Quality of Life in People with HIV at the End of Life: Preliminary Results from the Last Gift Observational Cohort Study.

BACKGROUND: As people living with HIV (PWH) age, they face new challenges that can have a negative impact on their quality of life (QOL) and mental health. SETTING: This study enrolled PWH at the end of life (EOL) who were actively engaged in cure-related research in Southern California, United States. EOL was defined as having a prognosis of six months or less to live. We examined the relationship between QOL, mental health, and research participation. METHODS: Structured assessments were used to collect comprehensive data on QOL and mental health. RESULTS: From 2017 to 2023, 35 PWH in their final stages of life who were actively engaged in cure-related research were enrolled. Their median age was 62.7 years, and most were White or otherwise non-Hispanic/non-Latino (90.6%), and male (86.7%). Changes in QOL and the presence of neurologic and psychiatric conditions, with a focus on depression and anxiety, were the primary outcomes assessed in this study. Participants had stable QOL scores throughout the study. There was an inverse relationship between QOL and BDI scores, with higher mean QOL scores being associated with lower mean BDI scores (p < 0.001). CONCLUSION: QOL remained stable among PWH who participate in cure-related research at EOL. The inverse relationship between QOL and depressive symptoms suggests that participation in cure-related research may improve QOL or reduce depressive symptoms in this population. Future interventions should look into ways to improve the well-being of PWH at EOL through research and customized mental health interventions.

Demographic, co-intoxicants and other characteristics of citalopram-involved overdose deaths.

Selective serotonin reuptake inhibitors (SSRIs) including citalopram are commonly used antidepressants that can be involved in drug-related deaths along with opioids and other substances. This study characterized citalopram involvement in West Virginia (WV) drug-related deaths compared to other SSRI and non-SSRI-related deaths. All 2005-2021 WV drug-related deaths were analyzed in this retrospective study. Demographics, other substances involved, and comorbidities in cases in which citalopram was listed on the death certificate were compared to other SSRI-related and total non-SSRI deaths. Citalopram concentrations and the association between citalopram presence with predicted fentanyl concentrations were determined. Citalopram was the most common antidepressant present in the deaths (4.5% of 14,363 total), with most (81%) unintentional. Male: female ratios in citalopram cases (0.9:1) were significantly lower than in non-SSRI deaths (2.3:1). Almost two-thirds of citalopram deaths had ≥ 4 substances involved compared to 26% of non-SSRI deaths. Overall, oxycodone was most frequently identified in citalopram deaths (fentanyl more commonly in recent years), followed by alprazolam and diazepam. Cardiovascular comorbidity was significantly more common in citalopram than non-SSRI deaths. No association was found between citalopram presence and predicted fentanyl concentrations. Most citalopram-related deaths were unintentional and involved proportionately more females, with larger numbers of concurrent substances present and more cardiovascular comorbidity compared to non-SSRI deaths. Citalopram is widely used and less toxic than many antidepressants. The extent to which it contributed to overdose deaths can be difficult to ascertain given the multiple substances usually present.

COVID-19 diagnosis, vaccination during pregnancy, and adverse pregnancy outcomes of 865,654 women in England and Wales: a population-based cohort study.

