructive processing of feared experiences, and strengthening new inhibitory learning. We examined variables thought to be associated with unproductive and constructive processing of traumatic experiences in a sample of 81 youth with elevated PTSD symptoms, who received Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for abuse or traumatic interpersonal loss. Sessions during the trauma narrative phase of TF-CBT were coded for indicators of unproductive processing (overgeneralization, rumination, avoidance) and constructive processing (decentering, accommodation of corrective information), as well as levels of negative emotion. In previous analyses of this trial (Ready et al., 2015), more overgeneralization during the narrative phase predicted less improvement in internalizing symptoms at posttreatment and a worsening of externalizing symptoms over the 12-month follow-up. In contrast, more accommodation predicted improvement in internalizing symptoms and also moderated the negative effects of overgeneralization on internalizing and externalizing symptoms. The current study examined correlates of overgeneralization and accommodation. Overgeneralization was associated with more rumination, less decentering, and more negative emotion, suggesting immersion in trauma-related material. Accommodation was associated with less avoidance and more decentering, suggesting a healthy distance from trauma-related material that might allow for processing and cognitive change. Decentering also predicted improvement in externalizing symptoms at posttreatment. Rumination and avoidance showed important associations with overgeneralization and accommodation, respectively, but did not predict treatment outcomes. This study identifies correlates of overgeneralization and accommodation that might shed light on how these variables relate to unproductive and constructive processing of traumatic experiences. [ABSTRACT FROM AUTHOR]

Prolonged exposure (PE) is an empirically supported treatment for posttraumatic stress disorder (PTSD). The current study examined multiple facilitators and indicators of emotional processing to identify key predictors of outcome in PE using observational coding methods. Participants were 42 adults with PTSD who received PE. Video recordings of sessions were coded to capture negative emotion activation, negative and positive trauma-related cognitions, and cognitive rigidity. Two variables emerged as predictors of PTSD symptom improvement assessed via self-report, but not clinical interview: a greater decrease in negative trauma-related cognitions and lower average cognitive rigidity. Peak emotion activation, reductions in negative emotions, and increases in positive cognitions did not predict PTSD improvement (self-report or clinical interview). Findings contribute to growing evidence highlighting the importance of cognitive change as part of emotional processing and as a key ingredient of PE, beyond activation and reduction in negative emotions. Implications for evaluating emotional processing theory and for clinical practice are discussed. • PE session recordings were coded to identify in-session predictors of PTSD outcome. • We examined multiple facilitators and indicators of emotional processing. • Decrease in negative cognitions and low cognitive rigidity predicted better outcome. • Emotional activation and change and positive cognitions did not predict outcome. • Findings were observed with self-report but not interview measures of PTSD. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that the rate at which Fe(II)-Fe(III) oxyhydroxide systems catalyze the reduction of reducible contaminants, such as 4-chloronitrobenzene, is well correlated to their thermodynamic reduction potential. Here we confirm this effect in the presence of Fe(III) oxyhydroxide phases not previously assessed, namely ferrihydrite and nano-goethite, as well as Fe(III) oxyhydroxide phases previously examined. In addition, silicate is found to decrease the extent of Fe(II) sorption to the Fe(III) oxyhydroxide surface, increasing the reduction potential of the Fe(II)-Fe(III) oxyhydroxide suspension and, accordingly, decreasing the rate of 4-chloronitrobenzene reduction. A linear relationship between the reduction potential of the Fe(II)-Fe(III) oxyhydroxide suspensions and the reduction rate of 4-chloronitrobenzene (normalized to surface area and concentration of sorbed Fe(II)) was obtained in the presence and absence of silicate. However, when ferrihydrite was doped with Si (through co-precipitation) the reduction of 4-chloronitrobenzene was much slower than predicted from its reduction potential. The results obtained have significant implications to the likely effectiveness of naturally occurring contaminant degradation processes involving Fe(II) and Fe(III) oxyhydroxides in groundwater environments containing high concentrations of silicate, or other species which compete with Fe(II) for sorption sites. [ABSTRACT FROM AUTHOR]

