Perspectives of paediatric providers on antibiotic stewardship in a high-prescribing rural region.

PURPOSE: Understanding drivers of antibiotic use is key to limiting the development of antimicrobial resistance. Outpatient antibiotic prescribing rates vary substantially across and within states. Kentucky is one of the highest prescribing states, and the southeastern region has rates that are drastically higher than the national average and urban areas of the state. We sought to examine provider perceptions of antibiotic use in this rural area to more effectively guide future interventions and policy. METHODS: This study utilized Medicaid prescription claims to identify providers who frequently prescribe antibiotics to children in southeastern Kentucky. Semistructured qualitative interviews were conducted to elicit provider perspectives on antibiotic overuse. FINDINGS: Individual, in-person interviews were conducted with 25 providers from a variety of practices and training backgrounds (private, nonprofit, retail, physician, advanced practice registered nurses, etc.). The following themes emerged as issues that prescribers consider to contribute to antibiotic overuse: (1) caregiver pressure, especially from grandparents or families who desire a 'quick fix'; (2) business concerns and competition and (3) cultural factors related to poverty and rural locations. Interviewed providers were supportive of public education and had mixed views on the effectiveness of delayed fill or provider feedback initiatives. CONCLUSIONS: This study highlights unique challenges associated with antibiotic prescribing in rural areas. Findings will guide future interventions through adaptation of existing strategies to better serve this vulnerable population.

Effects of PreOperative radiotherapy in a preclinical glioblastoma model: a paradigm-shift approach.

PURPOSE: PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model. METHODS: Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle. RESULTS: PreOperative RT group median survival was significantly higher than PostOperative RT (p < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors (p < 0.001) and induced senescence in PostOperative RT recurrent tumors (p < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors (p < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group. CONCLUSIONS: This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.

Wellness in the modulator era: An observational study of the impact of CFTR modulator therapy on the well-being of people with cystic fibrosis.

BACKGROUND: People with cystic fibrosis (PwCF) have experienced substantial improvements in health following use of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies. However, less is known about how modulator therapies impact well-being. METHODS: We used a cross-sectional observational study to identify relationships between CFTR modulator therapies, health-related quality of life (HRQoL), and well-being. Adult PwCF and caregivers of children with CF completed the Wellness in the Modulator Era (Well-ME) survey between June 22 and July 31, 2022. HRQoL was measured with PROMIS Global 10/Global 7 + 2 Parent Proxy. We used a mixed methods analysis to compare experiences and concerns of PwCF who currently (n = 665), no longer (n = 51), or never (n = 184) took modulator therapy. RESULTS: Adult PwCF taking a modulator (n = 416) reported better PROMIS global physical health than those who no longer (n = 37) or never took a modulator (n = 94) and better PROMIS global mental health than those who never took a modulator. Caregiver-reported HRQoL was similar across children with CF who currently, no longer, or never took a modulator. PwCF taking a modulator reported larger improvements in physical health, quality of life, social well-being, and treatment burden than those who no longer or never took a modulator. Nearly one-quarter (23 %) of PwCF taking modulator therapy reported worsening of mental well-being. CONCLUSIONS: This study expands our knowledge of well-being among PwCF in the CFTR modulator era as reported by patients and parents. Findings lay the groundwork for establishing future research priorities, policy efforts, and communications in areas that improve well-being for PwCF.

Correlates of Quality of Life in Autistic Individuals.

Background: Quality of life is an important outcome to autistic individuals. However, the correlates of quality of life in this population are not well known. The purpose of this project was to investigate the extent to which employment, depression, anxiety, and social participation were associated with quality of life in autistic individuals. We also explored potential associations between emotion dysregulation and quality of life. Method: Baseline data from two randomized control trials were used for analysis. A total of 125 autistic adolescents and adults aged 16-45 (M = 25.40) participated. Linear regression models were constructed to investigate whether employment, depression, anxiety, and social participation were associated with five domains of quality of life: overall, physical health, psychological, social relationships, and environment. Additional linear regression models explored whether emotion dysregulation was associated with the same quality of life domains. Results: Surprisingly, employment was not significantly associated with any quality of life domain. Greater depression severity was significantly associated with poorer quality of life across all domains. Greater social participation was associated with better quality of life, but only for individuals with lower anxiety. More severe dysphoria was associated with poorer overall quality of life and the psychological and physical health domains. Conclusions: Results suggest that mental health and emotion dysregulation are important predictors of quality of life for autistic people. They also suggest that anxiety symptoms may attenuate the beneficial effects of social participation. This study provides insight into the unique experiences of autistic individuals and highlights potential unmet need.

