Balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension: the initial German experience.

Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).We report on a prospective series of 56 consecutive patients who underwent 266 BPA interventions (median, five per patient) at two German institutions. All patients underwent a comprehensive diagnostic work-up including right heart catheterisation at baseline and 24 weeks after their last intervention.BPA resulted in improvements in WHO functional class, 6 min walk distance (mean change, +33 m), right ventricular function and haemodynamics, including a decline in mean pulmonary artery pressure by 18% and in pulmonary vascular resistance by 26%. Procedure-related adverse events occurred in 9.4% of the interventions. The most common complications were related to pulmonary vascular injury and consecutive pulmonary bleeding. Most of these events were asymptomatic and self-limiting, but one patient died from pulmonary bleeding, resulting in a mortality rate of 1.8%.BPA resulted in haemodynamic and clinical improvements but was also associated with a considerable number of complications, including one fatal pulmonary bleeding. As the effects of BPA on survival are unknown, randomised controlled outcome trials comparing BPA with approved medical therapies in patients with inoperable CTEPH are required to allow for appropriate risk-benefit assessments.

Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model.

The 2015 European pulmonary hypertension (PH) guidelines propose a risk stratification strategy for patients with pulmonary arterial hypertension (PAH). Low-, intermediate- and high-risk strata are defined by estimated 1-year mortality risks of <5%, 5-10% and >10%, respectively. This risk assessment strategy awaits validation.We analysed data from patients with newly diagnosed PAH enrolled into COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension), a European-based PH registry. An abbreviated version of the risk assessment strategy proposed by the European PH guidelines was applied, using the following variables: World Health Organization functional class, 6-min walking distance, brain natriuretic peptide or its N-terminal fragment, right atrial pressure, cardiac index and mixed venous oxygen saturation.Data from 1588 patients were analysed. Mortality rates were significantly different between the three risk strata (p<0.001 for all comparisons). In the entire patient population, the observed mortality rates 1 year after diagnosis were 2.8% in the low-risk cohort (n=196), 9.9% in the intermediate-risk cohort (n=1116) and 21.2% in the high-risk cohort (n=276). In addition, the risk assessment strategy proved valid at follow-up and in major PAH subgroups.An abbreviated version of the risk assessment strategy proposed by the current European PH guidelines provides accurate mortality estimates in patients with PAH.

Modeling microbial growth and dynamics.

Modeling has become an important tool for widening our understanding of microbial growth in the context of applied microbiology and related to such processes as safe food production, wastewater treatment, bioremediation, or microbe-mediated mining. Various modeling techniques, such as primary, secondary and tertiary mathematical models, phenomenological models, mechanistic or kinetic models, reactive transport models, Bayesian network models, artificial neural networks, as well as agent-, individual-, and particle-based models have been applied to model microbial growth and activity in many applied fields. In this mini-review, we summarize the basic concepts of these models using examples and applications from food safety and wastewater treatment systems. We further review recent developments in other applied fields focusing on models that explicitly include spatial relationships. Using these examples, we point out the conceptual similarities across fields of application and encourage the combined use of different modeling techniques in hybrid models as well as their cross-disciplinary exchange. For instance, pattern-oriented modeling has its origin in ecology but may be employed to parameterize microbial growth models when experimental data are scarce. Models could also be used as virtual laboratories to optimize experimental design analogous to the virtual ecologist approach. Future microbial growth models will likely become more complex to benefit from the rich toolbox that is now available to microbial growth modelers.

Adaptive and selective seed abortion reveals complex conditional decision making in plants.

Behavior is traditionally attributed to animals only. Recently, evidence for plant behavior is accumulating, mostly from plant physiological studies. Here, we provide ecological evidence for complex plant behavior in the form of seed abortion decisions conditional on internal and external cues. We analyzed seed abortion patterns of barberry plants exposed to seed parasitism and different environmental conditions. Without abortion, parasite infestation of seeds can lead to loss of all seeds in a fruit. We statistically tested a series of null models with Monte Carlo simulations to establish selectivity and adaptiveness of the observed seed abortion patterns. Seed abortion was more frequent in parasitized fruits and fruits from dry habitats. Surprisingly, seed abortion occurred with significantly greater probability if there was a second intact seed in the fruit. This strategy provides a fitness benefit if abortion can prevent a sibling seed from coinfestation and if nonabortion of an infested but surviving single seed saves resources invested in the fruit coat. Ecological evidence for complex decision making in plants thus includes a structural memory (the second seed), simple reasoning (integration of inner and outer conditions), conditional behavior (abortion), and anticipation of future risks (seed predation).

