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ABSTRACT IMPACT: This study characterizes interactions between human limbic circuitry and ventral temporal cortex using single pulse electrical stimulation, which may inform emerging stimulation therapies for epilepsy. OBJECTIVES/GOALS: The goal of electrical brain stimulation treatment is to modulate brain network function. However, stimulation inputs to different brain sites alter the network in a variety of ways. This study examines that variability by characterizing responses in a target region while stimulating multiple other brain sites. METHODS/STUDY POPULATION: We measured voltages in intracranial EEG in 6 patients who had electrodes implanted for epilepsy monitoring. We stimulated pairs of electrodes at multiple sites in the brain with a single pulse every 5 to 7 s and measured the resulting corticocortical evoked potential (CCEP) responses in the ventral temporal cortex (VTC). Using a novel clustering method, we uncovered sets of distinct canonical response shapes from the 20 to 500 ms post-stimulation period. This allowed us to group stimulation sites that evoked similar responses. We then related each group to high frequency, broadband, changes in spectral power as a reflection of local neuronal activity. RESULTS/ANTICIPATED RESULTS: We found that the VTC receives strong inputs specifically from the amygdala and hippocampus, both in terms of amplitude and broadband spectral power change. However, inputs from the hippocampus produced a different canonical shape than those from the amygdala. We also observed that VTC responses to inputs from the insula clustered in shape with those from the amygdala. These clustering patterns were consistent across subjects, although the actual shapes of the clusters showed variability. We further observed that some shapes were more associated with increases in overall neuronal activity than others, as reflected by broadband spectral power change. DISCUSSION/SIGNIFICANCE OF FINDINGS: Stimulation of connected sites may drive excitability at the target region in ways that are described by sets of full-time-course responses. By capturing their shapes, we can begin to decipher canonical input types at the circuit level. This approach might identify how stimulation inputs can be tailored to therapy while mitigating adverse effects.
There is evidence that depression can be prevented; however, traditional approaches face significant scalability issues. Digital technologies provide a potential solution, although this has not been adequately tested. The aim of this study was to evaluate the effectiveness of a new smartphone app designed to reduce depression symptoms and subsequent incident depression amongst a large group of Australian workers.
A randomized controlled trial was conducted with follow-up assessments at 5 weeks and 3 and 12 months post-baseline. Participants were employed Australians reporting no clinically significant depression. The intervention group (N = 1128) was allocated to use HeadGear, a smartphone app which included a 30-day behavioural activation and mindfulness intervention. The attention-control group (N = 1143) used an app which included a 30-day mood monitoring component. The primary outcome was the level of depressive symptomatology (PHQ-9) at 3-month follow-up. Analyses were conducted within an intention-to-treat framework using mixed modelling.
Those assigned to the HeadGear arm had fewer depressive symptoms over the course of the trial compared to those assigned to the control (F3,734.7 = 2.98, p = 0.031). Prevalence of depression over the 12-month period was 8.0% and 3.5% for controls and HeadGear recipients, respectively, with odds of depression caseness amongst the intervention group of 0.43 (p = 0.001, 95% CI 0.26–0.70).
This trial demonstrates that a smartphone app can reduce depression symptoms and potentially prevent incident depression caseness and such interventions may have a role in improving working population mental health. Some caution in interpretation is needed regarding the clinical significance due to small effect size and trial attrition.
Trial Registration Australian and New Zealand Clinical Trials Registry (www.anzctr.org.au/) ACTRN12617000548336
The foetal programming hypothesis posits that optimising early life factors e.g. maternal diets can help avert the burden of adverse childhood outcomes e.g. childhood obesity. To improve applicability to public health messaging, we investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity in a large consortium.
We harmonized and pooled individual participant data from up to 8,769 mother-child pairs in 7 European mother-offspring cohorts. Maternal early-, late-, and whole-pregnancy dietary quality and inflammatory potential were assessed with Dietary Approaches to Stop Hypertension (DASH) and energy-adjusted Dietary Inflammatory Index (E-DII), respectively. Primary outcome was childhood overweight and obesity (OWOB), defined as age- and sex-specific body-mass-index-z score (BMIz) > 85th percentile based on WHO growth standard. Secondary outcomes were sum-of-skinfold-thickness (SST), fat-mass-index (FMI) and fat-free-mass-index (FFMI) in available cohorts. Outcomes were assessed in early- [mean (SD) age: 2.8 (0.3) y], mid- [6.2 (0.6) y], and late-childhood [10.6 (1.2) y]. We used multivariable regression analyses to assess the associations of maternal E-DII and DASH with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effects meta-analyses. Analyses were adjusted for maternal age, pre-pregnancy BMI, parity, lifestyle factors, energy intake, educational attainment, offspring age and sex.