Effects of Rock Type and Food Availability on Bioerosion by the Purple Sea Urchin, Strongylocentrotus purpuratus.

Purple sea urchins (Strongylocentrotus purpuratus) profoundly impact nearshore rocky coasts through their feeding habits. Their intense grazing sculpts substrates through bioerosion using their teeth and spines and controls the alternative stable state dynamic between kelp bed and urchin barrens. These states have contrasting food availability for sea urchins, with abundant food in kelp beds and scarce food in barren grounds. However, the relationship between food availability and bioerosion is unknown. We predicted that when kelp is available, it would ameliorate the action of teeth on the substrate. Our 11-weeks long, 2 × 2 factorial experiment, crossed community state (kelp present vs absent) and rock type (sandstone vs mudstone). We also quantified the contribution of spine abrasion to bioerosion on the two rock types. The bioerosion rates did not differ between treatments with and without kelp. Although there was no significant difference in net bioerosion between the rock types, there was a large difference between the proportion of bioerosion from teeth vs spine abrasion. Approximately a third of the sandstone bioerosion was from spines whereas less than 2% of mudstone bioerosion could be attributed to spines. As anticipated, growth of sea urchins fed kelp ad-libitum was higher than food-limited sea urchins. Surprisingly, sea urchins on mudstone (which has a higher organic component) grew faster than sea urchins on sandstone. Although bioerosion rates may not differ on a per-urchin basis between community states, the sea urchin population densities between kelp beds and urchin barrens likely causes a difference in net bioerosion between these communities. Our results point to the importance of lithology on the mechanics of sea urchin bioerosion. Differences in texture, grain size, and hardness of rock substrates undoubtedly contribute to bioerosion rates and dynamics.

qPCR assay for detection of Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Elements from CAR-T and TCR-T cells in fresh and formalin-fixed tissue.

As adoptive cellular therapies become more commonplace in cancer care, there is a growing need to monitor site-specific localization of engineered cells-such as chimeric antigen receptor T (CAR-T) cells and T-cell receptor T (TCR-T) cells-in patients' tissues to understand treatment effectiveness as well as associated adverse events. Manufacturing CAR-T and TCR-T cells involves transduction with viral vectors commonly containing the WPRE gene sequence to enhance gene expression, providing a viable assay target unique to these engineered cells. Quantitative PCR (qPCR) is currently used clinically in fresh patient tissue samples and blood with target sequences specific to each immunotherapy product. Herein, we developed a WPRE-targeted qPCR assay that is broadly applicable for detection of engineered cell products in both fresh and archival formalin-fixed paraffin embedded (FFPE) tissues. Using both traditional PCR and SYBR Green PCR protocols, we demonstrate the use of this WPRE-targeted assay to successfully detect two CAR-T cell and two TCR-T cell products in FFPE tissue. Standard curve analysis reported a reproducible limit of detection at 100 WPRE copies per 20µL PCR reaction. This novel and inexpensive technique could provide better understanding of tissue abundance of engineered therapeutic T cells in both tumor and second-site toxicity tissues and provide quantitative assessment of immune effector cell trafficking in archival tissue.

Qualitative study on information, trust in and access to COVID-19 vaccines among adolescents at a healthcare center in Buenos Aires. / Estudio cualitativo sobre información, confianza y acceso a la vacunación contra COVID-19 en adolescentes en un centro de salud de Buenos Aires.

Introduction. During adolescence, individuals start to make autonomous decisions about their health. Vaccination involves contextual, group, and vaccine-specific dimensions. We sought to know the information, trust, and decision to receive the COVID-19 vaccine among adolescents who attended a healthcare center in Buenos Aires. Objectives. To identify settings and channels through which adolescents accessed information about the COVID-19 vaccine at a healthcare center in Buenos Aires. To describe their opinions about the different statements on vaccination. To describe their participation in COVID-19 vaccination. To identify barriers and facilitators to COVID-19 vaccination in this population. Population and methods. Qualitative study. Semi-structured interviews with adolescents who attended this healthcare facility. The sample was heterogeneous; the sample size was estimated by theoretical saturation. A thematic analysis of data was done. Results. A total of 14 interviews were conducted. Interviewees obtained information about the COVID-19 vaccine from their families, TV, and social media. All received information from both official campaigns and anti-vaccine communications. They analyzed the information they received and formed their own opinion. Their decision about the vaccine was not always respected. Hesitancy, a low perception of risk, fear of needles, administrative and geographic barriers were reasons for not receiving the vaccine. Conclusions. Communication strategies targeted at adolescents are required that encourage their involvement in access to vaccination.

