Distinct neural substrates of individual differences in components of reading comprehension in adults with or without dyslexia.

Reading comprehension is a complex task that depends on multiple cognitive and linguistic processes. According to the updated Simple View of Reading framework, in adults, individual variation in reading comprehension can be largely explained by combined variance in three component abilities: (1) decoding accuracy, (2) fluency, and (3) language comprehension. Here we asked whether the neural correlates of the three components are different in adults with dyslexia as compared to typically-reading adults and whether the relative contribution of these correlates to reading comprehension is similar in the two groups. We employed a novel naturalistic fMRI reading task to identify the neural correlates of individual differences in the three components using whole-brain and literature-driven regions-of-interest approaches. Across all participants, as predicted by the Simple View framework, we found distinct patterns of associations with linguistic and domain-general regions for the three components, and that the left-hemispheric neural correlates of language comprehension in the angular and posterior temporal gyri made the largest contributions to explaining out-of-scanner reading comprehension performance. These patterns differed between the two groups. In typical adult readers, better fluency was associated with greater activation of left occipitotemporal regions, better comprehension with lesser activation in prefrontal and posterior parietal regions, and there were no significant associations with decoding. In adults with dyslexia, better fluency was associated with greater activation of bilateral inferior parietal regions, better comprehension was associated with greater activation in some prefrontal clusters and lower in others, and better decoding skills were associated with lesser activation of bilateral prefrontal and posterior parietal regions. Extending the behavioral findings of skill-level differences in the relative contribution of the three components to reading comprehension, the relative contributions of the neural correlates to reading comprehension differed based on dyslexia status. These findings reveal some of the neural correlates of individual differences in the three components and the underlying mechanisms of reading comprehension deficits in adults with dyslexia.

Induction of specific brain oscillations may restore neural circuits and be used for the treatment of Alzheimer's disease.

Brain oscillations underlie the function of our brains, dictating how we both think and react to the world around us. The synchronous activity of neurons generates these rhythms, which allow different parts of the brain to communicate and orchestrate responses to internal and external stimuli. Perturbations of cognitive rhythms and the underlying oscillator neurons that synchronize different parts of the brain contribute to the pathophysiology of diseases including Alzheimer's disease, (AD), Parkinson's disease (PD), epilepsy and other diseases of rhythm that have been studied extensively by Gyorgy Buzsaki. In this review, we discuss how neurologists manipulate brain oscillations with neuromodulation to treat diseases and how this can be leveraged to improve cognition and pathology underlying AD. While multiple modalities of neuromodulation are currently clinically indicated for some disorders, nothing is yet approved for improving memory in AD. Recent investigations into novel methods of neuromodulation show potential for improving cognition in memory disorders. Here, we demonstrate that neuronal stimulation using audiovisual sensory stimulation that generated 40-HZ gamma waves reduced AD-specific pathology and improved performance in behavioural tests in mouse models of AD, making this new mode of neuromodulation a promising new avenue for developing a new therapeutic intervention for the treatment of dementia.

Impact of patient decision aids on appropriate and timely access to hip or knee arthroplasty for osteoarthritis: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of patient decision aids (PtDA) compared to usual education on appropriate and timely access to total joint arthroplasty in patients with osteoarthritis. METHOD: A randomized controlled trial (RCT) with patients undergoing orthopedic screening. Control and intervention arms received usual education; intervention arm also received a PtDA and a surgeon preference report. Wait times (primary outcome) were described using stratified Kaplan-Meier survival curves with patients censored at the time of death or loss to follow-up, and multivariable Cox proportional hazards regression. Secondary outcomes were compared using stratified Cochran-Mantel-Haenszel chi-squared tests. RESULTS: 343 patients were randomized to intervention (n = 174) or control (n = 169). The typical patient was 66 years old, retired, living with someone, and 51% had high school education or less. The intervention was associated with a trend towards reduction in wait time (hazard ratio (HR) 1.25, 95% confidence interval (CI) 0.99-1.60, P = 0.0653). Median wait times were 3 weeks shorter in intervention than in control at the community site with no difference at the academic site. Good decision quality was reached by 56.1% intervention and 44.5% control (Relative risk (RR) 1.25; 95% CI 1.00-1.56, P = 0.050). Surgery rates were 73.2% intervention and 80.5% controls (RR 0.91: 95% CI 0.81-1.03) with 12 intervention (7.3%) and eight control participants (4.9%) returning to have surgery within 2 years (P = 0.791). CONCLUSION: Compared to controls, decision aid recipients had shorter wait times at one site, fewer surgeries, and were more likely to reach good decision quality, but overall effect was not statistically significant. TRIALS REGISTRATION: The full trial protocol is available at ClinicalTrials.Gov (NCT00911638).

Categorical perception and influence of attention on neural consistency in response to speech sounds in adults with dyslexia.

