Changing Aesthetics in Biomolecular Graphics.

Aesthetics for the visualization of biomolecular structures have evolved over the years according to technological advances, user needs, and modes of dissemination. In this article, we explore the goals, challenges, and solutions that have shaped the current landscape of biomolecular imagery from the overlapping perspectives of computer science, structural biology, and biomedical illustration. We discuss changing approaches to rendering, color, human-computer interface, and narrative in the development and presentation of biomolecular graphics. With this historical perspective on the evolving styles and trends in each of these areas, we identify opportunities and challenges for future aesthetics in biomolecular graphics that encourage continued collaboration from multiple intersecting fields.

Considering best practices in color palettes for molecular visualizations.

Biomedical illustration and visualization techniques provide a window into complex molecular worlds that are difficult to capture through experimental means alone. Biomedical illustrators frequently employ color to help tell a molecular story, e.g., to identify key molecules in a signaling pathway. Currently, color use for molecules is largely arbitrary and often chosen based on the client, cultural factors, or personal taste. The study of molecular dynamics is relatively young, and some stakeholders argue that color use guidelines would throttle the growth of the field. Instead, content authors have ample creative freedom to choose an aesthetic that, e.g., supports the story they want to tell. However, such creative freedom comes at a price. The color design process is challenging, particularly for those without a background in color theory. The result is a semantically inconsistent color space that reduces the interpretability and effectiveness of molecular visualizations as a whole. Our contribution in this paper is threefold. We first discuss some of the factors that contribute to this array of color palettes. Second, we provide a brief sampling of color palettes used in both industry and research sectors. Lastly, we suggest considerations for developing best practices around color palettes applied to molecular visualization.

Semantic Snapping for Guided Multi-View Visualization Design.

Visual information displays are typically composed of multiple visualizations that are used to facilitate an understanding of the underlying data. A common example are dashboards, which are frequently used in domains such as finance, process monitoring and business intelligence. However, users may not be aware of existing guidelines and lack expert design knowledge when composing such multi-view visualizations. In this paper, we present semantic snapping, an approach to help non-expert users design effective multi-view visualizations from sets of pre-existing views. When a particular view is placed on a canvas, it is "aligned" with the remaining views-not with respect to its geometric layout, but based on aspects of the visual encoding itself, such as how data dimensions are mapped to channels. Our method uses an on-the-fly procedure to detect and suggest resolutions for conflicting, misleading, or ambiguous designs, as well as to provide suggestions for alternative presentations. With this approach, users can be guided to avoid common pitfalls encountered when composing visualizations. Our provided examples and case studies demonstrate the usefulness and validity of our approach.

Intimate Partner Violence and Structural Violence in the Lives of Incarcerated Women: A Mixed-Method Study in Rural New Mexico.

Intimate partner violence (IPV) is a common feature in the lives of incarcerated women returning to rural communities, enhancing their risk of mental ill-health, substance use, and recidivism. Women's experiences of IPV intersect with challenges across multiple social-ecological levels, including risky or criminalizing interpersonal relationships, geographic isolation, and persistent gender, racial, and economic inequities. We conducted quantitative surveys and qualitative interviews with 99 incarcerated women in New Mexico who were scheduled to return to micropolitan or non-core areas within 6 months. Quantitative and qualitative data were analyzed separately and then triangulated to identify convergences and divergences in data. The findings underscore how individual and interpersonal experiences of IPV, substance use, and psychological distress intersect with broad social inequities, such as poverty, lack of supportive resources, and reluctance to seek help due to experiences of discrimination. These results point to the need for a more proactive response to the mutually constitutive cycle of IPV, mental distress, incarceration, and structures of violence to improve reentry for women returning to rural communities. Policy and treatment must prioritize socioeconomic marginalization and expand community resources with attention to the needs of rural women of color.

Integrated Dual Analysis of Quantitative and Qualitative High-Dimensional Data.

The Dual Analysis framework is a powerful enabling technology for the exploration of high dimensional quantitative data by treating data dimensions as first-class objects that can be explored in tandem with data values. In this article, we extend the Dual Analysis framework through the joint treatment of quantitative (numerical) and qualitative (categorical) dimensions. Computing common measures for all dimensions allows us to visualize both quantitative and qualitative dimensions in the same view. This enables a natural joint treatment of mixed data during interactive visual exploration and analysis. Several measures of variation for nominal qualitative data can also be applied to ordinal qualitative and quantitative data. For example, instead of measuring variability from a mean or median, other measures assess inter-data variation or average variation from a mode. In this work, we demonstrate how these measures can be integrated into the Dual Analysis framework to explore and generate hypotheses about high-dimensional mixed data. A medical case study using clinical routine data of patients suffering from Cerebral Small Vessel Disease (CSVD), conducted with a senior neurologist and a medical student, shows that a joint Dual Analysis approach for quantitative and qualitative data can rapidly lead to new insights based on which new hypotheses may be generated.

