Tracking Drugs and Lipids: Quantitative Mass Spectrometry Imaging of Liposomal Doxorubicin Delivery and Bilayer Fate in Three-Dimensional Tumor Models.

Targeted therapy to the tumor would greatly advance precision medicine. Many drug delivery vehicles have emerged, but liposomes are cited as the most successful to date. Recent efforts to develop liposomal drug delivery systems focus on drug distribution in tissues and ignore liposomal fate. In this study, we developed a novel method to elucidate both drug and liposomal bilayer distribution in a three-dimensional cell culture model using quantitative matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI qMSI) alongside fluorescence microscopy. Imaging liposomal distribution in a cell culture model is challenging, as lipids forming the bilayer are endogenous to the model system. To resolve this issue, we functionalized the bilayer by chemically cross-linking a fluorescent tag to the alkyne-containing lipid hexynoyl phosphoethanolamine (HPE). We synthesized liposomes incorporating the tagged HPE lipid and encapsulated within them doxorubicin, yielding a theranostic liposome capable of both drug delivery and monitoring liposomal uptake. We employed an "in-tissue" MALDI qMSI approach to generate a calibration curve with R2 = 0.9687, allowing for quantification of doxorubicin within spheroid sections at multiple time points. After 72 h of treatment with the theranostic liposomes, full doxorubicin penetration was observed. The metabolites doxorubicinone and 7-deoxydoxorubicinone were also detected after 48 h. Modification of the bilayer allowed for fluorescence microscopy tracking of liposomes, while MALDI MSI simultaneously permitted the imaging of drugs and metabolites. While we demonstrated the utility of our method with doxorubicin, this system could be applied to examine the uptake, release, and metabolism of many other liposome-encapsulated drugs.

Spatial prey availability and pulsed reproductive tactics: Encounter risk in a canid-ungulate system.

Predation risk is a function of spatiotemporal overlap between predator and prey, as well as behavioural responses during encounters. Dynamic factors (e.g. group size, prey availability and animal movement or state) affect risk, but rarely are integrated in risk assessments. Our work targets a system where predation risk is fundamentally linked to temporal patterns in prey abundance and behaviour. For neonatal ungulate prey, risk is defined within a short temporal window during which the pulse in parturition, increasing movement capacity with age and antipredation tactics have the potential to mediate risk. In our coyote-mule deer (Canis latrans-Odocoileus hemionus) system, leveraging GPS data collected from both predator and prey, we tested expectations of shared enemy and reproductive risk hypotheses. We asked two questions regarding risk: (A) How does primary and alternative prey habitat, predator and prey activity, and reproductive tactics (e.g. birth synchrony and maternal defence) influence the vulnerability of a neonate encountering a predator? (B) How do the same factors affect behaviour by predators relative to the time before and after an encounter? Despite increased selection for mule deer and intensified search behaviour by coyotes during the peak in mule deer parturition, mule deer were afforded protection from predation via predator swamping, experiencing reduced per-capita encounter risk when most neonates were born. Mule deer occupying rabbit habitat (Sylvilagus spp.; coyote's primary prey) experienced the greatest risk of encounter but the availability of rabbit habitat did not affect predator behaviour during encounters. Encounter risk increased in areas with greater availability of mule deer habitat: coyotes shifted their behaviour relative to deer habitat, and the pulse in mule deer parturition and movement of neonatal deer during encounters elicited increased speed and tortuosity by coyotes. In addition to the spatial distribution of prey, temporal patterns in prey availability and animal behavioural state were fundamental in defining risk. Our work reveals the nuanced consequences of pulsed availability on predation risk for alternative prey, whereby responses by predators to sudden resource availability, the lasting effects of diversionary prey and inherent antipredation tactics ultimately dictate risk.

A Systematic Review and Meta-analysis of Chemical Exposures and Attention-Deficit/Hyperactivity Disorder in Children.

