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Gustave H Falciglia,1,2 Hernan Sierra-Fernandez,3 Melissa Freeman,2 Daniel Healy,2 Jennifer S Wicks,1,2 Daniel T Robinson1,2 1Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 2Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA; 3Department of Pediatrics, Rush University Medical Center, Chicago, IL, USACorrespondence: Gustave H Falciglia, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 E. Chicago Ave, Box #45, Chicago, IL, 60611, USA, Tel +1 312 848-3142, Email gustave-falciglia@northwestern.eduPurpose: Few clinical decision support systems (CDSSs) are available to help clinicians calculate nutrition intake in infants in the neonatal intensive care unit (NICU) despite improvement in the accuracy of calculations and quality of nutrition delivered. The aim of this manuscript is to qualitatively define the barriers associated with the implementation of CDSSs to calculate fluid and nutrition intake.Methods: After defining the data necessary to calculate fluid and nutrition intake, multidisciplinary groups analyzed CDSS capabilities and barriers to implementation at two academically affiliated NICUs. They implemented CDSSs to calculate intake received in the past (retrospective) and to estimate future intake from orders (prospective). Barriers and measures to reduce them are reported.Results: Barriers to implementation include simultaneous enteral feeding orders, the use of free text in the electronic health record (EHR), and a large variety of enteral feeding types for clinical use. These barriers made implementation of prospective CDSSs more difficult. CDSSs reported values that were normalized by both the most recent measured weight (usually obtained daily) and a dosing weight, a weight updated less frequently and used by pharmacies to facilitate prescribing.Conclusion: Despite using an EHR from the same vendor, different solutions were implemented at each NICU. CDSSs improved access to individual infant data on fluid and nutrition intake; however, none of the CDSSs easily exported data to monitor the quality of intake for the entire NICU or specific populations (eg, infants with bronchopulmonary dysplasia). Comprehensive CDSSs that include prospective intake and monitor the quality of nutrition intake through standardized values will require continued investigation and resources.Keywords: clinical decision support, nutrition, infant, neonatal intensive care unit

The unprecedented use of Earth's resources by humans, in combination with increasing natural variability in natural processes over the past century, is affecting the evolution of the Earth system. To better understand natural processes and their potential future trajectories requires improved integration with and quantification of human processes. Similarly, to mitigate risk and facilitate socio-economic development requires a better understanding of how the natural system (e.g. climate variability and change, extreme weather events, and processes affecting soil fertility) affects human processes. Our understanding of these interactions and feedback between human and natural systems has been formalized through a variety of modelling approaches. However, a common conceptual framework or set of guidelines to model human-natural-system feedbacks is lacking. The presented research lays out a conceptual framework that includes representing model coupling configuration in combination with the frequency of interaction and coordination of communication between coupled models. Four different approaches used to couple representations of the human and natural system are presented in relation to this framework, which vary in the processes represented and in the scale of their application. From the development and experience associated with the four models of coupled human-natural systems, the following eight lessons were identified that if taken into account by future coupled human-natural-systems model developments may increase their success: (1) leverage the power of sensitivity analysis with models, (2) remember modelling is an iterative process, (3) create a common language, (4) make code open-access, (5) ensure consistency, (6) reconcile spatio-temporal mismatch, (7) construct homogeneous units, and (8) incorporating feedback increases non-linearity and variability. Following a discussion of feedbacks, a way forward to expedite model coupling and increase the longevity and interoperability of models is given, which suggests the use of a wrapper container software, a standardized applications programming interface (API), the incorporation of standard names, the mitigation of sunk costs by creating interfaces to multiple coupling frameworks, and the adoption of reproducible workflow environments to wire the pieces together.

