Prenatal Screening for 22q11.2 Deletion Using a Targeted Microarray-Based Cell-Free DNA Test.

OBJECTIVE: To determine the performance of a targeted microarray-based cell-free DNA (cfDNA) test (Harmony Prenatal Test®) for the identification of pregnancies at increased risk for 22q11.2 deletion. METHODS: Test performance was determined in 2 steps including a total of 1,953 plasma samples. Analytical validation was performed in 1,736 plasma samples. Clinical verification of performance was performed in an additional 217 prospectively ascertained samples from pregnancies with fetal deletion status determined by diagnostic testing. RESULTS: Analytical sensitivity was 75.4% (95% CI: 67.1-82.2%) based on 122 samples with deletions ranging from 1.96 to 3.25 Mb. In 1,614 presumed unaffected samples, specificity was determined to be at least 99.5% (95% CI: 99.0-99.7%). In the clinical cohort, 5 of 7 samples from pregnancies affected with 22q11.2 deletion were determined to have a high probability of deletion. There were no false positive results in the 210 unaffected samples in this cohort. These clinical data are consistent with the performance demonstrated in the analytical validation. CONCLUSIONS: cfDNA testing using a targeted microarray-based technology is able to identify pregnancies at increased risk for 22q11.2 deletions of 3.0 Mb and smaller while maintaining a low false positive rate.

Comparing coronavirus (COVID-19) and climate change perceptions: Implications for support for individual and collective-level policies.

COVID-19 (coronavirus) and climate change are both global issues that have wide-reaching and serious consequences for human health, the economy, and social outcomes for populations around the world, and both require a combination of systemic governmental policies and community support for action. This paper compares people's responses to the coronavirus pandemic and climate change in the United Kingdom (UK). A representative survey of the UK population (n = 1,518) conducted in November and December 2020 explored public perceptions of (a) personal and government responsibility, (b) efficacy and trust, and (c) support for policies to address the two issues. The results show that, while there are a number of similarities between coronavirus and climate change, major differences exist regarding individual action. In comparison to the coronavirus pandemic, people feel less personal responsibility, think that their own personal actions are less efficacious, and express lower levels of support for (in particular individual-level) policies to address climate change. These findings suggest that experiences from the coronavirus pandemic cannot directly be translated to climate change, and thus that climate change is likely to require different policy responses and framing.

Fetal and maternal immune responses to methylmercury exposure: a cross-sectional study.

Methylmercury (MeHg) is a ubiquitous environmental contaminant with known neurodevelopmental effects. In humans, prenatal exposures primarily occur through maternal consumption of contaminated fish. In this study, we evaluated the association between prenatal exposure to MeHg and titers of total immunoglobulins (Ig) and specific autoantibodies in both mothers and fetuses by analyzing maternal and cord blood serum samples. We examined multiple immunoglobulin isotypes to determine if these biomarkers could inform as to fetal or maternal responses since IgG but not IgM can cross the placenta. Finally, we evaluated serum cytokine levels to further characterize the immune response to mercury exposure. The study was conducted using a subset of serum samples (N=61 pairs) collected from individuals enrolled in a population surveillance of MeHg exposures in the Brazilian Amazon during 2000/2001. Serum titers of antinuclear and antinucleolar autoantibodies were measured by indirect immunofluorescence. Serum immunoglobulins were measured by enzyme-linked immunosorbent assay (ELISA) and BioPlex multiplex assay. Serum cytokines were measured by BioPlex multiplex assay. In this population, the geometric mean mercury level was within the 95th percentile for US populations of women of childbearing age but the upper level of the range was significantly higher. Fetal blood mercury levels were higher (1.35 times) than those in their mothers, but highly correlated (correlation coefficient [r]=0.71; 95% CI: 0.54, 0.89). Total IgG (r=0.40; 95% CI: 0.19, 0.62) and antinuclear autoantibody (odds ratio [OR]=1.05; 95% CI: 1.02, 1.08) levels in paired maternal and fetal samples were also associated; in contrast, other immunoglobulin (IgM, IgE, and IgA) levels were not associated between pairs. Total IgG levels were significantly correlated with both maternal (r=0.60; 95% CI: 0.25, 0.96) and cord blood mercury levels (r=0.61; 95% CI: 0.25, 0.97), but individual isotypes were not. Serum cytokines, interleukin-1ß (r=0.37; 95% CI: 0.01, 0.73), interleukin-6 (r=0.34; 95% CI: 0.03, 0.65), and tumor necrosis factor-α (r=0.24; 95% CI: 0.015, 0.47), were positively correlated between maternal and fetal samples. Antinuclear and antinucleolar autoantibody titer and serum cytokine levels, in either maternal or cord blood, were not significantly associated with either maternal or cord blood mercury levels. These data provide further evidence that there are likely IgG biomarkers of mercury-induced immunotoxicity in this population since IgG levels were elevated with increased, and associated with, mercury exposure. However, unlike previous data from adult males and non-pregnant females, we found no evidence that antinuclear and antinucleolar autoantibody titer is a reliable biomarker of mercury immunotoxicity in this population.