Exposure to certain chemicals prenatally and in childhood can impact development and may increase risk for attention-deficit/hyperactivity disorder (ADHD). Leveraging a larger set of literature searches conducted to synthesize results from longitudinal studies of potentially modifiable risk factors for childhood ADHD, we present meta-analytic results from 66 studies that examined the associations between early chemical exposures and later ADHD diagnosis or symptoms. Studies were eligible for inclusion if the chemical exposure occurred at least 6 months prior to measurement of ADHD diagnosis or symptomatology. Included papers were published between 1975 and 2019 on exposure to anesthetics (n = 5), cadmium (n = 3), hexachlorobenzene (n = 4), lead (n = 22), mercury (n = 12), organophosphates (n = 7), and polychlorinated biphenyls (n = 13). Analyses are presented for each chemical exposure by type of ADHD outcome reported (categorical vs. continuous), type of ADHD measurement (overall measures of ADHD, ADHD symptoms only, ADHD diagnosis only, inattention only, hyperactivity/impulsivity only), and timing of exposure (prenatal vs. childhood vs. cumulative), whenever at least 3 relevant effect sizes were available. Childhood lead exposure was positively associated with ADHD diagnosis and symptoms in all analyses except for the prenatal analyses (odds ratios (ORs) ranging from 1.60 to 2.62, correlation coefficients (CCs) ranging from 0.14 to 0.16). Other statistically significant associations were limited to organophosphates (CC = 0.11, 95% confidence interval (CI): 0.03-0.19 for continuous measures of ADHD outcomes overall), polychlorinated biphenyls (CC = 0.08, 95% CI: 0.02-0.14 for continuous measures of inattention as the outcome), and both prenatal and childhood mercury exposure (CC = 0.02, 95% CI: 0.00-0.04 for continuous measures of ADHD outcomes overall for either exposure window). Our findings provide further support for negative impacts of prenatal and/or childhood exposure to certain chemicals and raise the possibility that primary prevention and targeted screening could prevent or mitigate ADHD symptomatology. Furthermore, these findings support the need for regular review of regulations as our scientific understanding of the risks posed by these chemicals evolves.

Lipidomics Profiling Reveals Differential Alterations after FAS Inhibition in 3D Colon Cancer Cell Culture Models.

Cancerous cells synthesize most of their lipids de novo to keep up with their rapid growth and proliferation. Fatty acid synthase (FAS) is a key enzyme in the lipogenesis pathway that is upregulated in many cancers and has gained popularity as a druggable target of interest for cancer treatment. The first FAS inhibitor discovered, cerulenin, initially showed promise for chemotherapeutic purposes until it was observed that it had adverse side effects in mice. TVB-2640 (Denifanstat) is part of the newer generation of inhibitors. With multiple generations of FAS inhibitors being developed, it is vital to understand their distinct molecular downstream effects to elucidate potential interactions in the clinic. Here, we profile the lipidome of two different colorectal cancer (CRC) spheroids treated with a generation 1 inhibitor (cerulenin) or a generation 2 inhibitor (TVB-2640). We observe that the cerulenin causes drastic changes to the spheroid morphology as well as alterations to the lipid droplets found within CRC spheroids. TVB-2640 causes higher abundances of polyunsaturated fatty acids (PUFAs) whereas cerulenin causes a decreased abundance of PUFAs. The increase in PUFAs in TVB-2640 exposed spheroids indicates it is causing cells to die via a ferroptotic mechanism rather than a conventional apoptotic or necrotic mechanism.

Enhancement of Lipid Signals in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry with Ammonium Fluoride as a Matrix Additive.

Lipids are essential macromolecules that play a crucial role in numerous biological events. Lipids are structurally diverse which allows them to fulfill multiple functional roles. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a powerful tool to understand the spatial localization of lipids within biological systems. Herein, we report the use of ammonium fluoride (NH4F) as a comatrix additive to enhance lipid detection in biological samples, with a signal increase of up to 200%. Emphasis was placed on anionic lipid enhancement with negative polarity measurements, with some preliminary work on cationic lipids detailed. We observed lipid signal enhancement of [M-H]- ions with the addition of NH4F additive attributed to a proton transfer reaction in several different lipid classes. Overall, our study demonstrates that the use of the NH4F comatrix additive substantially improves sensitivity for lipid detection in a MALDI system and is capable of being applied to a variety of different applications.

