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Risk assessment in pulmonary arterial hypertension (PAH) is fundamental to guiding treatment and improved outcomes. Clinical models are excellent at identifying high-risk patients, but leave uncertainty amongst moderate-risk patients. Can a multiple blood biomarker model of PAH, using previously described biomarkers, improve risk discrimination over current models? Using a multiplex enzyme-linked immunosorbent assay, we measured N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble suppressor of tumorigenicity, IL-6, endostatin, galectin 3, hepatoma derived growth factor, and insulin-like growth factor binding proteins (IGFBP1-7) in training (n = 1,623), test (n = 696), and validation (n = 237) cohorts. Clinical variables and biomarkers were evaluated by principal component analysis. NT-proBNP was not included to develop a model independent of NT-proBNP. Unsupervised k-means clustering classified participants into clusters. Transplant-free survival by cluster was examined using Kaplan-Meier and Cox proportional hazard regressions. Hazard by cluster was compared with NT-proBNP, Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL), and European Society of Cardiology and European Respiratory Society risk models alone and combined clinical and biomarker models. The algorithm generated five clusters with good risk discrimination using six biomarkers, weight, height, and age at PAH diagnosis. In the test and validation cohorts, the biomarker model alone performed equivalent to REVEAL (area under the receiver operating characteristic curve, 0.74). Adding the biomarker model to the European Society of Cardiology and European Respiratory Society score and REVEAL score improved the European Society of Cardiology and European Respiratory Society score and REVEAL score. The best overall model was the biomarker model adjusted for NT-proBNP with the best C statistic, Akaike information criterion, and calibration for the adjusted model compared with either the biomarker or NT-proBNP model alone. In this study, a multibiomarker model alone was equivalent to current PAH clinical mortality risk prediction models and improved performance when combined and added to NT-proBNP. Clinical risk scores offer excellent predictive models, but require multiple tests; adding blood biomarkers to models can improve prediction or can enable more frequent, noninvasive monitoring of risk in PAH to support therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Objective: To develop an instrument to examine tobacco-free campus policy components. Participants: Missouri two- and four-year, specialized/technical, and religious colleges and universities (N = 76). Methods: The instrument was informed via literature review and expert interviews. Coder agreement was strong (κ =.80). Qualitative policy language examples were identified. Results: Model policy components including consideration for population, prohibited products, location restrictions, enforcement, consequences, promotions, communications, cessation, designated smoking areas and exemptions; comprehensive policies included all populations, for all tobacco products, and at all locations on the campus. Nineteen campuses had comprehensive tobacco-free policies, five had comprehensive smoke-free policies (cigarettes and e-cigarettes), and no policy included all model components. Fifty-two were non-comprehensive. Conclusions: This instrument can allow campuses to identify components for comprehensive and model tobacco-free campus policies and assist officials in improving policy language. Future research can use this instrument to examine the effectiveness of components and their impact on tobacco use outcomes. [ABSTRACT FROM AUTHOR]

Numerous studies have demonstrated that endostatin (ES), a potent angiostatic peptide derived from collagen type XVIII α 1 chain and encoded by COL18A1, is elevated in pulmonary arterial hypertension (PAH). It is important to note that elevated ES has consistently been associated with altered hemodynamics, poor functional status, and adverse outcomes in adult and pediatric PAH. This study used serum samples from patients with Group I PAH and plasma and tissue samples derived from the Sugen/hypoxia rat pulmonary hypertension model to define associations between COL18A1/ES and disease development, including hemodynamics, right ventricle (RV) remodeling, and RV dysfunction. Using cardiac magnetic resonance imaging and advanced hemodynamic assessments with pressure–volume loops in patients with PAH to assess RV–pulmonary arterial coupling, we observed a strong relationship between circulating ES levels and metrics of RV structure and function. Specifically, RV mass and the ventricular mass index were positively associated with ES, whereas RV ejection fraction and RV–pulmonary arterial coupling were inversely associated with ES levels. Our animal data demonstrate that the development of pulmonary hypertension is associated with increased COL18A1/ES in the heart as well as the lungs. Disease-associated increases in COL18A1 mRNA and protein were most pronounced in the RV compared with the left ventricle and lung. COL18A1 expression in the RV was strongly associated with disease-associated changes in RV mass, fibrosis, and myocardial capillary density. These findings indicate that COL18A1/ES increases early in disease development in the RV and implicates COL18A1/ES in pathologic RV dysfunction in PAH. [ABSTRACT FROM AUTHOR]

Emerging fishing activity due to melting ice and poleward species distribution shifts in the rapidly‐warming Arctic Ocean challenges transboundary management and requires proactive governance. A 2021 moratorium on commercial fishing in the Arctic high seas provides a 16‐year runway for improved scientific understanding. Given substantial knowledge gaps, characterizing areas of highest uncertainty is a key first step. Marine ecosystem model ensembles that project future fish distributions could inform management of future Arctic fisheries, but Arctic‐specific variation has not yet been examined for global ensembles. We use the Fisheries and Marine Ecosystem Intercomparison Project ensemble driven by two Earth System Models (ESMs) under two Shared Socioeconomic Pathways (SSP1‐2.6 and SSP5‐8.5) to illustrate the current state of and uncertainty among biomass projections for the Arctic Ocean over the duration of the moratorium. The models generally project biomass increases in more northern Arctic ecosystems and decreases in southern ecosystems, but wide intra‐model variation exceeds projection means in most cases. The two ESMs show opposite trends for the main environmental drivers. Therefore, these projections are currently insufficient to inform policy actions. Investment in sustained monitoring and improving modeling capacity, especially for sea ice dynamics, is urgently needed. Concurrently, it will be necessary to develop frameworks for making precautionary decisions under continued uncertainty. We conclude that researchers should be transparent about uncertainty, presenting these model projections not as a source of scientific "answers," but as bounding for plausible, policy‐relevant questions to assess trade‐offs and mitigate risks. Plain Language Summary: As the Arctic Ocean gets warmer, melting ice is opening up new opportunities for fishing. However, we don't know where fish will go and how they can be managed sustainably. An important first step is to figure out which unknowns we can solve quickly with more research, and what is so uncertain that we will have to make decisions without ideal information. In this paper, we looked at uncertainty in a set of global models that predict how fish populations might shift in the next 10–25 years. Overall, these models show that fish populations might increase in the northern parts of the Arctic while decreasing in the south. But the models make very different predictions, and some disagree on whether fish populations will increase or decrease in certain areas. A major source of uncertainty is how sea ice will change, and how ocean life will respond. Therefore, this is a priority area to invest in long‐term research and better models. Overall, these models are too uncertain to rely on for specific management decisions about Arctic fishing. Instead, scientists and decision makers can use them to shape more informed discussions about potential trade‐offs and risks of future fishing in the Arctic. Key Points: Variation and disagreement in marine ecosystem model projections are too high to be informative for near‐term Arctic fisheries managementInsufficient inclusion and knowledge of sea ice cover and sea ice productivity dynamics are major drivers of uncertaintyResearchers should be transparent about uncertainty and risk; present model projections as the basis for hypotheses and scenario planning [ABSTRACT FROM AUTHOR]

