Examining the Interplay between the Cognitive and Emotional Aspects of Gender Differences in Spatial Processing.

Women reliably perform worse than men on measures of spatial ability, particularly those involving mental rotation. At the same time, females also report higher levels of spatial anxiety than males. What remains unclear, however, is whether and in what ways gender differences in these cognitive and affective aspects of spatial processing may be interrelated. Here, we tested for robust gender differences across six different datasets in spatial ability and spatial anxiety (N = 1257, 830 females). Further, we tested for bidirectional mediation effects. We identified indirect relations between gender and spatial skills through spatial anxiety, as well as between gender and spatial anxiety through spatial skills. In the gender → spatial anxiety → spatial ability direction, spatial anxiety explained an average of 22.4% of gender differences in spatial ability. In the gender → spatial ability → spatial anxiety direction, spatial ability explained an average of 25.9% of gender differences in spatial anxiety. Broadly, these results support a strong relation between cognitive and affective factors when explaining gender differences in the spatial domain. However, the nature of this relation may be more complex than has been assumed in previous literature. On a practical level, the results of this study caution the development of interventions to address gender differences in spatial processing which focus primarily on either spatial anxiety or spatial ability until such further research can be conducted. Our results also speak to the need for future longitudinal work to determine the precise mechanisms linking cognitive and affective factors in spatial processing.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.

"You need to be super smart to do well in math!" Young children's field-specific ability beliefs.

Success in science, technology, engineering, and mathematics (STEM) fields is often believed to require intellectual talent ("brilliance"). Given that many cultures associate men more than women with brilliance, this belief poses an obstacle to women's STEM pursuits. Here, we investigated the developmental roots of this phenomenon, focusing specifically on young children's beliefs about math (N = 174 U.S. students in Grades 1-4; 93 girls, 81 boys; 52% White, 17% Asian, 13% Hispanic/Latinx). We found that field-specific ability beliefs (FABs) that associate success in math (vs. reading/writing) with brilliance are already present in early elementary school. We also found that brilliance-oriented FABs about math are negatively associated with elementary school students' (and particularly girls') math motivation-specifically, their math self-efficacy and interest. The early emergence of brilliance-oriented FABs about math and the negative relation between FABs and math motivation underscore the need to understand the sources and long-term effects of these beliefs. RESEARCH HIGHLIGHTS: Field-specific ability beliefs (FABs) are beliefs about the extent to which intellectual talent (or "brilliance") is required for success in a particular field or context. Among adults, brilliance-oriented FABs are an obstacle to diversity in science and technology, but the childhood antecedents of these beliefs are not well understood. The present study (N = 174) found that FABs that associate success in math (vs. reading/writing) with brilliance were already present in Grades 1-4. Brilliance-oriented FABs about math were negatively associated with elementary school students' (and particularly girls') math motivation-specifically, their math self-efficacy and interest.

Unlocking the Power of Gesture: Using Movement-Based Instruction to Improve First Grade Children's Spatial Unit Misconceptions.

Gestures are hand movements that are produced simultaneously with spoken language and can supplement it by representing semantic information, emphasizing important points, or showing spatial locations and relations. Gestures' specific features make them a promising tool to improve spatial thinking. Yet, there is recent work showing that not all learners benefit equally from gesture instruction and that this may be driven, in part, by children's difficulty understanding what an instructor's gesture is intended to represent. The current study directly compares instruction with gestures to instruction with plastic unit chips (Action) in a linear measurement learning paradigm aimed at teaching children the concept of spatial units. Some children performed only one type of movement, and some children performed both: Action-then-Gesture [AG] or Gesture-then-Action [GA]. Children learned most from the Gesture-then-Action [GA] and Action only [A] training conditions. After controlling for initial differences in learning, the gesture-then-action condition outperformed all three other training conditions on a transfer task. While gesture is cognitively challenging for some learners, that challenge may be desirable-immediately following gesture with a concrete representation to clarify that gesture's meaning is an especially effective way to unlock the power of this spatial tool and lead to deep, generalizable learning.