DimLift: Interactive Hierarchical Data Exploration Through Dimensional Bundling.

The identification of interesting patterns and relationships is essential to exploratory data analysis. This becomes increasingly difficult in high dimensional datasets. While dimensionality reduction techniques can be utilized to reduce the analysis space, these may unintentionally bury key dimensions within a larger grouping and obfuscate meaningful patterns. With this work we introduce DimLift, a novel visual analysis method for creating and interacting with dimensional bundles. Generated through an iterative dimensionality reduction or user-driven approach, dimensional bundles are expressive groups of dimensions that contribute similarly to the variance of a dataset. Interactive exploration and reconstruction methods via a layered parallel coordinates plot allow users to lift interesting and subtle relationships to the surface, even in complex scenarios of missing and mixed data types. We exemplify the power of this technique in an expert case study on clinical cohort data alongside two additional case examples from nutrition and ecology.

Forty Years of Assessing Neurodevelopmental and Behavioral Effects of Prenatal Alcohol Exposure in Infants: What Have We Learned?

It has been known for over 4 decades that prenatal alcohol exposure (PAE) can adversely affect neurodevelopment and behavior (NDB). Yet, early detection of altered NDB due to PAE continues to present a major clinical challenge. Identification of altered NDB in the first 2 years of life, before higher-order cognitive processes develop, invites early interventions for affected children to improve long-term outcomes. Studies published in English from January of 1980 to July of 2018 were identified in PubMed/MEDLINE. The review focused on prospective birth cohort studies which used standardized NDB assessments in children up to 2 years of age, wherein PAE was the main exposure and NDB was the main outcome. NDB was categorized into the domains of neurocognitive, adaptive, and self-regulation based on the 2016 Updated Clinical Guidelines for Diagnosing fetal alcohol spectrum disorder. An initial search resulted in 1,867 articles for which we reviewed abstracts; 114 were selected for full-text review; and 3 additional abstracts were identified through review of references in eligible publications. Thirty-one publications met criteria and were included: of these, 24 reported neurocognitive outcomes, 24 reported adaptive behavior outcomes, and 12 reported outcomes in the domain of self-regulation. Although self-regulation was assessed in the fewest number of studies, 8/12 (75%) reported PAE-associated deficits. In contrast, results were mixed for the other 2 domains: 13/24 (54%) of the selected studies that included neurocognitive outcomes showed poorer performance following PAE, and 8/24 (33%) studies that assessed adaptive functioning found significant differences between PAE and comparison infants. There is considerable evidence to support the value of early-life assessments of infant NDB when PAE is known or suspected. More studies focusing on infant self-regulation, in particular, are needed to determine the utility of early evaluation of this critical developmental domain in infants with PAE.

Prenatal alcohol exposure prevalence as measured by direct ethanol metabolites in meconium in a Native American tribe of the southwest.

BACKGROUND: Although fetal alcohol spectrum disorders represent a significant public health problem, Native Americans are underrepresented in population and targeted screening programs. Prior reports suggest that Native American tribal communities may have a higher prevalence of alcohol use during pregnancy; however, systematic examination using ethanol biomarkers is lacking. METHODS: This study utilized data collected through the Navajo Birth Cohort Study (NBCS)-a birth cohort study of a Southwestern tribal community. Prevalence of prenatal alcohol exposure (PAE) was assessed by a battery of meconium biomarkers among 333 NBCS participants. Meconium samples were analyzed for nine individual fatty acid ethyl ester (FAEE) species, ethyl glucuronide (EtG), and ethyl sulfate (EtS) by LC-MS/MS. RESULTS: Participants were recruited from five hospitals at the Navajo Nation located in Arizona (Chinle, Tséhootsooí, Tuba City) and New Mexico (Gallup, Shiprock). All participants identified as Native American; most reported a personal income of <$20,000 per year (71.3%), and ≤high school education (55.3%). The most prevalent biomarker was EtS (7.8%) followed by ethyl oleate (6.9%); 5.4% of the sample were positive for at least two biomarkers. CONCLUSIONS: Results of this study on the prevalence of PAE in the Navajo Nation, obtained for the first time with an objective comprehensive panel of meconium biomarkers, indicate that the rates in the NBCS may be comparable to the general U.S. population and are in accord with recent U.S. national survey estimates. Our findings emphasize that drinking behaviors among Native American communities in the United States can vary, and generalization across all Native American populations is not warranted.