Systematic Review and Meta-analysis of the Relationship Between Exposure to Parental Substance Use and Attention-Deficit/Hyperactivity Disorder in Children.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by persistent patterns of inattention, hyperactivity, and impulsiveness. Among US children and adolescents aged 3-17 years, 9.4% have a diagnosis of ADHD. Previous research suggests possible links between parental substance use and ADHD among children. We conducted a systematic review and meta-analysis of 86 longitudinal or retrospective studies of prenatal or postnatal alcohol, tobacco, or other parental substance use and substance use disorders and childhood ADHD and its related behavioral dimensions of inattention and hyperactivity-impulsivity. Meta-analyses were grouped by drug class and pre- and postnatal periods with combined sample sizes ranging from 789 to 135,732. Prenatal exposure to alcohol or tobacco and parent substance use disorders were consistently and significantly associated with ADHD among children. Other parental drug use exposures resulted in inconsistent or non-significant findings. Prevention and treatment of parental substance use may have potential for impacts on childhood ADHD.

Crystalline Nanoparticles of Water-Soluble Covalent Basket Cages (CBCs) for Encapsulation of Anticancer Drugs.

We herein describe the preparation, assembly, recognition characteristics, and biocompatibility of novel covalent basket cage CBC-11, composed of four molecular baskets linked to four trivalent aromatic amines through amide groups. The cage is tetrahedral in shape and similar in size to small proteins (Mw =8637 g/mol) with a spacious nonpolar interior for accommodating multiple guests. While 24 carboxylates at the outer surface of CBC-11 render it soluble in aqueous phosphate buffer (PBS) at pH=7.0, the amphiphilic nature prompts its assembly into nanoparticles (d=250 nm, DLS). Cryo-TEM examination of nanoparticles revealed their crystalline nature with wafer-like shapes and hexagonally arranged cages. Nanoparticulate CBC-11 traps anticancer drugs irinotecan and doxorubicin, with each cage binding up to four drug molecules in a non-cooperative manner. The inclusion complexation resulted in nanoparticles growing in size and precipitating. In media containing mammalian cells (HCT 116, human colon carcinoma), the IC50 value of CBC-11 was above 100 µM. While this work presents the first example of a large covalent organic cage operating in water at the physiological pH and forming crystalline nanoparticles, it also demonstrates its biocompatibility and potential to act as a polyvalent binder of drugs for their sequestration or delivery.

Risky business: How an herbivore navigates spatiotemporal aspects of risk from competitors and predators.

Understanding factors that influence animal behavior is central to ecology. Basic principles of animal ecology imply that individuals should seek to maximize survival and reproduction, which means carefully weighing risk against reward. Decisions become increasingly complex and constrained, however, when risk is spatiotemporally variable. We advance a growing body of work in predator-prey behavior by evaluating novel questions where a prey species is confronted with multiple predators and a potential competitor. We tested how fine-scale behavior of female mule deer (Odocoileus hemionus) during the reproductive season shifted depending upon spatial and temporal variation in risk from predators and a potential competitor. We expected female deer to avoid areas of high risk when movement activity of predators and a competitor were high. We used GPS data collected from 76 adult female mule deer, 35 adult female elk, 33 adult coyotes, and six adult mountain lions. Counter to our expectations, female deer exhibited selection for multiple risk factors, however, selection for risk was dampened by the exposure to risk within home ranges of female deer, producing a functional response in habitat selection. Furthermore, temporal variation in movement activity of predators and elk across the diel cycle did not result in a shift in movement activity by female deer. Instead, the average level of risk within their home range was the predominant factor modulating the response to risk by female deer. Our results counter prevailing hypotheses of how large herbivores navigate risky landscapes and emphasize the importance of accounting for the local environment when identifying effects of risk on animal behavior. Moreover, our findings highlight additional behavioral mechanisms used by large herbivores to mitigate multiple sources of predation and potential competitive interactions.

Health Care Access and Use Among Adults With and Without Vision Impairment: Behavioral Risk Factor Surveillance System, 2018.