A multicenter virome analysis of blood, feces, and saliva in myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect 0.4%-2.5% of the global population. Most cases are unexplained; however, some patients describe an antecedent viral infection or response to antiviral medications. We report here a multicenter study for the presence of viral nucleic acid in blood, feces, and saliva of patients with ME/CFS using polymerase chain reaction and high-throughput sequencing. We found no consistent group-specific differences other than a lower prevalence of anelloviruses in cases compared to healthy controls. Our findings suggest that future investigations into viral infections in ME/CFS should focus on adaptive immune responses rather than surveillance for viral gene products.

Latent tuberculosis infection in the outpatient general medicine clinic: Efficacy of a nurse-run electronic directly observed treatment program.

Tuberculosis (TB) is a leading cause of infectious death worldwide, with nearly 2 billion currently infected globally. While the largest burden of active TB resides in low to middle-income countries, the US contributes to the global epidemic and can play a significant role in interrupting the spread of TB by recognizing and treating latent TB infection (LTBI). The vast majority of active TB in the US originates from the reactivation of LTBI. This cross-sectional study examines the prevalence of LTBI in a general medicine practice and explores the efficacy of a primary care nurse-run electronic directly observed therapy (eDOT) treatment program. 1221 patients were screened for the presence of historical risk factors for LTBI. Of those screened, 192 were offered QuantiFERON-TB Gold Plus (QFT-Plus) testing and a CXR if indicated, resulting in 35 being offered treatment for LTBI. After an initial provider visit to decide on the treatment regimen, patients received weekly nurse calls to verify adherence, assess for side effects and answer additional patient questions. Provider follow-up appointments occurred at the midpoint and completion of treatment. 33 (94%) of patients with LTBI completed treatment. Patients found the nurse calls very helpful to reassure them about their treatment and to address treatment concerns. Primary care providers are particularly well-positioned to identify and treat LTBI. Screening is simple and treatment is generally well tolerated. Utilization of a nurse-run eDOT) program can be quite helpful in facilitating adherence and treatment completion.

Parental intrusive homework support and math achievement: Does the child's mindset matter?

Prior research shows that when parents monitor, check, and assist in completing homework without an invitation, their children's motivation and academic achievement often decline. We propose that intrusive support from parents might also send the message that children are incompetent, especially if they believe their intelligence is fixed. We tested whether children's mindsets moderate the negative link between parents' intrusive homework support and achievement among first- and second-grade students followed for one academic year (Study 1, N = 563) and middle and high school students for two academic years (Study 2, N = 1,613). The samples were obtained from large urban areas in the United States. In both studies, intrusive homework support more strongly predicted a decrease in achievement over time for children with a fixed mindset. These findings suggest that the belief that intellectual ability cannot be changed may exacerbate the detrimental effects of uninvited help on academic work. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Recovery from Exercise in Persons with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Background and Objectives: Post-exertional malaise (PEM) is the hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), but there has been little effort to quantitate the duration of PEM symptoms following a known exertional stressor. Using a Symptom Severity Scale (SSS) that includes nine common symptoms of ME/CFS, we sought to characterize the duration and severity of PEM symptoms following two cardiopulmonary exercise tests separated by 24 h (2-day CPET). Materials and Methods: Eighty persons with ME/CFS and 64 controls (CTL) underwent a 2-day CPET. ME/CFS subjects met the Canadian Clinical Criteria for diagnosis of ME/CFS; controls were healthy but not participating in regular physical activity. All subjects who met maximal effort criteria on both CPETs were included. SSS scores were obtained at baseline, immediately prior to both CPETs, the day after the second CPET, and every two days after the CPET-1 for 10 days. Results: There was a highly significant difference in judged recovery time (ME/CFS = 12.7 ± 1.2 d; CTL = 2.1 ± 0.2 d, mean ± s.e.m., Chi2 = 90.1, p < 0.0001). The range of ME/CFS patient recovery was 1-64 days, while the range in CTL was 1-10 days; one subject with ME/CFS had not recovered after one year and was not included in the analysis. Less than 10% of subjects with ME/CFS took more than three weeks to recover. There was no difference in recovery time based on the level of pre-test symptoms prior to CPET-1 (F = 1.12, p = 0.33). Mean SSS scores at baseline were significantly higher than at pre-CPET-1 (5.70 ± 0.16 vs. 4.02 ± 0.18, p < 0.0001). Pharmacokinetic models showed an extremely prolonged decay of the PEM response (Chi2 > 22, p < 0.0001) to the 2-day CPET. Conclusions: ME/CFS subjects took an average of about two weeks to recover from a 2-day CPET, whereas sedentary controls needed only two days. These data quantitate the prolonged recovery time in ME/CFS and improve the ability to obtain well-informed consent prior to doing exercise testing in persons with ME/CFS. Quantitative monitoring of PEM symptoms may provide a method to help manage PEM.

Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances, and orthostatic intolerance. Here, we report a multi-omic analysis of a geographically diverse cohort of 106 cases and 91 healthy controls that revealed differences in gut microbiome diversity, abundances, functional pathways, and interactions. Faecalibacterium prausnitzii and Eubacterium rectale, which are both recognized as abundant, health-promoting butyrate producers in the human gut, were reduced in ME/CFS. Functional metagenomics, qPCR, and metabolomics of fecal short-chain fatty acids confirmed a deficient microbial capacity for butyrate synthesis. Microbiome-based machine learning classifier models were robust to geographic variation and generalizable in a validation cohort. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity. These findings demonstrate the functional nature of gut dysbiosis and the underlying microbial network disturbance in ME/CFS, providing possible targets for disease classification and therapeutic trials.

Young children interpret number gestures differently than nonsymbolic sets.

Researchers have long been interested in the origins of humans' understanding of symbolic number, focusing primarily on how children learn the meanings of number words (e.g., "one", "two", etc.). However, recent evidence indicates that children learn the meanings of number gestures before learning number words. In the present set of experiments, we ask whether children's early knowledge of number gestures resembles their knowledge of nonsymbolic number. In four experiments, we show that preschool children (n = 139 in total; age M = 4.14 years, SD = 0.71, range = 2.75-6.20) do not view number gestures in the same the way that they view nonsymbolic representations of quantity (i.e., arrays of shapes), which opens the door for the possibility that young children view number gestures as symbolic, as adults and older children do. A video abstract of this article can be viewed at https://youtu.be/WtVziFN1yuI HIGHLIGHTS: Children were more accurate when enumerating briefly-presented number gestures than arrays of shapes, with a shallower decline in accuracy as quantities increased. We replicated this finding with arrays of shapes that were organized into neat, dice-like configurations (compared to the random configurations used in Experiment 1). The advantage in enumerating briefly-presented number gestures was evident before children had learned the cardinal principle. When gestures were digitally altered to pit handshape configuration against number of fingers extended, children overwhelmingly based their responses on handshape configuration.

Telehealth Perceptions Among US Immigrant Patients at an Academic Internal Medicine Practice: Cross-sectional Study.

BACKGROUND: The use of telemedicine has increased dramatically through the COVID-19 pandemic. Although data are available about patient satisfaction with telemedicine, little is known about immigrant patients' experience. OBJECTIVE: We sought to investigate patients' experiences with telehealth compared to in- person visits between immigrants and nonimmigrants. We wanted to identify and describe next visit preferences within the Farmington University of Connecticut Internal Medicine practice to ultimately guide suggestions for more equitable use and accessibility of visit options. METHODS: A total of 270 patients including 122 immigrants and 148 nonimmigrants were seen by 4 Internal Medicine providers in an in-person (n=132) or telemedicine (n=138) university practice setting. Patients were queried between February and April 2021, using an adaptation of a previously validated patient satisfaction survey that contained standard questions developed by the Consumer Assessment of Healthcare Providers and Systems Program. Patients seen via in-person visits completed a paper copy of the survey. The same survey was administered by a follow-up phone call for telemedicine visits. Patients surveyed spoke English, Spanish, or Arabic and were surveyed in their preferred language. For televisits, the same survey was read to the patient by a certified translator. The survey consisted of 10 questions on a Likert scale of 1-5. Of them, 9 questions assessed patient satisfaction under the categories of access to care, interpersonal interaction, and quality of care. An additional question asked patients to describe and explain the reasons behind next visit preferences. Survey question responses were compared by paired t tests. RESULTS: Across both immigrant and nonimmigrant patient populations, satisfaction with perceived quality of care was high, regardless of visit type (P=.80, P=.60 for televisits and P=.76, P=.37 for in-person visits). During televisits, immigrants were more likely to feel providers spent sufficient time with them (P<.001). Different perceptions were noted among nonimmigrant patients. Nonimmigrants tended to perceive more provider time during in-person visits (P=.006). When asked to comment on reasons behind next televisit preference, nonimmigrant patients prioritized convenience, whereas immigrants noted not having to navigate office logistics. For those who chose in-person visits, both groups prioritized the need for a physical exam. CONCLUSIONS: Although satisfaction was high for both telemedicine and in-person visits across immigrant and nonimmigrant populations, significant differences in patient priorities were identified. Immigrants found televisits desirable because they felt they spent more time with providers and were able to avoid additional office logistics that are often challenging barriers for non-English speakers. This suggests opportunities to use information technology to provide cultural and language-appropriate information throughout immigrants' in-person and telemedicine visit experience. A focus on diminishing these barriers will help reduce health care inequities among immigrant patients.

