INTERPRETIVE BIAS AND ANXIETY VULNERABILITY IN BEHAVIORALLY INHIBITED CHILDREN: DISAMBIGUATING THE COGNITIVE AND EMOTIONAL EFFECTS ASSOCIATED WITH INTERPRETIVE BIAS ACQUISITION

Behavioral inhibition (BI), a temperament characterized by a fear of novel and unfamiliar people and situations, is associated with increased risk for anxiety problems throughout life. One mechanism thought to moderate the link between BI and anxiety is a child's interpretive bias (i.e., the manner in which emotional ambiguity is interpreted). Behaviorally inhibited children who consistently interpret ambiguous information in a threatening manner are thought to be at increased risk for anxiety. Conversely, behaviorally inhibited children who consistently interpret ambiguity as benign or non-threatening may be protected from such risk. Little research, however, has experimentally examined interpretive biases in behaviorally inhibited children. This dissertation investigates the causal relations between interpretive biases and anxiety vulnerability in behaviorally inhibited children. To examine if changes in interpretive biases affect anxiety vulnerability, a cognitive bias modification procedure was employed to induce a non-threatening interpretive bias in a group of 9-12 year old behaviorally inhibited children. After training, children were assessed on their mood, emotional vulnerability to stress, and attention bias toward threat in order to determine if bias modification affected anxiety vulnerability. The findings of this study demonstrate that the cognitive bias manipulation was successful; behaviorally inhibited children displayed decreased threat interpretations after training. No training effects on anxiety vulnerability were detected. As a result, the notion that interpretive biases are causally linked to a child's anxiety vulnerability is not supported by the findings of this study. The implications of these findings are discussed in this dissertation

The cognitive and emotional effects of cognitive bias modification in interpretations in behaviorally inhibited youth

Cognitive bias modification (CBM) procedures follow from the view that interpretive biases play an important role in the development and maintenance of anxiety. As such, understanding the link between interpretive biases and anxiety in youth at risk for anxiety (e.g., behaviorally inhibited children) could elucidate the mechanisms involved in the development of pediatric anxiety. However, to date, the majority of CBM-I work only studies adult populations. The present article presents the results of a CBM study examining effects of positive interpretive bias modification on mood, stress vulnerability, and threat-related attention bias in a group of behaviorally inhibited children (n = 45). Despite successful modification of interpretive bias in the at-risk youth, minimal effects on stress vulnerability or threat-related attention bias were found. The current findings highlight the need for continued research on cognitive biases in anxiety

A resting EEG study of neocortical hyperexcitability and altered functional connectivity in fragile X syndrome

(A) Scalp topographies of “local coupling”, showing correlations in each electrode between relative power of activity in the theta, and lower and upper alpha power bands and gamma power for male FXS and male healthy control participants, with significant group differences presented in the bottom row (p < 0.05, corrected), with dark blue reflecting no group difference. (B) Mean and standard error of correlations for all electrodes showing group differences as are plotted in A. * denotes correlations of spectral power in theta and upper alpha bands with gamma band power that are significantly different from zero based on the results of permutation analyses at p < 0.05. (TIF 4297 kb

The impact of the UK soft drink industry levy on the soft drink marketplace, 2017–2020: An interrupted time series analysis with comparator series

