Considerations for developing and implementing a safe list for alien taxa.

Many species have been intentionally introduced to new regions for their benefits. Some of these alien species cause damage, others do not (or at least have not yet). There are several approaches to address this problem: prohibit taxa that will cause damage, try to limit damages while preserving benefits, or promote taxa that are safe. In the present article, we unpack the safe list approach, which we define as "a list of taxa alien to the region of interest that are considered of sufficiently low risk of invasion and impact that the taxa can be widely used without concerns of negative impacts." We discuss the potential use of safe lists in the management of biological invasions; disentangle aspects related to the purpose, development, implementation, and impact of safe lists; and provide guidance for those considering to develop and implement such lists.

Food and Nutrition Insecurity: Experiences That Differ for Some and Independently Predict Diet-Related Disease, Los Angeles County, 2022.

BACKGROUND: National surveillance shows that food insecurity affects ∼1 in 10 Americans each year. Recently, experts have advocated for surveillance of nutrition insecurity alongside food insecurity. Nutrition security refers to the nutritional adequacy of accessible food and factors that impact one's ability to meet food preferences. OBJECTIVES: This study presents representative estimates of food insecurity and nutrition insecurity for Los Angeles County, CA, United States; compares predictors of these constructs; and examines whether they independently predict diet-related health outcomes. METHODS: In December 2022, a representative sample of Los Angeles County adults participating in the Understanding America Study (N = 1071) was surveyed about household food insecurity and nutrition insecurity over the past 12 months. Data were analyzed in 2023. RESULTS: Reported rates were similar for food insecurity (24%) and nutrition insecurity (25%), but the overlap of these subgroups was less than 60%. Logistic regression models indicated that non-Hispanic Asian individuals had higher odds of nutrition insecurity but not food insecurity. Moreover, nutrition insecurity was a stronger predictor of diabetes compared with food insecurity, and both constructs independently predicted poor mental health. CONCLUSIONS: Food and nutrition insecurity affect somewhat different populations. Both constructs are valuable predictors of diet-related health outcomes. Monitoring nutrition insecurity in addition to food insecurity can provide new information about populations with barriers to healthy diets.

Integrated Advanced Molecular Tools Predict In Situ cVOC Degradation Rates: Field Demonstration.

Chlorinated volatile organic compound (cVOC) degradation rate constants are crucial information for site management. Conventional approaches generate rate estimates from the monitoring and modeling of cVOC concentrations. This requires time series data collected along the flow path of the plume. The estimates of rate constants are often plagued by confounding issues, making predictions cumbersome and unreliable. Laboratory data suggest that targeted quantitative analysis of Dehalococcoides mccartyi (Dhc) biomarker genes (qPCR) and proteins (qProt) can be directly correlated with reductive dechlorination activity. To assess the potential of qPCR and qProt measurements to predict rates, we collected data from cVOC-contaminated aquifers. At the benchmark study site, the rate constant for degradation of cis-dichloroethene (cDCE) extracted from monitoring data was 11.0 ± 3.4 yr-1, and the rate constant predicted from the abundance of TceA peptides was 6.9 yr-1. The rate constant for degradation of vinyl chloride (VC) from monitoring data was 8.4 ± 5.7 yr-1, and the rate constant predicted from the abundance of TceA peptides was 5.2 yr-1. At the other study sites, the rate constants for cDCE degradation predicted from qPCR and qProt measurements agreed within a factor of 4. Under the right circumstances, qPCR and qProt measurements can be useful to rapidly predict rates of cDCE and VC biodegradation, providing a major advance in effective site management.

Smartphone GPS-Based Exposure to Greenspace and Walkability and Accelerometer-Assessed Physical Activity During Pregnancy and Early Postpartum-Evidence from the MADRES Cohort.