INTRODUCTION: Adults with vision impairment may have unique needs when accessing health care to maintain good health. Our study examined the relationship between vision status and access to and use of health care. METHODS: We analyzed data on adults aged 18 years or older who participated in the 2018 Behavioral Risk Factor Surveillance System. Vision impairment was identified by a yes response to the question "Are you blind or do you have serious difficulty seeing, even when wearing glasses?" Survey questions assessed health care access over the past year (having health insurance coverage, a usual health care provider, or unmet health care needs because of cost) and use of health care during that period (routine checkup and dental visit). We estimated age-adjusted prevalence of our outcomes of interest and used bivariate analyses to compare estimates of the outcomes by vision impairment status. RESULTS: The prevalence of self-reported vision impairment was 5.3%. Compared with adults without impaired vision, adults with vision impairment had a lower prevalence of having health insurance coverage (80.6% vs 87.6%), a usual health care provider (71.9% vs 75.7%), or a dental visit in the past year (52.9% vs 67.2%) and a higher prevalence of having an unmet health care need in the past year because of cost (29.2% vs 12.6%). CONCLUSION: Adults with vision impairment reported lower access to and use of health care than those without. Further research can better identify and understand barriers to care to improve access to and use of health care among this population.

All in the Family? A Systematic Review and Meta-analysis of Parenting and Family Environment as Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD) in Children.

Parenting and family environment have significant impact on child development, including development of executive function, attention, and self-regulation, and may affect the risk of developmental disorders including attention-deficit/hyperactivity disorder (ADHD). This paper examines the relationship of parenting and family environment factors with ADHD. A systematic review of the literature was conducted in 2014 and identified 52 longitudinal studies. A follow-up search in 2021 identified 7 additional articles, for a total of 59 studies that examined the association of parenting factors with ADHD outcomes: ADHD overall (diagnosis or symptoms), ADHD diagnosis specifically, or presence of the specific ADHD symptoms of inattention and hyperactivity/impulsivity. For parenting factors that were present in three or more studies, pooled effect sizes were calculated separately for dichotomous or continuous ADHD outcomes, accounting for each study's conditional variance. Factors with sufficient information for analysis were parenting interaction quality (sensitivity/warmth, intrusiveness/reactivity, and negativity/harsh discipline), maltreatment (general maltreatment and physical abuse), parental relationship status (divorce, single parenting), parental incarceration, and child media exposure. All factors showed a significant direct association with ADHD outcomes, except sensitivity/warmth which had an inverse association. Parenting factors predicted diagnosis and overall symptoms as well as inattentive and hyperactive symptoms when measured, but multiple factors showed significant heterogeneity across studies. These findings support the possibility that parenting and family environment influences ADHD symptoms and may affect a child's likelihood of being diagnosed with ADHD. Prevention strategies that support parents, such as decreasing parenting challenges and increasing access to parent training in behavior management, may improve children's long-term developmental health.

Childhood Physical Health and Attention Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Modifiable Factors.

Although neurobiologic and genetic factors figure prominently in the development of attention deficit/hyperactivity disorder (ADHD), adverse physical health experiences and conditions encountered during childhood may also play a role. Poor health is known to impact the developing brain with potential lifelong implications for behavioral issues. In attempt to better understand the relationship between childhood physical health and the onset and presence of ADHD symptoms, we summarized international peer-reviewed articles documenting relationships between a select group of childhood diseases or health events (e.g., illnesses, injuries, syndromes) and subsequent ADHD outcomes among children ages 0-17 years. Drawing on a larger two-phase systematic review, 57 longitudinal or retrospective observational studies (1978-2021) of childhood allergies, asthma, eczema, head injury, infection, or sleep problems and later ADHD diagnosis or symptomatology were identified and subjected to meta-analysis. Significant associations were documented between childhood head injuries, infections, and sleep problems with both dichotomous and continuous measures of ADHD, and between allergies with dichotomous measures of ADHD. We did not observe significant associations between asthma or eczema with ADHD outcomes. Heterogeneity detected for multiple associations, primarily among continuously measured outcomes, underscores the potential value of future subgroup analyses and individual studies. Collectively, these findings shed light on the importance of physical health in understanding childhood ADHD. Possible etiologic links between physical health factors and ADHD are discussed, as are implications for prevention efforts by providers, systems, and communities.

A Systematic Review and Meta-analysis of Prenatal, Birth, and Postnatal Factors Associated with Attention-Deficit/Hyperactivity Disorder in Children.