Objective: Involving caregivers in trauma-focused treatments for youth has been shown to result in better outcomes, but it is not dear which in-session caregiver behaviors enhance or inhibit this effect. The current study examined the associations between caregiver behaviors during Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and youth cognitive processes and symptoms. Method: Participants were a racially diverse sample of Medicaid-eligible youth (ages 7-17) and their nonoffending caregivers (N = 71 pairs) who received TF-CBT through an effectiveness study in a community setting. Caregiver and youth processes were coded from audio-recorded sessions, and outcomes were measured using the Child Behavior Checklist (CBCL) and UCLA PTSD Reaction Index for Diagnostic and Statistical Manual fo r Mental Disorders-Fourth Edition (DSM-IV: UPID) at 3,6,9, and 12 months postintake. Results: Piecewise linear growth curve modeling revealed that during the trauma narrative phase of TF-CBT, caregivers' cognitive-emotional processing of their own and their child's trauma-related reactions predicted decreases in youth internalizing and externalizing symptoms over treatment. Caregiver support predicted lower internalizing symptoms over follow-up. In contrast, caregiver avoidance and blame of the child predicted worsening of youth internalizing and externalizing symptoms over follow-up. Caregiver avoidance early in treatment also predicted worsening of externalizing symptoms over follow-up. During the narrative phase, caregiver blame and avoidance were correlated with more child overgeneralization of trauma beliefs, and blame was also associated with less child accommodation of balanced beliefs. Conchisions: The association between in-session caregiver behaviors and youth symptomatology during and after TF-CBT highlights the importance of assessing and targeting these behaviors to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Increasing concentrations of dissolved silicate progressively retard Fe(II) oxidation kinetics in the circum-neutral pH range 6.0-7.0. As Si:Fe molar ratios increase from 0 to 2, the primary Fe(III) oxidation product transitions from lepidocrocite to a ferrihydrite/silica-ferrihydrite composite. Empirical results, supported by chemical kinetic modeling, indicated that the decreased heterogeneous oxidation rate was not due to differences in absolute Fe(II) sorption between the two solids types or competition for adsorption sites in the presence of silicate. Rather, competitive desorption experiments suggest Fe(II) was associated with more weakly bound, outer-sphere complexes on silica-ferrihydrite compared to lepidocrocite. A reduction in extent of inner-sphere Fe(II) complexation on silica-ferrihydrite confers a decreased ability for Fe(II) to undergo surface-induced hydrolysis via electronic configuration alterations, thereby inhibiting the heterogeneous Fe(II) oxidation mechanism. Water samples from a legacy radioactive waste site (Little Forest, Australia) were shown to exhibit a similar pattern of Fe(II) oxidation retardation derived from elevated silicate concentrations. These findings have important implications for contaminant migration at this site as well as a variety of other groundwater/high silicate containing natural and engineered sites that might undergo iron redox fluctuations. [ABSTRACT FROM AUTHOR]

Objective: Sudden gains were investigated in cognitive–behavioral therapy (CBT) for treatment-resistant depression (TRD). Client and therapist processes in sessions proximal to sudden gains were examined to better understand the antecedents of sudden gains and potential mechanisms linking them to outcome. Method: Participants were 156 adults with TRD in a randomized controlled trial of CBT as an adjunct to pharmacotherapy (Wiles et al., 2013). Depression symptoms were assessed by the Beck Depression Inventory-11 at each session. In a subsample of 50 clients, audio-recordings of 125 therapy sessions were rated for hope, emotional processing, and therapist competence in case-conceptualization. Results: Sudden gains were experienced by 54% of participants. Those with gains reported significantly lower depression severity at 12-month follow-up and more remission of symptoms than those without gains. Sudden gains also predicted lower depression at follow-up, beyond the slope of linear change in symptoms across treatment. Therapists demonstrated greater competence in case conceptualization with clients who reported sudden gains, and those with gains expressed more hope in sessions prior to a gain. In addition, more hope and emotional processing in the pregain sessions predicted less depression at follow-up, controlling for depression scores in the prior session. Better therapist conceptualization skills and more client hope in the baseline and pregain sessions were also associated with more emotional processing in those same sessions. Conclusion: This study extends the phenomenon of sudden gains in CBT for depression to a treatment-resistant population and identified important therapy processes that predicted long-term outcomes: hope and emotional processing. [ABSTRACT FROM AUTHOR]