A growing number of studies have associated walkability and greenspace exposure with greater physical activity (PA) in women during pregnancy. However, most studies have focused on examining women's residential environments and neglected exposure in locations outside the home neighborhood. Using 350 person-days (N = 55 participants) of smartphone global positioning system (GPS) location and accelerometer data collected during the first and third trimesters and 4-6 months postpartum from 55 Hispanic pregnant women from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, we examined the day-level effect of women's exposure to walkability and greenspace on their PA outcomes during pregnancy and in the early postpartum period. Moderate-to-vigorous physical activity [MVPA] minutes per day was assessed using accelerometers. Walkability and greenspace were measured using geographic information systems (GIS) within women's daily activity spaces (i.e., places visited and routes taken) recorded using a smartphone GPS and weighted by time spent. We used a generalized linear mixed-effects model to estimate the effects of daily GPS-derived environmental exposures on day-level MVPA minutes. Results showed that women engaged in 23% more MVPA minutes on days when they had some versus no exposure to parks and open spaces in activity spaces (b = 1.23; 95%CI: 1.02-1.48). In addition, protective effects of daily greenspace and walkability exposure on MVPA were stronger in the first and third trimesters, among first-time mothers, and among women who had high pre-pregnancy body mass index (BMI) and lived in least-safe neighborhoods. Our results suggest that daily greenspace and walkability exposure are important for women's PA and associated health outcomes during pregnancy and early postpartum.

Socio-ecological factors linked with changes in adults' dietary intake in Los Angeles County during the peak of the coronavirus 2019 pandemic.

OBJECTIVE: Comprehensive studies examining longitudinal predictors of dietary change during the coronavirus disease 2019 pandemic are lacking. Based on an ecological framework, this study used longitudinal data to test if individual, social and environmental factors predicted change in dietary intake during the peak of the coronavirus 2019 pandemic in Los Angeles County and examined interactions among the multilevel predictors. DESIGN: We analysed two survey waves (e.g. baseline and follow-up) of the Understanding America Study, administered online to the same participants 3 months apart. The surveys assessed dietary intake and individual, social, and neighbourhood factors potentially associated with diet. Lagged multilevel regression models were used to predict change from baseline to follow-up in daily servings of fruits, vegetables and sugar-sweetened beverages. SETTING: Data were collected in October 2020 and January 2021, during the peak of the coronavirus disease 2019 pandemic in Los Angeles County. PARTICIPANTS: 903 adults representative of Los Angeles County households. RESULTS: Individuals who had depression and less education or who identified as non-Hispanic Black or Hispanic reported unhealthy dietary changes over the study period. Individuals with smaller social networks, especially low-income individuals with smaller networks, also reported unhealthy dietary changes. After accounting for individual and social factors, neighbourhood factors were generally not associated with dietary change. CONCLUSIONS: Given poor diets are a leading cause of death in the USA, addressing ecological risk factors that put some segments of the community at risk for unhealthy dietary changes during a crisis should be a priority for health interventions and policy.

Psychosocial impacts of being nil-by-mouth as an adult: A scoping review.

AIM: To map existing evidence and identify gaps in the literature concerning psychosocial impacts of being nil by mouth (NBM) as an adult. DESIGN: A scoping review of the literature was undertaken using JBI guidance. A protocol was registered on the Open Science Framework (osf.io/43g9y). Reporting was guided by Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR). METHODS: A comprehensive search of six databases (CINAHL, Embase, MEDLINE, PsycINFO, SCOPUS and Web of Science) was performed for studies published up to February 2023, with no restriction to study type. A scope of the grey literature was also undertaken. Two authors independently assessed eligibility and extracted data. Descriptive statistical analysis and narrative synthesis were used, and patient and public involvement included in funding discussions. RESULTS: A total of 23 papers were included in the review, consisting of 14 primary studies (7 qualitative and 7 quantitative) and 9 grey literature. Both global psychological distress and distress specific to being NBM (thirst, missing food and drink) were reported. Caregivers also experience distress from their family member being NBM. Furthermore, social impacts were reported for both patient and caregiver, primarily social isolation and subsequent low mood. CONCLUSION: Furthermore, research is needed to understand the prevalence of this population, how best to measure psychosocial impacts and to explore whether (and how) psychosocial impacts change over time. Advancement in this area would enable better service development to optimize care for this patient group. WHAT IS KNOWN ABOUT THIS TOPIC?: Eating and drinking provides more than nutrition and hydration. A wide range of conditions can lead to recommendations for no longer eating and drinking (nil by mouth). Being nil by mouth (NBM) for short periods such as pre-operative fasting causes distress; however, little is understood about impact on longer-term abstinence from eating and drinking. WHAT THIS PAPER ADDS?: Psychosocial consequences of being nil by mouth (NBM)have been investigated by both quantitative and qualitative studies. Being NBM impacts both patients and caregivers in various psychosocial aspects, including distress and social isolation. Several gaps remain, however, regarding ways to measure psychosocial impact of being NBM.