A more pro-inflammatory maternal diet, indicated by higher E-DII, was associated with a higher risk of offspring late-childhood OWOB [pooled-OR (95% CI) comparing highest vs. lowest E-DII quartiles: 1.22 (1.01,1.47) for whole-pregnancy and 1.38 (1.05,1.83) for early-pregnancy; both P < 0.05]. Moreover, higher late-pregnancy E-DII was associated with higher mid-childhood FMI [pooled-β (95% CI): 0.11 (0.003,0.22) kg/m2; P < 0.05]; trending association was observed for whole-pregnancy E-DII [0.12 (-0.01,0.25) kg/m2; P = 0.07]. A higher maternal dietary quality, indicated by higher DASH score, showed a trending inverse association with late-childhood OWOB (pooled-OR (95% CI) comparing highest vs. lowest DASH quartiles: 0.58 (0.32,1.02; P = 0.06). Higher early-pregnancy DASH was associated with lower late-childhood SST [pooled-β (95% CI): -1.9 (-3.6,-0.1) cm; P < 0.05] and tended to be associated with lower late-childhood FMI [-0.34 (-0.71,0.04) kg/m2; P = 0.08]. Higher whole-pregnancy DASH tended to associate with lower early-childhood SST [-0.33 (-0.72,0.06) cm; P = 0.10]. Results were similar when modelling DASH and E-DII continuously.
Analysis of pooled data suggests that pro-inflammatory, low-quality maternal antenatal diets may influence offspring body composition and obesity risk, especially during mid- or late-childhood. Due to variation of data availability at each timepoint, our results should be interpreted with caution. Because most associations were observed at mid-childhood or later, future studies will benefit from a longer follow-up.
Arachidonic acid (ARA) and DHA, supplied primarily from the mother, are required for early development of the central nervous system. Thus, variations in maternal ARA or DHA status may modify neurocognitive development. We investigated the relationship between maternal ARA and DHA status in early (11·7 weeks) or late (34·5 weeks) pregnancy on neurocognitive function at the age of 4 years or 6–7 years in 724 mother–child pairs from the Southampton Women’s Survey cohort. Plasma phosphatidylcholine fatty acid composition was measured in early and late pregnancy. ARA concentration in early pregnancy predicted 13 % of the variation in ARA concentration in late pregnancy (β=0·36, P<0·001). DHA concentration in early pregnancy predicted 21 % of the variation in DHA concentration in late pregnancy (β=0·46, P<0·001). Children’s cognitive function at the age of 4 years was assessed by the Wechsler Preschool and Primary Scale of Intelligence and at the age of 6–7 years by the Wechsler Abbreviated Scale of Intelligence. Executive function at the age of 6–7 years was assessed using elements of the Cambridge Neuropsychological Test Automated Battery. Neither DHA nor ARA concentrations in early or late pregnancy were associated significantly with neurocognitive function in children at the age of 4 years or the age of 6–7 years. These findings suggest that ARA and DHA status during pregnancy in the range found in this cohort are unlikely to have major influences on neurocognitive function in healthy children.
The Orion facility at the Atomic Weapons Establishment in the United Kingdom has the capability to operate one of its two 500 J, 500 fs short-pulse petawatt beams at the second harmonic, the principal reason being to increase the temporal contrast of the pulse on target. This is achieved post-compression, using 3 mm thick type-1 potassium dihydrogen phosphate crystals. Since the beam diameter of the compressed pulse is
mm, it is impractical to achieve this over the full aperture due to the unavailability of the large aperture crystals. Frequency doubling was originally achieved on Orion using a circular sub-aperture of 300 mm diameter. The reduction in aperture limited the output energy to 100 J. The second-harmonic capability has been upgraded by taking two square 300 mm
300 mm sub-apertures from the beam and combining them at focus using a single paraboloidal mirror, thus creating a 200 J, 500 fs, i.e., 400 TW facility at the second harmonic.