Introducción. En la adolescencia, se comienzan a tomar decisiones autónomas sobre la salud. En la vacunación intervienen dimensiones contextuales, grupales y relativas a cada vacuna. Se busca conocer el proceso de información, confianza y decisión de vacunarse contra COVID-19 en adolescentes usuarios de un centro de salud en Buenos Aires. Objetivos. Identificar ámbitos y canales a través de los cuales los adolescentes accedieron a información sobre la vacuna contra COVID-19 en un centro de salud de Buenos Aires. Describir sus opiniones respecto a los distintos discursos sobre vacunación. Describir su participación en la vacunación contra COVID-19. Identificar barreras y facilitadores respecto del acceso a la vacunación contra COVID-19 en esta población. Población y métodos. Investigación cualitativa. Se hicieron entrevistas semiestructuradas a adolescentes usuarios del efector. La muestra fue heterogénea; su tamaño se definió por saturación teórica. Se realizó un análisis temático de los datos. Resultados. Se realizaron 14 entrevistas. Los entrevistados recibieron información sobre la vacuna contra COVID-19 de sus familias, la televisión y las redes sociales. Todos recibieron tanto publicidad oficial como discursos reticentes a la vacunación. Analizaron la información recibida y formaron opinión autónoma. Su decisión sobre vacunarse no siempre fue respetada. La desconfianza, la baja percepción del riesgo, el temor a las inyecciones, las barreras administrativas y geográficas fueron motivos de no vacunación. Conclusiones. Se requieren estrategias de comunicación destinadas a adolescentes que promuevan su participación en el acceso a la vacunación.

The Role of Stigma and Resilience in Healthcare Engagement Among Transgender Latinas in the U.S. South: Baseline Findings from the ChiCAS Study.

Research demonstrates that stigma and resilience influence transgender peoples' healthcare use. Less is known about transgender Latinas in the U.S. South who face multilevel barriers to healthcare access. We used baseline data from the ChiCAS intervention study. Using logistic regression, we examined how stigma (perceived discrimination related to gender identity, race/ethnicity, sexual behavior and perceived documentation status and internalized transphobia), and resilience (ethnic group pride and social support) are associated with two healthcare outcomes (use of routine medical care and medically supervised gender-affirming hormones). We also explored barriers to accessing both types of care. After removing 13 participants with missing data, our sample size was 131 transgender Latinas in the U.S. South. Most participants (74.8%, n = 98) received routine medical care in the past year and 57.3% (n = 75) had ever received medically supervised gender-affirming hormones. Reports of discrimination were highest for gender identity and documentation status. Race/ethnicity-based discrimination was positively associated with accessing routine medical care in the past year (OR = 1.94, p = 0.048). Having more social support was positively associated with care (routine care: OR = 3.48, p = 0.002 and gender-affirming hormones: OR = 2.33, p = 0.003). The most commonly reported barriers to accessing both types of care included cost, insurance, and not knowing where to go. Findings highlight the importance of social support for healthcare use among transgender Latinas. Social support may be especially important when considering the unique experiences of discrimination faced by transgender Latinas in the U.S. South.

Effectiveness and durability of mRNA-1273 BA.4/BA.5 bivalent vaccine (mRNA-1273.222) against SARS-CoV-2 BA.4/BA.5 and XBB sublineages.

Emerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received any COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases (September 1, 2022 to June 30, 2023), were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to ≥2 or 0 doses of original monovalent vaccine, respectively. The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14-60 days and 121-180 days was 52.7% (46.9-57.8%) and 35.5% (-2.8-59.5%) for infection, and 59.3% (49.7-67.0%) and 33.2% (-28.2-68.0%) for Emergency Department/Urgent Care (ED/UC) encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9-85.1%) and 52.0% (-1.2-77.3%) at 14-60 days and 61-120 days, respectively. rVE against XBB at 14-60 days and 121-180 days was 48.8% (33.4-60.7%) and -3.9% (-18.1-11.3%) for infection, 70.7% (52.4-82.0%) and 15.7% (-6.0-33.2%) for ED/UC encounters, and 87.9% (43.8-97.4%) and 57.1% (17.0-77.8%) for hospitalization. VE and subgroup analyses (age, immunocompromised status, previous SARS-CoV-2 infection) results were similar to rVE analyses. rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic revaccination with vaccines targeting emerging variants may be important in reducing COVID-19 morbidity and mortality.

