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Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.
We performed a prospective study of 501 patients, regardless of symptoms, admitted to the hospital, to estimate the predictive value of a negative nasopharyngeal swab for severe acute respiratory coronavirus virus 2 (SARS-CoV-2). At a positivity rate of 10.2%, the estimated negative predictive value (NPV) was 97.2% and the NPV rose as prevalence decreased during the study.
This chapter discusses the critical role of discourse in politics, highlighting the benefits to development advocates that accrue when the voices of concerned citizens are silenced. Seeking consent for industrial development has always been a game of claimsmaking, involving what Sheila Jasanoff refers to as “sociotechnical imaginaries” designed to solicit endorsement for particular development pathways. But behind the curtain of overt claimsmaking lay efforts to keep certain claims out of the limelight, when those claims may be perceived as particularly threatening to development. Davidson explores the manifold strategies employed by development advocates to silence concerned rural residents in southern Alberta, where natural gas reserves are being extracted through hydraulic fracturing, a technique associated with a host of environmental, climate, and health risks.
Mindfulness meditation has become a common method for reducing stress, stress-related psychopathology and some physical symptoms. As mindfulness programs become ubiquitous, concerns have been raised about their unknown potential for harm. We estimate multiple indices of harm following Mindfulness-Based Stress Reduction (MBSR) on two primary outcomes: global psychological and physical symptoms. In secondary analyses, we estimate multiple indices of harm on anxiety and depressive symptoms, discomfort in interpersonal relations, paranoid ideation and psychoticism.
Intent-to-treat analyses with multiple imputations for missing data were used on pre- and post-test data from a large, observational dataset (n = 2155) of community health clinic MBSR classes and from MBSR (n = 156) and waitlist control (n = 118) participants from three randomized controlled trials conducted contemporaneous to community classes in the same city by the same health clinic MBSR teachers. We estimate the change in symptoms, proportion of participants with increased symptoms, proportion of participants reporting greater than a 35% increase in symptoms, and for global psychological symptoms, clinically significant harm.
We find no evidence that MBSR leads to higher rates of harm relative to waitlist control on any primary or secondary outcome. On many indices of harm across multiple outcomes, community MBSR was significantly preventative of harm.
Engagement in MBSR is not predictive of increased rates of harm relative to no treatment. Rather, MBSR may be protective against multiple indices of harm. Research characterizing the relatively small proportion of MBSR participants that experience harm remains important.
Given the prevalence of adolescent depression and the modest effects of current treatments, research ought to inform development of effective intervention strategies. Self-compassion is inversely associated with depression, and self-compassion interventions have demonstrated promising effects on reducing depression. However, little is known about the neural mechanisms underlying that relationship. Maladaptive self-processing is a characteristic of depression that contributes to the onset and chronicity of depression. Because our own face is an automatic and direct cue for self-processing, this study investigated whether self-compassion was associated with neural responses during sad v. neutral self-face recognition and explore their relationship with depression severity in depressed adolescents and healthy controls (HCs).
During functional magnetic resonance imaging, 81 depressed youth and 37 HCs were instructed to identify whether morphed self or other faces with sad, happy, or neutral expressions resembled their own.
Self-compassion correlated negatively with activity during sad v. neutral self-face recognition in the dorsal anterior cingulate cortex in the total sample, and in the right posterior cingulate cortex/precuneus in HCs, respectively. In depressed adolescents, higher self-compassion correlated with lower activity during sad v. neutral self-face recognition in the right dorsolateral prefrontal cortex (DLPFC), implying that less cognitive effort might be needed to avoid dwelling on sad self-faces and/or regulate negative affect induced by them. Moreover, higher self-compassion mediated the relationship between lower DLPFC activity and reduced depression severity.
Our findings imply that DLPFC activity might be a biological marker of a successful self-compassion intervention as potential treatment for adolescent depression.
Hoarding is associated with problems engaging in social activities, lower social support, increased isolation and poses substantial challenges to family functioning. The aim of this investigation was to explore the relationship between hoarding severity and family and social functioning variables in 60 treatment-seeking adults with hoarding disorder (HD). Participants completed a battery of self-report measures during a baseline assessment completed prior to treatment. Forty-seven percent of participants reported they live alone. Forty-eight percent of participants reported that family and friends never visit them in their home, and 33% indicated they never had visitors to their home, not even service workers or repair people. Twelve percent of participants indicated they never visit with family or friends outside of their home; however, 55% of participants endorsed phoning family or friends more than 9 times each month. Increased clutter and hoarding severity was associated with a lower frequency of family and friends visiting in the home. Family competence and conflict were both positively associated with hoarding severity. Our results shed light on family and social impairment in HD and their relationship with symptom severity; however, additional research should examine social dysfunction among non-treatment-seeking individuals who may be more impaired or isolated.