Developmental dyslexia is a common neurodevelopmental disorder that is associated with alterations in the behavioral and neural processing of speech sounds, but the scope and nature of that association is uncertain. It has been proposed that more variable auditory processing could underlie some of the core deficits in this disorder. In the current study, magnetoencephalography (MEG) data were acquired from adults with and without dyslexia while they passively listened to or actively categorized tokens from a /ba/-/da/ consonant continuum. We observed no significant group difference in active categorical perception of this continuum in either of our two behavioral assessments. During passive listening, adults with dyslexia exhibited neural responses that were as consistent as those of typically reading adults in six cortical regions associated with auditory perception, language, and reading. However, they exhibited significantly less consistency in the left supramarginal gyrus, where greater inconsistency correlated significantly with worse decoding skills in the group with dyslexia. The group difference in the left supramarginal gyrus was evident only when neural data were binned with a high temporal resolution and was only significant during the passive condition. Interestingly, consistency significantly improved in both groups during active categorization versus passive listening. These findings suggest that adults with dyslexia exhibit typical levels of neural consistency in response to speech sounds with the exception of the left supramarginal gyrus and that this consistency increases during active versus passive perception of speech sounds similarly in the two groups.

A simple, rapid, interpretable, actionable and implementable digital PCR based mortality index.

Mortality assessments are conducted for both civil and commercial purposes. Recent advances in epigenetics have resulted in DNA methylation tools to assess risk and aid in this task. However, widely available array-based algorithms are not readily translatable into clinical tools and do not provide a good foundation for clinical recommendations. Further, recent work shows evidence of heritability and possible racial bias in these indices. Using a publicly available array data set, the Framingham Heart Study (FHS), we develop and test a five-locus mortality-risk algorithm using only previously validated methylation biomarkers that have been shown to be free of racial bias, and that provide specific assessments of smoking, alcohol consumption, diabetes and heart disease. We show that a model using age, sex and methylation measurements at these five loci outperforms the 513 probe Levine index and approximates the predictive power of the 1030 probe GrimAge index. We then show each of the five loci in our algorithm can be assessed using a more powerful, reference-free digital PCR approach, further demonstrating that it is readily clinically translatable. Finally, we show the loci do not reflect ethnically specific variation. We conclude that this algorithm is a simple, yet powerful tool for assessing mortality risk. We further suggest that the output from this or similarly derived algorithms using either array or digital PCR can be used to provide powerful feedback to patients, guide recommendations for additional medical assessments, and help monitor the effect of public health prevention interventions.

p21ras initiates Rac-1 but not phosphatidyl inositol 3 kinase/PKB, mediated signaling pathways in T lymphocytes.

p21ras is activated by the T cell antigen receptor (TCR) and then co-ordinates important signaling pathways for T lymphocyte activation. Effector pathways for this guanine nucleotide binding protein in T cells are mediated by the serine/threonine kinase Raf-1 and the Ras-related GTPase Rac-1. In fibroblasts, an important effector for the Ras oncogene is Phosphatidylinositol 3-kinase (PtdIns 3-kinase). Activation of this lipid kinase is able to induce critical Rac-1 signaling pathways and can couple p21ras to cell survival mechanisms via the serine/threonine kinase Akt/PKB. The role of PtdIns 3-kinase in Ras signaling in T cells has not been explored. In the present study, we examined the ability of PtdIns 3-kinase to initiate the Rac-1 signaling pathways important for T cell activation. We also examined the possibility that Akt/PKB is regulated by Ras signaling pathways in T lymphocytes. The results show that Ras can initiate a Rac-1 mediated pathway that regulates the transcriptional function of AP-1 complexes. PtdIns 3-kinase signals cannot mimic p21ras and induce the Rac mediated responses of AP-1 transcriptional activation. Moreover, neither TCR or Ras activation of AP-1 is dependent on PtdIns 3-kinase. PKB is activated in response to triggering of the T cell antigen receptor; PtdIns 3-kinase activity is both required and sufficient for this TCR response. In contrast, p21ras signals are unable to induce Akt/PKB activity in T cell nor is Ras function required for Akt/PKB activation in response to the TCR. The present data thus highlight that PtdIns 3-kinase and Akt/PKB are not universal Ras effector molecules. Ras can initiate Rac-1 regulated signaling pathways in the context of T cell antigen receptor function independently of PtdIns 3-kinase activity.

Association between depression and mortality in older adults: the Cardiovascular Health Study.

BACKGROUND: Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals. OBJECTIVE: To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors. METHODS: A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality. RESULTS: Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46). CONCLUSIONS: High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.

Marital therapy: a viable treatment for depression and marital discord.