Previous studies have shown mixed results on the relationship between prenatal, birth, and postnatal ("pregnancy-related") risk factors and attention-deficit/hyperactivity disorder (ADHD). We conducted meta-analyses to identify potentially modifiable pregnancy-related factors associated with ADHD. A comprehensive search of PubMed, Web of Science, and EMBASE in 2014, followed by an updated search in January 2021, identified 69 articles published in English on pregnancy-related risk factors and ADHD for inclusion. Risk factors were included in the meta-analysis if at least three effect sizes with clear pregnancy-related risk factor exposure were identified. Pooled effect sizes were calculated for ADHD overall, ADHD diagnosis, inattention, and hyperactivity/impulsivity. Odds ratios (OR) were calculated for dichotomous measures and correlation coefficients (CC) for continuous measures. Prenatal factors (pre-pregnancy weight, preeclampsia, pregnancy complications, elevated testosterone exposure), and postnatal factors (Apgar score, neonatal illness, no breastfeeding) were positively associated with ADHD overall; the findings for ADHD diagnosis were similar with the exception that there were too few effect sizes available to examine pre-pregnancy weight and lack of breastfeeding. Prenatal testosterone was significantly associated with inattention and hyperactivity/impulsivity. Effect sizes were generally small (range 1.1-1.6 ORs, -0.16-0.11 CCs). Risk factors occurring at the time of birth (perinatal asphyxia, labor complications, mode of delivery) were not significantly associated with ADHD. A better understanding of factors that are consistently associated with ADHD may inform future prevention strategies. The findings reported here suggest that prenatal and postnatal factors may serve as potential targets for preventing or mitigating the symptoms of ADHD.

A Systematic Review and Meta-analysis of Parental Depression, Antidepressant Usage, Antisocial Personality Disorder, and Stress and Anxiety as Risk Factors for Attention-Deficit/Hyperactivity Disorder (ADHD) in Children.

Poor parental mental health and stress have been associated with children's mental disorders, including attention-deficit/hyperactivity disorder (ADHD), through social, genetic, and neurobiological pathways. To determine the strength of the associations between parental mental health and child ADHD, we conducted a set of meta-analyses to examine the association of parent mental health indicators (e.g., parental depression, antidepressant usage, antisocial personality disorder, and stress and anxiety) with subsequent ADHD outcomes in children. Eligible ADHD outcomes included diagnosis or symptoms. Fifty-eight articles published from 1980 to 2019 were included. We calculated pooled effect sizes, accounting for each study's conditional variance, separately for test statistics based on ADHD as a dichotomous (e.g., diagnosis or clinical cutoffs) or continuous measurement (e.g., symptoms of ADHD subtypes of inattentiveness and hyperactivity/impulsivity). Parental stress and parental depression were significantly associated with increased risk for ADHD overall and both symptoms and diagnosis. Specifically, maternal stress and anxiety, maternal prenatal stress, maternal depression, maternal post-partum depression, and paternal depression were positively associated with ADHD. In addition, parental depression was associated with symptoms of ADHD inattentive and hyperactive/impulsive subtypes. Parental antisocial personality disorder was also positively associated with ADHD overall and specifically ADHD diagnosis. Prenatal antidepressant usage was associated with ADHD when measured dichotomously only. These findings raise the possibility that prevention strategies promoting parental mental health and addressing parental stress could have the potential for positive long-term impacts on child health, well-being, and behavioral outcomes.

Factors Associated with Self-regulation in a Nationally Representative Sample of Children Ages 3-5 Years: United States, 2016.

OBJECTIVE: The aim of the present study was to describe self-regulation (the ability to influence or control one's thoughts or behavior in response to situational demands and social norms) in children ages 3-5 years using a nationally representative sample and examine risk and protective factors to identify opportunities to support children and families. METHODS: Using a cross-sectional design, we examined data from a parent-reported pilot measure of self-regulation from the 2016 National Survey of Children's Health (NSCH). We compared U.S. children aged 3-5 years who were described by parents as "on track" with self-regulation development with children who were not. In addition, we described how health care and developmental services, community, family, and child health and development factors are associated with children's self-regulation. RESULTS: The majority of children (4 of 5) were described by their parents to be developmentally on track with self-regulation. Compared to children described as not on track, children described as on track more often lived in financially and socially advantaged environments and less often experienced family adversity. They also had other positive health and development indicators, whether or not they were receiving developmental services. However, only half of children not on track received developmental surveillance, and only 1 in 4 children described as not on track received educational, mental health, or developmental services. CONCLUSION: The findings are a step towards using self-regulation as an indicator of healthy child development and as a potential strategy to identify groups of children who may need additional support.