Protocol to assess bioenergetics and mitochondrial fuel usage in murine autoreactive immunocytes using the Seahorse Extracellular Flux Analyzer.

Efficient metabolism, or the means by which cells produce energy resources, is critical for proper effector function. Here, we present a protocol for examining the bioenergetics and mitochondrial fuel utilization of primary murine autoreactive immunocytes using cellular metabolism-modulating drugs. We describe steps for plate calibration, isolation of primary immunocytes, and Seahorse assay plate preparation. We then detail procedures for performing the XF Cell Mito Stress Test followed by bioenergetics calculations and statistics. For complete details on the use and execution of this protocol, please refer to Wilson et al.1.

A mindful body approach to creating architecture: movement, models and spatial experiences.

If architecture is an expression of human creativity through multi-sensory embodiment, then learning, creating and experiencing architecture should also be multi-sensory and embodied. In this article, we challenge the separation of mind and body through Sheets-Johnstone's mindful bodies concept. We define a mindful body in architecture as one that documents, analyses and memory maps the moving body in different qualities of movement to create diverse spatial experiences. A mindful body approach to creating architecture involves: (i) engaging in meaningful movement and documenting the body, (ii) documenting embodied interactions with dynamic, animate elements in the built environment, (iii) connecting our body's movements with emotions and memories, (iv) designing spaces that produce diverse movements and atmospheres, and (v) designing architecture based on these spaces. We hypothesize that if designers engage in a mindful body approach to design, they can create spatial experiences that help us make sense of ourselves, others and the world. A mindful body approach to design can result in architectural spaces that activate our attentional switches, connect haptic experiences and memories and reveal wonders. This article is part of the theme issue 'Minds in movement: embodied cognition in the age of artificial intelligence'.

Image-Guided Navigation in Spine Surgery: From Historical Developments to Future Perspectives.

Intraoperative navigation is critical during spine surgery to ensure accurate instrumentation placement. From the early era of fluoroscopy to the current advancement in robotics, spinal navigation has continued to evolve. By understanding the variations in system protocols and their respective usage in the operating room, the surgeon can use and maximize the potential of various image guidance options more effectively. At the same time, maintaining navigation accuracy throughout the procedure is of the utmost importance, which can be confirmed intraoperatively by using an internal fiducial marker, as demonstrated herein. This technology can reduce the need for revision surgeries, minimize postoperative complications, and enhance the overall efficiency of operating rooms.

Tongue-tie in the Neonatal Intensive Care Unit Compared to Healthy Newborns.

OBJECTIVE: We sought to characterize the prevalence of ankyloglossia in our neonatal intensive care unit (NICU) population and to determine characteristics of this cohort compared to infants in the birth center (BC). METHODS: Prospective data were collected using a standardized flow sheet. Breastfeeding infants undergoing evaluation for tongue-tie in the BC and NICU were included. Coryllos type, tip to frenulum length, tongue function, frequency of frenotomy, and breastfeeding outcomes were compared. RESULTS: Of 20,879 infants birthed at or admitted to the institution during the study period, there were fewer patients diagnosed with ankyloglossia in the BC compared to the NICU (3.3% BC vs. 5.4% NICU, p < 0.01). Of these, 163 underwent frenotomy: 86 in the BC and 77 in the NICU. For those undergoing frenotomy, gestational age (39.1 ± 1.3 BC, 34.4 ± 4.4 NICU, p < 0.01) and age at time of procedure (3.2 days BC, 29.2 NICU, p < 0.01) were the only demographic factors significantly different between the groups. There was no difference in Coryllos type or function score. In a subset of NICU infants with multiple assessments over time, function scores after frenotomy were significantly improved compared to pre-frenotomy (p < 0.01). CONCLUSION: Standard assessment tools appear to be appropriate for use in infants in the NICU, despite the higher rates of prematurity, low birth weights, and increased comorbidities. Assessment and intervention for tongue-tie can be one critical intervention to move these patients closer to oral feeding and discharge to home. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

STING-Pathway Inhibiting Nanoparticles (SPINs) as a Platform for Treatment of Inflammatory Diseases.