Rumination has been consistently associated with the development and maintenance of a variety of psychological disorders. While recent research has investigated a number of strategies to counter rumination and its negative effects, few have investigated their efficacy outside of a clinical or laboratory context. The current study used a daily diary methodology to compare the efficacy of three such strategies in the everyday lives of a highly ruminative sample. Over the course of 10 days, participants (N = 154) were asked to apply one of three perspectives (distanced, immersed, or distraction) to their thoughts and emotions about the most stressful event of the day and then to write a short narrative about the event. Over the 10-day period, immersion was associated with an average increase in negative emotion from before to after the narrative, whereas distancing was associated with little reactivity, and distraction was associated with a decrease in negative emotion. Participants in the distanced condition showed less ruminative, unproductive processing and used fewer negative emotion words in the narratives than those in the immersed condition. These differences were maintained over the 10-day study period. In targeted analyses of the days with the highest level of ruminative processing and/or event-related stress for each individual, the distanced and immersed groups reported similar levels of negative emotion reactivity and word use, but the distanced group showed less ruminative processing in the narratives. An interaction emerged suggesting that ruminative processing was only associated with an increase in negative emotion in the immersed group and not in the distanced group. The findings are discussed in the context of decreasing risk for depression and related disorders by targeting emotion regulation strategies on a daily level. [ABSTRACT FROM AUTHOR]

Donnan dialysis has been applied to forty filtered drainage waters collected from five coastal lowland acid sulfate soil (CLASS) catchments across north-eastern NSW, Australia. Despite having average pH values < 3.9, 78 and 58% of Al and total Fe, respectively, were present as neutral or negatively-charged species. Complementary isotope dilution experiments with 55 Fe and 26 Al demonstrated that only soluble (i.e. no colloidal) species were present. Trivalent rare earth elements (REEs) were also mainly present (> 70%) as negatively-charged complexes. In contrast, the speciation of the divalent trace metals Co, Mn, Ni and Zn was dominated by positively-charged complexes and was strongly correlated with the alkaline earth metals Ca and Mg. Thermodynamic equilibrium speciation calculations indicated that natural organic matter (NOM) complexes dominated Fe(III) speciation in agreement with that obtained by Donnan dialysis. In the case of Fe(II), however, the free cation was predicted to dominate under thermodynamic equilibrium, whilst our results indicated that Fe(II) was mainly present as neutral or negatively-charged complexes (most likely with sulfate). For all other divalent metals thermodynamic equilibrium speciation calculations agreed well with the Donnan dialysis results. The proportion of Al and REEs predicted to be negatively-charged was also grossly underestimated, relative to the experimental results, highlighting possible inaccuracies in the stability constants developed for these trivalent Me(SO 4 ) 2 − and/or Me–NOM complexes and difficulties in modeling complex environmental samples. These results will help improve metal mobility and toxicity models developed for CLASS-affected environments, and also demonstrate that Australian CLASS environments can discharge REEs at concentrations an order of magnitude greater than previously reported. [ABSTRACT FROM AUTHOR]

The science of dynamic systems is the study of pattern formation and system change. Dynamic systems theory can provide a useful framework for understanding the chronicity of depression and its treatment. We propose a working model of therapeutic change with potential to organize findings from psychopathology and treatment research, suggest new ways to study change, facilitate comparisons across studies, and stimulate treatment innovation. We describe a treatment for depression that we developed to apply principles from dynamic systems theory and then present a program of research to examine the utility of this application. Recent methodological and technological developments are also discussed to further advance the search for mechanisms of therapeutic change. [ABSTRACT FROM AUTHOR]