Thirty-six maritally discordant couples with depressed wives were randomly assigned to marital therapy, cognitive therapy, or a waiting-list control condition. The women given marital or cognitive therapy showed significant and clinically meaningful reductions in their depression. The women given marital therapy showed greater increases in marital satisfaction than did those given cognitive therapy or no therapy; these differences were maintained at 1-year follow-up. These findings suggest that marital therapy may be the most effective and appropriate treatment for clinically significant marital discord with coexisting clinically significant depression.

Disease status in African American single mothers with HIV: the role of depressive symptoms.

The association between depressive symptoms and 2 measures of HIV disease status in 73 African American single mothers was examined. Hierarchical multiple regression analyses revealed that clinician-rated depressive symptoms predicted subjective, but not objective, parameters of disease status 12 to 14 months later. More symptoms of depression at the 1st assessment predicted an increase in physical complaints over the course of the study. Results suggest that researchers and clinicians interested in enhancing quality of life among African American single mothers with HIV infection, an understudied population within the HIV-AIDS literature, should consider both subjective and objective measures of the disease.

Marital therapy in the treatment of depression: toward a third generation of therapy and research.

Two generations of outcome research demonstrate the potential efficacy of marital therapy in the treatment of depression. After reviewing treatment outcome studies on marital therapy for depression, we examine basic research linking aspects of the marital relationship to depressive symptoms. In doing so, we highlight a number of theoretical perspectives and research findings that can inform work with couples in which one spouse is depressed. Finally, we identify potential innovations that may lead to a third generation of marital interventions for depression and several avenues of inquiry for a third generation of outcome research on marital therapy for depression.

Marital distress, depression, and attributions: is the marital distress-attribution association an artifact of depression?

We examined whether the association between marital distress and attributions is an artifact of depression. Study 1 showed that the attributions of 40 wives recruited from the community accounted for variance in their marital satisfaction after the effects of depression had been taken into account. Study 2 compared the attributions of 20 clinically depressed and maritally distressed wives (respondents to an advertisement offering therapy for depression and marital problems), 20 nondepressed but distressed wives (clients seeking marital therapy at a clinic), and a control group of 20 nondepressed and nondistressed wives (respondents to an advertisement for participants in a research project). The first two groups did not differ in attributions, but the attributions of both groups differed from those of the control group. Both studies therefore suggest that the association between attributions and marital satisfaction is not due to depression.

Attributions and behavior in functional and dysfunctional marriages.

The study examined whether spouses' attributions for partner behavior are related to their own behavior by assessing their attributions and observing the problem-solving discussions of couples in which (a) neither spouse was depressed or maritally distressed, (b) the wife was depressed and both spouses were maritally distressed, and (c) the wife was not depressed and both spouses were maritally distressed. To the extent they made maladaptive attributions, wives displayed less positive behavior and more negative behavior. Husbands' attributions and behavior were unrelated, and associations between attributions and behavior were not moderated by marital distress and depression. These results highlight the need to clarify how partner behavior contributes to the attributions spouses make and to reexamine interventions designed to modify attributions in marital therapy.

Life events, relationship quality, and depression: an investigation of judgment discontinuity in vivo.

Relationships among stressful life events, negative affect, and judged quality of intimate relationships were explored. Three studies and a mini-meta-analysis revealed that as negative life events increased, judgments of close relationships gradually became less favorable, jumped back toward positivity, and then, again, gradually became less favorable. The same methods of analysis revealed a relationship between negative life events and negative affect with no evidence of significant discontinuities. Moreover, the correlation between relationship satisfaction and negative affect (with negative events held constant), was maximized at the point of relationship-judgment discontinuity. Although the findings are complex, they are consistent with the authors' theoretical account and represent an initial attempt to conceptualize the effect of negative life events in light of the recent social judgment literature.

Attribution processes in distressed and nondistressed couples: 4. Self-partner attribution differences.

The importance of the self-other distinction for understanding the relation between attributions and marital satisfaction is examined in two studies. In Study 1, causal attributions for naturally occurring behavior by the self and spouse were investigated. Study 2 examined both causal and responsibility attributions for hypothetical behaviors. In both studies, the attributions of spouses seeking therapy were investigated in relation to those of happily married persons in the community. The results showed that self-other attribution differences varied as a function of marital distress. Nondistressed spouses showed a positive attribution bias by making more benign attributions for partner behavior as opposed to self-behavior, whereas distressed spouses showed a negative attribution bias by making less benign attributions for partner behavior than for self-behavior. These findings suggest that self-attributions may, in part, determine the impact of attributions for spouse behavior on marital satisfaction. The clinical relevance of the results and their implications for research on actor-observer attribution differences are outlined.

Pleasure and pain in doing well, together: an investigation of performance-related affect in close relationships.