Salmonella is a leading cause of bacterial foodborne illness. We report the collaborative investigative efforts of US and Canadian public health officials during the 2013–2014 international outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder. The investigation included open-ended interviews of ill persons, traceback, product testing, facility inspections, and trace forward. Ninety-four persons infected with outbreak strains from 16 states and four provinces were identified; 21% were hospitalized and none died. Fifty-four (96%) of 56 persons who consumed chia seed powder, reported 13 different brands that traced back to a single Canadian firm, distributed by four US and eight Canadian companies. Laboratory testing yielded outbreak strains from leftover and intact product. Contaminated product was recalled. Although chia seed powder is a novel outbreak vehicle, sprouted seeds are recognized as an important cause of foodborne illness; firms should follow available guidance to reduce the risk of bacterial contamination during sprouting.
Background: Disgust is thought to play a prominent role in multiple anxiety disorders and fears, including spider phobia, though little attention has been given to specific treatment strategies that may be effective for multiple disgust-based fears. Aims: In the present study, we evaluated contamination-focused exposure as a potential transdiagnostic treatment strategy for disgust-based fears in a spider fearful sample. Method: Women with significant spider fear were randomized to three 30-minute sessions of exposure therapy involving repeated contact with a dirt mixture (n=17) or a waitlist control condition (n=17). Assessments of spider fear and disgust were administered at baseline and at one-week posttreatment. Results: At high (but not low) levels of pretreatment disgust propensity, exposure led to lower in vivo spider fear and perceived danger than waitlist, though exposure had no effects on spider-related disgust. Similar effects of exposure on spider fear were found at high levels of pretreatment spider-related disgust. Exposure also reduced fear and danger perceptions, but not disgust, related to a separate contamination assessment (touching a toilet). No effects of treatment were found on self-report measures of spider fear or disgust propensity. Conclusions: These findings suggest contamination-focused exposure therapy may be an effective transdiagnostic treatment strategy for individuals with elevated disgust propensity. Limitations and directions for future research are discussed.
Individual placement and support (IPS) is a vocational rehabilitation
programme that was developed in the USA to improve employment outcomes
for people with severe mental illness. Its ability to be generalised to
other countries and its effectiveness in varying economic conditions
remains to be ascertained.
To investigate whether IPS is effective across international settings and
in different economic conditions.
A systematic review and meta-analysis of randomised controlled trials
comparing IPS with traditional vocational services was undertaken; 17
studies, as well as 2 follow-up studies, were included. Meta-regressions
were carried out to examine whether IPS effectiveness varied according to
geographic location, unemployment rates or gross domestic product (GDP)
The overall pooled risk ratio for competitive employment using IPS
compared with traditional vocational rehabilitation was 2.40 (95% CI
1.99–2.90). Meta-regressions indicated that neither geographic area nor
unemployment rates affected the overall effectiveness of IPS. Even when a
country's GDP growth was less than 2% IPS was significantly more
effective than traditional vocational training, and its benefits remained
evident over 2 years.
Individual placement and support is an effective intervention across a
variety of settings and economic conditions and is more than twice as
likely to lead to competitive employment when compared with traditional
The goal of this study was to gain insights into the decision-making processes used by California public health officials during real-time crises. The decision-making processes used by California public health officials during the 2009 H1N1 influenza pandemic were examined by a survey research team from the University of California Berkeley.
The survey was administered to local public health officials in California. Guidelines published by the Centers for Disease Control and Prevention had recommended school closure, and local public health officials had to decide whether to follow these recommendations. Chi-squared tests were used to make comparisons in the descriptive statistics.
The response rate from local public health departments was 79%. A total of 73% of respondents were involved in the decision-making process. Respondents stated whether they used or did not use 15 ethical, logistical, and political preselected criteria. They expressed interest in receiving checklists and additional training in decision-making.