Inhibition of fear generalization with new learning is an important process in treatments for anxiety disorders. Generalization of maladaptive cognitions related to traumatic experiences (overgeneralized beliefs) have been demonstrated to be associated with posttraumatic stress disorder (PTSD) in adult populations, whereas more balanced, accommodated beliefs are associated with symptom improvement. It is not yet clear whether (a) overgeneralization and accommodation are associated with PTSD treatment outcome in youth, or (b whether accommodated beliefs can interact with or inhibit cognitive overgeneralization, as has been demonstrated in research on behavior-based fear generalization. The current study examined the relationships between overgeneralized and accommodated beliefs, child age, and symptom reduction in a sample of 81 youth (age 7-17 years), who received Trauma-Focused Cognitive Behavioral Therapy. Overgeneralized and accommodated beliefs expressed during the exposure phase of treatment were coded in audio-recorded therapy sessions. Overgeneralization predicted (a) higher internalizing symptom scores at posttreatment, particularly for younger children, and less improvement over treatment, and (b) higher externalizing scores at 1-year follow-up and steeper symptom increases over this period. In contrast, accommodation was associated with (a) lower posttreatment internalizing symptoms and greater improvement over treatment, and (b) lower externalizing scores at 1-year follow-up, particularly for younger children. High levels of accommodation moderated the relationship between overgeneralization and worse symptom outcomes, except when predicting the slope of internalizing scores over treatment, and age did not moderate these effects. There were no significant predictors of child-reported PTSD-specific symptoms, although PTSD symptoms did decrease significantly over the course of treatment and maintain 1year after treatment. [ABSTRACT FROM AUTHOR]

Current behavioral paradigms of stress resilience traditionally employ forms of prior manipulation or subsequent testing. Recent work has reported adult rat ultrasonic vocalizations (USVs) emitted during intermittent swim stress (ISS) may serve as a predictor of resilience. ISS-induced USVs predicted resilience on several endpoints of behavioral depression and may be considered a forecast of innate resilience. However, a potential problem for these previous findings is the lack of generalizability to other contexts, because both the stress induction and post-stress testing occur in water. The current study tests the generalizability of USVs as a predictor of stress resilience in a non-water-based post-test, the juvenile social exploration test of anxiety. The results provide further support that USVs emitted during ISS predict resilience to depression- and anxiety-like behaviors. Extensions of this work to examine the neurobiology of innate resilience associated with ISS-induced USVs are discussed with comparisons to extant models of learned resilience. [ABSTRACT FROM AUTHOR]

In this study, the rates of Fe(II) oxidation by molecular oxygen in the presence of citrate, ethylenediaminetetraacetic acid (EDTA) and Suwannee River fulvic acid (SRFA) were determined over the pH range 4.0–5.5 and, for all of the ligands investigated, found to be substantially faster than oxidation rates in the absence of any ligand. EDTA was found to be particularly effective in enhancing the rate of Fe(II) oxidation when sufficient EDTA was available to complex all Fe(II) present in solution, with a kinetic model of the process found to adequately describe all results obtained. When Fe(II) was only partially complexed by EDTA, reactions with reactive oxygen species (ROS) and heterogeneous Fe(II) oxidation were found to contribute significantly to the removal rate of iron from solution at different stages of oxidation. This was possible due to the rapid rate at which EDTA enhanced Fe(II) oxidation and formed ROS and Fe(III). The rapid rate of Fe(III) generation facilitated the formation of free ferric ion activities in excess of those required for ferric oxyhydroxide precipitation following Fe(III)-EDTA dissociation. In comparison, the rate of Fe(II) oxidation was slower in the presence of citrate, and therefore the concentrations of free Fe(III) able to form in the initial stages of Fe(II) oxidation were much lower than those formed in the presence of EDTA, despite the resultant Fe(III)-citrate complex being less stable than that of Fe(III)-EDTA. The slower rate of citrate enhanced oxidation also resulted in slower rates of ROS generation, and, as such, oxidation of the remaining inorganic Fe(II) species by ROS was negligible. Overall, this study demonstrates that organic ligands may substantially enhance the rate of Fe(II) oxidation. Even under circumstances where the ligand is not present at sufficient concentrations to complex all of the Fe(II) in solution, ensuing oxidative processes may sustain an enhanced rate of Fe(II) oxidation relative to that of aqueous Fe(II) oxidation alone. [ABSTRACT FROM AUTHOR]