Neuroscience and climate change: How brain recordings can help us understand human responses to climate change.

There is little published neuroscience research on the psychology of climate change. This review outlines how carefully designed experiments that measure key neural processes, linked to specific cognitive processes, can provide powerful tools to answer research questions in climate change psychology. We review relevant literature from social neuroscience that can be applicable to environmental research-the neural correlates of fairness and cooperation, altruistic behaviour and personal values-and discuss important factors when translating environmental psychology constructs to neuroscientific measurement. We provide a practical overview of how to implement environmental neuroscience using electroencephalography, summarising important event-related potential components and how they can be used to answer questions in climate change psychology. Challenges for the field include accurate attribution of findings, both within and between studies, the need for interdisciplinary collaboration, peer review and reporting processes.

Climate Change From a Distance: An Analysis of Construal Level and Psychological Distance From Climate Change.

The public perception of climate change as abstract and distant may undermine climate action. According to construal level theory, whether a phenomenon is perceived as psychologically distant or close is associated with whether it is construed as abstract or concrete, respectively. Previous work has established a link between psychological distance and climate action, but the associated role of construal level has yet to be explored in depth. In two representative surveys of Australians (N = 217 and N = 216), and one experiment (N = 319), we tested whether construal level and psychological distance from climate change predicted pro-environmental intentions and policy support, and whether manipulating distance and construal increased pro-environmental behaviors such as donations. Results showed that psychological closeness to climate change predicted more engagement in pro-environmental behaviors, while construal level produced inconsistent results, and manipulations of both variables failed to produce increases in pro-environmental behaviors. In contrast with the central tenet of construal level theory, construal level was unrelated to psychological distance in all three studies. Our findings suggest that the hypothesized relationship between construal level and psychological distance may not hold in the context of climate change, and that it may be difficult to change pro-environmental behavior by manipulating these variables.

Mercury induces an unopposed inflammatory response in human peripheral blood mononuclear cells in vitro.

BACKGROUND: The human immune response to mercury is not well characterized despite the body of evidence that suggests that Hg can modulate immune responses, including the induction of autoimmune disease in some mouse models. Dysregulation of cytokine signaling appears to play an important role in the etiology of Hg-induced autoimmunity in animal models. OBJECTIVES: In this study, we systematically investigated the human immune response to Hg in vitro in terms of cytokine release. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated from 20 volunteers who donated blood six separate times. PBMCs were cultured with lipopolysaccharide and concentrations of mercuric chloride (HgCl(2)) up to 200 nM. Seven cytokines representing important pathways in physiologic and pathologic immune responses were measured in supernatants. We used multilevel models to account for the intrinsic clustering in the cytokine data due to experimental design. RESULTS: We found a consistent increase in the release of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha, and concurrent decrease in release of the antiinflammatory cytokines interleukin 1-receptor antagonist (IL-1Ra) and IL-10 in human PBMCs treated with subcytotoxic concentrations of HgCl(2). IL-4, IL-17, and interferon-gamma increased in a concentration-response manner. These results were replicated in a second, independently recruited population of 20 different volunteers. CONCLUSIONS: Low concentrations of HgCl(2) affect immune function in human cells by dysregulation of cytokine signaling pathways, with the potential to influence diverse health outcomes such as susceptibility to infectious disease or risk of autoimmunity.