Productivity denotes the rate of biomass synthesis in ecosystems and is a fundamental characteristic that frames ecosystem function and management. Limitation of productivity by nutrient availability ...is an established paradigm for lake ecosystems. Here, we assess the relevance of this paradigm for a majority of the world's small, nutrient-poor lakes, with different concentrations of coloured organic matter. By comparing small unproductive lakes along a water colour gradient, we show that coloured terrestrial organic matter controls the key process for new biomass synthesis (the benthic primary production) through its effects on light attenuation. We also show that this translates into effects on production and biomass of higher trophic levels (benthic invertebrates and fish). These results are inconsistent with the idea that nutrient supply primarily controls lake productivity, and we propose that a large share of the world's unproductive lakes, within natural variations of organic carbon and nutrient input, are limited by light and not by nutrients. We anticipate that our result will have implications for understanding lake ecosystem function and responses to environmental change. Catchment export of coloured organic matter is sensitive to short-term natural variability and long-term, large-scale changes, driven by climate and different anthropogenic influences. Consequently, changes in terrestrial carbon cycling will have pronounced effects on most lake ecosystems by mediating changes in light climate and productivity of lakes.
Amyotrophic lateral sclerosis (ALS) is an invariably lethal progressive disease, causing degeneration of neurons and muscle. No current treatment halts or reverses disease advance. This single arm, ...open label, clinical trial in patients with ALS investigated the safety and tolerability of a novel modified low molecular weight dextran sulphate (LMW-DS, named ILB®) previously proven safe for use in healthy volunteers and shown to exert potent neurotrophic effects in pre-clinical studies. Secondary endpoints relate to efficacy and exploratory biomarkers.
Thirteen patients with ALS were treated with 5 weekly subcutaneous injections of ILB®. Safety and efficacy outcome measures were recorded weekly during treatment and at regular intervals for a further 70 days. Functional and laboratory biomarkers were assessed before, during and after treatment.
No deaths, serious adverse events or participant withdrawals occurred during or after ILB® treatment and no significant drug-related changes in blood safety markers were evident, demonstrating safety and tolerability of the drug in this cohort of patients with ALS. The PK of ILB® in patients with ALS was similar to that seen in healthy controls. The ILB® injection elicited a transient elevation of plasma Hepatocyte Growth Factor, a neurotrophic and myogenic growth factor. Following the ILB® injections patients reported increased vitality, decreased spasticity and increased mobility. The ALSFRS-R rating improved from 36.31 ± 6.66 to 38.77 ± 6.44 and the Norris rating also improved from 70.61 ± 13.91 to 77.85 ± 14.24 by Day 36. The improvement of functions was associated with a decrease in muscle atrophy biomarkers. These therapeutic benefits decreased 3-4 weeks after the last dosage.
This pilot clinical study demonstrates safety and tolerability of ILB® in patients with ALS. The exploratory biomarker and functional measures must be cautiously interpreted but suggest clinical benefit and have a bearing on the mechanism of action of ILB®. The results support the drug's potential as the first disease modifying treatment for patients with ALS.
EudraCT 2017-005065-47.
1. We studied a perch Perca fluviatilis L. population that during a 9-year period switched between a phase of dominance of adult perch and a phase dominated by juvenile perch driven by cannibalism ...and intercohort competition. We investigated the effects of these population fluctuations on individual diet specialization and the mechanisms behind this specialization. 2. Due to cannibalism, the survival of young-of-the-year (YOY) perch was much lower when adult perch density was high than when adult perch density was low. 3. Both the individual niche breadth (if weighed for resource encounter) and the population niche breadth were highest when adult population density was high and, consequently, individual specialization was highest at high adult perch densities. 4. When adult perch density was low, the abundances of benthic invertebrate and YOY perch were high and dominated the diet of adult perch, whereas the density of zooplankton was low due to predation from YOY perch. At high perch densities, benthic invertebrate abundance was lower and zooplankton level was higher and some perch switched to feed on zooplankton. 5. Our results show that individual specialization may fluctuate with population density through feedback mechanisms via resource levels. Such fluctuations may have profound implications on the evolution of resource polymorphisms.
