Hepatitis B Birth Dose Vaccination Improvement Initiative: The 24-Hour Baby Bundle.

BACKGROUND: An estimated 25,000 infants are born to mothers diagnosed with hepatitis B virus (HBV) each year in the United States. Administration of the birth dose HBV vaccine prevents transmission during delivery. Despite national guidelines promoting vaccination within 24 hours of birth, fewer than 70% of infants receive the dose in their first 3 days of life. To improve compliance with national recommendations, Northwestern Medicine implemented a bundled care initiative in the well newborn nursery, entitled the 24-hour baby bundle (24-HBB). PURPOSE: Evaluate the 24-HBB's effect on improving time to HBV vaccine administration. METHODS: The 24-HBB was created by an interdisciplinary team and implemented on February 17, 2020. Bundled care begins at 23 hours of life, starting with the HBV vaccine, followed by bath, weight, and congenital heart disease screening, and ending with metabolic screening. We conducted a retrospective cohort study of 22,057 infants born at Northwestern Medicine Prentice Women's Hospital in Chicago, Illinois. Our sample included preintervention birthdates between February 16, 2019, and January 16, 2020, and postintervention birthdates between March 17, 2020, and February 16, 2021, with a 2-month washout education period between January 17, 2020, and March 16, 2020. RESULTS: Hepatitis B virus immunization within 24 hours increased significantly from 43.83% to 66.90% (P < .0001). In addition, overall hepatitis B immunization prior to discharge significantly increased after implementation of the 24-HBB (98.18% vs 98.82%, P < .0001). IMPLICATIONS FOR PRACTICE AND RESEARCH: The 24-HBB is effective at increasing rates of HBV immunization within 24 hours of birth. Newborn nurseries may benefit from similar initiatives to prevent hepatitis B infection, satisfy national recommendations, and promote childhood vaccination compliance.

The Digital Navigator: Standardizing Human Technology Support in App-Integrated Clinical Care.

Background: Mental health apps offer scalable care, yet clinical adoption is hindered by low user engagement and integration challenges into clinic workflows. Human support staff called digital navigators, trained in mental health technology, could enhance care access and patient adherence and remove workflow burdens from clinicians. While the potential of this role is clear, training staff to become digital navigators and assessing their impact are primary challenges. Methods: We present a detailed manual/framework for implementation of the Digital Navigator within a short-term, cognitive-behavioral therapy-focused hybrid clinic. We analyze patient engagement, satisfaction, and digital phenotyping data quality outcomes. Data from 83 patients, for the period spanning September 2022 to September 2023, included Digital Navigator satisfaction, correlated with demographics, mindLAMP app satisfaction, engagement, and passive data quality. Additionally, average passive data across 33 clinic patients from November 2023 to January 2024 were assessed for missingness. Results: Digital Navigator satisfaction averaged 18.8/20. Satisfaction was not influenced by sex, race, gender, or education. Average passive data quality across 33 clinic patients was 0.82 at the time this article was written. Digital Navigator satisfaction scores had significant positive correlation with both clinic app engagement and perception of that app. Conclusions: Results demonstrate preliminary support and patient endorsement for the Digital Navigator role and positive outcomes around digital engagement and digital phenotyping data quality. Through sharing training resources and standardizing the role, we aim to enable clinicians and researchers to adapt and utilize the Digital Navigator for their own needs.

Discrepancy Between Reported and Calculated Pain Reduction in Patients With Spinal Cord Stimulation Therapy and Lack of Agreement Between Patient Satisfaction and Degree of Pain Relief.