Community-Based Prevalence of Externalizing and Internalizing Disorders among School-Aged Children and Adolescents in Four Geographically Dispersed School Districts in the United States.

The Project to Learn About Youth-Mental Health (PLAY-MH; 2014-2018) is a school-based, two-stage study designed to estimate the prevalence of selected mental disorders among K-12 students in four U.S.-based sites (Colorado, Florida, Ohio, and South Carolina). In Stage 1, teachers completed validated screeners to determine student risk status for externalizing or internalizing problems or tics; the percentage of students identified as being at high risk ranged from 17.8% to 34.4%. In Stage 2, parents completed a structured diagnostic interview to determine whether their child met criteria for fourteen externalizing or internalizing disorders; weighted prevalence estimates of meeting criteria for any disorder were similar in three sites (14.8%-17.8%) and higher in Ohio (33.3%). PLAY-MH produced point-in-time estimates of mental disorders in K-12 students, which may be used to supplement estimates from other modes of mental disorder surveillance and inform mental health screening and healthcare and educational services.

Utilizing molecular resonance-localized surface plasmon resonance coupling for copper ion detection in plasma.

The rapid, point-of-care detection of copper in plasma can greatly aid in a large number of diseases where copper has been implicated to be an important factor, such as cancer, Alzheimer's and Diabetes mellitus. Localized surface plasmon resonance (LSPR) technologies show promise in the inexpensive detection of copper, whereas previous platforms are plagued with selectivity and sensitivity issues. Herein, we have created a sensitive and selective on-chip copper sensor which can produce a colorimetric reading in 60 minutes. The selectivity of the assay is based on 'Click' chemistry and is shown to have little interference with other metal ions present in plasma. The sensitivity of the assay is generated from the coupling of the molecular resonance of a dye and the LSPR of the gold nanoparticles. The assay is capable of measuring copper concentrations in human plasma as low as 4 µM and the linear range of sensitivity, 4 to 20 µM, is in the physiologically relevant range. This robust, colorimetric assay should prove useful in a point-of-care setting.

Functional responses in habitat selection: clarifying hypotheses and interpretations.

A fundamental challenge in habitat ecology and management is understanding the mechanisms generating animal distributions. Studies of habitat selection provide a lens into such mechanisms, but are often limited by unrealistic assumptions. For example, most studies assume that habitat selection is constant with respect to the availability of resources, such that habitat use remains proportional to availability. To the contrary, a growing body of work has shown the fallacy of this assumption, indicating that animals modify their behavior depending on the context at broader scales. This has been termed a functional response in habitat selection. Furthermore, a diversity of methods is employed to model functional responses in habitat selection, with little attention to how methodology might affect scientific and conservation conclusions. Here, we first review the conceptual and statistical foundations of methods currently used to model functional responses and clarify the ecological tests evaluated within each approach. We then use a combination of simulated and empirical data sets to evaluate the similarities and differences among approaches. Importantly, we identified multiple statistical issues with the most widely applied approaches to understand functional responses, including: (1) a complex and important role of random- or individual-level intercepts in adjusting individual-level regression coefficients as resource availability changes and (2) a sensitivity of results to poorly informed individual-level coefficients estimated for animals with low availability of a given resource. Consequently, we provide guidance on applying approaches that are insensitive to these issues with the goal of advancing our understanding of animal habitat ecology and management. Finally, we characterize the management implications of assuming similarity between the current approaches to model functional responses with two empirical data sets of federally threatened species: Canada lynx (Lynx canadensis) in the United States and woodland caribou (Rangifer tarandus caribou) in Canada. Collectively, our assessment helps clarify the similarities and differences among current approaches and, therefore, assists the integration of functional responses into the mainstream of habitat ecology and management.

Health Care, Family, and Community Factors Associated with Mental, Behavioral, and Developmental Disorders and Poverty Among Children Aged 2-8 Years - United States, 2016.