This pooled analysis compared the efficacy of venlafaxine extended-release (XR) versus placebo in the treatment of social anxiety disorder (SAD).
Data were pooled from 5 randomized studies of patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) SAD (N=1459) who were treated with venlafaxine XR 75 mg/d to 225 mg/d or placebo for 12 weeks (4 studies) or 28 weeks (1 study). Response and remission rates were calculated for the overall sample, as well as stratified by gender and level of physical symptom severity at baseline. Response was defined as a score of 1 or 2 on the Clinical Global Impressions–Improvement (CGI-I) scale. Remission was defined as a total score of <30 on the Leibowitz Social Anxiety Scale (LSAS).
At baseline the mean LSAS score was 88.1 and 86.6 for the venlafaxine and placebo arms, respectively. Overall response rates at week 12 were 55% for venlafaxine XR and 33% for placebo (P<0.0001); remission rates were 25% and 12%, respectively (P<0.0001). Among patients with less severe physical symptoms, response rates were 52% and 32% for venlafaxine XR and placebo, respectively (P<0.0001); remission rates were 27% and 14%, respectively (P<0.0001). Response rates among patients with more severe physical symptoms were 56% for venlafaxine XR and 33% for placebo (P<0.0001); remission rates were 24% and 11%, respectively (P<0.0001).
Venlafaxine XR is effective in the treatment of SAD, regardless of gender or severity of physical symptoms.
Health education programs that address risk factors for depression and promote positive mental health are approaches that can improve mental wellbeing. We investigated the effectiveness of a health promotion program for reducing levels of depression, anxiety and stress and for promoting appropriate help-seeking behaviour.
Fifty-five adults 55+years (43 female, 12 male) self-selected to attend the Healthy & Wise program - a group-based, 8 × 2hr session health-literacy program for promoting positive physical, mental and social functioning in a rural setting. A questionnaire was administered at base-line and post-intervention which included the DASS-21 to measure depression, anxiety and stress levels.
No significant change in depression scores (mean = 3.60pre-3.51post). Anxiety scores increased (mean 2.92pre-3.51post) (p = .036) correlating with age (p = .029) and change in physical health status (p = .002).
Stress scores increased (mean 4.81pre-5.59post) (p = .05) correlating with age (p = .033) and change in physical health status (p = .016).
Most participants (pre = 96.36%, post = 98%) indicated they would be likely to seek help from a GP if depressed. Men who mainly rely on their spouse for support were more likely to seek help from a psychologist or psychiatrist (p = .038).
There was no significant change in DASS-21 scores for depression. There was an increase in anxiety and stress levels which may be attributable to older participants experiencing a decline in physical health during the program. Participants remained firm in their preference for seeking help from their GP for depression. Further evaluation is needed to determine whether: at-risk-populations need to be targeted; the intervention has an impact at 12-month follow-up.
When considering antipsychotic treatments for patients with schizophrenia, efficacy must be balanced against the side effects associated with each available treatment option. This balance of benefit versus risk in the choice of treatment should not exclusively depend on the clinical symptoms exhibited by each patient, but should also consider the individual's health and lifestyle characteristics.
A number of agents are available for the management of schizophrenia. To evaluate the advantages and disadvantages of the available antipsychotics, clinicians can use a number of variables to examine available data, such as numbers of patients in the study, the clinical relevance of the scales used to measure efficacy, and statistical significance. In addition, the clinician's evaluation may include a consideration of monitoring of various physiological parameters, which is a requirement with some antipsychotics.
Good practice would dictate the regular monitoring of physical health needs as a matter of course, and may improve patient outcome. Monitoring of parameters such as weight gain, and dental health might enable a more effective relationship between clinician and patient. These physical heath parameters might differentiate patients whose treatment is effective against symptoms and those whose quality of life is being optimised. By drawing on the experience of clinicians, we considered which physical health parameters should be measured routinely, and which measures should be considered on an individual patient basis.
It is straightforward to combine individualised patient monitoring with antipsychotic and behavioural therapy and might increase the impact of treatments on patients' quality of life.
The objective of this paper was to examine the implementation and effectiveness of a community-based intervention for hoarding disorder (HD) using Cognitive Rehabilitation and Exposure/Sorting Therapy (CREST).