Metabolomic Evidence for Peroxisomal Dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease characterized by unexplained physical fatigue, cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. People with ME/CFS often report a prodrome consistent with infections. Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of plasma from 106 ME/CFS cases and 91 frequency-matched healthy controls. Subjects in the ME/CFS group had significantly decreased levels of plasmalogens and phospholipid ethers (p < 0.001), phosphatidylcholines (p < 0.001) and sphingomyelins (p < 0.001), and elevated levels of dicarboxylic acids (p = 0.013). Using machine learning algorithms, we were able to differentiate ME/CFS or subgroups of ME/CFS from controls with area under the receiver operating characteristic curve (AUC) values up to 0.873. Our findings provide the first metabolomic evidence of peroxisomal dysfunction, and are consistent with dysregulation of lipid remodeling and the tricarboxylic acid cycle. These findings, if validated in other cohorts, could provide new insights into the pathogenesis of ME/CFS and highlight the potential use of the plasma metabolome as a source of biomarkers for the disease.

Survey of Anti-Pathogen Antibody Levels in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Infectious pathogens are implicated in the etiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) because of the occurrence of outbreaks of the disease. While a number of different infectious agents have been associated with the onset of ME/CFS, the identity of a specific organism has been difficult to determine in individual cases. The aim of our study is to survey ME/CFS subjects for evidence of an infectious trigger and/or evidence of immune dysregulation via serological testing of plasma samples for antibodies to 122 different pathogen antigens. Immune profiles were compared to age-, sex-, and BMI-matched controls to provide a basis for comparison. Antibody levels to individual antigens surveyed in this study do not implicate any one of the pathogens in ME/CFS, nor do they rule out common pathogens that frequently infect the US population. However, our results revealed sex-based differences in steady-state humoral immunity, both within the ME/CFS cohort and when compared to trends seen in the healthy control cohort.

Prioritising and mapping barriers to achieve equitable surgical care in South Africa: a multi-disciplinary stakeholder workshop.

BACKGROUND: Surgical healthcare in South Africa is inequitable with a considerable lack of resources in the public health sector. Identifying barriers to care and creating research priorities to mitigate these barriers can contribute to strategic interventions to improve equitable access to quality surgical care. OBJECTIVE: To use the Four Delays Framework to map barriers to surgical care and identify priorities to achieve equitable and timely access to quality surgical care in South Africa. METHODS: A multi-disciplinary stakeholder workshop was held in Cape Town, South Africa in January 2020. A Four Delays Framework (delays in seeking care, reaching care, receiving care, and remaining in care) was used to identify barriers that occur at each delay and the top 10 priorities for intervention. Barriers were categorised into overarching themes and schematically mapped. RESULTS: Thirty-four stakeholders including health service users, health service providers, and community members participated in this exercise. In total, 34 barriers were identified with 73 connections to various delays. Specifically, 14 barriers were related to delays in seeking care, 11 were related to delays in reaching care, 20 were related to delays in receiving care, and 28 were related to delays in remaining in care. The highest priority barriers across the delays were Lack of service provider's knowledge, training and experience, and Limited surgical outreach. The barrier Lack of decentralised services was related to all four delays. Barriers were interconnected and potentially reinforcing. CONCLUSIONS: This workshop is the first of its kind to generate evidence on the delays to surgical care in South Africa. Mapping crucial interconnected, potentially reinforcing barriers, and priority interventions demonstrated how a multifaceted approach may be required to address delays to access. Further research focused on the identified priorities will contribute to efforts to promote equitable access to quality surgical care in South Africa.

Children's understanding of most is dependent on context.