Childhood mental, behavioral, and developmental disorders (MBDDs) are associated with adverse outcomes that can persist into adulthood (1,2). Pediatric clinical settings are important for identifying and treating MBDDs (3). Early identification and treatment of MBDDs can promote healthy development for all children (4), especially those living in poverty who are at increased risk for MBDDs (3,5) but might have reduced access to care (6). CDC analyzed data from the 2016 National Survey of Children's Health (NSCH) on MBDDs, risk factors, and use of federal assistance programs (e.g., Supplemental Nutrition Assistance Program [SNAP]) to identify points to reach children in poverty. In line with previous research (3,6), compared with children in higher-income households, those in lower-income households more often had ever received a diagnosis of an MBDD (22.1% versus 13.9%), and less often had seen a health care provider in the previous year (80.4% versus 93.8%). Among children living below 200% of the federal poverty level (FPL) who did not see a health care provider in the previous year, seven of 10 were in families receiving at least one public assistance benefit. Public assistance programs might offer collaboration opportunities to provide families living in poverty with information, co-located screening programs or services, or connection to care.

Forest structure provides the income for reproductive success in a southern population of Canada lynx.

Understanding intrinsic and extrinsic drivers of reproductive success is central to advancing animal ecology and characterizing critical habitat. Unfortunately, much of the work examining drivers of reproductive success is biased toward particular groups of organisms (e.g., colonial birds, large herbivores, capital breeders). Long-lived mammalian carnivores that are of conservation concern, solitary, and territorial present an excellent situation to examine intrinsic and extrinsic drivers of reproductive success, yet they have received little attention. Here, we used a Canada lynx (Lynx canadensis) data set, from the southern periphery of their range, to determine if reproductive success in a solitary carnivore was consistent with capital or income breeding. We radio-marked and monitored 36 female Canada lynx for 98 lynx years. We evaluated how maternal characteristics and indices of food supply (via forest structure) in core areas influenced variation in body condition and reproductive success. We characterized body condition as mass/length and reproductive success as whether a female produced a litter of kittens for a given breeding season. Consistent with life-history theory, we documented a positive effect of maternal age on body condition and reproductive success. In contrast to predictions of capital breeding, we observed no effect of pre-pregnancy body condition on reproductive success in Canada lynx. However, we demonstrated statistical effects of forest structure on reproductive success in Canada lynx, consistent with predictions of income breeding. The forest characteristics that defined high success included (1) abundant and connected mature forest and (2) intermediate amounts of small-diameter regenerating forest. These attributes are consistent with providing abundant, temporally stable, and accessible prey resources (i.e., snowshoe hares; Lepus americanus) for lynx and reinforce the bottom-up mechanisms influencing Canada lynx populations. Collectively, our results suggest that lynx on the southern range periphery exhibit an income breeding strategy and that forest structure supplies the income important for successful reproduction. More broadly, our insights advance the understanding of carnivore ecology and serve as an important example on integrating long-term field studies with ecological theory to improve landscape management.

Prevalence of Parent-Reported ADHD Diagnosis and Associated Treatment Among U.S. Children and Adolescents, 2016.

The purpose of this study is to estimate the national prevalence of parent-reported attention deficit/hyperactivity disorder (ADHD) diagnosis and treatment among U.S. children 2-17 years of age using the 2016 National Survey of Children's Health (NSCH). The NSCH is a nationally representative, cross-sectional survey of parents regarding their children's health that underwent a redesign before the 2016 data collection. It included indicators of lifetime receipt of an ADHD diagnosis by a health care provider, whether the child currently had ADHD, and receipt of medication and behavioral treatment for ADHD. Weighted prevalence estimates were calculated overall and by demographic and clinical subgroups (n = 45,736). In 2016, an estimated 6.1 million U.S. children 2-17 years of age (9.4%) had ever received an ADHD diagnosis. Of these, 5.4 million currently had ADHD, which was 89.4% of children ever diagnosed with ADHD and 8.4% of all U.S. children 2-17 years of age. Of children with current ADHD, almost two thirds (62.0%) were taking medication and slightly less than half (46.7%) had received behavioral treatment for ADHD in the past year; nearly one fourth (23.0%) had received neither treatment. Similar to estimates from previous surveys, there is a large population of U.S. children and adolescents who have been diagnosed with ADHD by a health care provider. Many, but not all, of these children received treatment that appears to be consistent with professional guidelines, though the survey questions are limited in detail about specific treatment types received. The redesigned NSCH can be used to annually monitor diagnosis and treatment patterns for this highly prevalent and high-impact neurodevelopmental disorder.