Heterodera schachtii nematodes interfere with aphid-plant relations on Brassica oleracea.

Aboveground and belowground herbivore species modify plant defense responses differently. Simultaneous attack can lead to non-additive effects on primary and secondary metabolite composition in roots and shoots. We previously found that aphid (Brevicoryne brassicae) population growth on Brassica oleracea was reduced on plants that were infested with nematodes (Heterodera schachtii) prior (4 weeks) to aphid infestation. Here, we examined how infection with root-feeding nematodes affected primary and secondary metabolites in the host plant and whether this could explain the increase in aphid doubling time from 3.8 to 6.7 days. We hypothesized that the effects of herbivores on plant metabolites would depend on the presence of the other herbivore and that nematode-induced changes in primary metabolites would correlate with reduced aphid performance. Total glucosinolate concentration in the leaves was not affected by nematode presence, but the composition of glucosinolates shifted, as gluconapin concentrations were reduced, while gluconapoleiferin concentrations increased in plants exposed to nematodes. Aphid presence increased 4-methoxyglucobrassicin concentrations in leaves, which correlated positively with the number of aphids per plant. Nematodes decreased amino acid and sugar concentrations in the phloem. Aphid population doubling time correlated negatively with amino acids and glucosinolate levels in leaves, whereas these correlations were non-significant when nematodes were present. In conclusion, the effects of an herbivore on plant metabolites were independent of the presence of another herbivore. Nematode presence reduced aphid population growth and disturbed feeding relations between plants and aphids.

A comparison of population viability measures.

The viability of populations can be quantified with several measures, such as the probability of extinction, the mean time to extinction, or the population size. While conservation management decisions can be based on these measures, it has not yet been explored systematically if different viability measures rank species and scenarios similarly and if one viability measure can be converted into another to compare studies. To address this challenge, we conducted a quantitative comparison of eight viability measures based on the simulated population dynamics of more than 4500 virtual species. We compared (a) the ranking of scenarios based on different viability measures, (b) assessed direct correlations between the measures, and (c) explored if parameters in the simulation models can alter the relationship between pairs of viability measures. We found that viability measures ranked species similarly. Despite this, direct correlations between the different measures were often weak and could not be generalized. This can be explained by the loss of information due to the aggregation of raw data into a single number, the effect of model parameters on the relationship between viability measures, and because distributions, such as the probability of extinction over time, cannot be ranked objectively. Similar scenario rankings by different viability measures show that the choice of the viability metric does in many cases not alter which population is regarded more viable or which management option is the best. However, the more two scenarios or populations differ, the more likely it becomes that different measures produce different rankings. We thus recommend that PVA studies publish raw simulation data, which not only describes all risks and opportunities to the reader but also facilitates meta-analyses of PVA studies.

Microbiology of the phyllosphere: a playground for testing ecological concepts.

Many concepts and theories in ecology are highly debated, because it is often difficult to design decisive tests with sufficient replicates. Examples include biodiversity theories, succession concepts, invasion theories, coexistence theories, and concepts of life history strategies. Microbiological tests of ecological concepts are rapidly accumulating, but have yet to tap into their full potential to complement traditional macroecological theories. Taking the example of microbial communities on leaf surfaces (i.e. the phyllosphere), we show that most explorations of ecological concepts in this field of microbiology focus on autecology and population ecology, while community ecology remains understudied. Notable exceptions are first tests of the island biogeography theory and of biodiversity theories. Here, the phyllosphere provides the unique opportunity to set up replicated experiments, potentially moving fields such as biogeography, macroecology, and landscape ecology beyond theoretical and observational evidence. Future approaches should take advantage of the great range of spatial scales offered by the leaf surface by iteratively linking laboratory experiments with spatial simulation models.