Enrollment into a prospective cohort study of mother-preterm infant dyads during the COVID-19 pandemic progressed slower than anticipated. Enrollment occurred during the first week after preterm birth, while infants were still hospitalized. We hypothesized that slower enrollment was attributable to mothers testing positive for COVID-19 as hospital policies restricted them from entering the neonatal intensive care unit, thus reducing interactions with research staff. However, only 4.5% of 245 screened mothers tested COVID-19 positive. Only 24.9% of those screened, far fewer than anticipated, were eligible for enrollment. Assumptions about pandemic-related enrollment barriers were not substantiated in this pediatric cohort., Competing Interests: Dr Robinson is an institutional principal investigator, with no salary funding, for a consortium database sponsored by Mead Johnson Nutrition and previously received compensation as a member of the Data Safety Monitoring Board for a clinical investigation sponsored by Fresenius Kabi. The other authors have nothing to disclose., (© The Author(s) 2024.)

In the United States, 10% of infants are born preterm (PT; <37 weeks gestational age) each year and are at higher risk of complications compared to full term infants. The burden of PT birth is borne disproportionately by Black versus non-Black families, with Black mothers significantly more likely to give birth to a PT infant. One proven strategy to improve short- and long-term health outcomes in PT infants is to feed mother's own milk (MOM; breast milk from the mother). However, mothers must make decisions about work and MOM provision following PT birth, and more time spent in paid work may reduce time spent in unpaid activities, including MOM provision. Non-Black PT infants are substantially more likely than Black PT infants to receive MOM during the birth hospitalization, and this disparity is likely to be influenced by the complex decisions mothers of PT infants make about allocating their time between paid and unpaid work. Work is a social determinant of health that provides a source of income and health insurance coverage, and at the same time, has been shown to create disparities through poorer job quality, lower earnings, and more precarious employment in racial and ethnic minority populations. However, little is known about the relationship between work and disparities in MOM provision by mothers of PT infants. This State of the Science review synthesizes the literature on paid and unpaid work and MOM provision, including: (1) the complex decisions that mothers of PT infants make about returning to work, (2) racial and ethnic disparities in paid and unpaid workloads of mothers, and (3) the relationship between components of job quality and duration of MOM provision. Important gaps in the literature and opportunities for future research are summarized, including the generalizability of findings to other countries.

Growing evidence demonstrates human milk's protective effect against necrotizing enterocolitis (NEC). Human milk derives these properties from biologically active compounds that influence intestinal growth, barrier function, microvascular development, and immunological maturation. Among these protective compounds are growth factors that are secreted into milk with relatively high concentrations during the early postnatal period, when newborns are most susceptible to NEC. This paper reviews the current knowledge on human milk growth factors and their mechanisms of action relevant to NEC prevention. It will also discuss the stability of these growth factors with human milk pasteurization and their potential for use as supplements to infant formulas with the goal of preventing NEC.

