Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

BackgroundHistologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD.MethodsThis was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0–4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0–2 vs F3 vs F4; LSM: 2·67; NFS: 0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226.FindingsOf 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44–63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33–91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62–0·81) for histology, 0·76 (0·70–0·83) for LSM-VCTE, 0·74 (0·64–0·82) for FIB-4, and 0·70 (0·63–0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression.InterpretationSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases

Determining cardinal temperatures for eight cover crop species

Abstract Growing degree days (GDD) is a tool to predict plant growth and can be adapted for use in any plant species, including cover crops. A limitation of the GDD calculation is accurate temperature parameters used to predict plant development. For most cover crop species, the cardinal temperatures are not well defined in the literature, leading to a less accurate calculation of GDD. The objective of this study was to determine the cardinal temperatures of eight cover crop species, including Austrian winter pea (Pisum sativum), balansa clover (Trifolium michelianum), barley (Hordeum vulgare), black‐seeded oats (Avena sativa), common vetch (Vicia sativa), cereal rye (Secale cereale), crimson clover (Trifolium incarnatum), and hairy vetch (Vicia villosa), using a growth chamber experiment. Seven different temperature regimes from 4 to 34°C were implemented, and the number of leaves was counted from day 0 to 21. As a result, the data were regressed to estimate the cardinal temperatures for each species. The results of this research identified base (2), optimum (3), and maximum (8) temperatures for cover crops that were not previously reported. Five cardinal temperatures determined in this study were different from what was previously recorded; base and optimum temperatures were −4.5 and 24.8°C for cereal rye, 3.9 and 26.6°C for crimson clover, and the base temperature was 3.4°C for balansa clover. The successful identification of these cardinal temperatures for cover crops will allow the development of plant growth and biomass prediction models to aid in cover crop termination decision support tools

Smart food policies for obesity prevention

Artículo de publicación ISIPrevention of obesity requires policies that work. In this Series paper, we propose a new way to understand how food policies could be made to work more effectively for obesity prevention. Our approach draws on evidence from a range of disciplines (psychology, economics, and public health nutrition) to develop a theory of change to understand how food policies work. We focus on one of the key determinants of obesity: diet. The evidence we review suggests that the interaction between human food preferences and the environment in which those preferences are learned, expressed, and reassessed has a central role. We identify four mechanisms through which food policies can affect diet: providing an enabling environment for learning of healthy preferences, overcoming barriers to the expression of healthy preferences, encouraging people to reassess existing unhealthy preferences at the point-of-purchase, and stimulating a food-systems response. We explore how actions in three specific policy areas (school settings, economic instruments, and nutrition labelling) work through these mechanisms, and draw implications for more effective policy design. We find that effective food-policy actions are those that lead to positive changes to food, social, and information environments and the systems that underpin them. Effective food-policy actions are tailored to the preference, behavioural, socioeconomic, and demographic characteristics of the people they seek to support, are designed to work through the mechanisms through which they have greatest effect, and are implemented as part of a combination of mutually reinforcing actions. Moving forward, priorities should include comprehensive policy actions that create an enabling environment for infants and children to learn healthy food preferences and targeted actions that enable disadvantaged populations to overcome barriers to meeting healthy preferences. Policy assessments should be carefully designed on the basis of a theory of change, using indicators of progress along the various pathways towards the long-term goal of reducing obesity rates.National Collaborative on Childhood Obesity Research (NCCOR) Envision Project from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 1R01HD0802

Scaling, similarity, and the fourth paradigm for hydrology

In this synthesis paper addressing hydrologic scaling and similarity, we posit that roadblocks in the search for universal laws of hydrology are hindered by our focus on computational simulation (the third paradigm) and assert that it is time for hydrology to embrace a fourth paradigm of data-intensive science. Advances in information-based hydrologic science, coupled with an explosion of hydrologic data and advances in parameter estimation and modeling, have laid the foundation for a data-driven framework for scrutinizing hydrological scaling and similarity hypotheses. We summarize important scaling and similarity concepts (hypotheses) that require testing; describe a mutual information framework for testing these hypotheses; describe boundary condition, state, flux, and parameter data requirements across scales to support testing these hypotheses; and discuss some challenges to overcome while pursuing the fourth hydrological paradigm. We call upon the hydrologic sciences community to develop a focused effort towards adopting the fourth paradigm and apply this to outstanding challenges in scaling and similarity

Hepatic Activin E mediates liver-adipose inter-organ communication, suppressing adipose lipolysis in response to elevated serum fatty acids