In this article, we explore to what extent it is possible to leverage on very small data to build machine learning (ML) models that predict acute exacerbations of chronic obstructive pulmonary ...disease (AECOPD).
We build ML models using the small data collected during the eHealth Diary telemonitoring study between 2013 and 2017 in Sweden. This data refers to a group of multimorbid patients, namely 18 patients with chronic obstructive pulmonary disease (COPD) as the major reason behind previous hospitalisations. The telemonitoring was supervised by a specialised hospital-based home care (HBHC) unit, which also was responsible for the medical actions needed.
We implement two different ML approaches, one based on time-dependent covariates and the other one based on time-independent covariates. We compare the first approach with standard COX Proportional Hazards (CPH). For the second one, we use different proportions of synthetic data to build models and then evaluate the best model against authentic data.
To the best of our knowledge, the present ML study shows for the first time that the most important variable for an increased risk of future AECOPDs is "maintenance medication changes by HBHC". This finding is clinically relevant since a sub-optimal maintenance treatment, requiring medication changes, puts the patient in risk for future AECOPDs.
The experiments return useful insights about the use of small data for ML.
There is extensive evidence that some species of ecological generalists, which use a wide diversity of resources, are in fact heterogeneous collections of relatively specialized individuals. This ...within-population variation, or "individual specialization," is a key requirement for frequency-dependent interactions that may drive a variety of types of evolutionary diversification and may influence the population dynamics and ecological interactions of species. Consequently, it is important to understand when individual specialization is likely to be strong or weak. The niche variation hypothesis (NVH) suggests that populations tend to become more generalized when they are released from interspecific competition. This niche expansion was proposed to arise via increased variation among individuals rather than increased individual niche breadth. Consequently, we expect ecological generalists to exhibit stronger individual specialization, but this correlation has been repeatedly rejected by empiricists. The drawback with previous empirical tests of the NVH is that they use morphological variation as a proxy for niche variation, ignoring the role of behavior and complex phenotype-function relationships. Here, we used diet data to directly estimate niche variation among individuals. Consistent with the NVH, we show that more generalized populations also exhibit more niche variation. This trend is quite general, appearing in all five case studies examined: three-spine stickleback, Eurasian perch, Anolis lizards, intertidal gastropods, and a community of neotropical frogs. Our results suggest that generalist populations may tend to be more ecologically variable. Whether this translates into greater genetic variation, evolvability, or ecological stability remains to be determined.
Loss of lysosomal membrane integrity results in leakage of lysosomal hydrolases to the cytosol which might harm cell function and induce cell death. Destabilization of lysosomes often precede ...apoptotic or necrotic cell death and occur during both physiological and pathological conditions. The weak base acridine orange readily enters cells and accumulates in the acidic environment of lysosomes. Vital staining with acridine orange is a well-proven technique to observe lysosomal destabilization using fluorescence microscopy and flow cytometry. These analyses are, however, time consuming and only adapted for discrete time points, which make them unsuitable for large-scale approaches. Therefore, we have developed a time-saving, high-throughput microplate reader-based method to follow destabilization of the lysosomal membrane in real-time using acridine orange. This protocol can easily be adopted for patient samples since the number of cells per sample is low and the time for analysis is short.
We investigated productivity at the basal trophic level in 15 unproductive lakes in a gradient ranging from clear-water to brown-water (humic) lakes in northern Sweden. Primary production and ...bacterial production in benthic and pelagic habitats were measured to estimate the variation in energy mobilization from external energy sources (primary production plus bacterial production on allochthonous organic carbon) along the gradient. Clear-water lakes were dominated by autotrophic energy mobilization in the benthic habitat, whereas humic lakes were dominated by heterotrophic energy mobilization in the pelagic habitat. Whole-lake (benthic + pelagic) energy mobilization was negatively correlated to the light-extinction coefficient, which was determined by colored terrestrial organic matter in the lake water. Thus, variation in the concentration of terrestrial organic matter and its light-absorbing characteristics exerts strong control on the magnitude, as well as on the processes and pathways, of energy mobilization in unproductive lakes. We suggest that unproductive lakes in general are sensitive to input of terrestrial organic matter because of its effects on basal energy mobilization in both benthic and pelagic habitats.
