Evolutionary radiations of woody taxa within arid environments were made possible by multiple trait innovations including deep roots and embolism-resistant xylem, but little is known about how... Show moreEvolutionary radiations of woody taxa within arid environments were made possible by multiple trait innovations including deep roots and embolism-resistant xylem, but little is known about how these traits have coevolved across the phylogeny of woody plants or how they jointly influence the distribution of species. We synthesized global trait and vegetation plot datasets to examine how rooting depth and xylem vulnerability across 188 woody plant species interact with aridity, precipitation seasonality, and water table depth to influence species occurrence probabilities across all biomes. Xylem resistance to embolism and rooting depth are independent woody plant traits that do not exhibit an interspecific trade-off. Resistant xylem and deep roots increase occurrence probabilities in arid, seasonal climates over deep water tables. Resistant xylem and shallow roots increase occurrence probabilities in arid, nonseasonal climates over deep water tables. Vulnerable xylem and deep roots increase occurrence probabilities in arid, nonseasonal climates over shallow water tables. Lastly, vulnerable xylem and shallow roots increase occurrence probabilities in humid climates. Each combination of trait values optimizes occurrence probabilities in unique environmental conditions. Responses of deeply rooted vegetation may be buffered if evaporative demand changes faster than water table depth under climate change. Show less
Dingemans, A.J.M.; Hinne, M.; Truijen, K.M.G.; Goltstein, L.; Reeuwijk, J. van; Leeuw, N. de; ... ; Vries, B.B.A. de 2023
Several molecular and phenotypic algorithms exist that establish genotype-phenotype correlations, including facial recognition tools. However, no unified framework that investigates both facial... Show moreSeveral molecular and phenotypic algorithms exist that establish genotype-phenotype correlations, including facial recognition tools. However, no unified framework that investigates both facial data and other phenotypic data directly from individuals exists. We developed PhenoScore: an open-source, artificial intelligence-based phenomics framework, combining facial recognition technology with Human Phenotype Ontology data analysis to quantify phenotypic similarity. Here we show PhenoScore's ability to recognize distinct phenotypic entities by establishing recognizable phenotypes for 37 of 40 investigated syndromes against clinical features observed in individuals with other neurodevelopmental disorders and show it is an improvement on existing approaches. PhenoScore provides predictions for individuals with variants of unknown significance and enables sophisticated genotype-phenotype studies by testing hypotheses on possible phenotypic (sub)groups. PhenoScore confirmed previously known phenotypic subgroups caused by variants in the same gene for SATB1, SETBP1 and DEAF1 and provides objective clinical evidence for two distinct ADNP-related phenotypes, already established functionally.PhenoScore is an open-source machine-learning tool that combines facial image recognition with Human Phenotype Ontology for genetic syndrome identification without genomic data, with applications to subgroup analysis and variants of unknown significance classification. Show less
Background and AimsWe aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn’s disease [CD] in stable... Show moreBackground and AimsWe aimed to assess cost-effectiveness of increasing adalimumab dose intervals compared to the conventional dosing interval in patients with Crohn’s disease [CD] in stable clinical and biochemical remission.DesignWe conducted a pragmatic, open-label, randomized controlled non-inferiority trial, comparing increased adalimumab intervals with the 2-weekly interval in adult CD patients in clinical remission. Quality of life was measured with the EQ-5D-5L. Costs were measured from a societal perspective. Results are shown as differences and incremental net monetary benefit [iNMB] at relevant willingness to accept [WTA] levels.ResultsWe randomized 174 patients to the intervention [n = 113] and control [n = 61] groups. No difference was found in utility (difference: −0.017, 95% confidence interval [−0.044; 0.004]) and total costs (−€943, [−€2226; €1367]) over the 48-week study period between the two groups. Medication costs per patient were lower (−€2545, [−€2780; −€2192]) in the intervention