Cytosolic action of phytochelatin synthase.

Glutathionylation of compounds is an important reaction in the detoxification of electrophilic xenobiotics and in the biosynthesis of endogenous molecules. The glutathione conjugates (GS conjugates) are further processed by peptidic cleavage reactions. In animals and plants, gamma-glutamyl transpeptidases initiate the turnover by removal of the glutamate residue from the conjugate. Plants have a second route leading to the formation of gamma-glutamylcysteinyl (gamma-GluCys) conjugates. Phytochelatin synthase (PCS) is well known to mediate the synthesis of heavy metal-binding phytochelatins. In addition, the enzyme is also able to catabolize GS conjugates to the gamma-GluCys derivative. In this study, we addressed the cellular compartmentalization of PCS and its role in the plant-specific gamma-GluCys conjugate pathway in Arabidopsis (Arabidopsis thaliana). Localization studies of both Arabidopsis PCS revealed a ubiquitous presence of AtPCS1 in Arabidopsis seedlings, while AtPCS2 was only detected in the root tip. A functional AtPCS1:eGFP (enhanced green fluorescent protein) fusion protein was localized to the cytosolic compartment. Inhibition of the vacuolar import of GS-bimane conjugate via azide treatment resulted in both a strong accumulation of gamma-GluCys-bimane and a massive increase of the cellular cysteine to GS-bimane ratio, which was not observed in PCS-deficient lines. These findings support a cytosolic action of PCS. Analysis of a triple mutant deficient in both Arabidopsis PCS and vacuolar gamma-glutamyl transpeptidase GGT4 is consistent with earlier observations of an efficient sequestration of GS conjugates into the vacuole and the requirement of GGT4 for their turnover. Hence, PCS contributes specifically to the cytosolic turnover of GS conjugates, and AtPCS1 plays the prominent role. We discuss a potential function of PCS in the cytosolic turnover of GS conjugates.

Characterization of non-extractable ¹4C- and ¹³C-sulfadiazine residues in soil including simultaneous amendment of pig manure.

Recently, we reported on soil fate of SDZ residues amended with pig manure treated with ¹4C-labeled sulfadiazine ¹4C-SDZ). The first objective of the present study was to determine whether this strategy can be substituted by application of ¹4C-SDZ to soil. The second objective was to characterize non-extractable SDZ residues by fractionation, size exclusion chromatography (SEC) and solid state ¹³C-NMR. The fate of ¹4C-SDZ was examined for 28 d, using two soils with and without amendment of pig manure. Mineralization of ¹4C-SDZ was low; extractable residues decreased to 7-30%. Compared to the previous study, results were similar. ¹4C-SDZ derived bound radioactivity was found in HCl-washings, fulvic, humic acids and humin. According to SEC, one bound ¹4C portion (70%) co-eluted with fulvic acids (above 910 g mol⁻¹); the other consisted of adsorbed/entrapped ¹4C-SDZ. The ¹³C-SDZ study was performed for 30 d; humic acids were examined by ¹³C-NMR. A signal (100-150 ppm) was referred to ¹³C-SDZ. SEC and ¹³C-NMR demonstrated rapid integration of SDZ into humics.

Reduction of rare soil microbes modifies plant-herbivore interactions.

Rare species are assumed to have little impact on community interactions and ecosystem processes. However, very few studies have actually attempted to quantify the role of rare species in ecosystems. Here we compare effects of soil community assemblages on plant-herbivore interactions and show that reduction of rare soil microbes increases both plant biomass and plant nutritional quality. Two crop plant species growing in soil where rare microbes were reduced, had tissues of higher nutritional quality, which theoretically makes them more susceptible to pest organisms such as shoot-feeding aphids and root-feeding nematodes. Reduction of rare microbes increased aphid body size in the absence of nematodes; nematodes always reduced aphid body size independent of the soil microbial community. This study is the first to show that rare soil microbes are not redundant but may play a role in crop protection by enhancing aboveground and belowground plant defence. It remains to be tested whether these are direct effects of rare soil microbes on plants and herbivores, or indirect effects via shifts in the microbial soil community assemblages.