Prevalence of alcohol use in pregnant women with substance use disorder.

BACKGROUND: Prenatal care programs for women with opioid use disorder (OUD) often focus treatment/counseling plans around illicit substances, while concurrent use of alcohol might present an equal or greater risk to the fetus. METHODS: This study evaluated self-reported prevalence of alcohol use in patients participating in a comprehensive prenatal care program for women with substance use disorder (SUD; n = 295), of which 95% are treated for OUD, and pregnant women being served through general obstetrical clinics at the University of New Mexico (n = 365). During the screening phase of a prospective study, patients were asked to report alcohol use in the periconceptional period, and between the last menstrual period and pregnancy recognition. RESULTS: The screening interview was conducted at 22.3 (median = 22; Q1 = 16; Q3 = 29) gestational weeks. Among patients screened at the SUD clinic, 28.8% and 24.1% reported at least one binge drinking episode in the periconceptional period and in early pregnancy, respectively. The prevalence of binge drinking was similar in the general obstetrics population (24.7% and 24.4%, respectively). Among those who reported drinking in early pregnancy, median number of binge drinking episodes was higher among patients screened at the SUD clinic (median = 3; Q1 = 1; Q3 = 10) compared to the general obstetrics group (median = 1; Q1 = 1; Q3 = 3; p < 0.001). CONCLUSIONS: This study demonstrates a high prevalence of prenatal alcohol use in early pregnancy in both groups, while patients with SUD/OUD consume more alcohol. These findings underscore the need for targeted screening and intervention for alcohol use in all pregnant women, especially those with SUD/OUD.

Role of caregiver-reported outcomes in identification of children with prenatal alcohol exposure during the first year of life.

BACKGROUND: Earlier identification of children with prenatal alcohol exposure (PAE) remains a challenge. The objective of this study was to identify neurobehavioral (NB) outcomes associated with PAE in infants. METHODS: This manuscript evaluates NB outcomes at 6.33±1.12 months of age in 93 infants (39 PAE and 54 No-PAE) recruited prospectively into the ENRICH cohort. PAE was assessed by prospective repeated TLFB interviews and a panel of ethanol biomarkers. NB outcomes were evaluated by the Bayley Scales of Infant Development (BSID-III), Parenting Stress Index (PSI), Infant Behavior Questionnaire (IBQ-R), and Infant Sensory Profile (ISP). RESULTS: Mean maternal age at enrollment was 28.18±5.75, and 64.52% were Hispanic/Latina. Across three TLFB calendars, absolute alcohol per day in the PAE group was 0.44±0.72, corresponding to low-moderate alcohol consumption. While no association was observed between PAE and BSID-III (P's>0.05), PAE was associated with higher scores on the PSI difficult child scale ([Formula: see text]=13.9; P=0.015), total stress ([Formula: see text]=13.9; P=0.010), and IBQ negative affect ([Formula: see text]=8.60; P=0.008) measures after adjustment for covariates. CONCLUSIONS: Caregiver-reported assessments may provide a currently unrecognized opportunity to identify behavioral deficits, point to early interventions, and should be included in clinical assessments of infants at-risk for fetal alcohol spectrum disorder.

Challenges of diagnosing fetal alcohol spectrum disorders in foster and adopted children.