group, but non-medication healthcare (+€474, [+€149; +€952]) and patient costs (+€365 [+€92; €1058]) were higher. Cost–utility analysis showed that the iNMB was €594 [−€2099; €2050], €69 [−€2908; €1965] and −€455 [−€4,096; €1984] at WTA levels of €20 000, €50 000 and €80 000, respectively. Increasing adalimumab dose intervals was more likely to be cost-effective at WTA levels below €53 960 per quality-adjusted life year. Above €53 960 continuing the conventional dose interval was more likely to be cost-effective.ConclusionWhen the loss of a quality-adjusted life year is valued at less than €53 960, increasing the adalimumab dose interval is a cost-effective strategy in CD patients in stable clinical and biochemical remission. Show less
Wang, L.P.; Pronk, A.C.; Poelgeest, E.P. van; Briggs, R.; Claassen, J.A.H.R.; Jansen, S.; ... ; Velde, N. van der 2023
Orthostatic hypotension (OH) is an established and common cardiovascular risk factor for falls. An in-depth understanding of the various interacting pathophysiological pathways contributing to OH... Show moreOrthostatic hypotension (OH) is an established and common cardiovascular risk factor for falls. An in-depth understanding of the various interacting pathophysiological pathways contributing to OH-related falls is essential to guide improvements in diagnostic and treatment opportunities. We applied systems thinking to multidisciplinary map out causal mechanisms and risk factors. For this, we used group model building (GMB) to develop a causal loop diagram (CLD). The GMB was based on the input of experts from multiple domains related to OH and falls and all proposed mechanisms were supported by scientific literature. Our CLD is a conceptual representation of factors involved in OH-related falls, and their interrelatedness. Network analysis and feedback loops were applied to analyze and interpret the CLD, and quantitatively summarize the function and relative importance of the variables. Our CLD contains 50 variables distributed over three intrinsic domains (cerebral, cardiovascular, and musculoskeletal), and an extrinsic domain (e.g., medications). Between the variables, 181 connections and 65 feedback loops were identified. Decreased cerebral blood flow, low blood pressure, impaired baroreflex activity, and physical inactivity were identified as key factors involved in OH-related falls, based on their high centralities. Our CLD reflects the multifactorial pathophysiology of OH-related falls. It enables us to identify key elements, suggesting their potential for new diagnostic and treatment approaches in fall prevention. The interactive online CLD renders it suitable for both research and educational purposes and this CLD is the first step in the development of a computational model for simulating the effects of risk factors on falls. Show less
As Earth's climate has varied strongly through geological time, studying the impacts of past climate change on biodiversity helps to understand the risks from future climate change. However, it... Show moreAs Earth's climate has varied strongly through geological time, studying the impacts of past climate change on biodiversity helps to understand the risks from future climate change. However, it remains unclear how paleoclimate shapes spatial variation in biodiversity. Here, we assessed the influence of Quaternary climate change on spatial dissimilarity in taxonomic, phylogenetic, and functional composition among neighboring 200-kilometer cells (beta-diversity) for angiosperm trees worldwide. We found that larger glacial-interglacial temperature change was strongly associated with lower spatial turnover (species replacements) and higher nestedness (richness changes) components of beta-diversity across all three biodiversity facets. Moreover, phylogenetic and functional turnover was lower and nestedness higher than random expectations based on taxonomic beta-diversity in regions that experienced large temperature change, reflecting phylogenetically and functionally selective processes in species replacement, extinction, and colonization during glacial-interglacial oscillations. Our results suggest that future human-driven climate change could cause local homogenization and reduction in taxonomic, phylogenetic, and functional diversity of angiosperm trees worldwide. Show less
Dam, C.J. van; Schrier, R. van der; Velzen, M. van; Lemmen, M. van; Simons, P.; Kuijpers, K.W.K.; ... ; Niesters, M. 2023