Background: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. Methods: Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. Results: Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P <.0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P <.001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P =.001), shorter 6-min walk distance (P =.001), and reduced cardiac performance (cardiac index, P =.016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P =.0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27–5.33; P <.0087). Comparisons of ML–derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62–0.79) for PAH. Conclusions: This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification. [ABSTRACT FROM AUTHOR]

In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100β, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRβ, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments. [ABSTRACT FROM AUTHOR]

Quantitative analysis of electroencephalography (qEEG) is a potential source of biomarkers for neonatal encephalopathy (NE). However, prior studies using qEEG in NE were limited in their generalizability due to individualized techniques for calculating qEEG features or labor-intensive pre-selection of EEG data. We piloted a fully automated method using commercially available software to calculate the suppression ratio (SR), absolute delta power, and relative delta, theta, alpha, and beta power from EEG of neonates undergoing 72 h of therapeutic hypothermia (TH) for NE between April 20, 2018, and November 4, 2019. We investigated the association of qEEG with degree of encephalopathy (modified Sarnat score), severity of neuroimaging abnormalities following TH (National Institutes of Child Health and Development Neonatal Research Network [NICHD-NRN] score), and presence of seizures. Thirty out of 38 patients met inclusion criteria. A more severe modified Sarnat score was associated with higher SR during all phases of TH, lower absolute delta power during all phases except rewarming, and lower relative delta power during the last 24 h of TH. In 21 patients with neuroimaging data, a worse NICHD-NRN score was associated with higher SR, lower absolute delta power, and higher relative beta power during all phases. QEEG features were not significantly associated with the presence of seizures after correction for multiple comparisons. Our results are consistent with those of prior studies using qEEG in NE and support automated qEEG analysis as an accessible, generalizable method for generating biomarkers of NE and response to TH. Additionally, we found evidence of an immature relative frequency composition in neonates with more severe brain injury, suggesting that automated qEEG analysis may have a use in the assessment of brain maturity. [ABSTRACT FROM AUTHOR]

Neonatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of acquired neonatal brain injury with the risk of developing serious neurological sequelae and death. An accurate and robust prediction of short- and long-term outcomes may provide clinicians and families with fundamental evidence for their decision-making, the design of treatment strategies, and the discussion of developmental intervention plans after discharge. Diffusion tensor imaging (DTI) is one of the most powerful neuroimaging tools with which to predict the prognosis of neonatal HIE by providing microscopic features that cannot be assessed by conventional magnetic resonance imaging (MRI). DTI provides various scalar measures that represent the properties of the tissue, such as fractional anisotropy (FA) and mean diffusivity (MD). Since the characteristics of the diffusion of water molecules represented by these measures are affected by the microscopic cellular and extracellular environment, such as the orientation of structural components and cell density, they are often used to study the normal developmental trajectory of the brain and as indicators of various tissue damage, including HIE-related pathologies, such as cytotoxic edema, vascular edema, inflammation, cell death, and Wallerian degeneration. Previous studies have demonstrated widespread alteration in DTI measurements in severe cases of HIE and more localized changes in neonates with mild-to-moderate HIE. In an attempt to establish cutoff values to predict the occurrence of neurological sequelae, MD and FA measurements in the corpus callosum, thalamus, basal ganglia, corticospinal tract, and frontal white matter have proven to have an excellent ability to predict severe neurological outcomes. In addition, a recent study has suggested that a data-driven, unbiased approach using machine learning techniques on features obtained from whole-brain image quantification may accurately predict the prognosis of HIE, including for mild-to-moderate cases. Further efforts are needed to overcome current challenges, such as MRI infrastructure, diffusion modeling methods, and data harmonization for clinical application. In addition, external validation of predictive models is essential for clinical application of DTI to prognostication. [ABSTRACT FROM AUTHOR]

Pyrosomes are colonial tunicates that form gelatinous tubes and occasionally produce bioluminescent swarms. The rapid "bloom‐bust" dynamics of pyrosomes have the potential to outcompete other zooplankton, restructure marine food webs, enhance carbon export, and interfere with human activities. Pyrosomes have been recorded for at least two centuries, yet much remains unknown about their physiology, bloom mechanisms, and ecosystem impacts. Recent bloom reports prompt the question of whether frequencies or densities are increasing, and whether potential population changes are caused by ocean change. This review clarifies current information on pyrosome biology and ecology and explores apparent contradictions in habitat preferences and diel vertical migration (DVM). We posit that the dominant species, Pyrosoma atlanticum, may preferentially inhabit waters below 18°C and alter its DVM activity to maintain overall body temperature near this threshold. Expanding our knowledge of pyrosomes is needed to facilitate their inclusion in ecosystem models and forecasts of future population distributions. [ABSTRACT FROM AUTHOR]