Aberrant activation of the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) pathway has been implicated in the development and progression of a myriad of inflammatory diseases including colitis, nonalcoholic steatohepatitis, amyotrophic lateral sclerosis (ALS), and age-related macular degeneration. Thus, STING pathway inhibitors could have therapeutic application in many of these inflammatory conditions. The cGAS inhibitor RU.521 and the STING inhibitor H-151 have shown promise as therapeutics in mouse models of colitis, ALS, and more. However, these agents require frequent high-dose intraperitoneal injections, which may limit translatability. Furthermore, long-term use of systemically administered cGAS/STING inhibitors may leave patients vulnerable to viral infections and cancer. Thus, localized or targeted inhibition of the cGAS/STING pathway may be an attractive, broadly applicable treatment for a variety of STING pathway-driven ailments. Here we describe STING-Pathway Inhibiting Nanoparticles (SPINS)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with RU.521 and H-151-as a platform for enhanced and sustained inhibition of cGAS/STING signaling. We demonstrate that SPINs are equally or more effective at inhibiting type-I interferon responses induced by cytosolic DNA than free H-151 or RU.521. Additionally, we describe a SPIN formulation in which PLGA is coemulsified with poly(benzoyloxypropyl methacrylamide) (P(HPMA-Bz)), which significantly improves drug loading and allows for tunable release of H-151 over a period of days to over a week by varying P(HPMA-Bz) content. Finally, we find that all SPIN formulations were as potent or more potent in inhibiting cGAS/STING signaling in primary murine macrophages, resulting in decreased expression of inflammatory M1-like macrophage markers. Therefore, our study provides an in vitro proof-of-concept for nanoparticle delivery of STING pathway inhibitors and positions SPINs as a potential platform for slowing or reversing the onset or progression of cGAS/STING-driven inflammatory conditions.

64Cu production via the 68Zn(p,nα)64Cu nuclear reaction: An untapped, cost-effective and high energy production route.

INTRODUCTION: Copper-64 (64Cu, t1/2 = 12.7 h) is a positron emitter well suited for theranostic applications with beta-emitting 67Cu for targeted molecular imaging and radionuclide therapy. The present work aims to evaluate the radionuclidic purity and radiochemistry of 64Cu produced via the 68Zn(p,nα)64Cu nuclear reaction. Macrocyclic chelators DOTA, NOTA, TETA, and prostate-specific membrane antigen ligand PSMA I&T were radiolabeled with purified 64Cu and tested for in vitro stability. [64Cu]Cu-PSMA I&T was used to demonstrate in vivo PET imaging using 64Cu synthesized via the 68Zn(p,nα)64Cu production route and its suitability as a theranostic imaging partner alongside 67Cu therapy. METHODS: 64Cu was produced on a 24 MeV TR-24 cyclotron at a beam energy of 23.5 MeV and currents up to 70 µA using 200 mg 68Zn encapsulated within an aluminum­indium-graphite sealed solid target assembly. 64Cu semi-automated purification was performed using a NEPTIS Mosaic-LC synthesis unit employing CU, TBP, and TK201 (TrisKem) resins. Radionuclidic purity was measured by HPGe gamma spectroscopy, while ICP-OES assessed elemental purity. Radiolabeling was performed with NOTA at room temperature and DOTA, TETA, and PSMA I&T at 95 °C. 64Cu incorporation was studied by radio-TLC. 64Cu in vitro stability of [64Cu]Cu-NOTA, [64Cu]Cu-DOTA, [64Cu]Cu-TETA, and [64Cu]Cu-PSMA I&T was assessed at 37 °C from 0 to 72 h in human blood serum. Preclinical PET imaging was performed at 1, 24, and 48 h post-injection with [64Cu]Cu-PSMA I&T in LNCaP tumor-bearing mice and compared with [68Ga]Ga-PSMA I&T. RESULTS: Maximum purified activity of 4.9 GBq [64Cu]CuCl2 was obtained in 5 mL of pH 2-3 solution, with 2.9 GBq 64Cu concentrated in 0.5 mL. HPGe gamma spectroscopy of purified 64Cu detected <0.3 % co-produced 67Cu at EOB with no other radionuclidic impurities. ICP-OES elemental analysis determined <1 ppm Al, Zn, In, Fe, and Cu in the [64Cu]CuCl2 product. NOTA, DOTA, TETA, and PSMA I&T were radiolabeled with 64Cu, resulting in maximum molar activities of 164 ± 6 GBq/µmol, 155 ± 31 GBq/µmol, 266 ± 34 GBq/µmol, and 117 ± 2 GBq/µmol, respectively. PET imaging in PSMA-expressing LNCaP xenografts resulted in high tumor uptake (SUVmean = 1.65 ± 0.1) using [64Cu]Cu-PSMA I&T, while [68Ga]Ga-PSMA I&T yielded an SUVmean of 0.76 ± 0.14 after 60 min post-injection. CONCLUSIONS: 64Cu was purified in a small volume amenable for radiolabeling, with yields suitable for preclinical and clinical application. The 64Cu production and purification process and the favourable PET imaging properties confirm the 68Zn(p,nα)64Cu nuclear reaction as a viable 64Cu production route for facilities with access to a higher energy proton cyclotron, compared to using expensive 64Ni target material and the 64Ni(p,n)64Cu nuclear reaction. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: Our 64Cu production technique provides an alternative production route with the potential to improve 64Cu availability for preclinical and clinical studies alongside 67Cu therapy.