OBJECTIVES: This study aimed to determine agreement between reported percentage pain reduction (RPPR) and calculated percentage pain reduction (CPPR) in patients with percutaneous spinal cord stimulation (SCS) implants, and to correlate RPPR and CPPR with patient satisfaction. We also sought to determine which patient-reported outcome measures are most improved in patients with SCS. MATERIALS AND METHODS: Fifty patients with percutaneous spinal cord stimulator implants with a mean follow-up of 51.1 months were interviewed and surveyed to assess their pain level, impression of degree of pain relief, satisfaction with the therapy, and desire to have the device again. Baseline pain level was obtained from their preimplant records. RESULTS: Overall, RPPR was found to be 53.3%, whereas CPPR was 44.4%. Of all patients, 21 reported <50% pain reduction; however, most of these (12/21, 57%) were satisfied with the outcome of therapy. In terms of individual improvement in outcomes, activities of daily life was the most improved measure at 82%, followed by mood, sleep, medication use, and health care utilization at 74%, 62%, 50%, and 48%, respectively. CONCLUSIONS: RPPR appears to be a complex outcome measure that may not agree with CPPR. Overall RPPR is greater than the CPPR. On the basis of our data, these independently valid measures should not be used interchangeably. A 50% pain reduction threshold is not a requisite for patient satisfaction and desire to have the device again. Activities of daily living was the most improved measure in this cohort, followed by mood, sleep, medication usage, and decrease in health care utilization.

Elucidating the Structure and Composition of Individual Bimetallic Nanoparticles in Supported Catalysts by Atom Probe Tomography.

Understanding and controlling the structure and composition of nanoparticles in supported metal catalysts are crucial to improve chemical processes. For this, atom probe tomography (APT) is a unique tool, as it allows for spatially resolved three-dimensional chemical imaging of materials with sub-nanometer resolution. However, thus far APT has not been applied for mesoporous oxide-supported metal catalyst materials, due to the size and number of pores resulting in sample fracture during experiments. To overcome these issues, we developed a high-pressure resin impregnation strategy and showcased the applicability to high-porous supported Pd-Ni-based catalyst materials, which are active in CO2 hydrogenation. Within the reconstructed volume of 3 × 105 nm3, we identified over 400 Pd-Ni clusters, with compositions ranging from 0 to 16 atom % Pd and a size distribution of 2.6 ± 1.6 nm. These results illustrate that APT is capable of quantitatively assessing the size, composition, and metal distribution for a large number of nanoparticles at the sub-nm scale in industrial catalysts. Furthermore, we showcase that metal segregation occurred predominately between nanoparticles, shedding light on the mechanism of metal segregation. We envision that the presented methodology expands the capabilities of APT to investigate porous functional nanomaterials, including but not limited to solid catalysts.

PROMIS: Physical, Mental and Social Health Outcomes Improve From Before to Early After LVAD Implant: Findings From the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) Study.

Study participants (n = 272) completed 12 Patient-Reported Outcomes Measurement Information System (PROMIS) physical, mental and social health measures (questionnaires) prior to implantation of a left ventricular assist device (LVAD) and again at 3 and 6 months postimplant. All but 1 PROMIS measure demonstrated significant improvement from pre-implant to 3 months; there was little change between 3 and 6 months. Because PROMIS measures were developed in the general population, patients with an LVAD, their caregivers and their clinicians can interpret the meaning of PROMIS scores in relation to the general population, helping them to monitor a return to normalcy in everyday life.

Inclusion of an Optimized Plasmodium falciparum Merozoite Surface Protein 2-Based Antigen in a Trivalent, Multistage Malaria Vaccine.