Habitat‐forming organisms provide three‐dimensional structure that supports abundant and diverse communities. Variation in the morphological traits of habitat formers will therefore likely influence how they facilitate associated communities, either via food and habitat provisioning, or by altering predator–prey interactions. These mechanisms, however, are typically studied in isolation, and thus, we know little of how they interact to affect associated communities. In response to this, we used naturally occurring morphological variability in the alga Sargassum vestitum to create habitat units of distinct morphotypes to test whether variation in the morphological traits (frond size and thallus size) of S. vestitum or the interaction between these traits affects their value as habitat for associated communities in the presence and absence of predation. We found morphological traits did not interact, instead having independent effects on epifauna that were negligible in the absence of predation. However, when predators were present, habitat units with large fronds were found to host significantly lower epifaunal abundances than other morphotypes, suggesting that large frond alga provided low‐value refuge from predators. The presence of predators also influenced the size structure of epifaunal communities from habitat units of differing frond size, suggesting that the refuge value of S. vestitum was also related to epifauna body size. This suggests that habitat formers may chiefly structure associated communities by mediating size‐selective predation, and not through habitat provisioning. Furthermore, these results also highlight that habitat traits cannot be considered in isolation, for their interaction with biotic processes can have significant implications for associated communities. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence-based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up-front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6-min walk distance, and NT-proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network. [ABSTRACT FROM AUTHOR]

Anthropogenic activities threaten global biodiversity and ecosystem services. Yet, area-based conservation efforts typically target biodiversity protection whilst minimising conflict with economic activities, failing to consider ecosystem services. Here we identify priority areas that maximise both the protection of mangrove biodiversity and their ecosystem services. We reveal that despite 13.5% of the mangrove distribution being currently strictly protected, all mangrove species are not adequately represented and many areas that provide disproportionally large ecosystem services are missed. Optimising the placement of future conservation efforts to protect 30% of global mangroves potentially safeguards an additional 16.3 billion USD of coastal property value, 6.1 million people, 1173.1 Tg C, and 50.7 million fisher days yr−1. Our findings suggest that there is a pressing need for including ecosystem services in protected area design and that strategic prioritisation and coordination of mangrove conservation could provide substantial benefits to human wellbeing. Mangroves provide ecosystem services but are threatened by anthropogenic activities. This study identifies priority areas that maximise the protection of mangrove biodiversity and ecosystem services. The authors show that biodiversity can be protected whilst maximising ecosystem benefits, with little or no increase in the protected area required. [ABSTRACT FROM AUTHOR]

Objective: To examine the influence of habitus on women's health behavior regarding breastfeeding and subsequent COVID‐19 vaccination. Design: A qualitative descriptive design, guided by Pierre Bourdieu's concept of habitus. Sample: Eighteen women who were postpartum, breastfeeding, and vaccinated against COVID‐ 19 either during pregnancy or while breastfeeding postpartum. Measures: Individual semi‐structured interviews. Results: Two major themes shaped participants' habitus: health‐focused knowledge, and attitudes and beliefs. Attitudes and beliefs included five subthemes: (1) exposure/acceptance/expectations from family, (2) community acceptance of breastfeeding and COVID‐19 vaccination, (3) socioeconomic status, (4) easily accessed support, and (5) outside experiences and exposure. Discussion: An individual's habitus impacts one's knowledge, attitudes, and beliefs and interacts with past behaviors when discussing options for infant feeding and health promoting behaviors such as vaccinations. A better understanding of how health care providers assess and utilize habitus in clinical management is needed. [ABSTRACT FROM AUTHOR]

Marine animal biomass is expected to decrease in the 21st century due to climate driven changes in ocean environmental conditions. Previous studies suggest that the magnitude of the decline in primary production on apex predators could be amplified through the trophodynamics of marine food webs, leading to larger decreases in the biomass of predators relative to the decrease in primary production, a mechanism called trophic amplification. We compared relative changes in producer and consumer biomass or production in the global ocean to assess the extent of trophic amplification. We used simulations from nine marine ecosystem models (MEMs) from the Fisheries and Marine Ecosystem Models Intercomparison Project forced by two Earth System Models under the high greenhouse gas emissions Shared Socioeconomic Pathways (SSP5-8.5) and a scenario of no fishing. Globally, total consumer biomass is projected to decrease by 16.7 ± 9.5% more than net primary production (NPP) by 2090–2099 relative to 1995–2014, with substantial variations among MEMs and regions. Total consumer biomass is projected to decrease almost everywhere in the ocean (80% of the world's oceans) in the model ensemble. In 40% of the world's oceans, consumer biomass was projected to decrease more than NPP. Additionally, in another 36% of the world's oceans consumer biomass is expected to decrease even as projected NPP increases. By analysing the biomass response within food webs in available MEMs, we found that model parameters and structures contributed to more complex responses than a consistent amplification of climate impacts of higher trophic levels. Our study provides additional insights into the ecological mechanisms that will impact marine ecosystems, thereby informing model and scenario development. [ABSTRACT FROM AUTHOR]

Insulin‐like growth factor (IGF) binding proteins (IGFBPs) are a family of growth factor modifiers, some of which are known to be independently associated with pulmonary arterial hypertension (PAH) survival. IGF factor binding protein 7 (IGFBP7) is a unique low‐affinity IGFBP that, independent of IGF, stimulates prostacyclin production. This study proposed to establish associations between IGFBP7 and PAH severity and survival, using enrollment and longitudinal samples. Serum IGFBP7 levels were significantly elevated in patients with PAH compared to controls. After adjusting for age and sex, logarithmic increases in IGFBP7 were associated with a 20 m shorter six‐minute walk distance (6MWD; p < 0.001), a 2−3 mmHg higher mean right atrial pressure (p < 0.001 and 0.02), and a higher likelihood of a greater REVEAL 2.0 risk category placement (p < 0.001). Kaplan−Meier analysis demonstrated significantly decreased survival with IGFBP7 above the median and Cox multivariable analysis adjusted for age and sex, demonstrated higher serum IGFBP7 was an independent predictor of survival. Though the exact mechanism is still unknown, given IGFBP7's role as a prostacyclin stimulant, it has potential use as a therapeutic target for disease modulation. [ABSTRACT FROM AUTHOR]