Correlates of Impairment and Growth in Families of Young Autistic Children.

The purpose of this project was to investigate potential correlates of family life impairment in families of young autistic children. This project incorporated measures of specific child and parent challenges in addition to a commonly used unidimensional measure of autism characteristics. In this way, we could assess whether such challenges explain variance in family life impairment, and whether their inclusion diminish associations between autism characteristics and family life impairment. Cross-sectional data were collected from 564 parents of autistic children aged 2 to 5 years who participated in a larger online study. Participants completed measures on child characteristics (autism characteristics, emotion dysregulation, speaking ability, flexibility, and sleep problems), parent depression, and family life impairment, using the Family Life Impairment Scale (FLIS). Multiple linear regression models were generated to examine whether any of the independent variables were associated with the four domains of the FLIS. Models controlled for child age and sex, parent education, and single-parent homes. All independent variables were associated with impairment in one or more FLIS domains. None of the primary independent variables were significantly associated with positive growth. More overt characteristics and behaviors (e.g., autism characteristics, reactivity, speaking ability, and flexibility) were associated with impairment in domains that reflected a family's ability to navigate the community. However, sleep challenges and parent and child emotional difficulties were most strongly associated with parent impairment. Findings suggests that families may have different needs across contexts and provide new avenues through which they might be better supported.

An online qualitative study exploring wants and needs for a cooking programme during pregnancy in the UK and Ireland.

BACKGROUND: Optimal maternal nutrition is associated with better pregnancy and infant outcomes. Culinary nutrition programmes have potential to improve diet quality during pregnancy. Therefore, this research aimed to understand the experiences of cooking and the wants and needs of pregnant women regarding a cooking and food skills programme in the United Kingdom (UK) and Republic of Ireland (ROI). METHODS: Online focus group discussions with pregnant women and those who had experienced a pregnancy in the UK or ROI were conducted between February and April 2022. Two researchers conducted a thematic analysis. Seven focus groups with ROI participants (n = 24) and six with UK participants (n = 28) were completed. RESULTS: Five themes were generated. These were (1) cooking during pregnancy: barriers, motivators and solutions; (2) food safety, stress and guilt; (3) need for cooking and food skills programmes and desired content; (4) programme structure; (5) barriers and facilitators to programme participation. Overall, there was support for a programme focusing on broad food skills, including planning, food storage, using leftovers and to manage pregnancy-specific physiological symptoms such as food aversions. Participants emphasised the importance of inclusivity for a diverse range of people and lifestyles for programme design and content. CONCLUSIONS: Current findings support the use of digital technologies for culinary nutrition interventions, potentially combined with in-person sessions using a hybrid structure to enable the development of a support network.

Repeated Hyposalinity Pulses Immediately And Persistently Impair The Sea Urchin Adhesive System.

Climate change will increase the frequency and intensity of extreme climatic events (e.g., storms) that result in repeated pulses of hyposalinity in nearshore ecosystems. Sea urchins inhabit these ecosystems and are stenohaline (restricted to salinity levels ∼ 32 ‰), thus are particularly susceptible to hyposalinity events. As key benthic omnivores, sea urchins use hydrostatic adhesive tube feet for numerous functions, including attachment to and locomotion on the substratum as they graze for food. Hyposalinity severely impacts sea urchin locomotor and adhesive performance but several ecologically-relevant and climate change-related questions remain. First, does sea urchin locomotion and adhesion acclimate to repeated pulses of hyposalinity? Second, how do tube feet respond to tensile forces during single and repeated hyposalinity events? Third, do the negative effects of hyposalinity exposure persist following return to normal salinity levels? To answer these questions, we repeatedly exposed green sea urchins (Strongylocentrotus droebachiensis) to pulses of three different salinities (control: 32 ‰, moderate hyposalinity: 22 ‰, severe hyposalinity: 16 ‰) over the course of two months and measured locomotor performance, adhesive performance, and tube foot tensile behavior. We also measured these parameters 20 hours after sea urchins returned to normal salinity levels. We found no evidence that tube feet performance and properties acclimate to repeated pulses of hyposalinity, at least over the timescale examined in this study. In contrast, hyposalinity has severe consequences on locomotion, adhesion, and tube foot tensile behavior and these impacts are not limited to the hyposalinity exposure. Our results suggest both moderate and severe hyposalinity events have the potential to increase sea urchin dislodgment and reduce movement, which may impact sea urchin distribution and their role in marine communities.