Background: The extent to which COVID-19 diagnosis and vaccination during pregnancy are associated with risks of common and rare adverse pregnancy outcomes remains uncertain. We compared the incidence of adverse pregnancy outcomes in women with and without COVID-19 diagnosis and vaccination during pregnancy. Methods: We studied population-scale linked electronic health records for women with singleton pregnancies in England and Wales from 1 August 2019 to 31 December 2021. This time period was divided at 8th December 2020 into pre-vaccination and vaccination roll-out eras. We calculated adjusted hazard ratios (HRs) for common and rare pregnancy outcomes according to the time since COVID-19 diagnosis and vaccination and by pregnancy trimester and COVID-19 variant. Findings: Amongst 865,654 pregnant women, we recorded 60,134 (7%) COVID-19 diagnoses and 182,120 (21%) adverse pregnancy outcomes. COVID-19 diagnosis was associated with a higher risk of gestational diabetes (adjusted HR 1.22, 95% CI 1.18-1.26), gestational hypertension (1.16, 1.10-1.22), pre-eclampsia (1.20, 1.12-1.28), preterm birth (1.63, 1.57-1.69, and 1.68, 1.61-1.75 for spontaneous preterm), very preterm birth (2.04, 1.86-2.23), small for gestational age (1.12, 1.07-1.18), thrombotic venous events (1.85, 1.56-2.20) and stillbirth (only within 14-days since COVID-19 diagnosis, 3.39, 2.23-5.15). HRs were more pronounced in the pre-vaccination era, within 14-days since COVID-19 diagnosis, when COVID-19 diagnosis occurred in the 3rd trimester, and in the original variant era. There was no evidence to suggest COVID-19 vaccination during pregnancy was associated with a higher risk of adverse pregnancy outcomes. Instead, dose 1 of COVID-19 vaccine was associated with lower risks of preterm birth (0.90, 0.86-0.95), very preterm birth (0.84, 0.76-0.94), small for gestational age (0.93, 0.88-0.99), and stillbirth (0.67, 0.49-0.92). Interpretation: Pregnant women with a COVID-19 diagnosis have higher risks of adverse pregnancy outcomes. These findings support recommendations towards high-priority vaccination against COVID-19 in pregnant women. Funding: BHF, ESRC, Forte, HDR-UK, MRC, NIHR and VR.

Male Predominance in West Virginia Unintentional Overdose Deaths is Influenced by Alcohol and Co-Intoxicants.

BACKGROUND: To examine sex differences in overdose (OD) mortality based upon substances involved. METHODS: A retrospective database analysis of West Virginia OD decedents (12,666 unintentional OD deaths, 2005-early 2023). Exposures were substances judged to contribute to death. The main outcome measure was determination of male to female death ratios with varying co-intoxicant involvement, particularly related to alcohol and fentanyl. Secondary outcomes included associations of fentanyl concentrations with alcohol concentrations and male sex, including fentanyl (F) and inactive metabolite norfentanyl (N) concentration variability between sexes. RESULTS: Alcohol co-intoxication in OD deaths was associated with higher male:female death ratios, from 2.0 (alcohol absent) to 3.3 (alcohol present). There was a greater increase over time in alcohol involvement in recent deaths involving females compared to males (relative increases of 52% vs. 6%, respectively). Male:female ratios with alcohol and fentanyl co-involvement ranged from 5.9:1 (only two drugs involved) to 2.4:1 (= 5 substances), with females significantly more likely to have multiple substances contributing to death. Overall, males had statistically significantly larger fentanyl (F) to norfentanyl (N) median concentration ratios compared to females (8.8 vs. 6.9, respectively). Multivariable analyses found alcohol presence was associated with a statistically significant 22% reduction in predicted fentanyl concentrations. CONCLUSIONS: Male:female ratios in unintentional OD deaths were higher with greater alcohol involvement and lower with fewer co-intoxicants. Fentanyl and norfentanyl concentration differences by sex were observed. It is important to determine possible contributors to sex differences in OD death rates to better target prevention and treatment initiatives.

Systematic Review of Clinical Prediction Models for the Risk of Emergency Caesarean Births.