BackgroundIn humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ9-tetrahydrocannabinol (THC) remains unknown, particularly when THC is... Show moreBackgroundIn humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ9-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depression, which is amplified when THC and oxycodone are combined.MethodsIn this randomised controlled crossover trial, healthy volunteers were administered inhaled Bedrocan® 100 mg (Bedrocan International B.V., Veendam, The Netherlands), a pharmaceutical-grade high-THC cannabis variant (21.8% THC; 0.1% cannabidiol), after placebo or oral oxycodone 20 mg pretreatment; THC was inhaled 1.5 and 4.5 h after placebo or oxycodone intake. The primary endpoint was isohypercapnic ventilation at an end-tidal Pco2 of 55 mm Hg or 7.3 kPa (VE55), measured at 1-h intervals for 7 h after placebo/oxycodone intake.ResultsIn 18 volunteers (age 22 yr [3]; 9 [50%] female), oxycodone produced a 30% decrease in VE55, whereas placebo was without effect on VE55. The first cannabis inhalation resulted in VE55 changing from 20.3 (3.1) to 23.8 (2.4) L min−1 (P=0.06) after placebo, and from 11.8 (2.8) to 13.0 (3.9) L min−1 (P=0.83) after oxycodone. The second cannabis inhalation also had no effect on VE55, but slightly increased sedation.ConclusionsIn humans, THC has no effect on ventilatory control after placebo or oxycodone pretreatment. Show less
Simons, P.; Schrier, R. van der; Lemmen, M. van; Jansen, S.; Kuijpers, K.W.K.; Velzen, M. van; ... ; Dahan, A. 2023
Background: Oliceridine is a G protein–biased μ-opioid, a drug class thatis associated with less respiratory depression than nonbiased opioids, suchas morphine. The authors quantified the... Show moreBackground: Oliceridine is a G protein–biased μ-opioid, a drug class thatis associated with less respiratory depression than nonbiased opioids, suchas morphine. The authors quantified the respiratory effects of oliceridine andmorphine in elderly volunteers. The authors hypothesized that these opioidsdiffer in their pharmacodynamic behavior, measured as effect on ventilation atan extrapolated end-tidal Pco2 at 55 mmHg, V̇E55.Methods: This four-arm double-blind, randomized, crossover study examinedthe respiratory effects of intravenous 0.5 or 2 mg oliceridine and 2 or8 mg morphine in 18 healthy male and female volunteers, aged 55 to 89 yr, onfour separate occasions. Participants’ CYP2D6 genotypes were determined,hypercapnic ventilatory responses were obtained, and arterial blood sampleswere collected before and for 6 h after treatment. A population pharmacokinetic–pharmacodynamic analysis was performed on V̇E55, the primary endpoint;values reported are median ± standard error of the estimate.Results: Oliceridine at low dose was devoid of significant respiratory effects.High-dose oliceridine and both morphine doses caused a rapid onset of respiratorydepression with peak effects occurring at 0.5 to 1 h after opioid dosing.After peak effect, compared with morphine, respiratory depression inducedby oliceridine returned faster to baseline. The effect-site concentrationscausing a 50% depression of V̇E55 were 29.9 ± 3.5 ng/ml (oliceridine) and21.5 ± 4.6 ng/ml (morphine), the blood effect-site equilibration half-lives differedby a factor of 5: oliceridine 44.3 ± 6.1 min and morphine 214 ± 27 min.Three poor CYP2D6 oliceridine metabolizers exhibited a significant differencein oliceridine clearance by about 50%, causing higher oliceridine plasma concentrationsafter both low- and high-dose oliceridine, compared with the otherparticipants.Conclusions: Oliceridine and morphine differ in their respiratory pharmacodynamicswith a more rapid onset and offset of respiratory depression foroliceridine and a smaller magnitude of respiratory depression over time. Show less
Results from comparative and ecological wood anatomy combined with a number of experimental studies on plant hydraulics have led to a pervasive and longstanding assumption that wider-diameter... Show moreResults from comparative and ecological wood anatomy combined with a number of experimental studies on plant hydraulics have led to a pervasive and longstanding assumption that wider-diameter vessels are more vulnerable to drought- induced embolism than narrower vessels. Although we agree that wider vessels tend to be more vulnerable than narrower vessels within stems and within roots across most species, our current understanding of the diameter-vulnerability link does not offer a mechanistic explanation for why increased vessel diameter should consistently lead to greater vulnerability or vice versa. Causes of drought-induced embolism formation and spread likely operate