Public health decision-makers do not appear to have a standard process for crisis decision-making and would benefit from having an organized decision-making model. The survey showed that ethical, logistical, and political criteria were considered but were not prioritized in any meaningful way. A new decision-making tool kit for public health decision-makers plus implementation training is warranted. (Disaster Med Public Health Preparedness. 2015;9:464–471)
This chapter addresses the role played by influences during intrauterine or early postnatal life in establishing the risk of osteoporosis in later years. At any age, the amount and quality of an individual's skeleton reflect their experiences from intrauterine life through the years of growth into young adulthood. Epidemiological evidence that the risk of osteoporosis might be modified by the intrauterine and early postnatal environment has emerged from two groups of studies. First, the retrospective cohort studies in which bone mineral measurements were undertaken. Second, mother-offspring cohorts relating the nutrition, body build and lifestyle of pregnant women to the bone mass of their offspring. The two most-studied forms of epigenetic marking are DNA methylation and histone modification. The key nutrients likely to influence fetal bone development include calcium and vitamin D, and therefore this axis provides a model for investigating the epigenetic regulation of bone mass.
Osteoporosis-related fractures have a major impact on health at the individual and societal levels, through associated morbidity and increased mortality. Up to 50% of women and 20% of men at age 50 years may have a fragility fracture in their remaining lifetimes. Nutrition is important throughout the life course. Thus, adequate Ca and vitamin D intake has been shown to reduce risk of fracture in old age. Other factors such as protein and vitamin K may also be important, although the evidence here is less strong. In childhood Ca or vitamin D supplementation trials have demonstrated modest short-term increases in bone mass, but the long-term implications have not been established. Over recent years it has become apparent that maternal nutrition may have critical and far-reaching persistent consequences for offspring health. Thus, reduced maternal fat stores and low levels of circulating 25-hydroxyvitamin D in pregnancy are associated with reduced bone mass in the offspring; placental Ca transport may be key to these relationships. Wider maternal dietary patterns have also been shown to predict offspring bone mass. These data suggest that an interventional approach aimed at specific micronutrients, such as vitamin D, should be complemented by general optimisation of the mother's diet and lifestyle in order to maximise intrauterine bone mineral accrual and postnatal skeletal growth and thus reduce the burden of osteoporotic fractures in future generations.
The impact of variations in current infant feeding practice on bone mineral accrual is not known. We examined the associations between duration of breast-feeding and compliance with infant dietary guidelines and later bone size and density at age 4 years. At total of 599 (318 boys) mother–child pairs were recruited from the Southampton Women's Survey. Duration of breast-feeding was recorded and infant diet was assessed at 6 and 12 months using FFQ. At 6 and 12 months the most important dietary pattern, defined by principal component analysis, was characterised by high consumption of vegetables, fruits and home-prepared foods. As this was consistent with infant feeding recommendations, it was denoted the ‘infant guidelines’ pattern. At age 4 years, children underwent assessment of whole-body bone size and density using a Hologic Discovery dual-energy X-ray absorptiometry instrument. Correlation methods were used to explore the relationships between infant dietary variables and bone mineral. There was no association between duration of breast-feeding in the first year of life and 4-year bone size or density. ‘Infant guidelines’ pattern scores at 6 and 12 months were also unrelated to bone mass at age 4 years. We observed wide variations in current infant feeding practice, but these variations were not associated with differences in childhood bone mass at age 4 years.
To investigate the association between fruit and vegetable consumption and self-reported physical and mental functional health measured by an anglicised short-form 36-item questionnaire (UK SF-36).
Population-based cross-sectional study.
General community in Norfolk, UK.
A total of 16 792 men and women aged 40–79 years recruited from general practice population registers as part of the European Prospective Investigation into Cancer (EPIC)–Norfolk study, who completed food-frequency questionnaires in 1993–1997 and Health and Life Experiences Questionnaires 18 months later, were enrolled in the study.
Mean SF-36 physical component summary scores increased significantly with increasing total fruit and vegetable consumption in both men and women (P < 0.0001 for trend). Men and women in the top quartile of consumption compared with the bottom quartile had a significantly higher likelihood of reporting good physical health (defined as a score ≥ 55); odds ratio (OR) 1.30, 95% confidence interval (CI) 1.11–1.53 for men and OR 1.28, 95% CI 1.11–1.48 for women, after controlling for age, body mass index, smoking, education, social class, prevalent illness and total energy intake. Exclusion of current smokers and people with prevalent illness did not alter the associations.
Higher fruit and vegetable consumption is associated with better self-reported physical functional health within a general population. Increasing daily intake by two portions of fruit and vegetables was associated with an 11% higher likelihood of good functional health. Since the current average consumption of fruit and vegetables in the UK is about three portions, the recommended ‘five a day’ strategy may have additional benefit for functional as well as other health outcomes in the population.