Summary: 1. Plant growth is a fundamental ecological process, integrating across scales from physiology to community dynamics and ecosystem properties. Recent improvements in plant growth modelling have allowed deeper understanding and more accurate predictions for a wide range of ecological issues, including competition among plants, plant–herbivore interactions and ecosystem functioning.2. One challenge in modelling plant growth is that, for a variety of reasons, relative growth rate (RGR) almost universally decreases with increasing size, although traditional calculations assume that RGR is constant. Nonlinear growth models are flexible enough to account for varying growth rates.3. We demonstrate a variety of nonlinear models that are appropriate for modelling plant growth and, for each, show how to calculate function‐derived growth rates, which allow unbiased comparisons among species at a common time or size. We show how to propagate uncertainty in estimated parameters to express uncertainty in growth rates. Fitting nonlinear models can be challenging, so we present extensive worked examples and practical recommendations, all implemented in R.4. The use of nonlinear models coupled with function‐derived growth rates can facilitate the testing of novel hypotheses in population and community ecology. For example, the use of such techniques has allowed better understanding of the components of RGR, the costs of rapid growth and the linkage between host and parasite growth rates. We hope this contribution will demystify nonlinear modelling and persuade more ecologists to use these techniques.

The indirect water-deprivation test is the current reference standard for the diagnosis of diabetes insipidus. However, it is technically cumbersome to administer, and the results are often inaccurate. The current study compared the indirect water-deprivation test with direct detection of plasma copeptin, a precursor-derived surrogate of arginine vasopressin.

Significance Statement: Treatment options for the syndrome of inappropriate antidiuresis (SIAD), the predominant cause of hyponatremia, are inadequate. The authors studied the effects of the sodium glucose cotransporter 2 inhibitor empagliflozin, which promotes osmotic diuresis via urinary glucose excretion, in a randomized trial of 87 hospitalized patients with SIAD-induced hyponatremia who were also treated with standard fluid restriction. Patients who received 4 days of empagliflozin had a significantly larger increase in plasma sodium compared with those who received placebo (10 versus 7 mmol/L, respectively). Profound hyponatremia (<125 mmol/L) and lower baseline osmolality levels increased the likelihood of response to treatment with empagliflozin. These findings suggest that further investigation of empagliflozin as a treatment option for hospitalized patients with SIAD-induced hyponatremia is warranted. Background: Treatment options to address the hyponatremia induced by the syndrome of inappropriate antidiuresis (SIAD) are inadequate. The sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresis via urinary glucose excretion and therefore, might offer a novel treatment option for SIAD. Methods: In this double-blind, randomized trial, we recruited 88 hospitalized patients with SIAD-induced hyponatremia <130 mmol/L at the University Hospital Basel from September 2016 until January 2019 and assigned patients to receive, in addition to standard fluid restriction of <1000 ml/24 h, a once-daily dose of oral empagliflozin or placebo for 4 days. The primary end point was the absolute change in plasma sodium concentration after 4 days of treatment. Secondary end points included predisposing factors for treatment response and safety of the intervention. Results: Of the 87 patients who completed the trial, 43 (49%) received treatment with empagliflozin, and 44 (51%) received placebo. Baseline plasma sodium concentrations were similar for the two groups (median 125.5 mmol/L for the empaflozin group and median 126 mmol/L for the placebo group). Patients treated with empagliflozin had a significantly higher increase of median plasma sodium concentration compared with those receiving placebo (10 versus 7 mmol/L, respectively; P=0.04). Profound hyponatremia (<125 mmol/L) and lower baseline osmolality levels increased the likelihood of response to treatment with empagliflozin. Treatment was well tolerated, and no events of hypoglycemia or hypotension occurred among those receiving empagliflozin. Conclusions: Among hospitalized patients with SIAD treated with fluid restriction, those who received empagliflozin had a larger increase in plasma sodium levels compared with those who received placebo. This finding indicates that empagliflozin warrants further study as a treatment for the disorder.

BACKGROUND: Alcohol use disorder has a detrimental impact on global health and new treatment targets are needed. Preclinical studies show attenuating effects of glucagon-like peptide-1 (GLP-1) agonists on addiction-related behaviors in rodents and nonhuman primates. Some trials have shown an effect of GLP-1 agonism on reward processes in humans; however, results from clinical studies remain inconclusive. METHODS: This is a predefined secondary analysis of a double-blind, randomized, placebo-controlled trial evaluating the GLP-1 agonist dulaglutide as a therapy for smoking cessation. The main objective was to assess differences in alcohol consumption after 12 weeks of treatment with dulaglutide compared to placebo. The effect of dulaglutide on alcohol consumption was analyzed using a multivariable generalized linear model. RESULTS: In the primary analysis, participants out of the cohort ( n = 255) who reported drinking alcohol at baseline and who completed 12 weeks of treatment ( n = 151; placebo n = 75, dulaglutide n = 76) were included. The median age was 42 (IQR 33–53) with 61% ( n = 92) females. At week 12, participants receiving dulaglutide drank 29% less (relative effect = 0.71, 95% CI 0.52–0.97, P = 0.04) than participants receiving placebo. Changes in alcohol consumption were not correlated with smoking status at week 12. CONCLUSION: These results provide evidence that dulaglutide reduces alcohol intake in humans and contribute to the growing body of literature promoting the use of GLP-1 agonists in treatment of substance use disorders. TRIAL REGISTRATION: ClinicalTrials.gov NCT03204396. FUNDING: Swiss National Foundation, Gottfried Julia Bangerter-Rhyner Foundation, Goldschmidt-Jacobson Foundation, Hemmi Foundation, University of Basel, University Hospital Basel, Swiss Academy of Medical Science.