at the nano-level, especially at gas-liquid-surfactant interfaces inside intervessel pit membranes. We evaluate here new perspectives on drought-induced embolism and its key anatomical and physico-chemical drivers, of which vessel diameter is one of the parameters involved, although its linkage to embolism vulnerability is likely indirect. As such, the diameter-vulnerability link does not imply that species with on average wider vessels are consistently more susceptible to drought-induced embolism compared to species with narrower vessels. Scientific priorities for future progress should focus on more accurate predictions of how water transport in plants is affected by drought, which requires a better mechanistic understanding of xylem network topology and biophysical processes at the nano-scale level in individual vessels that determine embolism formation and spread. Show less
Hydraulic failure resulting from drought-induced embolism in the xylem of plants is a key determinant of reduced productivity and mortality. Methods to assess this vulnerability are difficult to... Show moreHydraulic failure resulting from drought-induced embolism in the xylem of plants is a key determinant of reduced productivity and mortality. Methods to assess this vulnerability are difficult to achieve at scale, leading to alternative metrics and correlations with more easily measured traits. These efforts have led to the longstanding and pervasive assumed mechanistic link between vessel diameter and vulnerability in angiosperms. However, there are at least two problems with this assumption that requires critical re-evaluation: (1) our current understanding of drought-induced embolism does not provide a mechanistic explanation why increased vessel width should lead to greater vulnerability, and (2) the most recent advancements in nanoscale embolism processes suggest that vessel diameter is not a direct driver. Here, we review data from physiological and comparative wood anatomy studies, highlighting the potential anatomical and physicochemical drivers of embolism formation and spread. We then put forward key knowledge gaps, emphasising what is known, unknown and speculation. A meaningful evaluation of the diameter–vulnerability link will require a better mechanistic understanding of the biophysical processes at the nanoscale level that determine embolism formation and spread, which will in turn lead to more accurate predictions of how water transport in plants is affected by drought. Show less
Arkenbosch, J.H.C.; Beelen, E.M.J.; Dijkstra, G.; Romberg-Camps, M.; Duijvestein, M.; Hoentjen, F.; ... ; Dutch Initiative Crohns Colitis IC 2022
Background To prevent recurrence after ileocolonic resection [ICR] in Crohn's disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This... Show moreBackground To prevent recurrence after ileocolonic resection [ICR] in Crohn's disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This study aimed to evaluate postoperative CD recurrence after implementation of a clinical management algorithm and to determine the predictive value of clinical and histological risk factors [RFs]. Methods In this multicentre, prospective cohort study, CD patients [>= 16 years] scheduled for ICR were included. The algorithm advised no postoperative medication for low-risk patients, and treatment with prophylaxis [immunosuppressant/biological] for high-risk patients [>= 1 RF: active smoking, penetrating disease, prior ICR]. Clinical and histological RFs [active inflammation, granulomas, plexitis in resection margins] for endoscopic recurrence [Rutgeerts' score >= i2b at 6 months] were assessed using logistic regression and ROC curves based on predicted probabilities. Results In total, 213 CD patients after ICR were included [age 34.5 years; 65% women] (93 [44%] low-risk; 120 [56%] high-risk: 45 [38%] smoking; 51 [43%] penetrating disease; 51 [43%] prior ICR). Adherence to the algorithm was 82% in low-risk [no prophylaxis] and 51% in high-risk patients [prophylaxis]. Endoscopic recurrence was higher in patients treated without prophylaxis than with prophylaxis in both low [45% vs 16%, p = 0.012] and high-risk patients [49% vs 26%, p = 0.019]. Clinical risk stratification including the prescription of prophylaxis corresponded to an area under the curve [AUC] of 0.70 (95% confidence interval [CI] 0.61-0.79). Clinical RFs combined with histological RFs increased the AUC to 0.73 [95% CI 0.64-0.81]. Conclusion Adherence to this management algorithm is 65%. Prophylactic medication after ICR prevents endoscopic recurrence in low- and high-risk patients. Clinical risk stratification has an acceptable predictive value, but further refinement is needed. Show less