Climate change is already having profound effects on biodiversity, but climate change adaptation has yet to be fully incorporated into area‐based management tools used to conserve biodiversity, such as protected areas. One main obstacle is the lack of consensus regarding how impacts of climate change can be included in spatial conservation plans. We propose a climate‐smart framework that prioritizes the protection of climate refugia—areas of low climate exposure and high biodiversity retention—using climate metrics. We explore four aspects of climate‐smart conservation planning: (1) climate model ensembles; (2) multiple emission scenarios; (3) climate metrics; and (4) approaches to identifying climate refugia. We illustrate this framework in the Western Pacific Ocean, but it is equally applicable to terrestrial systems. We found that all aspects of climate‐smart conservation planning considered affected the configuration of spatial plans. The choice of climate metrics and approaches to identifying refugia have large effects in the resulting climate‐smart spatial plans, whereas the choice of climate models and emission scenarios have smaller effects. As the configuration of spatial plans depended on climate metrics used, a spatial plan based on a single measure of climate change (e.g., warming) will not necessarily be robust against other measures of climate change (e.g., ocean acidification). We therefore recommend using climate metrics most relevant for the biodiversity and region considered based on a single or multiple climate drivers. To include the uncertainty associated with different climate futures, we recommend using multiple climate models (i.e., an ensemble) and emission scenarios. Finally, we show that the approaches we used to identify climate refugia feature trade‐offs between: (1) the degree to which they are climate‐smart, and (2) their efficiency in meeting conservation targets. Hence, the choice of approach will depend on the relative value that stakeholders place on climate adaptation. By using this framework, protected areas can be designed with improved longevity and thus safeguard biodiversity against current and future climate change. We hope that the proposed climate‐smart framework helps transition conservation planning toward climate‐smart approaches. [ABSTRACT FROM AUTHOR]

Frontal eddies form on the shoreward edge of boundary currents, on average at weekly intervals and can last up to several weeks. This duration allows zooplankton production and completion of the larval stage of fish but may be too ephemeral for longer food chains with planktonic predators to establish. Therefore, frontal eddies may provide a suitable offshore nursery habitat, by entraining and retaining inner‐shelf water, preconditioned with coastal plankton and ichthyoplankton, into an upwelling favorable cyclonic eddy. Here, we briefly describe the behavior of frontal eddies formed by western boundary currents in the context of the fundamental ocean triad, which incorporates three processes for the successful reproduction of fish: nutrient enrichment, food concentration, and retention of larvae. We adapt this hypothesis for frontal eddies adjacent to the substantial fisheries production of continental shelves, creating conditions for enhanced recruitment potential of larval cohorts at a finer scale than previously considered. We review the evidence and investigations of frontal eddies in their capacity to entrain coastal water, sustain the plankton community through eddy uplift and retain distinctive coastal communities of larval fish offshore until larval development is complete. The process of frontal eddy formation is complex and such habitats are irregular yet ubiquitous, which present challenges and opportunities for their study. With the advance of ocean observing systems and integration of physical and biological sampling, frontal eddies provide a novel focus for understanding fisheries production and connectivity of coastal ecosystems. [ABSTRACT FROM AUTHOR]

Proteomic analysis of patients with pulmonary arterial hypertension (PAH) has demonstrated significant abnormalities in the insulin-like growth factor axis (IGF). This study proposed to establish associations between a specific binding protein, insulin-like growth factor binding protein 4 (IGFBP4), and PAH severity as well as survival across varying study cohorts. In all cohorts studied, serum IGFBP4 levels were significantly elevated in PAH compared to controls (p < 0.0001). IGFBP4 concentration was also highest in the connective tissue-associated PAH (CTD-PAH) and idiopathic PAH subtypes (876 and 784 ng/mL, median, respectively). After adjustment for age and sex, IGFBP4 was significantly associated with worse PAH severity as defined by a decreased 6-min walk distance (6MWD), New York heart association functional class (NYHA-FC), REVEAL 2.0 score and higher right atrial pressures. In longitudinal analysis provided by one of the study cohorts, IGFBP4 was prospectively significantly associated with a shorter 6MWD, worse NYHA-FC classification, and decreased survival. Cox multivariable analysis demonstrated higher serum IGFBP4 as an independent predictor of survival in the overall PAHB cohort. Therefore, this study established that higher circulating IGFBP4 levels were significantly associated with worse PAH severity, decreased survival and disease progression. Dysregulation of IGF metabolism/growth axis may play a significant role in PAH cardio-pulmonary pathobiology. [ABSTRACT FROM AUTHOR]

Context: Pomatomus saltatrix is one of few globally distributed pelagic mesopredators that is exploited heavily throughout its range. Despite the implementation of management strategies, the south-western Pacific Ocean (eastern Australian) population has few published estimates of the key life-history parameters including growth. Aims: To estimate the age and growth of P. saltatrix in the south-western Pacific and compare these with the age and growth in other populations. Methods: Age estimates were made using whole otolith readings and an age–length key was used with a length frequency distribution to estimate the age structure of the population. Eight different growth models were compared within a Bayesian framework for both juvenile and overall growth. Key results: The Schnute growth equation provided the best fit for overall growth and yielded parameter values of a = −0.15, b = 2.56, Size-at-age 1 = 24.38-cm fork length (FL) and Size-at-age 4 = 47.36 cm FL. Conclusions: P. saltatrix in the south-western Pacific has a growth rate similar to that in other populations of P. saltatrix. Implications: Despite its geographically and genetically distinct populations, P. saltatrix demonstrates a generally consistent life-history strategy of fast growth and high mortality, except for the north-western Atlantic population, which has lower mortality. This paper presents growth and mortality estimates for tailor (Pomatomus saltatrix) off eastern Australia. The population has a fast growth rate with a high mortality rate. These are generally similar to those in other global populations of P. saltatrix , except in the north-western Atlantic population, which shows lower mortality and regularly gets older and larger individuals. [ABSTRACT FROM AUTHOR]