Plasmodium falciparum merozoite surface protein (PfMSP)2 is a target of parasite-neutralizing Abs. Inclusion of recombinant PfMSP2 (rPfMSP2) as a component of a multivalent malaria vaccine is of interest, but presents challenges. Previously, we used the highly immunogenic PfMSP8 as a carrier to enhance production and/or immunogenicity of malaria vaccine targets. In this study, we exploited the benefits of rPfMSP8 as a carrier to optimize a rPfMSP2-based subunit vaccine. rPfMSP2 and chimeric rPfMSP2/8 vaccines produced in Escherichia coli were evaluated in comparative immunogenicity studies in inbred (CB6F1/J) and outbred (CD1) mice, varying the dose and adjuvant. Immunization of mice with both rPfMSP2-based vaccines elicited high-titer anti-PfMSP2 Abs that recognized the major allelic variants of PfMSP2. Vaccine-induced T cells recognized epitopes present in both PfMSP2 and the PfMSP8 carrier. Competition assays revealed differences in Ab specificities induced by the two rPfMSP2-based vaccines, with evidence of epitope masking by rPfMSP2-associated fibrils. In contrast to aluminum hydroxide (Alum) as adjuvant, formulation of rPfMSP2 vaccines with glucopyranosyl lipid adjuvant-stable emulsion, a synthetic TLR4 agonist, elicited Th1-associated cytokines, shifting production of Abs to cytophilic IgG subclasses. The rPfMSP2/8 + glucopyranosyl lipid adjuvant-stable emulsion formulation induced significantly higher Ab titers with superior durability and capacity to opsonize P. falciparum merozoites for phagocytosis. Immunization with a trivalent vaccine including PfMSP2/8, PfMSP1/8, and the P. falciparum 25 kDa sexual stage antigen fused to PfMSP8 (Pfs25/8) induced high levels of Abs specific for epitopes in each targeted domain, with no evidence of antigenic competition. These results are highly encouraging for the addition of rPfMSP2/8 as a component of an efficacious, multivalent, multistage malaria vaccine.

What is typical: Atypical in young children's attention regulation?: Characterizing the developmental spectrum with the Multidimensional Assessment Profiles-Attention Regulation Infant-Toddler (MAPS-AR-IT) Scale.

While attention dysregulation is a promising early indicator of neurodevelopmental risk, in particular attention-deficit/hyperactivity disorder (ADHD), it is difficult to characterize clinical concern due to its developmental expectability at the transition to toddlerhood. Thus, explicating the typical:atypical continuum of risk indicators is among the key future directions for research to promote early identification and intervention, and prevent decrements in the attainment of developmental milestones into early childhood. In this paper, we present the Multidimensional Assessment Profiles-Attention Regulation Infant-Toddler (MAPS-AR-IT) Scale, a novel parent-report survey of dimensional, developmentally specified indicators of attention (dys)regulation. Item Response Theory was employed to characterize the typical:atypical spectrum of both normative and more concerning dysregulation (including the contexts in which behavior occurs). We provide evidence of the validity of this measure in capturing the full typical:atypical spectrum via a longitudinal sample of typically developing children at 12-18 months of age (baseline) via concurrent scores on well-validated temperament and clinical measures. We also examine longitudinal stability and predictive validity if the MAPS-AR-IT via a clinical interview of ADHD symptoms at 24-30 months (follow-up). While not diagnostic, we present evidence of the utility of the MAPS-AR-IT in explicating individual neurodevelopmental risk and elucidating the broader typicality of behaviors related to attention (dys)regulation.

Aunque la desregulación de la atención es un prometedor indicador temprano del riesgo neural de desarrollo, en particular el trastorno de déficit en la atención/hiperactividad (ADHD), es difícil caracterizar las preocupaciones clínicas debido al factor de expectativa de desarrollo al momento de la transición a la temprana niñez. De manera que explicar la progresión típica:atípica de indicadores de riesgo está entre las futuras directrices claves para la investigación con el fin de promover la temprana identificación e intervención, y prevenir disminuciones en el alcance de hitos críticos hacia la temprana niñez. En este ensayo, presentamos la Escala de Perfiles de Evaluación Multidimensional - Regulación de la Atención del Infante-Niño Pequeñito (MAPS-AR-IT) una novedosa encuesta de reporte del progenitor, acerca de la (des)regulación de la atención, dimensional y específica para el desarrollo. Aportamos evidencia de la validez de esta medida para captar la completa gama típica:atípica por medio de una muestra longitudinal de niños típicamente en desarrollo, a los 12-18 meses de edad (edad base) por medio de puntajes concurrentes sobre el temperamento bien validado y las medidas clínicas, así como también la estabilidad longitudinal y la validez de predicción por medio de una entrevista clínica de síntomas de ADHD a los 24-30 meses (seguimiento). Se empleó la Teoría de Respuesta al Asunto para caracterizar la gama típica:atípica tanto de la desregulación normativa como de la más preocupante (incluyendo los contextos en los cuales ocurre el comportamiento). Aunque no se trata de diagnóstico, presentamos evidencia de la utilidad de MAPS-AR-IT para explicar el riesgo individual de desarrollo neural y elucidar el más amplio aspecto típico de comportamientos relacionados con la (des)regulación de la atención.