Arkenbosch, J.H.C.; Beelen, E.M.J.; Dijkstra, G.; Romberg-Camps, M.; Duijvestein, M.; Hoentjen, F.; ... ; Dutch Initiative Crohns Colitis IC 2022
BackgroundTo prevent recurrence after ileocolonic resection [ICR] in Crohn’s disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This... Show moreBackgroundTo prevent recurrence after ileocolonic resection [ICR] in Crohn’s disease [CD], postoperative prophylaxis based on risk stratification is recommended in international guidelines. This study aimed to evaluate postoperative CD recurrence after implementation of a clinical management algorithm and to determine the predictive value of clinical and histological risk factors [RFs].MethodsIn this multicentre, prospective cohort study, CD patients [≥16 years] scheduled for ICR were included. The algorithm advised no postoperative medication for low-risk patients, and treatment with prophylaxis [immunosuppressant/biological] for high-risk patients [≥1 RF: active smoking, penetrating disease, prior ICR]. Clinical and histological RFs [active inflammation, granulomas, plexitis in resection margins] for endoscopic recurrence [Rutgeerts’ score ≥i2b at 6 months] were assessed using logistic regression and ROC curves based on predicted probabilities.ResultsIn total, 213 CD patients after ICR were included [age 34.5 years; 65% women] (93 [44%] low-risk; 120 [56%] high-risk: 45 [38%] smoking; 51 [43%] penetrating disease; 51 [43%] prior ICR). Adherence to the algorithm was 82% in low-risk [no prophylaxis] and 51% in high-risk patients [prophylaxis]. Endoscopic recurrence was higher in patients treated without prophylaxis than with prophylaxis in both low [45% vs 16%, p = 0.012] and high-risk patients [49% vs 26%, p = 0.019]. Clinical risk stratification including the prescription of prophylaxis corresponded to an area under the curve [AUC] of 0.70 (95% confidence interval [CI] 0.61–0.79). Clinical RFs combined with histological RFs increased the AUC to 0.73 [95% CI 0.64–0.81].ConclusionAdherence to this management algorithm is 65%. Prophylactic medication after ICR prevents endoscopic recurrence in low- and high-risk patients. Clinical risk stratification has an acceptable predictive value, but further refinement is needed. Show less
In this retrospective cohort study of the outcomes of infants born <32 week's gestation, moving from a traditional open bay neonatal unit to a new single-room unit was not associated with... Show moreIn this retrospective cohort study of the outcomes of infants born <32 week's gestation, moving from a traditional open bay neonatal unit to a new single-room unit was not associated with significant improvements in morbidity or mortality. Objective: In response to the increasing focus on family-centred care, neonatal intensive care unit (NICU) environments have gradually shifted towards the single-room design. However, the assumed benefits of this emerging design remain a subject of debate. Our goal was to evaluate the impact of single-room versus open-bay care on the risk of neonatal morbidity and mortality in preterm neonates. Design: Retrospective cohort study. Setting: Level III NICU. Patients: Neonates born Main outcome measures: Mortality and morbidities of a cohort of neonates admitted to a new, single-room unit (SRU) were compared with a historical cohort of neonates admitted to an open-bay unit (OBU). Group differences were evaluated and multivariable logistic regression analyses were performed. Results: Three-hundred and fifty-six and 343 neonates were admitted to the SRU and OBU, respectively. No difference in neonatal morbidities and mortality were observed between cohorts (bronchopulmonary dysplasia: OR 1.08, 95% CI 0.73 to 1.58, p=0.44; retinopathy of the prematurity stage >= 2: OR 1.36, 95% CI 0.84 to 2.22, p=0.10; intraventricular haemorrhage: OR 0.89, 95% CI 0.59 to 1.34, p=0.86; mortality: OR 1.55, 95% CI 0.75 to 3.20, p=0.28). In adjusted regression models, single-room care was independently associated with a decreased risk of symptomatic patent ductus arteriosus (adjusted OR 0.54, 95% CI 0.31 to 0.95). No independent association between single-room care and any of the other investigated outcomes was observed. Conclusions: Implementation of single-rooms in our NICU did not lead to a significant reduction in neonatal morbidity and mortality outcomes. Show less
Dahan, A.; Lemmen, M. van; Jansen, S.; Simons, P.; Schrier, R. van der 2022