EFForTS-LGraf: A landscape generator for creating smallholder-driven land-use mosaics.

Spatially-explicit simulation models are commonly used to study complex ecological and socio-economic research questions. Often these models depend on detailed input data, such as initial land-cover maps to set up model simulations. Here we present the landscape generator EFFortS-LGraf that provides artificially-generated land-use maps of agricultural landscapes shaped by small-scale farms. EFForTS-LGraf is a process-based landscape generator that explicitly incorporates the human dimension of land-use change. The model generates roads and villages that consist of smallholder farming households. These smallholders use different establishment strategies to create fields in their close vicinity. Crop types are distributed to these fields based on crop fractions and specialization levels. EFForTS-LGraf model parameters such as household area or field size frequency distributions can be derived from household surveys or geospatial data. This can be an advantage over the abstract parameters of neutral landscape generators. We tested the model using oil palm and rubber farming in Indonesia as a case study and validated the artificially-generated maps against classified satellite images. Our results show that EFForTS-LGraf is able to generate realistic land-cover maps with properties that lie within the boundaries of landscapes from classified satellite images. An applied simulation experiment on landscape-level effects of increasing household area and crop specialization revealed that larger households with higher specialization levels led to spatially more homogeneous and less scattered crop type distributions and reduced edge area proportion. Thus, EFForTS-LGraf can be applied both to generate maps as inputs for simulation modelling and as a stand-alone tool for specific landscape-scale analyses in the context of ecological-economic studies of smallholder farming systems.

Peritoneal dialysis as therapeutic option in heart failure patients.

AIMS: Each episode of acute decompensated heart failure (HF) incrementally adds to mortality. Peritoneal dialysis (PD) offers an alternative therapeutic option in refractory HF and reduces the incidence of decompensation episodes. The objective of this study was to determine the efficacy of PD, in terms of functional status, surrogate endpoints, rate of hospitalizations, and mortality. METHODS AND RESULTS: This study is based on the registry of the German Society of Nephrology, involving 159 patients receiving PD treatment due to refractory HF between January 2010 and December 2014. Body weight was reduced by PD (82.2 ± 14.9 to 78.4 ± 14.8 kg, P < 0.001), and significant improvements in New York Heart Association functional class (3.38 ± 0.55 to 2.85 ± 0.49, P < 0.001) were found already after 3 months. Left ventricular ejection fraction did not change (31.5 ± 13.8 to 34.0 ± 15.7%, P = 0.175). C-reactive protein improved with PD treatment (33.7 ± 52.6 to 17.1 ± 26.3 mg/L, P = 0.004). Blood urea nitrogen/creatinine ratio decreased significantly (148.7 ± 68.3 to 106.7 ± 44.8 mg/dL, P < 0.001). Hospitalization rates decreased significantly (total number 2.86 ± 1.88 to 1.90 ± 1.78, P = 0.001, and 39.2 ± 30.7 to 27.1 ± 25.2 days, P = 0.004). One year mortality was 39.6% in end-stage HF patients treated with PD. CONCLUSIONS: Peritoneal dialysis offers an additional therapeutic option in end-stage HF and is associated with improved New York Heart Association classification and reduced hospitalization. Although PD treatment was associated with various benefits, further studies are necessary to identify which patients benefit the most from PD.

Ca2+ sensitizer superior to catecholamine during myocardial stunning?