BACKGROUND: Globally, caesarean births (CB), including emergency caesareans births (EmCB), are rising. It is estimated that nearly a third of all births will be CB by 2030. OBJECTIVES: Identify and summarise the results from studies developing and validating prognostic multivariable models predicting the risk of EmCBs. Ultimately understanding the accuracy of their development, and whether they are operationalised for use in routine clinical practice. SEARCH STRATEGY: Studies were identified using databases: MEDLINE, CINAHL, Cochrane Central and Scopus with a search strategy tailored to models predicting EmCBs. SELECTION CRITERIA: Prospective studies developing and validating clinical prediction models, with two or more covariates, to predict risk of EmCB. DATA COLLECTION AND ANALYSIS: Data were extracted onto a proforma using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS: In total, 8083 studies resulted in 56 unique prediction modelling studies and seven validating studies, with a total of 121 different predictors. Frequently occurring predictors included maternal height, maternal age, parity, BMI and gestational age. PROBAST highlighted 33 studies with low overall bias, and these all internally validated their model. Thirteen studies externally validated; only eight of these were graded an overall low risk of bias. Six models offered applications that could be readily used, but only one provided enough time to offer a planned caesarean birth (pCB). These well-refined models have not been recalibrated since development. Only one model, developed in a relatively low-risk population, with data collected a decade ago, remains useful at 36 weeks for arranging a pCB. CONCLUSION: To improve personalised clinical conversations, there is a pressing need for a model that accurately predicts the timely risk of an EmCB for women across diverse clinical backgrounds. TRIAL REGISTRATION: PROSPERO registration number: CRD42023384439.

Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People with Obesity and Type 2 Diabetes.

Muscle sn-1,2-diacylglycerol (DAG) and C18:0 ceramide accumulation in sarcolemmal and mitochondrial compartments have been proposed to regulate muscle insulin sensitivity. Here, we evaluated whether weight loss-induced improvements in insulin sensitivity were associated with changes in muscle sn-1,2-DAG and ceramide content in people with obesity and type 2 diabetes. We measured skeletal muscle insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose tracer infusion, and skeletal muscle sn-1,2-DAG and ceramide contents by using liquid chromatography-tandem mass spectrometry after subcellular fractionation and DAG isomer separation in 14 adults with obesity and type 2 diabetes before and after marked (18.6 ± 2.1%) weight loss. Whole-body insulin sensitivity doubled after weight loss. Sarcolemmal sn-1,2-DAG and C18:0 ceramide contents after weight loss were not different than values before weight loss. In contrast, mitochondrial/ER C18:0 ceramide content decreased by ∼20% after weight loss (from 2.16 ± 0.08 to 1.71 ± 0.13 nmol/g, P<0.005). These results suggest a decrease in muscle mitochondrial/ER C18:0 ceramide content could contribute to the beneficial effect of weight loss on skeletal muscle insulin sensitivity.

The War on Drugs, Racialized Capitalism, and Health Care Utilization Among White People Who Use Drugs in 22 Rural Appalachian Counties.

Objectives. To analyze War on Drugs encounters and their relationships to health care utilization among White people who use drugs (PWUD) in 22 Appalachian rural counties in Kentucky, West Virginia, Ohio, and North Carolina. Methods. We recruited White PWUD using chain referral sampling in 2018 to 2020. Surveys asked about criminal-legal encounters, unmet health care needs, and other covariates. We used generalized estimating equations to regress unmet need on criminal-legal encounters in multivariable models. Results. In this sample (n = 957), rates of stop and search, arrest, incarceration, and community supervision were high (44.0%, 26.8%, 36.3%, and 31.1%, respectively), as was unmet need (68.5%). Criminal-legal encounters were unrelated to unmet need (stops: adjusted prevalence ratio [APR] = 1.13; 95% confidence interval [CI] = 0.97, 1.32; arrest: APR = 0.95; 95% CI = 0.78, 1.15; incarceration: APR = 1.01; 95% CI = 0.89, 1.14; community supervision: APR = 0.99; 95% CI = 0.90, 1.09). Conclusions. Contrasting with findings from predominantly Black urban areas, criminal-legal encounters and unmet need were unrelated among White Appalachian PWUD. Research should explore whether and under what conditions White supremacy's benefits might buffer adverse impacts of the War on Drugs in Appalachia. (Am J Public Health. 2024;114(10):1086-1096. https://doi.org/10.2105/AJPH.2024.307744).

Strategies used to reduce harms associated with fentanyl exposure among rural people who use drugs: multi-site qualitative findings from the rural opioid initiative.