Use of CompEx in eosinophilic patients with severe, uncontrolled asthma on benralizumab.

Background: CompEx Asthma, a composite end-point for asthma exacerbations, captures clinically relevant, diary-based acute worsening events (AWEs) (defined as deterioration in daily peak expiratory flow concurrent with deterioration in asthma symptoms and/or rescue therapy use) and severe exacerbations (SevEx) (defined by American Thoracic Society/European Respiratory Society guidelines). We hypothesised that CompEx and SevEx would show similar benralizumab treatment effects and correlations to blood eosinophil counts in patients with severe asthma. Methods: This post hoc analysis of pooled 12-month data from two phase 3 studies included patients aged ≥16 years with severe, uncontrolled asthma who were randomised to benralizumab 30 mg or placebo. Annualised event rates were analysed using a negative binomial model. The impact of blood eosinophil count on treatment effect was assessed. Results: Among patients with a blood eosinophil count ≥300 cells·µL-1 (n=913), benralizumab reduced the annualised event rate versus placebo for CompEx (1.57 versus 2.57; risk ratio 0.61, 95% CI 0.53-0.70, p<0.001), SevEx (0.94 versus 1.55; risk ratio 0.60, 95% CI 0.52-0.70, p<0.001) and AWE (0.92 versus 1.57; risk ratio 0.59, 95% CI 0.48-0.72, p<0.001), with greater treatment effects observed for higher blood eosinophil counts. In patients with blood eosinophil count ≥300 cells·µL-1, benralizumab was associated with shorter median event duration (CompEx: 10.5 days versus 17.0 days; SevEx: 10.0 days versus 15.0 days; AWE: 5.0 days versus 6.0 days). Conclusions: Benralizumab reduced the risk of CompEx events with treatment effects similar to those for SevEx and AWEs across a range of blood eosinophil counts. Use of CompEx supports the evaluation of benralizumab and other novel drugs in clinical studies.

Are autistic females at greater risk of suicide? A call for clarity to advance suicide prevention for the whole community.

Understanding suicide risk is critical for supporting prevention. A growing body of evidence shows autistic people are at greater risk for multiple suicide-related outcomes than non-autistic people. This commentary is in response to an observed pattern of miscommunication in scientific and community spaces about autistic females having higher risk of suicide. However, it is not always clear who they are being compared with in these statements. To address this confusion, we summarize the current population-based evidence on autistic suicide risk, highlighting findings related to sex similarities and differences, which actually indicates comparable rates of suicide death among autistic males and females, and mixed findings related to sex differences in risk of other suicidal behaviors. We call for greater clarity in suicide risk communication moving forward focused on outcomes, measurement, sampling methods, and comparison groups to reflect accurate conclusions about existing evidence. Further research is needed about the full range of suicide-related outcomes for autistic people, including a greater understanding of sex differences as well as potential gender differences to include transgender and nonbinary autistic people. However, studies of sex and gender differences should not overshadow the compelling need for efforts to understand and address the elevated risk of suicidal thoughts, behaviors, and death among autistic people across sex and gender boundaries.

Beyond change scores: Employing an improved statistical approach to analyze the impact of entry fitness on physical performance during British Army basic training in men and women.