Background: In April 2018, the UK government implemented a levy on soft drinks importers and manufacturers, tiered according to the amount of sugar in drinks. The stated aim was to encourage manufacturers to reduce sugar and portion sizes. Previous evidence suggests that the policy has been successful in reducing sugar in drinks in the short-term since implementation, but their sustained effects have not been explored. This study aimed to assess the impact of the soft drink industry levy (SDIL) on sugar levels, price, portion size and use of non-sugar sweeteners in the medium-term. Methods and findings: Product data from 30 November 2017 to 14 March 2020 from one major UK retail supermarket were analysed (112,452 observations, 126 weekly time points). We used interrupted time series analysis, to assess the impact of the soft-drink industry levy (SDIL) on levy-eligible soft drinks, with exempt drinks (i.e. 100% fruit juices, milks, flavoured milks) acting as a comparator series. At the point of implementation of the SDIL (April 2018) there was a step change in the proportion of eligible drinks with sugar content below the SDIL levy threshold (5g per 100ml) (+0.08, 95%CI: +0.04, +0.12), with a similar sized decrease in the proportion in the highest levy category (> = 8g sugar per 100ml) (-0.06, 95%CI: -0.10, -0.03). Between April 2018 and March 2020, the proportion of eligible drinks below the SDIL levy threshold continued to gradually increase (p = 0.003), while those in the highest levy category decreased (p = 0.007). There was a step change in price of eligible drinks in the higher levy category at the point of implementation of +£0.049 (95%CI: +£0.034, +£0.065) per 100mL (for comparison, the levy is set at £0.024 per 100mL for this group). Trends in price for the high levy category were not altered by the SDIL. In the no levy category, there was a step change in price at the implementation (+£0.012 per 100mL, 95%CI: +£0.008, +£0.023), followed by a second step change in October 2018 (-£0.018p per 100mL, 95%CI: -£0.033, -£0.001p). The volume of products in the higher levy group decreased at the time of the implementation (-305mL on average including multipacks, 95%CI: -511, -99). The change in trend for the product volume of drinks in the higher levy group between April 2018 and March 2020 was in the increasing direction (+704mL per year, 95%CI: -95, 1504), but it did not meet our threshold for statistical significance (p = 0.084). There were no changes observed in the volume of lower levy drinks or no levy drinks. There was a step change in the proportion of drinks with non-sugar sweeteners at the implementation of the SDIL (+0.04, 95%CI: +0.02, +0.06). Conclusion: These results suggest that the SDIL was successful in [1] producing reductions in sugar levels that were maintained over the medium term up to March 2020 and [2] a reduction in product volume for higher tier drinks that may be diminishing over time. Our results also show that the SDIL was associated with a maintained price differential between high and low sugar drinks

Core pathway mutations induce de-differentiation of murine astrocytes into glioblastoma stem cells that are sensitive to radiation but resistant to temozolomide

Glioma stem cells (GSCs) from human glioblastomas (GBMs) are resistant to radiation and chemotherapy and may drive recurrence. Treatment efficacy may depend on GSCs, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype

Modification of the association between recreational physical activity and survival after breast cancer by promoter methylation in breast cancer-related genes

Background: Mechanisms underlying the inverse association between physical activity and survival after breast cancer are unresolved, but DNA methylation may play a role. We hypothesized that promoter methylation of breast cancer-related genes, as well as global methylation, may modify the association between prediagnostic recreational physical activity (RPA) and breast cancer mortality. Methods: Using a population-based sample of 1254 women diagnosed with first primary breast cancer, we examined modification of the RPA-mortality association by gene-specific promoter methylation and global methylation. Average lifetime RPA was assessed from menarche to diagnosis through structured in-home interviews. Promoter methylation of 13 breast cancer-related genes was evaluated in archived tumor by methylation-specific polymerase chain reaction and MethyLight assay. Global methylation in white blood cell DNA was determined at long interspersed nucleotide element 1 and by the luminometric methylation assay. After approximately 15 years of follow-up, 486 patients had died, and 186 of the deaths were breast cancer-related. We used Cox proportional hazards regression to estimate HRs and 95% CIs as well as likelihood ratio tests to assess multiplicative interactions. Results: All-cause mortality was lower only among physically active women with methylated promoter of APC (HR 0.60, 95% CI 0.40–0.80), CCND2 (HR 0.56, 95% CI 0.32–0.99), HIN (HR 0.55, 95% CI 0.38–0.80), and TWIST1 (HR 0.28, 95% CI 0.14–0.56) in tumors, but not among those with unmethylated tumors (significant interaction p < 0.05). We found no interaction between RPA and global methylation. Conclusions: The improved survival after breast cancer that is associated with RPA may be more pronounced in women with promoter tumor methylation in biologically plausible genes

The impact of the COVID-19 pandemic on children’s conduct problems and callous-unemotional traits