Objective: The liver is a central regulator of energy metabolism exerting its influence both through intrinsic processing of substrates such as glucose and fatty acid as well as by secreting endocrine factors, known as hepatokines, which influence metabolism in peripheral tissues. Human genome wide association studies indicate that a predicted loss-of-function variant in the Inhibin βE gene (INHBE), encoding the putative hepatokine Activin E, is associated with reduced abdominal fat mass and cardiometabolic disease risk. However, the regulation of hepatic Activin E and the influence of Activin E on adiposity and metabolic disease are not well understood. Here, we examine the relationship between hepatic Activin E and adipose metabolism, testing the hypothesis that Activin E functions as part of a liver-adipose, inter-organ feedback loop to suppress adipose tissue lipolysis in response to elevated serum fatty acids and hepatic fatty acid exposure. Methods: The relationship between hepatic Activin E and non-esterified fatty acids (NEFA) released from adipose lipolysis was assessed in vivo using fasted CL 316,243 treated mice and in vitro using Huh7 hepatocytes treated with fatty acids. The influence of Activin E on adipose lipolysis was examined using a combination of Inhbe knockout mice, a mouse model of hepatocyte-specific overexpression of Activin E, and mouse brown adipocytes treated with Activin E enriched media. Results: Increasing hepatocyte NEFA exposure in vivo by inducing adipose lipolysis through fasting or CL 316,243 treatment increased hepatic Inhbe expression. Similarly, incubation of Huh7 human hepatocytes with fatty acids increased expression of INHBE. Genetic ablation of Inhbe in mice increased fasting circulating NEFA and hepatic triglyceride accumulation. Treatment of mouse brown adipocytes with Activin E conditioned media and overexpression of Activin E in mice suppressed adipose lipolysis and reduced serum FFA levels, respectively. The suppressive effects of Activin E on lipolysis were lost in CRISPR-mediated ALK7 deficient cells and ALK7 kinase deficient mice. Disruption of the Activin E-ALK7 signaling axis in Inhbe KO mice reduced adiposity upon HFD feeding, but caused hepatic steatosis and insulin resistance. Conclusions: Taken together, our data suggest that Activin E functions as part of a liver-adipose feedback loop, such that in response to increased serum free fatty acids and elevated hepatic triglyceride, Activin E is released from hepatocytes and signals in adipose through ALK7 to suppress lipolysis, thereby reducing free fatty acid efflux to the liver and preventing excessive hepatic lipid accumulation. We find that disrupting this Activin E-ALK7 inter-organ communication network by ablation of Inhbe in mice increases lipolysis and reduces adiposity, but results in elevated hepatic triglyceride and impaired insulin sensitivity. These results highlight the liver-adipose, Activin E-ALK7 signaling axis as a critical regulator of metabolic homeostasis

Scaling, similarity, and the fourth paradigm for hydrology

In this synthesis paper addressing hydrologic scaling and similarity, we posit that roadblocks in the search for universal laws of hydrology are hindered by our focus on computational simulation (the third paradigm) and assert that it is time for hydrology to embrace a fourth paradigm of data-intensive science. Advances in information-based hydrologic science, coupled with an explosion of hydrologic data and advances in parameter estimation and modeling, have laid the foundation for a data-driven framework for scrutinizing hydrological scaling and similarity hypotheses. We summarize important scaling and similarity concepts (hypotheses) that require testing; describe a mutual information framework for testing these hypotheses; describe boundary condition, state, flux, and parameter data requirements across scales to support testing these hypotheses; and discuss some challenges to overcome while pursuing the fourth hydrological paradigm. We call upon the hydrologic sciences community to develop a focused effort towards adopting the fourth paradigm and apply this to outstanding challenges in scaling and similarity.Water Resource

Island colonisation leads to rapid behavioural and morphological divergence in Anolis lizards

Islands are hotspots of endemism and often function as engines of adaptive radiation. Nevertheless, we lack a deep understanding of the processes that generate phenotypic divergence when populations first colonise islands. Important questions include: (1) Do populations experience shifts in habitat use and behaviour with reduced competition and predation, and how fast do these changes occur? (2) Do shifts in niche occupancy result in morphological divergence from mainland populations? To investigate these questions, we transplanted 210 slender anole lizards (Anolis apletophallus) from mainland Panama to three islands in the Panama Canal that are likely species-poor compared to the mainland. We compared habitat use, flight initiation distance, and morphology among populations across two generations of divergence. We found that island lizards changed their behaviour immediately after colonisation, perching on lower and broader surfaces and allowing observers to approach more closely before fleeing. Although we found only weak evidence for an association between survival and morphological trait variation, trait means in the second generation often shifted in the direction expected if selection had acted on the founders. Our results indicate that colonising individuals can change their behaviour rapidly to exploit new structural niches, and that substantial shifts in morphology can occur after only a single generation. These changes, which are probably facilitated by ecological release, may represent the first steps in adaptive radiation of island lineages