Bien que la dysrégulation de l'attention soit un indicateur précoce prometteur du risque neurodéveloppemental, en particulier le trouble déficitaire de l'attention/hyperactivité (TDHA) il est difficile de caractériser la préoccupation clinique du fait de sa prévisibilité développementale à la transition à la petite enfance. Par conséquent, expliquer le continuum typique:atypique des indicateurs de risque s'avère être une des directions futures de recherches clé pour promouvoir l'identification et l'intervention précoce, et prévenir les baisses dans la réalisation d'étapes développementales importantes jusque dans la petite enfance. Dans cet article nous présentons l'Echelle Multidimensional Assessment Profiles - Attention Regulation Infant-Toddler (MAPS-AR-IT) (échelle de profils d'évaluation multidimensionnelle - régulation de l'attention bébé-petit enfant, abrégée selon l'anglais MAP-AR-IT), une étude nouvelle basée sur les rapports faits par les parents de la (dys)régulation de l'attention dimensionnelle et spécifiée selon le développement. Nous démontrons la validité de cette mesure en capturant l'éventail total typique:atypique au moyen d'un échantillon longitudinal d'enfants se développement typiquement, à 12-18 mois (ligne de case) au moyen de scores concurrents de mesures cliniques et de tempérament bien validées, ainsi qu''une stabilité longitudinale et d'une validité prédictive au moyen d'un entretien Clinique des symptômes THHA à 24-30 mois (suivi). La Item Response Theory (IRT) a été employée pour caractériser l'éventail typique:atypique de la dysrégulation à la fois normative et celle plus inquiétante (y compris les contextes dans lesquels le comportement prend place). Bien que cela ne soit pas diagnostique, nous présentons la preuve de l'utilité de la MAPS-AR-IT en expliquant le risqué neurodéveloppemental individuel et en élucidant la typicalité plus large de comportements liés à la (dys)régulation de l'attention.

No overall impact on rate of weight gain with integrase inhibitor-containing regimens in antiretroviral-naïve adults.

OBJECTIVES: Integrase strand transfer inhibitors (INSTIs) are commonplace in modern antiretroviral therapy (ART). Increased weight gain with their use is increasingly scrutinized. We evaluated weight changes in treatment-naïve adults with HIV-1 attending a UK centre who started regimens including raltegravir or dolutegravir. METHODS: A retrospective cohort study of adults prescribed an INSTI between January 2015 and March 2020 were categorized as having started an ART regimen containing raltegravir, dolutegravir, a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Individuals with one or more weight measurement ≤ 5 years both pre- and post-ART initiation, who started a three-drug regimen with ≥ 6 months duration and achieved virological suppression (< 50 copies/mL) within 6 months were included. A random effects model with linear slope pre- and post-ART was used, adjusting for age, gender, ethnicity, ART regimen, backbone and year of initiation. RESULTS: The cohort included 390 adults; 88.7% were male, 66.4% were of white ethnicity, their median age was 40 years, there was a median of six weight measurements, 2.2 years from diagnosis to ART initiation, 2.9 years from ART to the last weight measurement, and weight and body mass index at initiation were 75 kg and 24.1 kg/m2 respectively. Of these, 254 (65%) started an INSTI. The average pre-ART rate of weight gain was 0.44 kg/year [95% confidence interval (CI): 0.19-0.70], increasing to 0.88 kg/year (0.63-1.10, p = 0.04) after ART initiation. Our adjusted model found no evidence of an association between ART regimen and rate of weight gain. CONCLUSIONS: Weight increased in the cohort both pre- and post-ART. We found no evidence of a higher rate of weight gain following ART initiation with an INSTI compared with other regimens.