Children struggle with the quantifier "most". Often, this difficulty is attributed to an inability to interpret most proportionally, with children instead relying on absolute quantity comparisons. However, recent research in proportional reasoning more generally has provided new insight into children's apparent difficulties, revealing that their overreliance on absolute amount is unique to contexts in which the absolute amount can be counted and interferes with proportional information. Across two experiments, we test whether 4- to 6-year-old children's interpretation of most is similarly dependent on the discreteness of the stimuli when comparing two different quantities (e.g., who ate most of their chocolate?) and when verifying whether a single amount can be described with the term most (e.g., is most of the butterfly colored in?). We find that children's interpretation of most does depend on the stimulus format. When choosing between absolutely more vs. proportionally more as depicting most, children showed stronger absolute-based errors with discrete stimuli than continuous stimuli, and by 6-years-old were able to reason proportionally with continuous stimuli, despite still demonstrating strong absolute interference with discrete stimuli. In contrast, children's yes/no judgements of single amounts, where conflicting absolute information is not a factor, showed a weaker understanding of most for continuous stimuli than for discrete stimuli. Together, these results suggest that children's difficulty with most is more nuanced than previously understood: it depends on the format and availability of proportional vs. absolute amounts and develops substantially from 4- to 6-years-old.

Connecting symbolic fractions to their underlying proportions using iterative partitioning.

Fractions are a challenging mathematics topic for many elementary and middle school students, and even for adults. However, a growing body of developmental research suggests that young children can reason about visually presented proportions, well before fraction instruction, providing insight into how fractions might be introduced to improve learning. We designed a card game to teach first and second grade children (N = 195, including a racially and economically diverse sample from the United States) about fractions in one of three ways. In the Actively Divided condition we iteratively divided an area model into equal-sized units, in the Predivided condition we used an area model with the end-state of the Actively Divided condition, and in the Nondivided condition we used a continuous representation of the fraction magnitude that was not divided into unit-sized parts. Children in the actively divided condition demonstrated larger improvements matching symbolic fractions and visual fractions (i.e., pie charts) than children in the other two conditions. Posthoc analyses of children's gameplay revealed that the actively divided condition may have provided a more optimal level of difficulty for young children than the predivided condition, which was particularly difficult, and the nondivided condition, which was trivially easy. These differences in gameplay performance provide insights into possible mechanisms for our results. We discuss open research questions highlighted by this work and implications of these findings for both the development of proportional reasoning and fraction learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effort(less) exam preparation: Math anxiety predicts the avoidance of effortful study strategies.

Previous research suggests that math anxiety, or feelings of apprehension about math, leads individuals to engage in math avoidance behaviors that negatively impact their future math performance. However, much of the research on this topic explores global avoidance behaviors in situations where math can be avoided entirely rather than more localized avoidance behaviors that occur within a mathematics context. Since the option to completely avoid math is not common in most formal education systems, we investigated how and if math avoidance behaviors manifest for math-anxious high school students enrolled in math courses. Given previous research highlighting the utility of effortful study strategies as well as recent findings identifying a relation between math anxiety and the avoidance of math-related effort, we hypothesized that math anxiety would be associated with decreased planned engagement of effortful study strategies by students and that such effort avoidance would result in worse performance on a high-stakes mathematics exam. We found (N = 190) that the majority of students ranked problem-solving as the most effortful study strategy and that math anxiety was associated with less planned engagement with effortful problem-solving during studying. Moreover, the avoidance of effortful problem-solving engagement partially mediated the association between math anxiety and exam performance, marking it as a potential target for intervention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Plasma metabolomics reveals disrupted response and recovery following maximal exercise in myalgic encephalomyelitis/chronic fatigue syndrome.

Post-exertional malaise (PEM) is a hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). We monitored the evolution of 1157 plasma metabolites in 60 ME/CFS (45 female, 15 male) and 45 matched healthy control participants (30 female, 15 male) before and after 2 maximal cardiopulmonary exercise test (CPET) challenges separated by 24 hours, with the intent of provoking PEM in patients. Four time points allowed exploration of the metabolic response to maximal energy-producing capacity and the recovery pattern of participants with ME/CFS compared with the healthy control group. Baseline comparison identified several significantly different metabolites, along with an enriched percentage of yet-to-be identified compounds. Additionally, temporal measures demonstrated an increased metabolic disparity between cohorts, including unknown metabolites. The effects of exertion in the ME/CFS cohort predominantly highlighted lipid-related as well as energy-related pathways and chemical structure clusters, which were disparately affected by the first and second exercise sessions. The 24-hour recovery period was distinct in the ME/CFS cohort, with over a quarter of the identified pathways statistically different from the controls. The pathways that are uniquely different 24 hours after an exercise challenge provide clues to metabolic disruptions that lead to PEM. Numerous altered pathways were observed to depend on glutamate metabolism, a crucial component of the homeostasis of many organs in the body, including the brain.