Background: Evidence documenting whether diet quality, particularly dietary fatty acids, is associated with preterm birth (PTB) is limited., Objective: The aim was to measure associations between dietary fatty acid intake prior to pregnancy, specifically n-3 (ɷ-3) PUFAs and odds of PTB in US women and determine if associations differed by prepregnancy BMI., Methods: We designed a secondary analysis of dietary intake in nulliparous women enrolled in a longitudinal cohort (NCT01322529). Participants completed an FFQ, modified to assess detailed PUFA intake, during the 3 mo preceding pregnancy. Inclusion in this analytic cohort required total energy intake within 2 SDs of the group mean. Prepregnancy BMI was categorized as underweight, normal, overweight, or obese. The primary exposure was estimated intake of EPA and DHA (combined EPA+DHA), in the context of a recommended intake of 250 mg. The primary outcome was PTB (<37 wk). Adjusted regression models controlled for maternal factors relevant to PTB and evaluated associations with PUFAs. Interaction terms estimated effect modification of BMI. A false discovery rate (FDR) correction accounted for multiple comparisons., Results: Median daily intake of combined EPA+DHA in 7365 women was 70 mg (IQR: 32, 145 mg). A significant interaction term indicated the effects of EPA+DHA on odds of PTB were different for different BMI categories ( P  < 0.01). Specifically, higher intake of combined EPA+DHA was nominally associated with reduced odds of PTB in women with underweight (OR: 0.67; 95% CI: 0.46-0.98) and normal BMI (OR: 0.87; 95% CI: 0.78-0.96), yet was associated with increased odds of overweight BMI (OR: 1.21; 95% CI: 1.02-1.44). Associations remained significant after FDR correction., Conclusions: Based on a cohort of US women designed to identify predictors of adverse pregnancy outcomes, dietary intake of combined EPA+DHA was considerably lower than recommended. Associations between intake of these recommended n-3 fatty acids and risk of PTB differ by maternal BMI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Human milk samples were prospectively obtained from women who delivered prior to the 32nd week of gestation [1]. The 36 preterm human milk samples analysed in this dataset were collected at week 1 and week 4 of lactation. Samples were categorized as being from women with normal pre-pregnancy body mass index (BMI 18-24.9 kg/m 2 ) versus overweight/obese (BMI ≥25). Whole milk samples were frozen at -80 Celsius without prior processing and shipped for analysis on dry ice. Untargeted metabolomic and lipidomic platforms using UPLC-MS/MS and infusion-MS analysis for select lipids were performed by Metabolon. Lipidomic analysis included detection of complex lipids found in the milk fat globule membrane. Data were categorized by maternal BMI, week of lactation as well as gestational age at delivery. Data sheets are separated based on whether they report metabolomics versus lipidomics, as well as whether they report output from samples collected at week 1 versus week 4 of lactation. These data allow calculating relationships between clinical variables and human milk components. As an illustrative example, correlations between pre-pregnancy BMI and total milk fatty acids were calculated for this report using the Spearman correlation. These data will inform scientists of variability in milk composition attributable to maternal pre-pregnancy BMI as well as changes in milk composition as milk matures during lactation from week 1 to week 4. These data may best be used for generating hypotheses and justification of future work investigating whether maternal pre-pregnancy body mass index impacts preterm human milk composition., Competing Interests: None., (© 2020 The Authors.)

Concordance among wetland physicochemical conditions, vegetation, and surrounding land cover may result from the influence of land cover on the sources of plant propagules, on physicochemical conditions, and their subsequent determination of growing conditions. Alternatively, concordance may result if differences in climate, soils, and species pools are spatially confounded with differences in human population density and land conversion. Further, we expect that land cover within catchment boundaries will be more predictive than land cover in symmetrical buffers if runoff is a major pathway. We measured concordance between land cover, wetland vegetation and physicochemical conditions in 48 prairie pothole wetlands, controlling for inter-wetland distance. We contrasted land-cover data collected over a four-year period by multiple extraction approaches including topographically-delineated catchments and nested 30 m to 5,000 m radius buffers. After factoring out inter-wetland distance, physiochemical conditions were significantly concordant with land cover. Vegetation was not significantly concordant with land cover, though it was strongly and significantly concordant with physicochemical conditions. More, concordance was as strong when land cover was extracted from buffers <500 m in radius as from catchments, indicating the mechanism responsible is not topographically constrained. We conclude that local landscape structure does not directly influence wetland vegetation composition, but rather that vegetation depends on 1) physicochemical conditions in the wetland that are affected by surrounding land cover and on 2) regional factors such as the vegetation species pool and geographic gradients in climate, soil type, and land use., Competing Interests: The authors have declared that no competing interests exist.