Lions and brown bears colonized North America in multiple synchronous waves of dispersal across the Bering Land Bridge.

The Bering Land Bridge connecting North America and Eurasia was periodically exposed and inundated by oscillating sea levels during the Pleistocene glacial cycles. This land connection allowed the intermittent dispersal of animals, including humans, between Western Beringia (far northeast Asia) and Eastern Beringia (northwest North America), changing the faunal community composition of both continents. The Pleistocene glacial cycles also had profound impacts on temperature, precipitation and vegetation, impacting faunal community structure and demography. While these palaeoenvironmental impacts have been studied in many large herbivores from Beringia (e.g., bison, mammoths, horses), the Pleistocene population dynamics of the diverse guild of carnivorans present in the region are less well understood, due to their lower abundances. In this study, we analyse mitochondrial genome data from ancient brown bears (Ursus arctos; n = 103) and lions (Panthera spp.; n = 39), two megafaunal carnivorans that dispersed into North America during the Pleistocene. Our results reveal striking synchronicity in the population dynamics of Beringian lions and brown bears, with multiple waves of dispersal across the Bering Land Bridge coinciding with glacial periods of low sea levels, as well as synchronous local extinctions in Eastern Beringia during Marine Isotope Stage 3. The evolutionary histories of these two taxa underline the crucial biogeographical role of the Bering Land Bridge in the distribution, turnover and maintenance of megafaunal populations in North America.

Measuring PROMIS® Emotional Distress in Early Childhood.

OBJECTIVE: Create and validate developmentally sensitive parent-report measures of emotional distress for children ages 1-5 years that conceptually align with the Patient-Reported Outcome Measurement Information System (PROMIS®) pediatric measures. METHODS: Initial items were generated based on expert and parent input regarding core components of emotional distress in early childhood and review of theoretical and empirical work in this domain. Items were psychometrically tested using data from two waves of panel surveys. Item response theory (IRT) was applied to develop item calibration parameters (Wave 1), and scores were centered on a general U.S. population sample (Wave 2). Final PROMIS early childhood (EC) instruments were compared with existing measures of related constructs to establish construct validity. RESULTS: Experts and parents confirmed the content validity of the existing PROMIS Pediatric emotional distress domains (i.e., anger, anxiety, and depressive symptoms) as developmentally salient for young children. Existing items were adapted and expanded for early childhood by employing best practices from developmental measurement science. Item banks as well as 4- and 8-item short forms, free from differential item functioning across sex and age, were constructed for the three domains based on rigorous IRT analyses. Correlations with subscales from previously validated measures provided further evidence of construct validity. CONCLUSIONS: The PROMIS EC Anger/Irritability, Anxiety, and Depressive Symptoms measures demonstrated good reliability and initial evidence of validity for use in early childhood. This is an important contribution to advancing brief, efficient measurement of emotional distress in young children, closing a developmental gap in PROMIS pediatric emotional distress assessment.

Which Clinical Features of Children on Initial Presentation to the Emergency Department With Head Injury Are Associated With Clinically Important Traumatic Brain Injury, Classification as Abuse, and Poor Prognosis?