Fetal Alcohol Spectrum Disorders (FASD) might be 10-15 times more prevalent among foster/adopted children compared to the general population; however, many of these children remain undiagnosed or misdiagnosed. The lack of confirmed prenatal alcohol exposure (PAE) may be a key barrier to diagnosis. Our sample included 681 patients evaluated for FASD, according to the University of Washington 4-Digit Diagnostic Code, at a pediatric specialty clinic. Guardianship status and other patient characteristics were evaluated by multinomial logistic regression as potential predictors of being classified into one of the following FASD groups: 1) full or partial Fetal Alcohol Syndrome (FAS/pFAS; n = 97); 2) Static Encephalopathy/Alcohol-Exposed (SE/AE) or Neurobehavioral Disorder/Alcohol-Exposed (ND/AE) (n = 135); and 3) some features of FASD (equivalent to pFAS, SE/AE or ND/AE phenotypes) but unknown PAE (n = 449). Median age at assessment was 7.0 years, non-Hispanic White constituted the predominant racial/ethnic group (49.5%), and the majority (81.8%) lacked involvement from a biological parent/relative. Many patients (66.0%) had some features of FASD but lacked reliable PAE information. Children classified into the 'some features/unknown PAE' group had higher median age of assessment (8 years) compared to other groups (6 years; p < 0.001). No association was observed between race/ethnicity or child's sex and FASD outcomes (p > 0.05). Adopted/foster children were 2.8 times as likely (95% CI: 1.6; 4.8) to be classified into the 'some features/unknown PAE' group compared to children living with a parent/relative after adjusting for covariates. This study's findings indicate that adopted/foster children are more likely to have unknown PAE and not receive a FASD diagnosis, potentially denying them access to specialized services, treatment, and rehabilitation.

Dietary Intake Among Opioid- and Alcohol-Using Pregnant Women.

BACKGROUND: Substance abuse in nonpregnant adults has been associated with increased intake in calories and decreased intake of nutrient-dense foods; however, studies examining dietary intake in opioid-using and alcohol-using pregnant women are lacking. OBJECTIVE: The objective of this study was to evaluate dietary intake in opioid-using pregnant women with or without concurrent light-to-moderate alcohol use as compared to abstaining controls. METHODS: This prospective birth cohort included 102 pregnant women classified into four study groups: controls (n = 27), medication-assisted treatment (MAT; n = 26), alcohol (ALC; n = 22), and concurrent use of both substances (MAT + ALC; n = 27). Percentage differences in macro- and micronutrient intake were estimated from the food frequency questionnaire and compared among the study groups. Proportions of participants with intakes below the estimated average requirements (EAR) based on diet and diet with supplements were estimated. RESULTS: Three exposed groups had lower prevalence of multivitamin use in periconceptional period (11.5-31.8%) than controls (44.4%). Unadjusted mean energy intake was significantly higher in the MAT + ALC group compared to controls, while micronutrient intake per 1000 kcal was the highest in the control group for almost all of the micronutrients analyzed. After adjustment for energy intake and sociodemographic characteristics, MAT group had lower estimated dietary intake of iron (-15.0%, p = 0.04) and folate (-16.8%, p = 0.04) compared to controls. A high proportion of participants in all study groups had dietary intake below the EAR for vitamin E, iron, and folate. CONCLUSION: Results highlight the need for targeted dietary interventions for opioid-using pregnant women.

Perspectives from Community-Based Organizational Managers on Implementing and Sustaining Evidence-Based Interventions in Child Welfare.

The managers of community-based organizations that are contracted to deliver publicly funded programs, such as in the child welfare sector, occupy a crucial role in the implementation and sustainment of evidence-based interventions to improve the effectiveness of services, as they exert influence across levels of stakeholders in multitiered systems. This study utilized qualitative interviews to examine the perspectives and experiences of managers in implementing Safe Care®, an evidence-based intervention to reduce child maltreatment. Factors influencing managers' abilities to support SafeCare® included policy and ideological trends, characteristics of leadership in systems and organizations, public-private partnerships, procurement and contracting, collaboration and coopetition, and support for organizational staff.

Validity of Self-Reported Drug Use Information Among Pregnant Women.

INTRODUCTION: This study assesses validity of self-report for the use of major classes of illicit drugs and opioid-maintenance therapy among pregnant women at a substance abuse treatment program. METHODS: Analyses used data collected from 83 pregnant women in a prospective cohort study at the University of New Mexico. Study participants with a history of substance abuse were screened and, if eligible, enrolled during an early prenatal care visit. A follow-up interview was conducted shortly after delivery. Self-reported information about drug use later in pregnancy was compared with urine drug screen (UDS) results collected during the third trimester. Simple kappa (k) and prevalence-and-bias-adjusted kappa (PABAK) coefficients were calculated as the measures of agreement. Sensitivity and specificity of self-report for each drug class were estimated using UDS as the 'gold standard'. RESULTS: The sample included a large proportion of ethnic minority (80% Hispanic/Latina and 7% American Indian) and socially disadvantaged (50% less than high school education and 94% Medicaid-insured) pregnant women. On average, patients had 4.8 ± 3.0 urine drug screens during the third trimester. Sensitivity of self-report was low (<60%) for all classes of illicit drugs; however, marijuana and opioids demonstrated slightly higher sensitivity (57.9 and 58.3%, respectively) than other classes (<47%). CONCLUSIONS: This study found substantial underreporting for all classes of illicit drugs among pregnant women in a substance abuse treatment program. Rates of underreporting are expected to be higher among the general population of pregnant women.