Estimating demographic changes in a population requires the measurement of some minimal combination of several vital rates, including the flux of individuals into a population, the population growth rate, individual growth rates and mortality rates. For larval fishes, the ratio of instantaneous mortality to growth (i.e., their 'recruitment potential') has been used to make inferences of cohort trajectory where measures of population growth rates are not attainable. Attaining estimates of mortality and growth is an arduous task, and use of the recruitment potential metric has been limited. Here, we relate size spectra of the broader plankton community to the recruitment potential of simultaneously sampled larval Pacific sardines (Sardinops sagax), from three voyages off eastern Australia. As the size structure of a population is determined by the ratio of mortality to growth, and there is remarkable consistency in size spectra across ecosystems, we test the hypothesis that the recruitment potential of larval fish is reflected in community‐level measures of plankton size spectra. Contrary to expectations, results from this study demonstrate a negative relationship between the slope of the plankton size spectra and the recruitment potential of larval Pacific sardine. However, we also demonstrate several other stronger relationships between recruitment potential and physical oceanographic parameters. Together, results suggest plankton size spectra are unlikely to reflect recruitment potential directly. Incorporating some size‐based aspects of the plankton community into a broader modelling framework with a range of oceanographic parameters could further our ability to determine how larval success varies across a seascape. [ABSTRACT FROM AUTHOR]

Continental shelves are key to societal interactions with the oceans, supporting >90% of the world's fisheries through highly productive ecosystems. Previous research has shown that phytoplankton biomass is generally higher on the inner continental shelves, often due to increased nutrient inputs from upwelling or coastal run‐off. However, consistency in observed vertical and horizontal gradients (in abundance, biomass or size) of larger particulates, including zooplankton, on continental shelves has not been established. Using an optical plankton counter and CTD mounted on an undulating towed body, we present high‐resolution vertically resolved profiles of pelagic particle size structure across a continental shelf. Biomass was highest inshore, declining with distance from shore and with depth in the top 100 m of the water column, although the presence of frontal zones can alter this pattern. In the region adjacent to the East Australian Current (EAC), uplift generated by either the EAC interacting with the continental slope or upwelling‐favorable winds, correlated with smaller geometric mean sizes and steeper size spectrum slopes, particularly in the presence of frontal features. South of the EAC separation, the continental shelf water mass was more homogenous but still displayed the same horizontal and vertical patterns in particulate biomass and mean size. By combining our observations in a global comparison, we demonstrate consistent particulate distributions on continental shelves where the inner shelf has higher biomass with a steeper size spectrum slope compared to offshore. The highly productive inner shelf supports zooplankton communities vital to temperate ecosystems and coastal fisheries, through their consistently high biomass. Plain Language Summary: It is commonly accepted that chlorophyll a and phytoplankton are more abundant on continental shelves compared to the open ocean due to nutrient enrichment from either upwelling or terrestrial inputs. Little is known about the consistency in larger particulates, including zooplankton. We present the first depth resolved cross‐shelf transects of zooplankton sized particulates. We show globally consistent patterns where close to the coast there is higher abundance and biomass, smaller geometric mean size and a steeper size spectrum slope representing a more productive community. Key Points: We present the first depth resolved cross‐shelf transects of the abundance, biomass, and geometric mean size of particulate matterHigher biomass and abundance were generally found close to the coast likely representing a more productive communityThese patterns were consistent globally but can show significant small‐scale variation around frontal zones [ABSTRACT FROM AUTHOR]

Alterations of serine/threonine phosphorylation of the cardiac proteome are a hallmark of heart failure. However, the contribution of tyrosine phosphorylation (pTyr) to the pathogenesis of cardiac hypertrophy remains unclear. We use global mapping to discover and quantify site-specific pTyr in two cardiac hypertrophic mouse models, i.e., cardiac overexpression of ErbB2 (TgErbB2) and α myosin heavy chain R403Q (R403Q-αMyHC Tg), compared to control hearts. From this, there are significant phosphoproteomic alterations in TgErbB2 mice in right ventricular cardiomyopathy, hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM) pathways. On the other hand, R403Q-αMyHC Tg mice indicated that the EGFR1 pathway is central for cardiac hypertrophy, along with angiopoietin, ErbB, growth hormone, and chemokine signaling pathways activation. Surprisingly, most myofilament proteins have downregulation of pTyr rather than upregulation. Kinase-substrate enrichment analysis (KSEA) shows a marked downregulation of MAPK pathway activity downstream of k-Ras in TgErbB2 mice and activation of EGFR, focal adhesion, PDGFR, and actin cytoskeleton pathways. In vivo ErbB2 inhibition by AG-825 decreases cardiomyocyte disarray. Serine/threonine and tyrosine phosphoproteome confirm the above-described pathways and the effectiveness of AG-825 Treatment. Thus, altered pTyr may play a regulatory role in cardiac hypertrophic models. Quantitative global phosphotyrosine proteomics of two mouse models of hypertrophic cardiomyopathy reveals that tyrosine kinase inhibitors may be a future therapeutic approach for treating hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Larval dispersal and connectivity have important implications for fisheries management, especially for species with life cycles influenced by ocean boundary currents. Giant Mud Crab (Scylla serrata) and Blue Swimmer Crab (Portunus armatus) are two estuarine portunid crabs (Family: Portunidae) that support significant commercial and recreational harvest in eastern Australia. Giant Mud Crab migrate to coastal waters to spawn, and while Blue Swimmer Crab spawn primarily within estuaries they occasionally migrate to coastal waters to spawn, followed by larval dispersal in the East Australian Current (EAC). Here, we coupled a high‐resolution oceanographic model with a Lagrangian particle tracking framework to simulate larval dispersal and determine the extent of population connectivity in this region. Our simulations indicate broad‐scale connectivity (~40–400 km), characterised by high inter‐estuary connectivity. Overall, our results suggest a north‐to‐south source‐sink structure for both species, with contributions of particles from the north ranging from 51% to 99%. Recruitment to a given estuary is dependent on the proximity of mesoscale oceanographic features of the EAC. Most notably, the EAC separation acts as a barrier to recruitment between spawning and settlement to the north/south of this region. This significantly limits interjurisdictional connectivity for these species, especially Blue Swimmer Crab, likely due to a shorter pelagic larval duration than Giant Mud Crab. Our results provide evidence to inform the assessment and management of these species. [ABSTRACT FROM AUTHOR]