BACKGROUND: Pediatric traumatic brain injury (TBI) and abusive head trauma (AHT) are leading causes of morbidity and mortality. Clinicians may not be aware of AHT at presentation to the emergency department (ED). OBJECTIVE: The objective of this study was to determine which clinical features associated with head injury in children on initial presentation to the ED trauma bay predict 3 outcomes including clinically important TBI (CiTBI), classification as confirmed abuse by Child Protection Team (CPT), and poor neurologic status on hospital discharge. PARTICIPANTS AND SETTING: Inclusion for this study were children 3 years or younger, presenting to the ED with significant TBI. In addition, presentations where the mechanism of injury was not verifiable such as with falls, being struck by object, or no mechanism of injury reported by caregiver were included. METHODS: Researchers used 3 sources of information for this analysis: a regional trauma registry, hospital records, and the CPT database. Clinical features included demographics, mechanisms of injury, physical, radiological findings, and CPT classification. RESULTS: On pairwise analysis, seizures, apnea, and no mechanism of injury reported by caregiver were the only clinical features related to all 3 outcomes (P < 0.001). Rib fractures (relative risk [RR], 3.3; P < 0.001), long bone fractures (RR, 3.1; P < 0.001), retinal hemorrhages (RR, 3.0; P < 0.001), seizures (RR, 3.6; P < 0.001), apnea (RR, 4.4; P < 0.001), and younger than 6 months (RR, 1.8; P < 0.001) were related to AHT. On multivariable logistic regression, no mechanism of injury reported by caregiver and seizures remained significantly related to CiTBI; seizures and retinal hemorrhage remained significantly related to classification as abuse by CPT, and no mechanism of injury by the caregiver, apnea, and seizures were significantly related to poor outcome on hospital discharge. CONCLUSIONS: No mechanism of injury reported by the caregiver, seizures, and apnea at the time of presentation to the ED are important features associated with CiTBI, classification as AHT, and poor prognosis. In addition, younger age, retinal hemorrhage, rib, and long bone fractures were found to be important clinical features associated with AHT.

The promise of curriculum in the post-Covid world: Eclecticism, deliberation, and a return to the practical and the prophetic.

This article focuses on the possibilities through which curriculum on the other side of the Covid-19 pandemic might contribute more proactively to future social and political crises that are multifarious yet interconnected in nature. The Covid-19 pandemic is a global crisis that touches every aspect of social life, including politics, the economy, healthcare systems, poverty, forced human migration, climate change, and importantly, education. To potentially address future crises through curriculum, the article first problematizes the present in education and society-specifically, the 50-year neoliberal project that has transformed society and education. It connects the crisis in education to a transformed social, political, and economic system that has introduced what Gordon Lafer has called a revolution of falling expectations through a hollowing-out of public institutions. The article then returns to the crisis of curriculum, contextualized in Joseph Schwab's The Practical: A Language for Curriculum, which presaged the reconceptualization of the curriculum field. It dialogues with Schwab's advocacy for an eclectic, deliberative, and practical curricular ethic as a form of post-reconceptualization curriculum study to contribute to understanding and managing future disruptions, such as those inevitably associated with the climate crisis. Finally, the article connects to the concept of liquidity in curriculum, through which to embody curricular eclecticism and provoke teachers and students to author a vision for a more just future that will not reinscribe the pathologies of the past.

The Proximity of Spatial Clusters of Low Birth Weight and Risk Factors: Defining a Neighborhood for Focused Interventions.

BACKGROUND: Low birth weight (LBW) is associated with significant mortality and morbidity and remains a significant preventable problem. Risk factors include socioeconomic, demographics, and characteristics of the environment. Spatial analysis can uncover unusual frequencies of health problems in neighborhoods, eventually leading to insights for targeted interventions. OBJECTIVES: This study's goals were to 1. Evaluate the geographic distribution of spatial clusters of LBW births and maternal risk factors. 2. Determine the spatial relationship between risk factors and LBW. METHODS: This study obtained data on LBW newborns and risk factors from 19,013 births over 5 years (2012-2016) for Escambia County Census Tracts, extracted from FloridaCharts.com. Software was used to detect significant spatial clusters; these clusters were then plotted on a map. Poisson regression determined the statistical relationship between Census Tract risk factors and LBW. A separate analysis of the LBW cluster controlling for risk factors was also performed. RESULTS: All risk factor clusters resided in similar locations as the LBW cluster. The multiple Poisson regression model containing all risk factors fully explained the LBW cluster. On bivariate Poisson regression all risk factors in the Census Tract were significantly related to LBW whereas in multivariable Poisson regression, the proportion of births to African American women in the Census Tract remained significant after adjusting for other risk factors (p < 0.001). CONCLUSIONS FOR PRACTICE: Clusters of LBW and risk factors were located in the same region of the county, with the proportion of births to African American women in the Census Tract remaining significant on multiple Poisson Regression. Targeted interventions should be directed at the geographic level.