The COVID-19 pandemic has dramatically altered family life, but whether family exposures to and worries about the COVID-19 pandemic has impacted child conduct problems (CP) and callous-unemotional (CU) traits is unknown. Thus, we evaluated 303 parents (Mage = 38.04; SD = 5.21; 92.4% biological mothers) and children (Mage = 6.43; SD = 2.13; 51.8% female) during a four-month period early in the pandemic. We examined associations between parental exposures to COVID-19, parental worries about the pandemic, harsh and warm parenting practices, and child CP and CU traits. Although more parental worries were not directly related to parenting practices, more worry about COVID-19 was specifically related to higher levels of child CP, particularly parental worries about themselves or family members contracting the virus. Our findings add to a growing literature demonstrating the burden that the pandemic has placed on families and its implications for children’s mental health.Published versio

What sources of bereavement support are perceived helpful by bereaved people and why? Empirical evidence for the compassionate communities approach

YesAims: To determine who provides bereavement support in the community, what sources are perceived to be the most or least helpful and for what reason, and to identify the empirical elements for optimal support in developing any future compassionate communities approach in palliative care. Design: A population-based cross-sectional investigation of bereavement experiences. Sources of support (informal, community and professional) were categorised according to the Public Health Model of Bereavement Support; most helpful reasons were categorised using the Social Provisions Scale, and least helpful were analysed using inductive content analysis. Setting and participants: Bereaved people were recruited from databases of funeral providers in Australia via an anonymous postal survey (2013–2014). Results: In total, 678 bereaved people responded to the survey. The most frequently used sources of support were in the informal category such as family, friends and funeral providers. While the professional category sources were the least used, they had the highest proportions of perceived unhelpfulness whereas the lowest proportions of unhelpfulness were in the informal category. The functional types of helpful support were Attachment, Reliable Alliance, Social Integration and Guidance. The five themes for least helpful support were: Insensitivity, Absence of Anticipated Support, Poor Advice, Lack of Empathy and Systemic Hindrance. Conclusion: A public health approach, as exemplified by compassionate communities policies and practices, should be adopted to support the majority of bereaved people as much of this support is already provided in informal and other community settings by a range of people already involved in the everyday lives of those recently bereaved. This study has provided further support for the need to strengthen the compassionate communities approach, not only for end of life care for dying patients but also along the continuum of bereavement support.Health Department of Western Australia

DNA methylation modifies the association between obesity and survival after breast cancer diagnosis

Mechanisms underlying the poor breast cancer prognosis among obese women are unresolved. DNA methylation levels are linked to obesity and to breast cancer survival. We hypothesized that obesity may work in conjunction with the epigenome to alter prognosis. Using a population-based sample of women diagnosed with first primary breast cancer, we examined modification of the obesity-mortality association by DNA methylation. In-person interviews were conducted approximately 3 months after diagnosis. Weight and height were assessed [to estimate body mass index (BMI)], and blood samples collected. Promoter methylation of 13 breast cancer-related genes was assessed in archived tumor by methylation-specific PCR and Methyl Light. Global methylation in white blood cell DNA was assessed by analysis of long interspersed elements-1 (LINE-1) and with the lumino-metric methylation assay (LUMA). Vital status among 1308 patients (with any methylation biomarker and complete BMI assessment) was determined after approximately 15 years of follow-up (N = 194/441 deaths due to breast cancer-specific/all-cause mortality). We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) using two-sided p values of 0.05. Breast cancer-specific mortality was higher among obese (BMI ≥ 30) patients with promoter methylation in APC (HR = 2.47; 95 % CI = 1.43–4.27) and TWIST1 (HR = 4.25; 95 % CI = 1.43–12.70) in breast cancer tissue. Estimates were similar, but less pronounced, for all-cause mortality. Increased all-cause (HR =1.81; 95 % CI = 1.19–2.74) and breast cancer-specific (HR = 2.61; 95 % CI = 1.45–4.69) mortality was observed among obese patients with the lowest LUMA levels. The poor breast cancer prognosis associated with obesity may depend on methylation profiles, which warrants further investigation