Although zooplankton play a substantial role in the biological carbon pump and serve as a crucial link between primary producers and higher trophic level consumers, the skillful representation of zooplankton is not often a focus of ocean biogeochemical models. Systematic evaluations of zooplankton in models could improve their representation, but so far, ocean biogeochemical skill assessment of Earth system model (ESM) ensembles have not included zooplankton. Here we use a recently developed global, observationally based map of mesozooplankton biomass to assess the skill of mesozooplankton in six CMIP6 ESMs. We also employ a biome‐based assessment of the ability of these models to reproduce the observed relationship between mesozooplankton biomass and surface chlorophyll. The combined analysis found that most models were able to reasonably simulate the large regional variations in mesozooplankton biomass at the global scale. Additionally, three of the ESMs simulated a mesozooplankton‐chlorophyll relationship within the observational bounds, which we used as an emergent constraint on future mesozooplankton projections. We highlight where differences in model structure and parameters may give rise to varied mesozooplankton distributions under historic and future conditions, and the resultant wide ensemble spread in projected changes in mesozooplankton biomass. Despite differences, the strength of the mesozooplankton‐chlorophyll relationships across all models was related to the projected changes in mesozooplankton biomass globally and in regional biomes. These results suggest that improved observations of mesozooplankton and their relationship to chlorophyll will better constrain projections of climate change impacts on these important animals. Plain Language Summary: Zooplankton are marine animals that have a key role in transferring carbon from the atmosphere deeper into the ocean. They also serve as a crucial link in food chains between microscopic marine plants (phytoplankton) and predators like fish and whales. Researchers have created mathematical representations (models) of the linked processes of the oceans, atmosphere, and land, most of which include zooplankton. Yet how well these models represent zooplankton has not been adequately tested. We compared observations of zooplankton biomass to model estimates. We explored if these models reproduce the observed relationship between zooplankton biomass and chlorophyll concentration, which is useful for assessing how well the models represent predator‐prey relationships. Five of six models had similar patterns and comparable average biomasses across the global ocean as the observations. The historic relationship in three models fell within the observed relationship. The strength of the relationships across all models was related to how much zooplankton biomass will decrease with climate change. To improve the representation of zooplankton in models, we need better observations of the relationships between organisms. This would advance estimates of carbon transfer to the deep sea and carbon available to fish, and how they will change with climate change. Key Points: On the global scale, five of six models that include mesozooplankton perform moderately well with respect to the observationsWe identify an emergent constraint using the mesozooplankton versus chlorophyll relationship that can help constrain zooplankton projectionsMore attention needs to be paid to prey preferences, food web structure and temperature sensitivity in addition to existing key parameters [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal acquired brain injury. Although conventional MRI may predict neurodevelopmental outcomes, accurate prognostication remains difficult. As diffusion tensor imaging (DTI) may provide an additional diagnostic and prognostic value over conventional MRI, we aimed to develop a composite DTI (cDTI) score to relate to short-term neurological function. Sixty prospective neonates treated with therapeutic hypothermia (TH) for HIE were evaluated with DTI, with a voxel size of 1 x 1 x 2 mm. Fractional anisotropy (FA) and mean diffusivity (MD) from 100 neuroanatomical regions (FA/MD *100 = 200 DTI parameters in total) were quantified using an atlas-based image parcellation technique. A least absolute shrinkage and selection operator (LASSO) regression was applied to the DTI parameters to generate the cDTI score. Time to full oral nutrition [short-term oral feeding (STO) score] was used as a measure of short-term neurological function and was correlated with extracted DTI features. Seventeen DTI parameters were selected with LASSO and built into the final unbiased regression model. The selected factors included FA or MD values of the limbic structures, the corticospinal tract, and the frontotemporal cortices. While the cDTI score strongly correlated with the STO score (rho = 0.83, p = 2.8 x 10-16), it only weakly correlated with the Sarnat score (rho = 0.27, p = 0.035) and moderately with the NICHD-NRN neuroimaging score (rho = 0.43, p = 6.6 x 10-04). In contrast to the cDTI score, the NICHD-NRN score only moderately correlated with the STO score (rho = 0.37, p = 0.0037). Using a mixed-model analysis, interleukin-10 at admission to the NICU (p = 1.5 x 10-13) and tau protein at the end of TH/rewarming (p = 0.036) and after rewarming (p = 0.0015) were significantly associated with higher cDTI scores, suggesting that high cDTI scores were related to the intensity of the early inflammatory response and the severity of neuronal impairment after TH. In conclusion, a data-driven unbiased approach was applied to identify anatomical structures associated with some aspects of neurological function of HIE neonates after cooling and to build a cDTI score, which was correlated with the severity of short-term neurological functions. [ABSTRACT FROM AUTHOR]

Knowing the distribution of fish larvae can inform fisheries science and resource management in several ways, by: 1) providing information on spawning areas; 2) identifying key areas to manage and conserve; and 3) helping to understand how fish populations are affected by anthropogenic pressures, such as overfishing and climate change. With the expansion of industrial fishing activity after 1945, there was increased sampling of fish larvae to help better understand variation in fish stocks. However, large-scale larval records are rare and often unavailable. Here we digitize data from Nishikawa et al. (1985), which were collected from 1956–1981 and are near-global (50°N–50°S), seasonal distribution maps of fish larvae of 18 mainly commercial pelagic taxa of the families Scombridae, Xiphiidae, Istiophoridae, Scombrolabracidae, and Scomberesocidae. Data were collected from the Pacific, Atlantic, and Indian Oceans. We present four seasonal 1° × 1° resolution maps per taxa representing larval abundance per grid cell and highlight some of the main patterns. Data are made available as delimited text, raster, and vector files. Measurement(s) larva abundance Technology Type(s) tows Factor Type(s) location of tows Sample Characteristic - Organism fish taxa Sample Characteristic - Environment open-ocean Sample Characteristic - Location near-global (Atlantic, Pacific, and Indian Oceans) [ABSTRACT FROM AUTHOR]