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11ß-hydroxylase deficiency.

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11ß-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11ß-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11ß-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11ß-hydroxylase deficiency CAH.

Multi-method assessment of irritability and differential linkages to neurophysiological indicators of attention allocation to emotional faces in young children.

Facilitated attention toward angry stimuli (attention bias) may contribute to anger proneness and temper outbursts exhibited by children with high irritability. However, most studies linking attention bias and irritability rely on behavioral measures with limited precision and no studies have explored these associations in young children. The present study explores irritability-related attention biases toward anger in young children (N = 128; ages 4-7 years) engaged in a dot-probe task with emotional faces, as assessed with event-related brain potential (ERP) indices of early selective attention and multi-method assessment of irritability. Irritability assessed via semi-structured clinical interview predicted larger anterior N1 amplitudes to all faces. In contrast, irritability assessed via a laboratory observation paradigm predicted reduced P1 amplitudes to angry relative to neutral faces. These findings suggest that altered early attentional processing occurs in young children with high irritability; however, the nature of these patterns may vary with methodological features of the irritability assessments. Future investigations using different assessment tools may provide greater clarity regarding the underlying neurocognitive correlates of irritability. Such studies may also contribute to the ongoing debates about how to best define and measure irritability across the developmental spectrum in a manner that is most informative for linkage to neural processes.

Differentiating typical from atypical perpetration of sibling-directed aggression during the preschool years.

BACKGROUND: Sibling aggression is common and often viewed as benign. Although sibling aggression can be harmful for the victims, it may also be a marker of clinical risk for the aggressor. We differentiated typical from atypical levels of perpetration of sibling-directed aggression among preschoolers, a developmental period in which aggression is a normative misbehavior, by (a) identifying how frequently aggressive behaviors targeted at a sibling must occur to be psychometrically atypical; (b) mapping the dimensional spectrum of sibling-directed aggression from typical, more commonly occurring behaviors to rarer, more atypical, actions; and (c) comparing the psychometric atypicality and typical-to-atypical spectrum of sibling-directed aggression and peer-directed aggression. METHODS: Parents (N = 1,524) of 3- (39.2%), 4-(36.7%), and 5-(24.1%) year-olds (51.9% girls, 41.1% African-American, 31.9% Hispanic; 44.0% below the federal poverty line) completed the MAP-DB, which assesses how often children engage in aggressive behaviors. We used item-response theory (IRT) to address our objectives. RESULTS: Most aggressive behaviors toward siblings were psychometrically atypical when they occurred 'most days' or more; in contrast, most behaviors targeted at peers were atypical when they occurred 'some days' or more. With siblings, relational aggression was more atypical than verbal aggression, whereas with peers, both relational and physical aggression were more atypical than verbal aggression. In both relationships, the most typical behavior was a verbally aggressive action. Results were broadly replicated in a second, independent sample. CONCLUSIONS: These findings are a first step toward specifying features of sibling aggression that are markers of clinical risk and belie the notion that sibling aggression is inherently normative.

Temporally sensitive neural measures of inhibition in preschool children across a spectrum of irritability.

Irritability is a prominent feature of chronic mental disorders and a developmental marker of their early emergence. The most salient feature of irritability in early childhood is temper tantrums. While temper tantrums are normative in young children, they can be clinically concerning when they are dysregulated, very frequent, and/or occur in unexpected contexts. The present study uses behavioral and event-related brain potential (ERP) measures to characterize the relationship between irritability and neural markers of response inhibition in very young children. Forty-six children (ages 4-7 years) completed a go/no-go task under nonfrustrating and frustrating conditions. ERPs elicited by go and no-go stimuli were examined as a function of frustration condition and irritability, operationalized via the well-validated Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB). Higher Temper Loss scores were associated with larger N2no-go amplitudes and reduced no-go accuracy during frustration. This suggests that higher levels of irritability corresponded with increased conflict monitoring and poorer task performance during frustration. These findings add to a developing literature identifying the neurocognitive markers of varying levels of irritability in young children.