Fetal Growth Outcomes in a Cohort of Polydrug- and Opioid-Dependent Patients.

OBJECTIVES: To evaluate the effects of prenatal polydrug and exclusive opioid use on fetal growth outcomes. METHODS: This analysis relied on the data obtained from two prospective cohorts at the University of New Mexico. For both cohorts, pregnant women were recruited during one of their prenatal care visits and followed up to delivery. The merged sample included 59 polydrug users, 22 exclusive opioid users, and 278 abstinent controls. Continuous growth measures (birth weight, height, occipital frontal circumference [OFC], and corresponding sex-specific percentiles) were compared by ANOVA and ANCOVA in bivariate and multivariable analyses, respectively. Categorical outcomes (prevalence of small-for-gestational age [SGA] for weight, length, and OFC) were compared among groups by Chi-square and multivariable logistic regression analyses.. RESULTS: The sample included a large proportion of ethnic minorities (78.8% Hispanic) and patients with low educational attainment (68% ≤ high school). The risk of microcephaly (OFC<10th percentile) was significantly greater in the polydrug (OR=4.7; 95% CI: 2.0; 10.8) and exclusive opioid (OR=2.8; 95% CI: 1.0; 8.1) groups compared to abstinent controls. CONCLUSION: Given that microcephaly is often associated with serious neurocognitive and behavioral deficits later in life, our finding of 49.2% incidence of microcephaly among polydrug users is alarming and requires further investigation.

Anatomical enablers and the evolution of C4 photosynthesis in grasses.

C(4) photosynthesis is a series of anatomical and biochemical modifications to the typical C(3) pathway that increases the productivity of plants in warm, sunny, and dry conditions. Despite its complexity, it evolved more than 62 times independently in flowering plants. However, C(4) origins are absent from most plant lineages and clustered in others, suggesting that some characteristics increase C(4) evolvability in certain phylogenetic groups. The C(4) trait has evolved 22-24 times in grasses, and all origins occurred within the PACMAD clade, whereas the similarly sized BEP clade contains only C(3) taxa. Here, multiple foliar anatomy traits of 157 species from both BEP and PACMAD clades are quantified and analyzed in a phylogenetic framework. Statistical modeling indicates that C(4) evolvability strongly increases when the proportion of vascular bundle sheath (BS) tissue is higher than 15%, which results from a combination of short distance between BS and large BS cells. A reduction in the distance between BS occurred before the split of the BEP and PACMAD clades, but a decrease in BS cell size later occurred in BEP taxa. Therefore, when environmental changes promoted C(4) evolution, suitable anatomy was present only in members of the PACMAD clade, explaining the clustering of C(4) origins in this lineage. These results show that key alterations of foliar anatomy occurring in a C(3) context and preceding the emergence of the C(4) syndrome by millions of years facilitated the repeated evolution of one of the most successful physiological innovations in angiosperm history.

Efforts to reduce mortality to hydroelectric turbine-passed fish: locating and quantifying damaging shear stresses.

Severe fluid forces are believed to be a source of injury and mortality to fish that pass through hydroelectric turbines. A process is described by which laboratory bioassays, computational fluid dynamics models, and field studies can be integrated to evaluate the significance of fluid shear stresses that occur in a turbine. Areas containing potentially lethal shear stresses were identified near the stay vanes and wicket gates, runner, and in the draft tube of a large Kaplan turbine. However, under typical operating conditions, computational models estimated that these dangerous areas comprise less than 2% of the flow path through the modeled turbine. The predicted volumes of the damaging shear stress zones did not correlate well with observed fish mortality at a field installation of this turbine, which ranged from less than 1% to nearly 12%. Possible reasons for the poor correlation are discussed. Computational modeling is necessary to develop an understanding of the role of particular fish injury mechanisms, to compare their effects with those of other sources of injury, and to minimize the trial and error previously needed to mitigate those effects. The process we describe is being used to modify the design of hydroelectric turbines to improve fish passage survival.