Safety and timing of early therapeutic anticoagulation therapy after craniotomy.

Background: To date, there are few guidelines and studies to guide the timing of initiation of therapeutic anticoagulation (AC) after craniotomy. The goal of this study was to assess the timing, safety, and outcomes of patients following the administration of therapeutic AC after craniotomy. Methods: A retrospective case-control study was performed evaluating all craniotomy patients from August 2017 to July 2021. Cases were selected if they received therapeutic AC within ten days of craniotomy. Nineteen out of 1013 craniotomy patients met the inclusion criteria. Indications for therapeutic AC were diverse, including deep venous thrombosis, pulmonary embolism, dural venous sinus thrombosis, mechanical heart valve, and left ventricular thrombus. Results: The mean and median time to therapeutic AC were 5.35 and 5 days, respectively. Three patients developed intracerebral hemorrhage (ICH) that was stable on repeat imaging and did not require any surgical intervention or result in new neurologic deficits. There was no significant association between therapeutic AC and postoperative ICH (P = 0.067). Conclusion: This study demonstrated that the initiation of therapeutic AC in postoperative craniotomy patients from postoperative days 2 to 10 did not result in any major complications. A prospective study is warranted to clarify the indications and safety of therapeutic AC after craniotomy.

Global latitudinal gradients and the evolution of body size in dinosaurs and mammals.

Global climate patterns fundamentally shape the distribution of species and ecosystems. For example, Bergmann's rule predicts that homeothermic animals, including birds and mammals, inhabiting cooler climates are generally larger than close relatives from warmer climates. The modern world, however, lacks the comparative data needed to evaluate such macroecological rules rigorously. Here, we test for Bergmann's rule in Mesozoic dinosaurs and mammaliaforms that radiated within relatively temperate global climate regimes. We develop a phylogenetic model that accounts for biases in the fossil record and allows for variable evolutionary dispersal rates. Our analysis also includes new fossil data from the extreme high-latitude Late Cretaceous Arctic Prince Creek Formation. We find no evidence for Bergmann's rule in Mesozoic dinosaurs or mammaliaforms, the ancestors of extant homeothermic birds and mammals. When our model is applied to thousands of extant dinosaur (bird) and mammal species, we find that body size evolution remains independent of latitude. A modest temperature effect is found in extant, but not in Mesozoic, birds, suggesting that body size evolution in modern birds was influenced by Bergmann's rule during Cenozoic climatic change. Our study provides a general approach for studying macroecological rules, highlighting the fossil record's power to address longstanding ecological principles.

STING-Activating Polymer-Drug Conjugates for Cancer Immunotherapy.