Background: Implications of donor milk feedings on infant growth in resource limited settings remain uncertain. This knowledge gap includes the impact of donor milk availability on infant intake of mother's own milk. Therefore, this investigation aimed to measure intake and growth in infants receiving donor milk when born to women from resource limited backgrounds with high rates of human immunodeficiency virus (HIV)., Methods: A retrospective cohort study enrolled eligible infants admitted to a South African combined neonatal intensive and secondary high care unit, within a one year admission period during 2015, with signed consent for donor milk feedings. A certified milk bank provided donor milk. Daily nutritional intake during the first month was recorded. Details included proportional intake of donor milk, mother's own milk and infant formula. The primary outcome of infant growth velocity from day back to birth weight to discharge was calculated when length of stay was ≥14 days. Analyses primarily used T-tests; mixed effects models compared weekly calorie intake., Results: One hundred five infants with donor milk consent were born at 30.9 ± 3.6 weeks of gestation, weighing 1389 ± 708 g. Forty percent of mothers had HIV. Infant growth velocity did not differ based on percent of feedings as donor milk (≥ 50%: 11.8 ± 4.9 g/kg/d; < 50%: 13.5 ± 5.3 g/kg/d; p  = 0.3). Percent of feedings from donor milk was similar based on maternal HIV status (positive: 31 ± 25%; negative: 36 ± 29%; p  = 0.4), as was percent of feedings as mother's milk (positive: 53 ± 35%; negative: 58 ± 30%; p  = 0.4). Calorie intake increased markedly during the first two weeks and then plateaued ( p  < 0.0001)., Conclusions: Donor milk feedings in higher proportions did not further impair growth of infants managed in a South African combined neonatal intensive and secondary high care unit with growth rates already below reference ranges. The provision of donor milk contributed to feedings being composed of primarily human milk during the first month. Increasing early calorie intake may improve infant growth in this center., Competing Interests: The Human Research Ethics Committees for the University of Cape Town and Mowbray Maternity Hospital approved this human subject research (#236/2016). A waiver of consent was provided for this retrospective study.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Extremely-low-birth-weight (ELBW) infants accrue large deficits in docosahexaenoic acid (DHA) and arachidonic acid (ARA) and require improved supplementation strategies. We hypothesized that once daily DHA+ARA drops applied to buccal mucosa will increase blood levels., Methods: Thirty ELBW infants were randomized to receive DHA 20 mg/kg/d + ARA 40 or 60 mg/kg/d + ARA 120 mg/kg/d or placebo within 72 h of age for 8 wk duration. Red blood cell phospholipid levels of DHA (primary) and ARA (secondary) were measured at 2 and 8 wk of age., Results: Twenty-eight survivors with a median birth weight of 806 g completed dosing and sampling. Red blood cell levels were similar between the three groups at 2 wk (DHA: 4.62 wt% (interquartile range (IQR) 4.1-5.5) for all, P = 0.29 between groups; ARA: 21.1 wt% (IQR 18.78-22.6) for all, P = 0.41 between groups) and 8 wk (DHA: 6.0 wt% (IQR 5.1-7.1) for all, P = 0.57 between groups; ARA: 20.1 wt% (IQR 18.3-23.1) for all, P = 0.63 between groups). DHA in all infants showed a median increase of 31% from 2 to 8 wk (P < 0.04). ARA levels did not significantly change over time (P > 0.6)., Conclusion: Daily buccal DHA and ARA supplements did not affect fatty acid levels in ELBW infants.