AIM: Illicitly manufactured fentanyl and its analogs are the primary drivers of opioid overdose deaths in the United States (U.S.). People who use drugs may be exposed to fentanyl or its analogs intentionally or unintentionally. This study sought to identify strategies used by rural people who use drugs to reduce harms associated with unintentional fentanyl exposure. METHODS: This analysis focused on 349 semi-structured qualitative interviews across 10 states and 58 rural counties in the U.S conducted between 2018 and 2020. Interview guides were collaboratively standardized across sites and included questions about drug use history (including drugs currently used, frequency of use, mode of administration) and questions specific to fentanyl. Deductive coding was used to code all data, then inductive coding of overdose and fentanyl codes was conducted by an interdisciplinary writing team. RESULTS: Participants described being concerned that fentanyl had saturated the drug market, in both stimulant and opioid supplies. Participants utilized strategies including: (1) avoiding drugs that were perceived to contain fentanyl, (2) buying drugs from trusted sources, (3) using fentanyl test strips, 4) using small doses and non-injection routes, (5) using with other people, (6) tasting, smelling, and looking at drugs before use, and (7) carrying and using naloxone. Most people who used drugs used a combination of these strategies as there was an overwhelming fear of fatal overdose. CONCLUSION: People who use drugs living in rural areas of the U.S. are aware that fentanyl is in their drug supply and use several strategies to prevent associated harms, including fatal overdose. Increasing access to harm reduction tools (e.g., fentanyl test strips, naloxone) and services (e.g., community drug checking, syringe services programs, overdose prevention centers) should be prioritized to address the polysubstance-involved overdose crisis. These efforts should target persons who use opioids and other drugs that may contain fentanyl.

Stereotyped spatiotemporal dynamics of spontaneous activity in visual cortex prior to eye-opening.

Over the course of development, functional sensory representations emerge in the visual cortex. Prior to eye-opening, modular patterns of spontaneous activity form long-range networks that may serve as a precursor for mature network organization. Although the spatial structure of these networks has been well studied, their temporal features, which may contribute to their continued plasticity and development, remain largely uncharacterized. To address this, we imaged hours of spontaneous network activity in the visual cortex of developing ferrets of both sexes utilizing a fast calcium indicator (GCaMP8m) and widefield imaging at high temporal resolution (50Hz), then segmented out spatiotemporal events. The spatial structure of this activity was highly modular, exhibiting spatially segregated active domains consistent with prior work. We found that the vast majority of events showed a clear dynamic component in which modules activated sequentially across the field of view, but only a minority of events were well-fit with a linear traveling wave. We found that spatiotemporal events occur in repeated and stereotyped motifs, reoccurring across hours of imaging. Finally, we found that the most frequently occurring single-frame spatial activity patterns were predictive of future activity patterns over hundreds of milliseconds. Together, our results demonstrate that spontaneous activity in the early developing cortex exhibits a rich spatiotemporal structure, suggesting a potential role in the maturation and refinement of future functional representations.

A systematic review of validity of US survey measures for assessing substance use and substance use disorders.

BACKGROUND: The steep rise in substance use and substance use disorder (SUD) shows an urgency to assess its prevalence using valid measures. This systematic review summarizes the validity of measures to assess the prevalence of substance use and SUD in the US estimated in population and sub-population-based surveys. METHODS: A literature search was performed using nine online databases. Studies were included in the review if they were published in English and tested the validity of substance use and SUD measures among US adults at the general or sub-population level. Independent reviews were conducted by the authors to complete data synthesis and assess the risk of bias. RESULTS: Overall, 46 studies validating substance use/SUD (n = 46) measures were included in this review, in which 63% were conducted in clinical settings and 89% assessed the validity of SUD measures. Among the studies that assessed SUD screening measures, 78% examined a generic SUD measure, and the rest screened for specific disorders. Almost every study used a different survey measure. Overall, sensitivity and specificity tests were conducted in over a third of the studies for validation, and 10 studies used receiver operating characteristics curve. CONCLUSION: Findings suggest a lack of standardized methods in surveys measuring and reporting prevalence of substance use/SUD among US adults. It highlights a critical need to develop short measures for assessing SUD that do not require lengthy, time-consuming data collection that would be difficult to incorporate into population-based surveys assessing a multitude of health dimensions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022298280.