Relations Between Toddler Expressive Language and Temper Tantrums in a Community Sample.

This study examined the frequent clinical observation that toddlers with less expressive language have more severe temper tantrums. A representative sample of 2,001 mothers reported on their toddler's expressive vocabulary and frequency of different temper tantrum behaviors, a prominent feature of irritability and an emergent marker of mental health risk. Results revealed that 12- to 38-month-olds with fewer spoken words demonstrated more severe (frequent and dysregulated) temper tantrums. Toddlers who were late talkers at 24-30 months also had more severe tantrums; their relative risk of having severe tantrums was 1.96 times greater than peers with typical language. These results are the first to show that language and temper tantrums are related, and that this relation is present in the second year of life. These findings point to the importance of assessing both language and mental health risk in order to promote earlier identification and intervention for early childhood disorders.

Evaluation of a Plasmodium-Specific Carrier Protein To Enhance Production of Recombinant Pfs25, a Leading Transmission-Blocking Vaccine Candidate.

Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multiantigen vaccine. Attempting to resolve these issues, we focused on the use of highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that a genetic fusion of the C-terminal 19-kDa fragment of merozoite surface protein 1 (MSP119) to P. falciparum MSP8 (PfMSP8) facilitated antigen production and folding and the induction of neutralizing antibodies to conformational B cell epitopes of MSP119 Here, using the PfMSP1/8 construct, we further optimized the recombinant PfMSP8 (rPfMSP8) carrier by the introduction of two cysteine-to-serine substitutions (CΔS) to improve the yield of the monomeric product. We then sought to test the broad applicability of this approach using the transmission-blocking vaccine candidate Pfs25. The production of rPfs25-based vaccines has presented challenges. Antibodies directed against the four highly constrained epidermal growth factor (EGF)-like domains of Pfs25 block sexual-stage development in mosquitoes. The sequence encoding mature Pfs25 was codon harmonized for expression in Escherichia coli We produced a rPfs25-PfMSP8 fusion protein [rPfs25/8(CΔS)] as well as unfused, mature rPfs25. rPfs25 was purified with a modest yield but required the incorporation of refolding protocols to obtain a proper conformation. In comparison, chimeric rPfs25/8(CΔS) was expressed and easily purified, with the Pfs25 domain bearing the proper conformation without renaturation. Both antigens were immunogenic in rabbits, inducing IgG that bound native Pfs25 and exhibited potent transmission-reducing activity. These data further demonstrate the utility of PfMSP8 as a parasite-specific carrier protein to enhance the production of complex malaria vaccine targets.

A step forward for an attenuated blood-stage malaria vaccine.

Efforts to develop an effective malaria vaccine have encountered multiple challenges, and have had limited success to date. As the need remains urgent, novel approaches must be explored. One concept that has gained attention uses whole malaria parasites. Building on preclinical studies in animal models, Stanisic et al. describe the development of a vaccine based on chemically attenuated Plasmodium falciparum blood-stage parasites, with an evaluation of safety and immunogenicity in malaria-naïve human subjects. The vaccine was shown to be safe, well tolerated, and capable of priming antigen-specific T cells. This work, and the completion of an initial clinical trial in human subjects, represents a significant advance. While the path forward for this attenuated vaccine remains challenging, these initial findings are encouraging. Importantly, the results provide the foundation and framework for testing modified immunization protocols, and designing subsequent clinical trials to further evaluate safety, test for enhanced immunogenicity, and ultimately measure protective efficacy.Please see related article: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-018-1173-9.