The aim was to use a robust statistical approach to examine whether physical fitness at entry influences performance changes between men and women undertaking British Army basic training (BT). Performance of 2 km run, seated medicine ball throw (MBT) and isometric mid-thigh pull (MTP) were assessed at entry and completion of Standard Entry (SE), Junior Entry-Short (JE-Short), and Junior Entry-Long (JE-Long) training for 2350 (272 women) recruits. Performance change was analyzed with entry performance as a covariate (ANCOVA), with an additional interaction term allowing different slopes for courses and genders (p < 0.05). Overall, BT courses saw average improvements in 2 km run performance (SE: -6.8% [-0.62 min], JE-Short: -4.6% [-0.43 min], JE-Long: -7.7% [-0.70 min]; all p < 0.001) and MBT (1.0-8.8% [0.04-0.34 m]; all p < 0.05) and MTP (4.5-26.9% [6.5-28.8 kg]; all p < 0.001). Regression models indicate an expected form of "regression to the mean" whereby test performance change was negatively associated with entry fitness in each course (those with low baseline fitness exhibit larger training improvements; all interaction effects: p < 0.001, η p 2 $$ {\eta}_{\mathrm{p}}^2 $$ > 0.006), particularly for women. However, when matched for entry fitness, men displayed considerable improvements in all tests, relative to women. Training courses were effective in developing recruit physical fitness, whereby the level of improvement is, in large part, dependent on entry fitness. Factors including age, physical maturity, course length, and physical training, could also contribute to the variability in training response between genders and should be considered when analyzing and/or developing physical fitness in these cohorts for future success of military job-task performance.

Characterization of per- and polyfluoroalkyl substances (PFAS) concentrations in a community-based sample of infants from Samoa.

Per- and polyfluoroalkyl substances (PFAS) are persistent contaminants with documented harmful health effects. Despite increasing research, little attention has been given to studying PFAS contamination in low- and middle-income countries, including Samoa. Using data and biosamples collected through the Foafoaga o le Ola ("Beginning of Life") Study, which recruited a sample of mothers and infants from Samoa, we conducted an exploratory study to describe concentrations of 40 PFAS analytes in infant cord blood collected at birth (n = 66) and infant dried blood spots (DBS) collected at 4 months post-birth (n = 50). Of the 40 PFAS analytes tested, 19 were detected in cord blood, with 10 detected in >50% of samples (PFBA, PFPeA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFHxS, PFOS, and 9Cl-PF3ONS); and 12 analytes were detected in DBS, with 3 detected in >50% of samples (PFBA, PFHxS, and PFOS). PFAS concentrations were generally lower than those reported in existing literature, with the exception of PFHxS, which was detected at higher concentrations. In cord blood, we noted suggestive (p < 0.05) or significant (p < 0.006) associations between higher PFHxS and male sex; higher PFPeA and residence in Northwest 'Upolu (NWU) compared to the Apia Urban Area (AUA); lower PFUnA and 9Cl-PF3ONS and greater socioeconomic resources; lower PFOA and higher parity; higher PFDA and higher maternal age; and lower PFUnA, PFTrDA, and 9Cl-PF3ONS and higher maternal BMI. In DBS, we found suggestive (p < 0.05) or significant (p < 0.025) associations between lower PFBA and residence in NWU versus AUA; lower PFBA and PFHxS and higher maternal age; and higher PFBA and higher maternal BMI. Finally, we observed associations between nutrition source at 4 months and DBS PFBA and PFHxS, with formula- or mixed-fed infants having higher concentrations compared to exclusively breastfed infants. This study represents the first characterization of PFAS contamination in Samoa. Additional work in larger samples is needed to identify potentially modifiable determinants of PFAS concentrations, information that is critical for informing environmental and health policy measures.

Irritability in Youths: A Critical Integrative Review.

Irritability, defined as proneness to anger that may impair an individual's functioning, is common in youths. There has been a recent upsurge in relevant research. The authors combine systematic and narrative review approaches to integrate the latest clinical and translational findings and provide suggestions for addressing research gaps. Clinicians and researchers should assess irritability routinely, and specific assessment tools are now available. Informant effects are prominent, are stable, and vary by age and gender. The prevalence of irritability is particularly high among individuals with attention deficit hyperactivity disorder, autism spectrum disorder, and mood and anxiety disorders. Irritability is associated with impairment and suicidality risk independent of co-occurring diagnoses. Developmental trajectories of irritability (which may begin early in life) have been identified and are differentially associated with clinical outcomes. Youth irritability is associated with increased risk of anxiety, depression, behavioral problems, and suicidality later in life. Irritability is moderately heritable, and genetic associations differ based on age and comorbid illnesses. Parent management training is effective for treating psychological problems related to irritability, but its efficacy in treating irritability should be tested rigorously, as should novel mechanism-informed interventions (e.g., those targeting exposure to frustration). Associations between irritability and suicidality and the impact of cultural context are important, underresearched topics. Analyses of large, diverse longitudinal samples that extend into adulthood are needed. Data from both animal and human research indicate that aberrant responses to frustration and threat are central to the pathophysiology of irritability, revealing important translational opportunities.