BACKGROUND: After open-chest cardiac surgery, ventricular function remains depressed (myocardial stunning). Catecholamines (epinephrine) improve ventricular function by increasing the intracellular Ca(2+) concentration. In parallel, the oxygen consumption is increased, so that the hitherto intact myocardium can be jeopardized. In the very insufficient ventricle, epinephrine can even become ineffective. Since Ca(2+) sensitizers provide another therapeutic avenue, the effects of epinephrine and levosimendan on postischemic hemodynamics were investigated. METHODS: After hemodynamic steady state, isolated, blood (erythrocyte-enriched Krebs-Henseleit solution)-perfused rabbit hearts were subjected to 25 min normothermic, no-flow ischemia and 20 min reperfusion. Heart rate (HR), cardiac output (CO), left ventricular pressure (LVP), coronary blood flow (CBF), and arterio-venous oxygen difference (AVDO(2)) were recorded during reperfusion and after administration of either epinephrine (n=16; 0.03 micromol), or levosimendan (n=11; 0.75 micromol) or epinephrine plus levosimendan (n=5). RESULTS: Epinephrine increased HR (19%, p=0.01) and improved hemodynamics in terms of CO (62%, p=0.0006), stroke volume SV (46%, p=0.02), stroke work W (158%, p=0.01), LVP(max) (58%, p=0.0001), maximal pressure increase dP/dt(max)(140%, p=0.0004), minimal pressure increase dP/dt(min) (104%, p=0.0002), LVP(ed) (-26%, p=0.02), and increased coronary resistance CR (31%, p=0.05). Epinephrine impaired hemodynamics in terms of AVDO(2) (+63%, p=0.003), myocardial oxygen consumption MVO(2) (+67%, p=0.0003) and MVO(2)/beat (+36%, p=0.01). External efficiency eta was increased by 92% (p=0.02). Levosimendan in postischemic hearts increased HR (32%, p=0.009) and improved hemodynamics in terms of CO (85%, p=0.01), SV (44%, p=0.03), W (115%, p=0.04), LVP(max) (95%, p=0.04), dP/dt(max) (133%, p=0.009), dP/dt(min) (121%, p=0.007), LVP(ed) (-63%, p=0.0006), and CR (-17%; n.s., p=0.1). It altered hemodynamics in terms of AVDO(2) (+7.0%; n.s., p=0.3) and MVO(2) (+32%, p=0.007) and MVO(2)/beat (+2.3%; n.s., p=0.4). External efficiency was increased by 307% (p=0.04). In five additional extremely dysfunctional rabbit hearts, epinephrine was ineffective. Additional levosimendan increased hemodynamics in terms of HR (56%; n.s., p=0.1), CO (159%, p=0.04), SV (89%, p=0.03), W (588%, p=0.02), LVP(max) (168%, p=0.03), dP/dt(max) (102%, p=0.005), dP/dt(min) (78%, p=0.006), LVP(ed) (-98%, p=0.0006), and CR (-50%, p=0.02). It altered hemodynamics in terms of AVDO(2) (-11%; n.s., p=0.05), MVO(2) (+131%, p=0.04) and MVO(2)/beat (+171%, p=0.03). External efficiency was increased by 212% (p=0.04). CONCLUSION: In contrast to epinephrine, levosimendan improves ventricular function without increasing oxygen demand, thereby considerably improving external efficiency. Even during epinephrine resistance in extremely dysfunctional hearts, levosimendan successfully improves ventricular function.

The role of biotic factors during plant establishment in novel communities assessed with an agent-based simulation model.

BACKGROUND: Establishment success of non-native species is not only influenced by environmental conditions, but also by interactions with local competitors and enemies. The magnitude of these biotic interactions is mediated by species traits that reflect competitive strength or defence mechanisms. Our aim was to investigate the importance of species traits for successful establishment of non-native species in a native community exhibiting biotic resistance in the form of competition and herbivory. METHODS: We developed a trait-based, individual-based simulation model tracking the survival of non-native plants in a native community. In the model, non-native plants are characterized by high or low values of competition and defence traits. Model scenarios included variation of initial number of non-natives, intensity of competitive interaction, density of herbivores and density as well as mixture of the native community. RESULTS: Traits related to competition had a much greater impact on survival of non-native species than traits related to defence. Survival rates of strong competitors never fell below 50% while survival of weak competitors averaged at about 10%. Weak competitors were also much more susceptible to competitive pressures such as community density, composition and competition intensity. Strong competitors responded negatively to changes in competition intensity, but hardly to composition or density of the native community. High initial numbers of non-native individuals decreased survival rate of strong competitors, but increased the survival rate of weak competitors. Survival under herbivore attack was only slightly higher for plants with high defensive ability than for those with low defensive ability. Surprisingly, though, herbivory increased survival of species classified as weak competitors. DISCUSSION: High survival rates of strong non-native competitors relate to a higher probability of successful establishment than for weak competitors. However, the reduced survival of strong competitors at high initial numbers indicates a self-thinning effect, probably mediated by a strongly competitive milieu. For weak competitors, our model emphasizes positive effects of high propagule pressure known from field studies. General effects of herbivory or defence abilities on survival were not supported by our model. However, the positive effect of herbivory on survival of weak competitors indicated side effects of herbivory, such as weakening resident competitors. This might play an important role for establishment of non-natives in a new community.