Purpose: Cerebral microvascular disease is associated with dementia. Differences in the topography of the retinal vascular network may be a marker for cerebrovascular disease. The association between cerebral microvascular state and non-pathological cognitive ageing is less clear, particularly because studies are rarely able to adjust for pre-morbid cognitive ability level. We measured retinal vascular fractal dimension (Df) as a potential marker of cerebral microvascular disease. We examined the extent to which it contributes to differences in non-pathological cognitive ability in old age, after adjusting for childhood mental ability. Methods: Participants from the Lothian Birth Cohort 1936 Study (LBC1936) had cognitive ability assessments and retinal photographs taken of both eyes aged around 73 years (n = 648). IQ scores were available from childhood. Retinal vascular Df was calculated with monofractal and multifractal analysis, performed on custom-written software. Multiple regression models were applied to determine associations between retinal vascular Df and general cognitive ability (g), processing speed, and memory. Results: Only three out of 24 comparisons (two eyes × four Df parameters × three cognitive measures) were found to be significant. This is little more than would be expected by chance. No single association was verified by an equivalent association in the contralateral eye. Conclusions: The results show little evidence that fractal measures of retinal vascular differences are associated with non-pathological cognitive ageing. [ABSTRACT FROM AUTHOR]

In this study, the kinetics of Fe(II) oxidation in the presence of the iron oxyhydroxides ferrihydrite, Si-ferrihydrite, schwertmannite, lepidocrocite and goethite are investigated over the pH range 4–5.5. Despite limited sorption of Fe(II), the rate of Fe(II) oxidation is up to 70-fold faster than in the absence of any Fe oxyhydroxide phase over pH 4.5–5.5. Enhanced Fe(II) oxidation was minor or negligible at pH 4 with undetectable amounts of Fe(II) adsorbed to the iron oxyhydroxides at this pH. Heterogeneous rate constants derived from kinetic modeling were normalized to the concentration of adsorbed Fe(II) and deviated by no more than 13.8% at pH 4.5, 5 and 5.5, indicating that oxidation is proportional to the concentration of adsorbed Fe(II). Average rate constants were found to be: 2.12 ± 0.20, 1.30 ± 0.09, 1.69 ± 0.22, 1.20 ± 0.08 and 0.68 ± 0.09 M −1 s −1 for ferrihydrite, goethite, lepidocrocite, schwertmannite and Si-ferrihydrite, respectively. The role of reactive oxygen species, such as hydrogen peroxide, the hydroxyl radical and superoxide, towards the overall oxidation of Fe(II) was examined but found to have only a minor impact on Fe(II) oxidation when compared to the effect of heterogeneous oxidation. [ABSTRACT FROM AUTHOR]

Although efforts to understand the basis for inter-strain phenotypic variation in the most virulent malaria species, Plasmodium falciparum, have benefited from advances in genomic technologies, there have to date been few metabolomic studies of this parasite. Using ¹H-NMR spectroscopy, we have compared the metabolite profiles of red blood cells infected with different P. falciparum strains. These included both chloroquine-sensitive and chloroquine-resistant strains, as well as transfectant lines engineered to express different isoforms of the chloroquine-resistance-conferring pfcrt (P. falciparum chloroquine resistance transporter). Our analyses revealed strain-specific differences in a range of metabolites. There was marked variation in the levels of the membrane precursors choline and phosphocholine, with some strains having >30-fold higher choline levels and >5-fold higher phosphocholine levels than others. Chloroquineresistant strains showed elevated levels of a number of amino acids relative to chloroquine-sensitive strains, including an approximately 2-fold increase in aspartate levels. The elevation in amino acid levels was attributable to mutations in pfcrt. Pfcrt-linked differences in amino acid abundance were confirmed using alternate extraction and detection (HPLC) methods. Mutations acquired to withstand chloroquine exposure therefore give rise to significant biochemical alterations in the parasite. [ABSTRACT FROM AUTHOR]