The stimulator of interferon genes (STING) pathway links innate and adaptive antitumor immunity and therefore plays an important role in cancer immune surveillance. This has prompted widespread development of STING agonists for cancer immunotherapy, but pharmacological barriers continue to limit the clinical impact of STING agonists and motivate the development of drug delivery systems to improve their efficacy and/or safety. To address this challenge, we developed SAPCon, a STING-activating polymer-drug conjugate platform based on strain-promoted azide-alkyne cycloaddition of dimeric-amidobenzimidazole (diABZI) STING agonists to hydrophilic polymer chains through an enzyme-responsive chemical linker. To synthesize a first-generation SAPCon, we designed a diABZI prodrug modified with a DBCO reactive handle a cathepsin B-cleavable spacer for intracellular drug release and conjugated this to pendant azide groups on a 100 kDa poly(dimethyla acrylamide-co-azide methacrylate) copolymer backbone to increase circulation time and enable passive tumor accumulation. We found that intravenously administered SAPCon accumulated at tumor sites where they it was endocytosed by tumor-associated myeloid cells, resulting in increased STING activation in tumor tissue compared to a free diABZI STING agonist. Consequently, SAPCon promoted an immunogenic tumor microenvironment, characterized by increased frequency of activated macrophages and dendritic cells and improved infiltration of CD8+ T cells, resulting in inhibition of tumor growth, prolonged survival, and increased response to anti-PD-1 immune checkpoint blockade in orthotopic models of breast cancer. Collectively, these studies position SAPCon as a modular and programmable platform for improving the efficacy of systemically administered STING agonists for cancer immunotherapy.

Momentum-exchange interactions in a Bragg atom interferometer suppress Doppler dephasing.

Large ensembles of laser-cooled atoms interacting through infinite-range photon-mediated interactions are powerful platforms for quantum simulation and sensing. Here we realize momentum-exchange interactions in which pairs of atoms exchange their momentum states by collective emission and absorption of photons from a common cavity mode, a process equivalent to a spin-exchange or XX collective Heisenberg interaction. The momentum-exchange interaction leads to an observed all-to-all Ising-like interaction in a matter-wave interferometer. A many-body energy gap also emerges, effectively binding interferometer matter-wave packets together to suppress Doppler dephasing in analogy to Mössbauer spectroscopy. The tunable momentum-exchange interaction expands the capabilities of quantum interaction-enhanced matter-wave interferometry and may enable the realization of exotic behaviors, including simulations of superconductors and dynamical gauge fields.

IL3-Driven T Cell-Basophil Crosstalk Enhances Antitumor Immunity.

Cytotoxic T lymphocytes (CTL) are pivotal in combating cancer, yet their efficacy is often hindered by the immunosuppressive tumor microenvironment, resulting in CTL exhaustion. This study investigates the role of interleukin-3 (IL3) in orchestrating antitumor immunity through CTL modulation. We found that intratumoral CTLs exhibited a progressive decline in IL3 production, which was correlated with impaired cytotoxic function. Augmenting IL3 supplementation, through intraperitoneal administration of recombinant IL3, IL3-expressing tumor cells, or IL3-engineered CD8+ T cells, conferred protection against tumor progression, concomitant with increased CTL activity. CTLs were critical for this therapeutic efficacy as IL3 demonstrated no impact on tumor growth in Rag1 knockout mice or following CD8+ T-cell depletion. Rather than acting directly, CTL-derived IL3 exerted its influence on basophils, concomitantly amplifying antitumor immunity within CTLs. Introducing IL3-activated basophils retarded tumor progression, whereas basophil depletion diminished the effectiveness of IL3 supplementation. Furthermore, IL3 prompted basophils to produce IL4, which subsequently elevated CTL IFNγ production and viability. Further, the importance of basophil-derived IL4 was evident from the absence of benefits of IL3 supplementation in IL4 knockout tumor-bearing mice. Overall, this research has unveiled a role for IL3-mediated CTL-basophil cross-talk in regulating antitumor immunity and suggests harnessing IL3 sustenance as a promising approach for optimizing and enhancing cancer immunotherapy. See related Spotlight, p. 798.

Resting Frontal Gamma Power is Associated with Both Expressive Language and Non-verbal Cognitive Abilities in Young Autistic Children.