This was a mixed-method, pre-post quasi-experimental study informed by the Practical, Robust Implementation and Sustainability Model for implementation science.
Program activities took place in San Diego County, mainly within clients’ homes or community, with some activities in-office.
Participants were aged 60 years or older, met eligibility for Medi-Cal or were uninsured, and met criteria for HD.
A manualized, mobile protocol that incorporated CREST was utilized.
The Clutter Image Rating and Hoarding Rating Scale were used as effectiveness outcomes. An investigator-created staff questionnaire was used to evaluate implementation.
Thirty-seven clients were reached and enrolled in treatment and 15 completed treatment during the initial 2 years of the program. There were significant changes in hoarding severity and clutter volume. Based on the initial 2 years of the program, funding was provided for expansion to cover additional San Diego County regions and hire more staff clinicians in year three.
Preliminary data suggest that the CREST intervention can be successfully implemented in a community setting with positive results for older adults with HD.
The association of MeHg exposure through fish consumption on human autoimmunity remains unclear. Fish also contain n-3 long chain polyunsaturated fatty acids (LCPUFA) that are known to regulate inflammation and mitigate autoimmune disease symptoms. We studied the association of low-level exposure to methylmercury (MeHg) through fish consumption in the SCDS. We examined this association at age 19 years in the SCDS Main Cohort (n = 497). We measured MeHg exposure at 3 time points [prenatal, weighted average (6 months to 19 years) and concurrent (19 years) and LCPUFA status and a panel of 13 autoimmune markers at age 19 years. The autoimmune markers included antinuclear antibodies (ANA), anti-dsDNA and anti-RNP, and total (non-specific) immunoglobulins (Ig) IgG, IgA, and IgM. A combined ANA variable was also calculated based on being within or above reference range for any of the ANA markers; 56% of the subjects met this criterion. Multivariable regression models adjusted for prenatal MeHg, sex and waist circumference, with and without adjustment for LCPUFA, were fit for the three MeHg exposure metrics and each immune marker. Mean (SD) prenatal, weighted average and concurrent MeHg was 6.84 (4.55), 7.46 (2.82), and 10.23 (6.02) ppm, respectively. Combined ANA was positively associated with concurrent MeHg following adjustment for the n6:n3 LCPUFA ratio (β = 0.036, 95%; CI: 0.001, 0.073). Prenatal and average MeHg exposures were not significantly associated with any individual ANA. IgM was negatively associated with concurrent (β = -0.016, 95%CI: -0.016, -0.002), and average (β = -0.042, 95%CI: -0.042, -0.009) MeHg exposure in the models adjusted for n-3, n-6 LCPUFA and when separately adjusted for the n6:n3 LCPUFA ratio. Total (19-year) n-3 PUFA status was negatively associated with anti-RNP (β = -20.355, 95%CI: -36.89, -4.34) and IgG (β = -1.384, 95%CI: -2.682, -0.087). Total n-3 LCPUFA was associated with lower markers of autoimmunity. MeHg exposure at 19 years was associated with higher ANA and lower IgM but only following adjustment for LCPUFA. The clinical significance of these findings is unclear and further research is warranted to determine if these associations precede autoimmune disease development.
Optimal maternal polyunsaturated fatty acid (PUFA) status is essential for foetal development. The desaturase enzymes, encoded by the fatty acid desaturase (FADS) genes, are involved in the endogenous synthesis of long chain (LC)PUFA and influence maternal LCPUFA concentrations. The minor allele of various FADS SNPs has been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of the LCPUFA arachidonic acid (AA) and docosahexaenoic acid (DHA); however, there is limited research to date on the influence of FADS genotype on cord PUFA status. The aim of the current study was to investigate the influence of maternal and child genetic variation on cord blood PUFA status in a high fish-eating cohort.
Cord blood samples collected from mother-child pairs (n = 1088) taking part in the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Maternal (n = 1088) and child genotype (n = 592) were determined for the FADS SNPs rs174537, rs174561, rs174575, and rs3834458. Regression analysis determined associations between maternal and child FADS genotype and cord PUFA status. In all regression models, the major allele homozygote genotype for each SNP was used as the reference group.