Land-use change in oil palm dominated tropical landscapes-An agent-based model to explore ecological and socio-economic trade-offs.

Land-use changes have dramatically transformed tropical landscapes. We describe an ecological-economic land-use change model as an integrated, exploratory tool used to analyze how tropical land-use change affects ecological and socio-economic functions. The model analysis seeks to determine what kind of landscape mosaic can improve the ensemble of ecosystem functioning, biodiversity, and economic benefit based on the synergies and trade-offs that we have to account for. More specifically, (1) how do specific ecosystem functions, such as carbon storage, and economic functions, such as household consumption, relate to each other? (2) How do external factors, such as the output prices of crops, affect these relationships? (3) How do these relationships change when production inefficiency differs between smallholder farmers and learning is incorporated? We initialize the ecological-economic model with artificially generated land-use maps parameterized to our study region. The economic sub-model simulates smallholder land-use management decisions based on a profit maximization assumption. Each household determines factor inputs for all household fields and decides on land-use change based on available wealth. The ecological sub-model includes a simple account of carbon sequestration in above-ground and below-ground vegetation. We demonstrate model capabilities with results on household consumption and carbon sequestration from different output price and farming efficiency scenarios. The overall results reveal complex interactions between the economic and ecological spheres. For instance, model scenarios with heterogeneous crop-specific household productivity reveal a comparatively high inertia of land-use change. Our model analysis even shows such an increased temporal stability in landscape composition and carbon stocks of the agricultural area under dynamic price trends. These findings underline the utility of ecological-economic models, such as ours, to act as exploratory tools which can advance our understanding of the mechanisms underlying the trade-offs and synergies of ecological and economic functions in tropical landscapes.

Quantitation of Perfused Lung Volume Using Hybrid SPECT/CT Allows Refining the Assessment of Lung Perfusion and Estimating Disease Extent in Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: We evaluated the feasibility of perfusion SPECT/CT for providing quantitative data for estimation of perfusion defect extent in chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirty patients with CTEPH underwent Tc-human serum albumin lung perfusion SPECT/CT. Perfusion defects were quantified using 3 different methods: (1) visual, semiquantitative scoring of perfusion defect extent in each lung segment, (2) threshold-based segmentation of perfused lung volumes, and (3) threshold-based segmentation of perfused lung volumes divided by segmented lung volumes at CT (perfusion index). Imaging findings were correlated with right-sided heart catheterization results and N-terminal pro-B-type natriuretic peptide. Receiver operating characteristic analysis was performed to identify SPECT thresholds for mean pulmonary arterial pressure (PAPm) greater than 50 mm Hg. RESULTS: Assessment of lung perfusion provided similar results using all 3 methods. The perfusion defect score correlated with PAPm (rs = 0.60, P = 0.0005) and was associated with serum levels of N-terminal pro-B-type natriuretic peptide (rs = 0.37, P = 0.04). Perfused lung volume (40% threshold, rs = -0.48, P = 0.007) and perfusion index (40% threshold, rs = -0.50, P = 0.005) decreased as PAPm increased. Receiver operating characteristic analysis showed that perfusion defect score (sensitivity, 88%; specificity, 77%; area under the curve [AUC] = 0.89, P = 0.001), perfused lung volume (sensitivity, 88%; specificity, 64%; AUC = 0.80, P = 0.01), and perfusion index (sensitivity, 88%; specificity, 64%; AUC = 0.82, P = 0.009) could identify patients with PAPm of greater than 50 mm Hg. CONCLUSIONS: Quantitative analysis of perfusion defects at SPECT is feasible, provides a measure of disease severity, and correlates with established clinical parameters. Quantitation of perfusion SPECT may refine the diagnostic approach in CTEPH providing a quantitative imaging biomarker, for example, for therapy monitoring.