Exurban residential land (one housing unit per 0.2-16.2 ha) is growing in importance as a human-dominated land use. Carbon storage in the soils and vegetation of exurban land is poorly known, as are the effects on C storage of choices made by developers and residents. We studied C storage in exurban yards in southeastern Michigan, USA, across a range of parcel sizes and different types of neighborhoods. We divided each residential parcel into ecological zones (EZ) characterized by vegetation, soil, and human behavior such as mowing, irrigation, and raking. We found a heterogeneous mixture of trees and shrubs, turfgrasses, mulched gardens, old-field vegetation, and impervious surfaces. The most extensive zone type was turfgrass with sparse woody vegetation (mean 26% of parcel area), followed by dense woody vegetation (mean 21% of parcel area). Areas of turfgrass with sparse woody vegetation had trees in larger size classes (> 50 cm dbh) than did areas of dense woody vegetation. Using aerial photointerpretation, we scaled up C storage to neighborhoods. Varying C storage by neighborhood type resulted from differences in impervious area (8-26% of parcel area) and area of dense woody vegetation (11-28%). Averaged and multiplied across areas in differing neighborhood types, exurban residential land contained 5240 ± 865 g C/m 2 in vegetation, highly sensitive to large trees, and 13 800 ± 1290 g C/m 2 in soils (based on a combined sampling and modeling approach). These contents are greater than for agricultural land in the region, but lower than for mature forest stands. Compared with mature forests, exurban land contained more shrubs and less downed woody debris and it had similar tree size-class distributions up to 40 cm dbh but far fewer trees in larger size classes. If the trees continue to grow, exurban residential land could sequester additional C for decades. Patterns and processes of C storage in exurban residential land were driven by land management practices that affect soil and vegetation, reflecting the choices of designers, developers, and residents. This study provides an example of human-mediated C storage in a coupled human-natural system., (© 2016 by the Ecological Society of America.)

Systemic administration of small molecule toll-like receptor (TLR)-7 agonists leads to potent activation of innate immunity and to the generation of anti-tumor immune responses. However, activation of TLRs with small molecule agonists may lead to the induction of TLR tolerance, defined as a state of hyporesponsiveness to subsequent agonism, which may limit immune activation, the generation of anti-tumor responses and clinical response. Our data reveal that dose scheduling impacts on the efficacy of systemic therapy with the selective TLR7 agonist, 6-amino-2-(butylamino)-9-((6-(2-(dimethylamino)ethoxy)pyridin-3-yl)methyl)-7,9-dihydro-8H-purin-8-one (DSR-6434). In a preclinical model of renal cell cancer, systemic administration of DSR-6434 dosed once weekly resulted in a significant anti-tumor response. However, twice weekly dosing of DSR-6434 led to the induction of TLR tolerance, and no anti-tumor response was observed. We show that TLR7 tolerance was independent of type I interferon (IFN) negative feedback because induction of TLR7 tolerance was also observed in IFN-α/β receptor knockout mice treated with DSR-6434. Moreover, our data demonstrate that treatment of bone marrow-derived plasmacytoid dendritic cells (BM-pDC) with DSR-6434 led to downregulation of TLR7 expression. From our data, dose scheduling of systemically administered TLR7 agonists can impact on anti-tumor activity through the induction of TLR tolerance. Furthermore, TLR7 expression on pDC may be a useful biomarker of TLR7 tolerance and aid in the optimization of dosing schedules involving systemically administered TLR7 agonists.

Components of diet, including the total amounts and specific types of fat, affect the composition of the intestinal microbiome in both animal models and cohort studies of humans. Amounts of total fat and specific fatty acids (FA) are some of the most variable nutritional components of breast milk. Evaluations of the microbiome in premature infants have shown decreased diversity of species and increased proportions of potentially pathogenic bacteria. Microbial patterns in premature infants may be affected by nutritional fat intake, altering risk of diseases such as necrotizing enterocolitis. Dietary FA may also impact disease susceptibility through molecular mechanisms. Specifically, intestinal Toll-like receptor 4 expression is altered by manipulation of FA in murine models. Abnormal increased expression of Toll-like receptor 4, the receptor for lipopolysaccharide, has been implicated in necrotizing enterocolitis. This report will review the role of dietary fat in the composition of the intestinal microbiome, the extreme variability of FA intake in premature infants, and associations of both dysbiosis and FA intake with the development of necrotizing enterocolitis.