Directions of significant associations were as predicted. In mothers, the minor allele homozygote genotype for SNPs rs174537, rs174561 and rs3834458 was associated with lower cord DHA and lower total n-3 PUFA when compared to the major allele homozygous genotype (p < 0.05 for all). The heterozygous genotype was associated with increased concentrations of LA compared to the reference genotype for rs174561 (p = 0.021) and rs383448 (p = 0.023). In children, the heterozygous genotype was associated with lower AA concentrations and lower cord n-6:n-3 ratio for all SNPs (p < 0.05 for all) compared to those with the major allele homozygous genotype. A lower cord AA:LA ratio was also observed for children heterozygous for rs174547, rs174561 and rs174575 (p < 0.05 for all). Contrary to expected, there were no associations between cord PUFA concentrations and child minor allele homozygous genotype.
The current study indicates that variation in maternal and child FADS genotype influences cord PUFA concentrations, despite the high intake of preformed dietary LCPUFA from fish in this population. The sample size for minor allele homozygous children was likely too small to observe any statistically significant associations in the current analysis. Further research is needed to determine whether increased dietary intake can compensate for lower PUFA status as a result of FADS genotype.
Many institutions evaluate applications for local seed funding by recruiting peer reviewers from their own institutional community. Smaller institutions, however, often face difficulty locating qualified local reviewers who are not in conflict with the proposal. As a larger pool of reviewers may be accessed through a cross-institutional collaborative process, nine Clinical and Translational Science Award (CTSA) hubs formed a consortium in 2016 to facilitate reviewer exchanges. Data were collected to evaluate the feasibility and preliminary efficacy of the consortium.
The CTSA External Reviewer Exchange Consortium (CEREC) has been supported by a custom-built web-based application that facilitates the process and tracks the efficiency and productivity of the exchange.
All nine of the original CEREC members remain actively engaged in the exchange. Between January 2017 and May 2019, CEREC supported the review process for 23 individual calls for proposals. Out of the 412 reviews requested, 368 were received, for a fulfillment ratio of 89.3%. The yield on reviewer invitations has remained consistently high, with approximately one-third of invitations being accepted, and of the reviewers who agreed to provide a review, 88.3% submitted a complete review. Surveys of reviewers and pilot program administrators indicate high satisfaction with the process.
These data indicate that a reviewer exchange consortium is feasible, adds value to participating partners, and is sustainable over time.
We examined the prevalence and correlates of Helicobacter pylori (H. pylori) infection according to cytotoxin-associated gene A (CagA) phenotype, a main virulence antigen, among the ethnically diverse population groups of Jerusalem. A cross-sectional study was undertaken in Arab (N = 959) and Jewish (N = 692) adults, randomly selected from Israel's national population registry in age-sex and population strata. Sera were tested for H. pylori immunoglobulin G (IgG) antibodies. Positive samples were tested for virulence IgG antibodies to recombinant CagA protein, by enzyme-linked immunosorbent assay. Multinomial regression models were fitted to examine associations of sociodemographic factors with H. pylori phenotypes. H. pylori IgG antibody sero-prevalence was 83.3% (95% confidence interval (CI) 80.0%–85.5%) and 61.4% (95% CI 57.7%–65.0%) among Arabs and Jews, respectively. Among H. pylori positives, the respective CagA IgG antibody sero-positivity was 42.3% (95% CI 38.9%–45.8%) and 32.5% (95% CI 28.2%–37.1%). Among Jews, being born in the Former Soviet Union, the Middle East and North Africa, vs. Israel and the Americas, was positively associated with CagA sero-positivity. In both populations, sibship size was positively associated with both CagA positive and negative phenotypes; and education was inversely associated. In conclusion, CagA positive and negative infection had similar correlates, suggesting shared sources of these two H. pylori phenotypes.
We consider the life cycle of an axisymmetric laminar thermal starting from the initial condition of a Gaussian buoyant blob. We find that, as time progresses, the thermal transitions through a number of distinct stages, undergoing several morphological changes before ending up as a vortex ring. Whilst each stage is interesting in its own right, one objective of this study is to set out a consistent mathematical framework under which the entire life cycle can be studied. This allows examination of the transition between the different stages, as well as shedding light on some unsolved questions from previous works. We find that the early stages of formation are key in determining the properties of the final buoyant vortex ring and that, since they occur on a time scale where viscosity has little effect, the final properties of the ring display an independence above a critical Reynolds number. We also find that rings consistently contain the same proportion of the initial heat and have a consistent vorticity flux. By considering the effect of Prandtl number, we show that thermal diffusion can have a significant impact on development, smoothing out the temperature field and inhibiting the generation of vorticity. Finally, by considering the wake left behind as well as the vortex ring that is generated, we observe that the wake can itself roll up to form a second mushroom cap and subsequently a secondary vortex ring that follows the first.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.