Barriers to Healthcare and Social Service Utilization Among Rural Older Adults Who Use Drugs.

The objective of this study was to understand barriers to healthcare and social service utilization among older adults residing in rural areas who use drugs. A cross-sectional survey of persons who use opioids or inject drugs in rural counties with high overdose rates across ten states was conducted. For this analysis, participants were restricted to only the 375 individuals aged 50 and older. They were asked about barriers to utilizing healthcare and social services. Multivariate analyses were conducted. The most common barriers were a lack of transportation and a fear of stigma. The average number of barriers was 2.53. Those who were either uninsured or homeless endorsed 37% more barriers. For every five-year increase in age, the number of barriers reduced by 15%. Efforts to reduce these barriers may include expanding eligibility for transportation and housing services and leveraging trusted community members to broker linkages to providers to overcome stigma.

Developmental maturation of millimeter-scale functional networks across brain areas.

Interacting with the environment to process sensory information, generate perceptions, and shape behavior engages neural networks in brain areas with highly varied representations, ranging from unimodal sensory cortices to higher-order association areas. Recent work suggests a much greater degree of commonality across areas, with distributed and modular networks present in both sensory and non-sensory areas during early development. However, it is currently unknown whether this initially common modular structure undergoes an equally common developmental trajectory, or whether such a modular functional organization persists in some areas-such as primary visual cortex-but not others. Here we examine the development of network organization across diverse cortical regions in ferrets of both sexes using in vivo widefield calcium imaging of spontaneous activity. We find that all regions examined, including both primary sensory cortices (visual, auditory, and somatosensory-V1, A1, and S1, respectively) and higher order association areas (prefrontal and posterior parietal cortices) exhibit a largely similar pattern of changes over an approximately 3 week developmental period spanning eye opening and the transition to predominantly externally-driven sensory activity. We find that both a modular functional organization and millimeter-scale correlated networks remain present across all cortical areas examined. These networks weakened over development in most cortical areas, but strengthened in V1. Overall, the conserved maintenance of modular organization across different cortical areas suggests a common pathway of network refinement, and suggests that a modular organization-known to encode functional representations in visual areas-may be similarly engaged in highly diverse brain areas.

Self-organization of modular activity in immature cortical networks.

During development, cortical activity is organized into distributed modular patterns that are a precursor of the mature columnar functional architecture. Theoretically, such structured neural activity can emerge dynamically from local synaptic interactions through a recurrent network with effective local excitation with lateral inhibition (LE/LI) connectivity. Utilizing simultaneous widefield calcium imaging and optogenetics in juvenile ferret cortex prior to eye opening, we directly test several critical predictions of an LE/LI mechanism. We show that cortical networks transform uniform stimulations into diverse modular patterns exhibiting a characteristic spatial wavelength. Moreover, patterned optogenetic stimulation matching this wavelength selectively biases evoked activity patterns, while stimulation with varying wavelengths transforms activity towards this characteristic wavelength, revealing a dynamic compromise between input drive and the network's intrinsic tendency to organize activity. Furthermore, the structure of early spontaneous cortical activity - which is reflected in the developing representations of visual orientation - strongly overlaps that of uniform opto-evoked activity, suggesting a common underlying mechanism as a basis for the formation of orderly columnar maps underlying sensory representations in the brain.

Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity.