Long-term safety and outcome of intravenous treprostinil via an implanted pump in pulmonary hypertension.

BACKGROUND: We examined safety and long-term outcomes of intravenous treprostinil administered via the implantable LENUS Pro pump in patients with severe pulmonary hypertension (PH). METHODS: Patients with PH undergoing pump implantation between December 2009 and October 2016 in German referral centers were retrospectively analyzed (end of follow-up: May 2017). The primary objective was to determine long-term safety of the implantable pump. Secondary end points were 3-year survival and prognostic relevance of pre-implantation hemodynamics. RESULTS: We monitored 129 patients (120 with pulmonary arterial hypertension, 1 with PH due to lung diseases, and 8 with inoperable chronic thromboembolic PH) for 260 patient-years (median follow-up, 19 months; interquartile range, 11-34 months). There were 82 complications/peri-procedural events in 60 patients; of these, 57 were serious adverse events (0.60 per 1,000 treatment-days), including 2 periprocedural deaths due to right heart failure. The incidence of complications related to the pump, catheter, infection, and pump pocket per 1,000 treatment-days was 0.074, 0.264, 0.032 (3 local infections; no bloodstream infections), and 0.380, respectively. Three-year overall and transplant-free survival were 66.5% and 55.7%, respectively (39 patients died; 16 underwent lung transplantation). Baseline cardiac index independently predicted transplant-free survival (multivariate hazard ratio, 1.90; 95% confidence interval, 1.11-3.28; p = 0.019; n = 95). CONCLUSIONS: Our data suggest that intravenous treprostinil via the LENUS Pro pump in advanced PH is associated with a very low risk of bloodstream infections, but other serious adverse events may occur. Therefore, this therapy needs standardization and should be offered in specialized PH centers only. Further technical advances of the pump system and prospective studies are needed.

How patch size and refuge availability change interaction strength and population dynamics: a combined individual- and population-based modeling experiment.

Knowledge on how functional responses (a measurement of feeding interaction strength) are affected by patch size and habitat complexity (represented by refuge availability) is crucial for understanding food-web stability and subsequently biodiversity. Due to their laborious character, it is almost impossible to carry out systematic empirical experiments on functional responses across wide gradients of patch sizes and refuge availabilities. Here we overcame this issue by using an individual-based model (IBM) to simulate feeding experiments. The model is based on empirically measured traits such as body-mass dependent speed and capture success. We simulated these experiments in patches ranging from sizes of petri dishes to natural patches in the field. Moreover, we varied the refuge availability within the patch independently of patch size, allowing for independent analyses of both variables. The maximum feeding rate (the maximum number of prey a predator can consume in a given time frame) is independent of patch size and refuge availability, as it is the physiological upper limit of feeding rates. Moreover, the results of these simulations revealed that a type III functional response, which is known to have a stabilizing effect on population dynamics, fitted the data best. The half saturation density (the prey density where a predator consumes half of its maximum feeding rate) increased with refuge availability but was only marginally influenced by patch size. Subsequently, we investigated how patch size and refuge availability influenced stability and coexistence of predator-prey systems. Following common practice, we used an allometric scaled Rosenzweig-MacArthur predator-prey model based on results from our in silico IBM experiments. The results suggested that densities of both populations are nearly constant across the range of patch sizes simulated, resulting from the constant interaction strength across the patch sizes. However, constant densities with decreasing patch sizes mean a decrease of absolute number of individuals, consequently leading to extinction of predators in the smallest patches. Moreover, increasing refuge availabilities also allowed predator and prey to coexist by decreased interaction strengths. Our results underline the need for protecting large patches with high habitat complexity to sustain biodiversity.