Buprenorphine is a partial agonist at the mu opioid receptor. Due to its relatively low maximum effect on respiratory depression it is considered by some to be a safe opioid. But it can produce... Show moreBuprenorphine is a partial agonist at the mu opioid receptor. Due to its relatively low maximum effect on respiratory depression it is considered by some to be a safe opioid. But it can produce serious respiratory depression, particularly when combined with sedatives such as benzodiazepines. Show less
Wagner, M.; Boer, M.C. den; Jansen, S.; Groepel, P.; Visser, R.; Witlox, R.S.G.M.; ... ; Pas, A.B. te 2021
Objective The aim of this study was to determine the experience with, and the feasibility of, point-of-view video recordings using eye-tracking glasses for training and reviewing neonatal... Show moreObjective The aim of this study was to determine the experience with, and the feasibility of, point-of-view video recordings using eye-tracking glasses for training and reviewing neonatal interventions during the COVID-19 pandemic. Design Observational prospective single-centre study. Setting Neonatal intensive care unit at the Leiden University Medical Center. Participants All local neonatal healthcare providers. Intervention There were two groups of participants: proceduralists, who wore eye-tracking glasses during procedures, and observers who later watched the procedures as part of a video-based reflection. Main outcome measures The primary outcome was the feasibility of, and the proceduralists and observers' experience with, the point-of-view eye-tracking videos as an additional tool for bedside teaching and video-based reflection. Results We conducted 12 point-of-view recordings on 10 different patients (median gestational age of 30.9 +/- 3.5 weeks and weight of 1764 g) undergoing neonatal intubation (n=5), minimally invasive surfactant therapy (n=5) and umbilical line insertion (n=2). We conducted nine video-based observations with a total of 88 observers. The use of point-of-view recordings was perceived as feasible. Observers further reported the point-of-view recordings to be an educational benefit for them and a potentially instructional tool during COVID-19. Conclusion We proved the practicability of eye-tracking glasses for point-of-view recordings of neonatal procedures and videos for observation, educational sessions and logistics considerations, especially with the COVID-19 pandemic distancing measures reducing bedside teaching opportunities.Single centre evaluation of the use of eye-tracking glasses during neonatal procedures as an additional tool for outside teaching and video-based reflection. The feasibility and potential benefit during a pandemic is reported. Show less
Jansen, S.; Lopriore, E.; Naaktgeboren, C.; Sueters, M.; Limpens, J.; Leeuwen, E. van; Bekker, V. 2020
Background: While epidural analgesia (EA) is associated with maternal fever during labor, the impact on the risk for maternal and/or neonatal sepsis is unknown. Objectives: The aim of this... Show moreBackground: While epidural analgesia (EA) is associated with maternal fever during labor, the impact on the risk for maternal and/or neonatal sepsis is unknown. Objectives: The aim of this systematic review was to investigate the effect of epidural-related intrapartum fever on maternal and neonatal outcomes. Methods: OVID MEDLINE, OVID Embase, the Cochrane Library, Cochrane Controlled Register of Trials, and clinical trial registries were searched for randomized controlled trials (RCT) and observational cohort studies from inception to November 2018. A total of 761 studies were identified with 100 eligible for full-text review. Only articles investigating the relationship between EA and maternal fever during labor were eligible for inclusion. Study quality was assessed using the Cochrane's Risk of Bias tool and National Institute of Health Quality Assessment Tool. Two meta-analyses - one each for the RCT and observational cohort groups - were performed using the random-effects model of Mantel-Haenszel to produce summary risk ratios (RR) with 95% CI. Results: Twelve RCTs and 16 observational cohort studies involving 579,157 parturients were included. RRs for maternal fever for the RCT and cohort analyses were 3.54 (95% CI 2.61-4.81) and 5.60 (95% CI 4.50-6.97), respectively. Meta-analyses of RR for maternal infection in both groups were infeasible given few occurrences. Meta-analysis of data from observational studies showed an increased risk for maternal antibiotic treatment in the epidural group (RR 2.60; 95% CI 1.31-5.17). For both analyses, neonates born to women with an epidural were not evaluated more often for suspected sepsis. Neither analysis reported an increased rate of neonatal bacteremia or neonatal antibiotic treatment after EA, although data precluded conclusiveness. Conclusion: EA increases the risk of intrapartum fever and maternal antibiotic treatment. However, a definite conclusion on whether EA increases the risk for a proven maternal and/or neonatal bacteremia cannot be drawn due to the low quality of data. Further research on whether epidural-related intrapartum fever is of infectious origin or not is therefore needed. Show less