In a series of four studies, the self-evaluation maintenance (SEM) model is used to predict peoples' self-reported affective responses to doing better or worse than their partners. Both self-protective reactions to comparison (i.e., those predicted by the original SEM model) and empathic reactions to the partner's response (i.e., those predicted by the extended SEM model) were obtained. In addition, as predicted on the basis of both models, comparisons with romantic partners resulted in a different pattern of self-reported affect than did comparisons with strangers. Unexpectedly, it appeared that empathic effects were minimal or absent among dating partners when comparisons were in areas of high self-relevance.

Negative and positive health effects of caring for a disabled spouse: longitudinal findings from the caregiver health effects study.

Data from the first 2 waves of the Caregiver Health Effects Study (n = 680) were analyzed to examine the effects of changes in caregiving involvement on changes in caregiver health-related outcomes in a population-based sample of elders caring for a disabled spouse. Caregiving involvement was indexed by levels of (a) spouse physical impairment, (b) help provided to the spouse, and (c) strain associated with providing help. Health-related outcomes included perceived health, health-risk behaviors, anxiety symptoms, and depression symptoms. Increases in spouse impairment and caregiver strain were generally related to poorer outcomes over time (poorer perceived health, increased health-risk behaviors, and increased anxiety and depression), whereas increased helping was related to better outcomes (decreased anxiety and depression). Results suggest that caring for a disabled spouse is a complex phenomenon that can have both deleterious and beneficial consequences.

When primary and secondary caregivers disagree: predictors and psychosocial consequences.

The purpose of this study was to investigate primary caregiving spouses' and their lay helpers' divergent opinions about the caregiving environment. Through parallel assessments, both primary and secondary caregivers of a patient with Alzheimer's disease were asked to rate the degree of patient problem behaviors; the degree of strain the primary caregiver was experiencing; and primary care-giver efficacy, or perceived ability to cope with caregiving demands. Analyses concentrated on the general levels of disagreement in these domains, as well as on potential predictors and consequences of such disagreement. Results revealed a substantial divergence in perceptions across caregiving domains, with relatively less disagreement about patient problem behaviors and primary caregiver strain than about primary caregiver coping efficacy. Primary caregivers with relatively pessimistic secondary caregivers experienced relatively less psychosocial distress than primary caregivers with more optimistic helpers. These findings were strongest among female-female caregiving dyads. Theoretical implications and methodological limitations of the study are discussed, along with suggestions for future research.

The 5' Third of Cauliflower mosaic virus Gene VI Conditions Resistance Breakage in Arabidopsis Ecotype Tsu-0.

ABSTRACT Arabidopsis thaliana ecotypes vary in their responses to viruses. In this study, we analyzed the variation in response of A. thaliana ecotype Tsu-0 to Cauliflower mosaic virus (CaMV). This ecotype was previously reported to be resistant to two CaMV isolates (CM1841 and CM4-184), but susceptible to W260. In this study, we show that Tsu-0 is resistant to four additional CaMV isolates. CaMV propagated within the rosette leaves of Tsu-0 plants, but did not appear to spread systemically into the inflorescence. However, virus viability in rosette leaves of Tsu-0 plants apparently was not compromised because infectious CaMV could be recovered from these organs. W260 overcomes Tsu-0 resistance by a passive mechanism (i.e., this virus avoids activating plant defenses). The portion of the viral genome responsible for W260 resistance breakage was mapped to the 5' third of gene VI, which we have termed RBR-1. This region is also responsible for controlling the ability of CaMV to infect different types of solanaceous plants. Hence, the pathways by which plants of different families interact with CaMV may be conserved through evolution.

Modifying repetitive verbalizations of community-dwelling patients with AD.

Seven caregivers of a home-dwelling spouse with Alzheimer's disease were trained during 12 weekly home visits to implement behavior management programs including written cuing procedures in response to repetitive verbalizations. Data from 7 trained caregivers and 7 matched control caregivers who only tracked repetitive behavior were compared. Results revealed that trained caregivers were successful at decreasing patient repetitions using written cues. Patients of control subjects showed no systematic changes in behavioral disturbances due to behavior tracking. In addition, intervention effects lasted for 16 weeks or longer and several caregivers reported applying the cuing intervention to other, nontargeted behaviors. Trained caregivers' perceptions of their efficacy in managing difficult patient behavior improved significantly at the 3-month follow-up assessment when program staff were no longer visiting them weekly.

Attributions in marriage: examining the entailment model in dyadic context.

The entailment model of attributions is examined for the first time using a dyadic approach and longitudinal data. In a sample of 229 married partners with children, causal attributions were distinguished empirically from responsibility attributions and, consistent with the entailment model, the effect of causal attributions on conflict was mediated through attributions of responsibility. Only 1 path was influenced by spouse gender. Examination of cross-spouse effects revealed significant effects and provided a better fit than a model with no cross-spouse effects. The importance of including cross-spouse effects in attributional models is discussed.