A large number of studies have presented empirical arguments for the existence of alternative stable states (ASS) in a wide range of ecological systems. However, most of these studies have used ...non-manipulative, indirect methods, which findings remain open for alternative explanations. Here, we review the direct evidence for ASS resulting from manipulation experiments. We distinguish four conclusive experimental approaches which test for predictions made by the hysteresis effect: (1) discontinuity in the response to an environmental driving parameter, (2) lack of recovery potential after a perturbation, (3) divergence due to different initial conditions and (4) random divergence. Based on an extensive literature search we found 35 corresponding experiments. We assessed the ecological stability of the reported contrasting states using the minimum turnover of individuals in terms of life span and classified the studies according to 4 categories: (1) experimental system, (2) habitat type, (3) involved organisms and (4) theoretical framework. 13 experiments have directly demonstrated the existence of alternative stable states while 8 showed the absence of ASS in other cases. 14 experiments did not fulfil the requirements of a conclusive test, mostly because they applied a too short time scale. We found a bias towards laboratory experiments compared to field experiments in demonstrating bistability. There was no clear pattern of the distribution of ASS over categories. The absence of ASS in 38% of the tested systems indicates that ASS are just one possibility of how ecological systems can behave. The relevance of the concept of ASS for natural systems is discussed, in particular under consideration of the observed laboratory bias, perturbation frequency and variable environments. It is argued, that even for a permanently transient system, alternative attractors may still be of relevance.
Conceptual models of lake ecosystem structure and function have generally assumed that energy in pelagic systems is derived from
in situ photosynthesis and that its use by higher trophic levels ...depends on the average properties of individuals in consumer populations. These views are challenged by evidence that allochthonous subsidies of organic carbon greatly influence energy mobilization and transfer and the trophic structure of pelagic food webs, and that size variation within consumer species has major ramifications for lake community dynamics and structure. These discoveries represent conceptual shifts that have yet to be integrated into current views on lake ecosystems. Here, we assess key aspects of energy mobilization and size-structured community dynamics, and show how these processes are intertwined in pelagic food webs.
Chronic airflow limitation (CAL) can be defined as fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.70 after bronchodilation. It is unclear which is the most ...optimal ratio in relation to respiratory morbidity. The aim was to investigate to what extent different ratios of FEV1/FVC were associated with any respiratory symptom. In a cross‐sectional general population study, 15,128 adults (50–64 years of age), 7,120 never‐smokers and 8,008 ever‐smokers completed a respiratory questionnaire and performed FEV1 and FVC after bronchodilation. We calculated different ratios of FEV1/FVC from 0.40 to 1.0 using 0.70 as reference category. We analysed odds ratios (OR) between different ratios and any respiratory symptom using adjusted multivariable logistic regression. Among all subjects, regardless of smoking habits, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.82, OR 0.48 (95% CI 0.41–0.56). Among never‐smokers, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.81, OR 0.53 (95% CI 0.41–0.70). Among ever‐smokers, the odds for any respiratory symptom was lowest at FEV1/FVC = 0.81, OR 0.43 (95% CI 0.16–1.19), although the rate of inclining in odds was small in the upper part, that is FEV1/FVC = 0.85 showed similar odds, OR 0.45 (95% CI 0.38–0.55). We concluded that the odds for any respiratory symptoms continuously decreased with higher FEV1/FVC ratios and reached a minimum around 0.80–0.85, with similar results among never‐smokers. These results indicate that the optimal threshold associated with respiratory symptoms may be higher than 0.70 and this should be further investigated in prospective longitudinal studies.
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