The antimalarial spiroindolones disrupt P lasmodium falciparum Na+ regulation and induce an alkalinization of the parasite cytosol. It has been proposed that they do so by inhibiting PfATP4, a parasite plasma membrane P-type ATPase postulated to export Na+ and import H+ equivalents. Here, we screened the 400 antiplasmodial compounds of the open access ' Malaria Box' for their effects on parasite ion regulation. Twenty eight compounds affected parasite Na+ and pH regulation in a manner consistent with PfATP4 inhibition. Six of these, with chemically diverse structures, were selected for further analysis. All six showed reduced antiplasmodial activity against spiroindolone-resistant parasites carrying mutations in pfatp4. We exposed parasites to incrementally increasing concentrations of two of the six compounds and in both cases obtained resistant parasites with mutations in pfatp4. The finding that diverse chemotypes have an apparently similar mechanism of action indicates that PfATP4 may be a significant Achilles' heel for the parasite. [ABSTRACT FROM AUTHOR]

Expressive writing (EW) can be a useful supplement to psychotherapy, regardless of therapeutic orientation. In an open trial of exposure-based cognitive therapy for depression, 43 participants used EW before each session, producing 928 EW samples. Using examples from these, we discuss how EW can be used to both promote and track therapeutic change. Specifically, we review the impact of EW on therapeutic growth, via self-monitoring, increased awareness, and exposure/emotional processing. We then discuss how EW can be used to track important predictors of change such as symptoms, therapeutic alliance, social support, avoidance, and hopelessness. We conclude by discussing potential limitations to the use of EW in therapy and by recommending specific strategies for incorporating EW into clinical practice. [ABSTRACT FROM AUTHOR]

As it grows and replicates within the erythrocytes of its host the malaria parasite takes up nutrients from the extracellular medium, exports metabolites and maintains a tight control over its internal ionic composition. These functions are achieved via membrane transport proteins, integral membrane proteins that mediate the passage of solutes across the various membranes that separate the biochemical machinery of the parasite from the extracellular environment. Proteins of this type play a key role in antimalarial drug resistance, as well as being candidate drug targets in their own right. This review provides an overview of recent work on the membrane transport biology of the malaria parasite-infected erythrocyte, encompassing both the parasite-induced changes in the membrane transport properties of the host erythrocyte and the cell physiology of the intracellular parasite itself. [ABSTRACT FROM AUTHOR]

Abstract: Sofia, a novel, fluorescent lateral-flow immunoassay was compared with two conventional colorimetric assays, Quickvue Influenza A+B and Directigen FLU A+B, to identify influenza viral antigen from patient nasopharyngeal specimens. A total of 118 frozen original influenza-positive specimens and 57 prospective specimens were examined. Using rt-PCR as a referee assay, sensitivity values (%) for influenza A/B of 80.0/74.8, 73.3/59.3 and 73.3/40.7 were obtained using the Sofia, Quickvue and Directigen assays, respectively. All assays demonstrated reduced sensitivity for influenza B as compared with influenza A virus. With respect to the Sofia assay, the sensitivity of influenza B for the Directigen assay was significantly diminished. False positive results were not observed in the Sofia and Directigen assays. The Quickvue assay produced 3 false-positive results (2 influenza A and 1 influenza B) resulting in a specificity (%) of 96 and 98 for influenza A and B, respectively. Cross-reactivity to other respiratory viruses was not observed among immunoassays. A sensitivity rank (highest to low) of rt-PCR>culture>Sofia>Quickvue>Directigen was established using dilutions of influenza A and B. Sofia provides enhanced sensitivity and objective result interpretation over conventional colorimetric immunoassays. [Copyright &y& Elsevier]