There is considerable heterogeneity in the cardiometabolic abnormalities associated with obesity. We evaluated multi-organ system metabolic function in 20 adults with metabolically healthy obesity (MHO; normal fasting glucose and triglycerides, oral glucose tolerance, intrahepatic triglyceride content, and whole-body insulin sensitivity), 20 adults with metabolically unhealthy obesity (MUO; prediabetes, hepatic steatosis, and whole-body insulin resistance), and 15 adults who were metabolically healthy lean. Compared with MUO, people with MHO had (1) altered skeletal muscle biology (decreased ceramide content and increased expression of genes involved in BCAA catabolism and mitochondrial structure/function); (2) altered adipose tissue biology (decreased expression of genes involved in inflammation and extracellular matrix remodeling and increased expression of genes involved in lipogenesis); (3) lower 24-h plasma glucose, insulin, non-esterified fatty acids, and triglycerides; (4) higher plasma adiponectin and lower plasma PAI-1 concentrations; and (5) decreased oxidative stress. These findings provide a framework of potential mechanisms responsible for MHO and the metabolic heterogeneity of obesity. This study was registered at ClinicalTrials.gov (NCT02706262).

Self-organization of modular activity in immature cortical networks.

During development, cortical activity is organized into distributed modular patterns that are a precursor of the mature columnar functional architecture. Theoretically, such structured neural activity can emerge dynamically from local synaptic interactions through a recurrent network with effective local excitation with lateral inhibition (LE/LI) connectivity. Utilizing simultaneous widefield calcium imaging and optogenetics in juvenile ferret cortex prior to eye opening, we directly test several critical predictions of an LE/LI mechanism. We show that cortical networks transform uniform stimulations into diverse modular patterns exhibiting a characteristic spatial wavelength. Moreover, patterned optogenetic stimulation matching this wavelength selectively biases evoked activity patterns, while stimulation with varying wavelengths transforms activity towards this characteristic wavelength, revealing a dynamic compromise between input drive and the network's intrinsic tendency to organize activity. Furthermore, the structure of early spontaneous cortical activity - which is reflected in the developing representations of visual orientation - strongly overlaps that of uniform opto-evoked activity, suggesting a common underlying mechanism as a basis for the formation of orderly columnar maps underlying sensory representations in the brain.

Association between maternal hemoglobin concentration and educational attainment in mid-childhood in a high-resource obstetric setting: a prospective cohort study.

BACKGROUND: Although maternal hemoglobin levels during pregnancy are commonly associated with perinatal outcomes, their link to childhood neurodevelopment remains uncertain. OBJECTIVE: This study aimed to examine the associations between maternal hemoglobin in early and late pregnancy and the educational attainment of offspring mid-childhood in a high-resource obstetric setting. STUDY DESIGN: Pregnancy data from a prospective birth cohort (Pregnancy Outcome Prediction Study, Cambridge, United Kingdom, 2008-2012, N=3285) were linked to mid-childhood educational outcomes (Department for Education, United Kingdom). Regression models adjusted for maternal, child, and socioeconomic factors were used to determine associations between maternal hemoglobin, pregnancy complications, and offspring educational outcomes (aged 5-7 years). RESULTS: No association was observed between maternal hemoglobin at 12 weeks and the likelihood of either adverse pregnancy outcomes or children meeting expected educational standards between ages 5-7 years. Higher maternal hemoglobin at 28 weeks was associated with an increased risk of small-for-gestational-age infants (adjusted odds ratio, 1.26 [95% confidence interval, 1.11-1.59]; P=.002) and preterm birth (adjusted odds ratio, 1.38 [95% confidence interval, 1.11-1.81]; P=.005). There were no adverse birth outcomes associated with anemia. However, children of mothers who were anemic at 28 weeks had ∼40% increased risk of not attaining expected educational standards at age 5 (adjusted odds ratio, 1.42 [95% confidence interval, 1.03-1.95]; P=.03). There was no association between maternal anemia at 28 weeks and educational performance at ages 6-7. No associations were found between high maternal hemoglobin concentrations (top decile) or change in hemoglobin concentrations between 12 and 28 weeks and childhood educational attainment. CONCLUSION: Maternal anemia at 28 weeks of pregnancy is associated with reduced educational attainment at 5 years old but not at older ages (6-7 years old). A proactive approach to increasing maternal hemoglobin in high-resource settings is unlikely to impact long-term childhood educational attainment.