Background: More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during... Show moreBackground: More people on immunosuppression live in or wish to travel to yellow fever virus (YFV)-endemic areas. Data on the safety and immunogenicity of yellow fever vaccination (YFVV) during immunosuppression are scarce. The aim of this study was to compare the safety and immunogenicity of a primary YFVV between travellers on methotrexate and controls.Methods: We conducted a prospective multi-centre controlled observational study from 2015 to 2017 in six Swiss travel clinics. 15 adults (nine with rheumatic diseases, five with dermatologic conditions and one with a gastroenterological disease) on low-dose methotrexate (<= 20 mg/week) requiring a primary YFVV and 15 age and sex-matched controls received a YFVV. Solicited/unsolicited adverse reactions were recorded, YFV-RNA was measured in serum samples on Days 3, 7, 10, 14, 28 and neutralizing antibodies on Days 0, 7, 10, 14, 28.Results: Patients' and controls' median ages were 53 and 52 years; 9 patients and 10 controls were female. 43% of patients and 33% of controls showed local side effects (P = 0.71); 86% of patients and 66% of controls reported systemic reactions (P = 0.39). YFV-RNA was detected in patients and controls on Day 3-10 post-vaccination and was never of clinical significance. Slightly more patients developed YFV-RNAaemia (Day 3: n= 5 vs n= 2, Day 7: n= 9 vs n= 7, Day 10: n= 3 vs n= 2, all P > 0.39). No serious reactions occurred. On Day 10, a minority of vaccinees was seroprotected (patients: n= 2, controls: n= 6). On Day 28, all vaccinees were seroprotected.Conclusions: First-time YFVV was safe and immunogenic in travellers on low-dose methotrexate. Larger studies are needed to confirm these promising results. Show less
The leaf economic spectrum is a widely studied axis of plant trait variability that defines a trade-off between leaf longevity and productivity. While this has been investigated at the global scale... Show moreThe leaf economic spectrum is a widely studied axis of plant trait variability that defines a trade-off between leaf longevity and productivity. While this has been investigated at the global scale, where it is robust, and at local scales, where deviations from it are common, it has received less attention at the intermediate scale of plant functional types (PFTs). We investigated whether global leaf economic relationships are also present within the scale of plant functional types (PFTs) commonly used by Earth System models, and the extent to which this global-PFT hierarchy can be used to constrain trait estimates. We developed a hierarchical multivariate Bayesian model that assumes separate means and covariance structures within and across PFTs and fit this model to seven leaf traits from the TRY database related to leaf longevity, morphology, biochemistry, and photosynthetic metabolism. Although patterns of trait covariation were generally consistent with the leaf economic spectrum, we found three approximate tiers to this consistency. Relationships among morphological and biochemical traits (specific leaf area [SLA], N, P) were the most robust within and across PFTs, suggesting that covariation in these traits is driven by universal leaf construction trade-offs and stoichiometry. Relationships among metabolic traits (dark respiration [R-d], maximum RuBisCo carboxylation rate [V-c,V-max], maximum electron transport rate [J(max)]) were slightly less consistent, reflecting in part their much sparser sampling (especially for high-latitude PFTs), but also pointing to more flexible plasticity in plant metabolistm. Finally, relationships involving leaf lifespan were the least consistent, indicating that leaf economic relationships related to leaf lifespan are dominated by across-PFT differences and that within-PFT variation in leaf lifespan is more complex and idiosyncratic. Across all traits, this covariance was an important source of information, as evidenced by the improved imputation accuracy and reduced predictive uncertainty in multivariate models compared to univariate models. Ultimately, our study reaffirms the value of studying not just individual traits but the multivariate trait space and the utility of hierarchical modeling for studying the scale dependence of trait relationships. Show less