Climate change is expected to profoundly affect key food production sectors, including fisheries and agriculture. However, the potential impacts of climate change on these sectors are rarely considered jointly, especially below national scales, which can mask substantial variability in how communities will be affected. Here, we combine socioeconomic surveys of 3,008 households and intersectoral multi-model simulation outputs to conduct a sub-national analysis of the potential impacts of climate change on fisheries and agriculture in 72 coastal communities across five Indo-Pacific countries (Indonesia, Madagascar, Papua New Guinea, Philippines, and Tanzania). Our study reveals three key findings: First, overall potential losses to fisheries are higher than potential losses to agriculture. Second, while most locations (> 2/3) will experience potential losses to both fisheries and agriculture simultaneously, climate change mitigation could reduce the proportion of places facing that double burden. Third, potential impacts are more likely in communities with lower socioeconomic status. Responses of agriculture and fisheries to climate change are interlinked, yet rarely studied together. Here, the authors analyse more than 3000 households from 5 tropical countries and forecast mid-century climate change impacts, finding that communities with higher fishery dependence and lower socioeconomic status communities face greater losses. [ABSTRACT FROM AUTHOR]

Context: Zooplanktivorous fish are a key link between abundant zooplankton and higher trophic levels but the foraging behaviour of zooplanktivorous fish is not fully understood. Selective feeding behaviours have been observed, with many species of planktivorous fish targeting certain species and sizes of zooplankton for prey. However, why certain size classes of zooplankton are preferred remains unclear. Aim: This study investigated prey selection by three zooplanktivorous fish species through the lens of optimal foraging theory. Methods: We assessed the size structure of zooplankton in the environment and compared this with the size distribution of zooplankton in gut contents from three zooplanktivorous fish. Key results: The targeted prey size of Atypichthys strigatus and Scorpis lineolata aligns with the prey size classes in the environment that contain the highest overall biomass. Trachurus novaezelandiae showed little evidence of targeting these size classes. Conclusions: These prey sizes therefore represent the most efficient prey to target because the return on foraging effort is greatest. By contrast, T. novaezelandiae showed only an underselection of large and small prey. Implications: By incorporating this information on this key trophic link between zooplankton and fish, ecosystem models could better resolve the size dependant predation, particularly in size-based models. This paper shows that 2 of 3 species of estuarine fish target specific sizes of zooplankton rather than eating everything they encounter. This pattern is driven by the fish attempting to maximise the biomass consumed by targeting the zooplankton size classes with the most overall biomass in the environment. [ABSTRACT FROM AUTHOR]

Predicting recruitment remains a fundamental problem in fisheries science. The Mortality/Growth ratio (M/G) of larval fish summarizes the competing rates of M and G in relation to cohort survival and potential recruitment. The larval cohort biomass initially declines after spawning (M > G) until transition (M/G = 1), after which the cohort may grow in biomass (M < G). A major challenge is to obtain routine fine‐scale measurements of M/G and integrate them over broad scales. Here, we propose the M/G size‐spectrum hypothesis, whereby the M/G ratio of larval fish is correlated with the slope (S) of the zooplankton size‐frequency distribution. S represents the tension between faster and more efficient growth (flatter S) and mortality (steeper S) among particles the size of larval fish. S is explicitly driven by the ratio of mortality to growth of zooplankton, and the range of published values of S (−0.4 to −2) is consistent with M/G ratios reported for larval fish. As S can be measured at fine and large spatial scales using towed optical plankton counters, the M/G size‐spectrum hypothesis provides a context to help quantify the recruitment potential of larval fish. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by sustained elevations of pulmonary artery pressure. To date, we lack circulating, diagnostic, and prognostic markers that correlate to clinical and functional parameters. In this study, we performed mass spectrometry‐based proteomics analysis to identify circulating biomarkers of PAH. Plasma samples from patients with idiopathic pulmonary arterial hypertension (IPAH, N=9) and matched normal controls (N = 9) were digested with trypsin and analyzed using data‐dependent acquisition on an Orbitrap mass spectrometer. A total of 826 (false discovery rate [FDR] 0.047) and 461 (FDR 0.087) proteins were identified across all plasma samples obtained from IPAH and control subjects, respectively. Of these, 153 proteins showed >2 folds change (p < 0.05) between groups. Circulating levels of carbonic anhydrase 2 (CA2), plasma kallikrein (KLKB1), and the insulin‐like growth factor binding proteins (IGFBP1‐7) were quantified by immunoassay in an independent verification cohort (N=36 PAH and N = 35 controls). CA2 and KLKB1 were significantly different in PAH versus control but were not associated with any functional or hemodynamic measurements. Whereas, IGFBP1 and 2 were associated with higher pulmonary vascular resistance, IGFBP2, 4, and 7 with decreased 6‐min walk distance (6MWD), and IGFBP1, 2, 4, and 7 with worse survival. This plasma proteomic discovery analysis suggests the IGF axis may serve as important new biomarkers for PAH and play an important role in PAH pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Neonates are at risk of gastrointestinal emergencies including necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP). Identifying biomarkers to aid in diagnosis is imperative. We hypothesized that circulating intestinal-specific protein concentrations would distinguish infants with intestinal injury from controls. Aims: To identify serum concentrations of intestinal-specific protein(s) in infants with intestinal injury and controls. Methods: We used an in silico approach to identify intestinal-specific proteins. We collected serum from control infants and infants with NEC or SIP and measured protein concentrations using ELISA. If baseline concentrations were near the detection limit in initial control assays, we proceeded to assess concentrations in a larger cohort of controls and infants with injury. Control infants were frequency matched to infants with injury and compared with nonparametric and mixed-effects models analysis. Results: We evaluated four proteins with high intestinal expression: Galectin-4 (Gal-4), S100G, Trefoil Factor-3, and alanyl aminopeptidase. Only Gal-4 demonstrated consistent results near the lower limit of quantification in controls and was studied in the larger cohorts. Gal-4 concentration was low in 111 control infants (median 0.012 ng/ml). By contrast, Gal-4 was significantly increased at diagnosis in infants with surgical NEC and SIP (n = 14, p ≤ 0.001 and n = 8, p = 0.031) compared to matched controls, but not in infants with medical NEC (n = 32, p = 0.10). Conclusions: Of the intestinal-specific proteins evaluated, circulating Gal-4 concentrations were at the assay detection limit in control infants. Gal-4 concentrations were significantly elevated in infants with surgical NEC or SIP, suggesting that Gal-4 may serve as a biomarker for neonatal intestinal injury. [ABSTRACT FROM AUTHOR]