Enhanced SARS-CoV-2 case prediction using public health data and machine learning models.

Objectives: The goal of this study is to propose and test a scalable framework for machine learning (ML) algorithms to predict near-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases by incorporating and evaluating the impact of real-time dynamic public health data. Materials and Methods: Data used in this study include patient-level results, procurement, and location information of all SARS-CoV-2 tests reported in West Virginia as part of their mandatory reporting system from January 2021 to March 2022. We propose a method for incorporating and comparing widely available public health metrics inside of a ML framework, specifically a long-short-term memory network, to forecast SARS-CoV-2 cases across various feature sets. Results: Our approach provides better prediction of localized case counts and indicates the impact of the dynamic elements of the pandemic on predictions, such as the influence of the mixture of viral variants in the population and variable testing and vaccination rates during various eras of the pandemic. Discussion: Utilizing real-time public health metrics, including estimated Rt from multiple SARS-CoV-2 variants, vaccination rates, and testing information, provided a significant increase in the accuracy of the model during the Omicron and Delta period, thus providing more precise forecasting of daily case counts at the county level. This work provides insights on the influence of various features on predictive performance in rural and non-rural areas. Conclusion: Our proposed framework incorporates available public health metrics with operational data on the impact of testing, vaccination, and current viral variant mixtures in the population to provide a foundation for combining dynamic public health metrics and ML models to deliver forecasting and insights in healthcare domains. It also shows the importance of developing and deploying ML frameworks in rural settings.

Common modular architecture across diverse cortical areas in early development.

In order to deal with a complex environment, animals form a diverse range of neural representations that vary across cortical areas, ranging from largely unimodal sensory input to higher-order representations of goals, outcomes, and motivation. The developmental origin of this diversity is currently unclear, as representations could arise through processes that are already area-specific from the earliest developmental stages or alternatively, they could emerge from an initially common functional organization shared across areas. Here, we use spontaneous activity recorded with two-photon and widefield calcium imaging to reveal the functional organization across the early developing cortex in ferrets, a species with a well-characterized columnar organization and modular structure of spontaneous activity in the visual cortex. We find that in animals 7 to 14 d prior to eye-opening and ear canal opening, spontaneous activity in both sensory areas (auditory and somatosensory cortex, A1 and S1, respectively), and association areas (posterior parietal and prefrontal cortex, PPC and PFC, respectively) showed an organized and modular structure that is highly similar to the organization in V1. In all cortical areas, this modular activity was distributed across the cortical surface, forming functional networks that exhibit millimeter-scale correlations. Moreover, this modular structure was evident in highly coherent spontaneous activity at the cellular level, with strong correlations among local populations of neurons apparent in all cortical areas examined. Together, our results demonstrate a common distributed and modular organization across the cortex during early development, suggesting that diverse cortical representations develop initially according to similar design principles.

Plant-pollinator network architecture does not impact intraspecific microbiome variability.

Variation in how individuals interact with food resources can directly impact, and be affected by, their microbial interactions due to the potential for transmission. The degree to which this transmission occurs, however, may depend on the structure of forager networks, which determine the community-scale transmission opportunities. In particular, how the community-scale opportunity for transfer balances individual-scale barriers to transmission is unclear. Examining the bee-flower and bee-microbial interactions of over 1000 individual bees, we tested (1) the degree to which individual floral visits predicted microbiome composition and (2) whether plant-bee networks with increased opportunity for microbial transmission homogenized the microbiomes of bees within that network. The pollen community composition carried by bees was associated with microbiome composition at some sites, suggesting that microbial transmission at flowers occurred. Contrary to our predictions, however, microbiome variability did not differ based on transfer opportunity: bee microbiomes in asymmetric networks with high opportunity for microbial transfer were similarly variable compared to microbiomes in networks with more evenly distributed links. These findings suggest that microbial transmission at flowers is frequent enough to be observed at the community level, but that community network structure did not substantially change the dynamics of this transmission, perhaps due to filtering processes in host guts.