Sluijs, P.J. van der; Jansen, S.; Vergano, S.A.; Adachi-Fukuda, M.; Alanay, Y.; AlKindy, A.; ... ; Santen, G.W.E. 2019
Aim Plant trait databases often contain traits that are correlated, but for whom direct (undirected statistical dependency) and indirect (mediated by other traits) connections may be confounded.... Show moreAim Plant trait databases often contain traits that are correlated, but for whom direct (undirected statistical dependency) and indirect (mediated by other traits) connections may be confounded. The confounding of correlation and connection hinders our understanding of plant strategies, and how these vary among growth forms and climate zones. We identified the direct and indirect connections across plant traits relevant to competition, resource acquisition and reproductive strategies using a global database and explored whether connections within and between traits from different tissue types vary across climates and growth forms. Location Global. Major taxa studied Plants. Time period Present. Methods We used probabilistic graphical models and a database of 10 plant traits (leaf area, specific leaf area, mass- and area-based leaf nitrogen and phosphorous content, leaf life span, plant height, stem specific density and seed mass) with 16,281 records to describe direct and indirect connections across woody and non-woody plants across tropical, temperate, arid, cold and polar regions. Results Trait networks based on direct connections are sparser than those based on correlations. Land plants had high connectivity across traits within and between tissue types; leaf life span and stem specific density shared direct connections with all other traits. For both growth forms, two groups of traits form modules of more highly connected traits; one related to resource acquisition, the other to plant architecture and reproduction. Woody species had higher trait network modularity in polar compared to temperate and tropical climates, while non-woody species did not show significant differences in modularity across climate regions. Main conclusions Plant traits are highly connected both within and across tissue types, yet traits segregate into persistent modules of traits. Variation in the modularity of trait networks suggests that trait connectivity is shaped by prevailing environmental conditions and demonstrates that plants of different growth forms use alternative strategies to cope with local conditions. Show less
Mencuccini, M.; Rosa, T.; Rowland, L.; Choat, B.; Cornelissen, H.; Jansen, S.; ... ; Martinez-Vilalta, J. 2019
Biomass and area ratios between leaves, stems and roots regulate many physiological and ecological processes. The Huber value H-v (sapwood area/leaf area ratio) is central to plant water balance... Show moreBiomass and area ratios between leaves, stems and roots regulate many physiological and ecological processes. The Huber value H-v (sapwood area/leaf area ratio) is central to plant water balance and drought responses. However, its coordination with key plant functional traits is poorly understood, and prevents developing trait-based prediction models. Based on theoretical arguments, we hypothesise that global patterns in H-v of terminal woody branches can be predicted from variables related to plant trait spectra, that is plant hydraulics and size and leaf economics. Using a global compilation of 1135 species-averaged H-v, we show that H-v varies over three orders of magnitude. Higher H-v are seen in short small-leaved low-specific leaf area (SLA) shrubs with low K-s in arid relative to tall large-leaved high-SLA trees with high K-s in moist environments. All traits depend on climate but climatic correlations are stronger for explanatory traits than H-v. Negative isometry is found between H-v and K-s, suggesting a compensation to maintain hydraulic supply to leaves across species. This work identifies the major global drivers of branch sapwood/leaf area ratios. Our approach based on widely available traits facilitates the development of accurate models of above-ground biomass allocation and helps predict vegetation responses to drought. Show less