Plankton is a massive and phylogenetically diverse group of thousands of prokaryotes, protists (unicellular eukaryotic organisms), and metazoans (multicellular eukaryotic organisms; Fig. It is essential that plankton data - including plankton EOVs - are available together with physical and biogeochemical EOV data/metadata (environmental data along with physiological and functional trait data). The Marine Biodiversity Observation Network Plankton Workshops: Plankton Ecosystem Function, Biodiversity, and Forecasting - Research Requirements and Applications. [Extracted from the article]

Hepatoma‐derived growth factor (HDGF) was previously shown to be associated with increased mortality in a small study of idiopathic and connective tissue disease‐associated pulmonary arterial hypertension (PAH). In this study, we measured serum HDGF levels in a large multicenter cohort (total 2017 adult PAH‐Biobank enrollees), we analyzed the associations between HDGF levels and various clinical measures using linear or logistic regression models. Higher HDGF levels were found to be significantly associated with worse pulmonary hemodynamics, prostacyclin treatment; among PAH subtypes, higher HDGF levels were most associated with portopulmonary hypertension (beta = 0.469, p < 0.0001). Both Kaplan–Meier curve and Cox proportional hazard regression demonstrated that higher HDGF levels are associated with a higher risk of mortality (COX hazard ratio 1.31, p < 0.0001). Further, in the Sugen hypoxia (SuHx) rat model, the highest HDGF levels were post‐pulmonary circulation, and HDGF levels significantly increased with the development of PAH. In pulmonary arteries, immunohistochemistry staining showed that HDGF was highly expressed in pulmonary smooth muscle cells in both PAH patients and SuHx rats. In conclusion, we found that higher serum HDGF was linked with increased mortality, and associated with disease severity in a large multi‐center adult PAH cohort (n = 2017). In the SuHX PAH models, circulating HDGF levels are pulmonary in origin and increase with PAH progression. HDGF may be actively involved in vascular remodeling in PAH. [ABSTRACT FROM AUTHOR]

Objective: To determine the changes due to therapeutic hypothermia (TH) exposure in the strength of association between traditional clinical and biochemical indicators of severity of neonatal hypoxic-ischemic encephalopathy (HIE) and serum biomarkers. We hypothesized that culmination of TH changes the strength of the relationships between traditional indicators of severity of HIE and serum biomarkers. Methods: This was a single-center observational cohort study of 178 neonates with HIE treated with TH and followed with serum biomarkers: (i) brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) (neurotrophins); (ii) tau and glial fibrillary acidic protein (GFAP) (neural cell injury); and (iii) interleukin 6 (IL-6), IL-8, and IL-10 (cytokines), during their first week of life. Adjusted mixed-effect models tested associations with HIE indicators in relation to TH exposure. Results: At admission, lower Apgar scores and base excess (BE) and higher lactate and nucleated red blood cell (NRBC) count correlated with higher Sarnat scores. These indicators of worse HIE severity, including higher Sarnat score, correlated with lower VEGF and higher tau, GFAP, and IL-10 levels at different time points. Within the first 24 h of life, patients with a Sarnat score >2 had lower VEGF levels, whereas only those with score of 3 also had higher GFAP and IL-10 levels. Tau levels increased during TH in patients with Sarnat score of 3, whereas tau and GFAP increased after TH in those with scores of 2. After adjustments, lower VEGF levels during TH and higher tau, GFAP, and IL-10 levels during and after TH were associated with worse Sarnat scores. Tau and GFAP relationship with Sarnat score became stronger after TH. Conclusion: Therapeutic hypothermia exerts an independent modulatory effect in the relationships between traditional indicators of severity of HIE and serum biomarkers after adjustments. Thus, the timing of biomarker testing in relation to TH exposure must be carefully considered if biomarkers are proposed for patient stratification in novel clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Several short‐term readmission and mortality prediction models have been developed using clinical risk factors or biomarkers among patients undergoing coronary artery bypass graft (CABG) surgery. The use of biomarkers for long‐term prediction of readmission and mortality is less well understood. Given the established association of cardiac biomarkers with short‐term adverse outcomes, we hypothesized that 5‐year prediction of readmission or mortality may be significantly improved using cardiac biomarkers. Materials and Methods: Plasma biomarkers from 1149 patients discharged alive after isolated CABG surgery from eight medical centers were measured in a cohort from the Northern New England Cardiovascular Disease Study Group between 2004 and 2007. We assessed the added predictive value of a biomarker panel with a clinical model against the clinical model alone and compared the model discrimination using the area under the receiver operating characteristic (AUROC) curves. Results: In our cohort, 461 (40%) patients were readmitted or died within 5 years. Long‐term outcomes were predicted by applying the STS ASCERT clinical model with an AUROC of 0.69. The biomarker panel with the clinical model resulted in a significantly improved AUROC of 0.74 (p value <.0001). Across 5 years, the hazard ratio for patients in the second to fifth quintile predicted probabilities from the biomarker augmented STS ASCERT model ranged from 2.2 to 7.9 (p values <.001). Conclusions: We report that a panel of biomarkers significantly improved prediction of long‐term readmission or mortality risk following CABG surgery. Our findings suggest biomarkers help clinical care teams better assess the long‐term risk of readmission or mortality. [ABSTRACT FROM AUTHOR]