The ecosystem service concept has emphasized the role of people within socio-ecological systems (SESs). In this paper, we review and discuss alternative ways of representing people, their behaviour and decision-making processes in SES models using an agent-based modelling (ABM) approach. We also explore how ABM can be empirically grounded using information from social survey. The capacity for ABM to be generalized beyond case studies represents a crucial next step in modelling SESs, although this comes with considerable intellectual challenges. We propose the notion of human functional types, as an analogy of plant functional types, to support the expansion (scaling) of ABM to larger areas. The expansion of scope also implies the need to represent institutional agents in SES models in order to account for alternative governance structures and policy feedbacks. Further development in the coupling of human-environment systems would contribute considerably to better application and use of the ecosystem service concept.

Although determining iron intakes is essential in assessing adequacy of iron in the diet, estimating iron availability may be more useful for evaluating whether iron requirements are met. Our objectives were to describe the dietary information, analytical steps, and computer algorithms needed for iron bioavailability adjustments and to demonstrate the effects of various dietary factors on calculated iron absorption. Our study was based on 9890 women and children participating in the Russian Longitudinal Monitoring Survey. Between August 1992 and February 1993, two 24-h recalls were collected from each participant, and total, heme and nonheme iron intakes were calculated. Nonheme iron availability was adjusted for meat, fish and poultry and vitamin C consumed in the same meal and then further adjusted for tea and phytates. We found mean total iron intakes to be comparable to those of women of reproductive age in the United States and lower than those of United States children. When these intakes were adjusted for enhancers and inhibitors of absorption, the iron bioavailability in these vulnerable Russian groups was extremely low. Mean bioavailable iron as well as the 25th-75th percentile ranges of intake were below the bottom of the range of requirements, indicating that iron adequacy in this population may be considerably less than expected based on total iron intakes alone. Furthermore, rural and urban food availability had a significant effect on iron bioavailability. Future research on dietary iron adequacy should be based on estimates of available iron by collecting meal-level dietary data and using detailed information on mixed dishes and phytates.

A double-blind placebo-controlled study of minocycline in 221 men with non-gonococcal urethritis (NGU) was undertaken. Techniques were used which enabled diagnoses of chlamydial and mycoplasmal infections to be made within 24 hours of a patient attending a clinic. All patients from whom Chlamydia trachomatis was isolated were treated with minocycline, while patients from whom Ureaplasma urealyticum or Mycoplasma hominis was isolated, or from whom no micro-organisms were isolated, were treated on a double-blind basis with either minocycline or placebo. Chlamydia were isolated from 77 (35%) patients and were eradicated by minocycline from 76 (99%). Ureaplasmas were isolated initially from 96 (43%) patients. Treatment with minocycline eradicated them from 43 of 52 (83%) patients, and they disappeared from six of 31 (19%) patients who were treated with placebo. After one week significantly more patients had responded clinically to minocycline than to placebo. The response to minocycline was not influenced by the microbiological status of the patients, which suggests that ureaplasmas are playing a similar role to chlamydia in the pathogenesis of the disease and that an antibiotic-sensitive micro-organism may be producing disease in the isolate-negative group. An immunological approach is required to resolve the problem of the persistent urethral inflammation which occurred despite eradication of the micro-organisms.

The effect of Mycoplasma pulmonis suspension on mouse on mouse fertilization and preimplantation development in vitro was examined. When sperm were preincubated with M. pulmonis, fertilization of eggs occured less consistently than when untreated sperm were used. There was also a highly significant and consistent reduction in embryonic develoment in the treated group, with relatively few embryos reaching the blastocyst stage. The adverse effects were not seen with M. fermentans or with M. pulmonis organisms inactivated by heating or sonication before incubation with gametes. Likewise, preincubation of M. pulmonis in medium containing tetracycline, an antibiotic which interferes with protein synthesis, resulted in embryonic development similar to that seen in the untreated group. These results suggest that the deleterious effects obtained with viable mycoplasmas are due to some substance produced by their active metabolism. Other results indicate that the egg is susceptible to M. pulmonis for a limited time, since incubation of two-cell embryos with mycoplasmas had no effect on development to the blastocyst stage. The findings are discussed in relation to the possible association between human infertility and mycoplasma infection.