Stress generation research has historically examined the link between depression and stressful life events, particularly interpersonal events. Stress generation theory has rarely been applied to personality disorders, which are characterized by longstanding, pervasive, and often self-perpetuating interpersonal difficulties. In addition, there is little research on the specific types of interpersonal deficits associated with personality disorders. We examined the associations between symptoms of Avoidant Personality Disorder (AVPD), interpersonal competence, and daily stress generation. College students completed measures of personality disorder symptoms, interpersonal competence, and a 7-day diary of daily negative events. Multilevel mediation models showed that lower Conflict Management skills mediated the relation between AVPD symptoms and daily negative events. These results suggest that a daily model of stress generation might apply to these personality disorder symptoms and that interpersonal competence is an important mediator of the process of daily stress generation. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum resistance to chloroquine, the former gold standard antimalarial drug, is mediated primarily by mutant forms of the chloroquine resistance transporter (PfCRT). These mutations impart upon PfCRT the ability to efflux chloroquine from the intracellular digestive vacuole, the site of drug action. Recent studies reveal that PfCRT variants can also affect parasite fitness, protect immature gametocytes against chloroquine action, and alter P. falciparum susceptibility to current first-line therapies. These results highlight the need to be vigilant in screening for the appearance of novel pfcrt alleles that could contribute to new multi-drug resistance phenotypes. [ABSTRACT FROM AUTHOR]

In her History of Our Lord, Elizabeth Eastlake completed Anna Jameson’s ‘series’ on Christian iconography as the fi rst extended study of Christological imagery in the English literature of art. Applying trinitarian doctrine to her material, she criticized what she considered Michelangelo’s dereliction in representing God the Father as Creator on the Sistine ceiling, while exonerating of the same charge, for its artistic value, Raphael’s Creation of Light (Vatican Loggia). The experience of an antinomian relation between religion and art, adumbrated earlier when Eastlake castigated Ruskin for elevating idea-content over the artist’s means, marks a crisis of interpretation in the Victorian historiography of art. It implicitly challenged artists and critics of the aesthetic movement to frame non-creedal or syncretic approaches to the sacred, as instanced in writings of Swinburne and Pater and in paintings by Millais, Rossetti and Burne-Jones. [ABSTRACT FROM AUTHOR]

Abstract: Mitochondrial DNA (mtDNA) is essential for proper mitochondrial function and encodes 22 tRNAs, 2 rRNAs and 13 polypeptides that make up subunits of complex I, III, IV, in the electron transport chain and complex V, the ATP synthase. Although mitochondrial dysfunction has been implicated in processes such as premature aging, neurodegeneration, and cancer, it has not been shown whether persistent mtDNA damage causes a loss of oxidative phosphorylation. We addressed this question by treating mouse embryonic fibroblasts with either hydrogen peroxide (H2O2) or the alkylating agent methyl methanesulfonate (MMS) and measuring several endpoints, including mtDNA damage and repair rates using QPCR, levels of mitochondrial- and nuclear-encoded proteins using antibody analysis, and a pharmacologic profile of mitochondria using the Seahorse Extracellular Flux Analyzer. We show that a 60min treatment with H2O2 causes persistent mtDNA lesions, mtDNA loss, decreased levels of a nuclear-encoded mitochondrial subunit, a loss of ATP-linked oxidative phosphorylation and a loss of total reserve capacity. Conversely, a 60min treatment with 2mM MMS causes persistent mtDNA lesions but no mtDNA loss, no decrease in levels of a nuclear-encoded mitochondrial subunit, and no mitochondrial dysfunction. These results suggest that persistent mtDNA damage is not sufficient to cause mitochondrial dysfunction. [Copyright &y& Elsevier]

Evolution by natural selection, the unifying theory of all biological sciences, provides a basis for understanding how phenotypic variability is generated at all levels of organization from genes to behavior. However, it is important to distinguish what is the target of selection vs. what is transmitted across generations. Physical traits, behaviors, and the extended phenotype are all selected features of an individual, but genes that covary with different aspects of the targets of selection are inherited. Here we review the variability in cortical organization, morphology, and behavior that have been observed across species and describe similar types of variability within species. We examine sources of variability and the constraints that limit the types of changes that evolution has and can produce. Finally, we underscore the importance of how genes and genetic regulatory networks are deployed and interact within an individual, and their relationship to external, physical forces within the environment that shape the ultimate phenotype. [ABSTRACT FROM AUTHOR]