Previous research links resting frontal gamma power to key developmental outcomes in young neurotypical (NT) children and infants at risk for language impairment. However, it remains unclear whether gamma power is specifically associated with language or with more general cognitive abilities among young children diagnosed with autism spectrum disorder (ASD). The current study evaluates differences in resting frontal gamma power between young autistic and NT children and tests whether gamma power is uniquely associated with individual differences in expressive language, receptive language and non-verbal cognitive abilities in autistic and NT children. Participants included 48 autistic children and 58 age- and sex-matched NT children (ages 22-60 months). Baseline electroencephalography (EEG) recordings were acquired from each participant. Children also completed the Mullen Scales of Early Learning (MSEL). We found that frontal gamma power at rest did not differ between autistic and NT children. Among autistic children, reduced frontal gamma power was significantly associated with both higher expressive language skills and higher non-verbal cognitive skills, controlling for age and sex. The interaction between frontal gamma power and diagnostic status no longer explained unique variance in expressive language skills after controlling for variance associated with non-verbal cognitive skills across autistic and NT children. Together, these findings suggest that reduced gamma power is associated with both better expressive language and non-verbal cognitive skills among young autistic children. Moreover, associations between high frequency neural activity and cognition are not specific to verbal abilities but reflect neural mechanisms associated with general higher-order cognitive abilities in ASD.

New insights into grocery store visits among east Los Angeles residents using mobility data.

In this study, we employed spatially aggregated population mobility data, generated from mobile phone locations in 2021, to investigate patterns of grocery store visits among residents east and northeast of Downtown Los Angeles, in which 60% of the census tracts had previously been designated as "food deserts". Further, we examined whether the store visits varied with neighborhood sociodemographics and grocery store accessibility. We found that residents averaged 0.4 trips to grocery stores per week, with only 13% of these visits within home census tracts, and 40% within home and neighboring census tracts. The mean distance from home to grocery stores was 2.2 miles. We found that people visited grocery stores more frequently when they lived in neighborhoods with higher percentages of Hispanics/Latinos, renters and foreign-born residents, and a greater number of grocery stores. This research highlights the utility of mobility data in elucidating grocery store use, and factors that may facilitate or be a barrier to store access. The results point to limitations of using geographically constrained metrics of food access like food deserts.

A Cancer Nanovaccine for Co-Delivery of Peptide Neoantigens and Optimized Combinations of STING and TLR4 Agonists.

Immune checkpoint blockade (ICB) has revolutionized cancer treatment and led to complete and durable responses, but only for a minority of patients. Resistance to ICB can largely be attributed to insufficient number and/or function of antitumor CD8+ T cells in the tumor microenvironment. Neoantigen targeted cancer vaccines can activate and expand the antitumor T cell repertoire, but historically, clinical responses have been poor because immunity against peptide antigens is typically weak, resulting in insufficient activation of CD8+ cytotoxic T cells. Herein, we describe a nanoparticle vaccine platform that can overcome these barriers in several ways. First, the vaccine can be reproducibly formulated using a scalable confined impingement jet mixing method to coload a variety of physicochemically diverse peptide antigens and multiple vaccine adjuvants into pH-responsive, vesicular nanoparticles that are monodisperse and less than 100 nm in diameter. Using this approach, we encapsulated synergistically acting adjuvants, cGAMP and monophosphoryl lipid A (MPLA), into the nanocarrier to induce a robust and tailored innate immune response that increased peptide antigen immunogenicity. We found that incorporating both adjuvants into the nanovaccine synergistically enhanced expression of dendritic cell costimulatory markers, pro-inflammatory cytokine secretion, and peptide antigen cross-presentation. Additionally, the nanoparticle delivery increased lymph node accumulation and uptake of peptide antigen by dendritic cells in the draining lymph node. Consequently, nanoparticle codelivery of peptide antigen, cGAMP, and MPLA enhanced the antigen-specific CD8+ T cell response and delayed tumor growth in several mouse models. Finally, the nanoparticle platform improved the efficacy of ICB immunotherapy in a murine colon carcinoma model. This work establishes a versatile nanoparticle vaccine platform for codelivery of peptide neoantigens and synergistic adjuvants to enhance responses to cancer vaccines.