Evidence for Peroxisomal Dysfunction and Dysregulation of the CDP-Choline Pathway in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease that is characterized by unexplained physical fatigue unrelieved by rest. Symptoms also include cognitive and sensory dysfunction, sleeping disturbances, orthostatic intolerance, and gastrointestinal problems. A syndrome clinically similar to ME/CFS has been reported following well-documented infections with the coronaviruses SARS-CoV and MERS-CoV. At least 10% of COVID-19 survivors develop post acute sequelae of SARS-CoV-2 infection (PASC). Although many individuals with PASC have evidence of structural organ damage, a subset have symptoms consistent with ME/CFS including fatigue, post exertional malaise, cognitive dysfunction, gastrointestinal disturbances, and postural orthostatic intolerance. These common features in ME/CFS and PASC suggest that insights into the pathogenesis of either may enrich our understanding of both syndromes, and could expedite the development of strategies for identifying those at risk and interventions that prevent or mitigate disease. METHODS: Using regression, Bayesian and enrichment analyses, we conducted targeted and untargeted metabolomic analysis of 888 metabolic analytes in plasma samples of 106 ME/CFS cases and 91 frequency-matched healthy controls. RESULTS: In ME/CFS cases, regression, Bayesian and enrichment analyses revealed evidence of peroxisomal dysfunction with decreased levels of plasmalogens. Other findings included decreased levels of several membrane lipids, including phosphatidylcholines and sphingomyelins, that may indicate dysregulation of the cytidine-5’-diphosphocholine pathway. Enrichment analyses revealed decreased levels of choline, ceramides and carnitines, and increased levels of long chain triglycerides (TG) and hydroxy-eicosapentaenoic acid. Elevated levels of dicarboxylic acids were consistent with abnormalities in the tricarboxylic acid cycle. Using machine learning algorithms with selected metabolites as predictors, we were able to differentiate female ME/CFS cases from female controls (highest AUC=0.794) and ME/CFS cases without self-reported irritable bowel syndrome (sr-IBS) from controls without sr-IBS (highest AUC=0.873). CONCLUSION: Our findings are consistent with earlier ME/CFS work indicating compromised energy metabolism and redox imbalance, and highlight new abnormalities that may provide insights into the pathogenesis of ME/CFS. ONE SENTENCE SUMMARY: Plasma levels of plasmalogens are decreased in patients with myalgic encephalomyelitis/chronic fatigue syndrome suggesting peroxisome dysfunction.

Spatial and mathematics skills: Similarities and differences related to age, SES, and gender.

Performance on a range of spatial and mathematics tasks was measured in a sample of 1592 students in kindergarten, third grade, and sixth grade. In a previously published analysis of these data, performance was analyzed by grade only. In the present analyses, we examined whether the relations between spatial skill and mathematics skill differed across socio-economic levels, for boys versus girls, or both. Our first aim was to test for group differences in spatial skill and mathematics skill. We found that children from higher income families showed significantly better performance on both spatial and mathematics measures, and boys outperformed girls on spatial measures in all three grades, but only outperformed girls on mathematics measures in kindergarten. Further, comparisons using factor analysis indicated that the income-related gap in mathematics performance increased across the grade levels, while the income-related gap in spatial performance remained constant. Our second aim was to test whether spatial skill mediated any of these effects, and we found that it did, either partially or fully, in all four cases. Our third aim was to test whether the "separate but correlated" two-factor latent structure previously reported for spatial skill and mathematics skill was (Mix et al., 2016; Mix et al., 2017) replicated across grade, SES, and sex. Multi-group confirmatory factor analyses conducted for each of these subgroups indicated that the same latent structure was present, despite differences in overall performance. These findings replicate and extend prior work on SES and sex differences related to spatial and mathematics skill, but provide evidence that the relations between the domains are stable and consistent across subgroups.