Montane Temperate-Boreal Forests Retain the Leaf Economic Spectrum Despite Intraspecific Variability

Trait-based analyses provide powerful tools for developing a generalizable, physiologically grounded understanding of how forest communities are responding to ongoing environmental changes. Key challenges lie in (1) selecting traits that best characterize the ecological performance of species in the community and (2) determining the degree and importance of intraspecific variability in those traits. Recent studies suggest that globally evident trait correlations (trait dimensions), such as the leaf economic spectrum, may be weak or absent at local scales. Moreover, trait-based analyses that utilize a mean value to represent a species may be misleading. Mean trait values are particularly problematic if species trait value rankings change along environmental gradients, resulting in species trait crossover. To assess how plant traits (1) covary at local spatial scales, (2) vary across the dominant environmental gradients, and (3) can be partitioned within and across taxa, we collected data on 9 traits for 13 tree species spanning the montane temperate—boreal forest ecotones of New York and northern New England. The primary dimension of the trait ordination was the leaf economic spectrum, with trait variability among species largely driven by differences between deciduous angiosperms and evergreen gymnosperms. A second dimension was related to variability in nitrogen to phosphorous levels and stem specific density. Levels of intraspecific trait variability differed considerably among traits, and was related to variation in light, climate, and tree developmental stage. However, trait rankings across species were generally conserved across these gradients and there was little evidence of species crossover. The persistence of the leaf economics spectrum in both temperate and high-elevation conifer forests suggests that ecological strategies of tree species are associated with trade-offs between resource acquisition and tolerance, and may be quantified with relatively few traits. Furthermore, the assumption that species may be represented with a single trait value may be warranted for some trait-based analyses provided traits were measured under similar light levels and climate conditions

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.</p> <p>Methods/Design</p> <p>This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.</p> <p>Discussion</p> <p>NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00980356</p

CMV Late Phase-Induced mTOR Activation Is Essential for Efficient Virus Replication in Polarized Human Macrophages : Antiviral Effects of mTOR Inhibitors

Human cytomegalovirus (CMV) remains one of the most important pathogens following solid-organ transplantation. Mounting evidence indicates that mammalian target of rapamycin (mTOR) inhibitors may decrease the incidence of CMV infection in solid- organ recipients. Here we aimed at elucidating the molecular mechanisms of this effect by employing a human CMV (HCMV) infection model in human macrophages, since myeloid cells are the principal in vivo targets of HCMV. We demonstrate a highly di- vergent host cell permissiveness for HCMV with opti- mal infection susceptibility in M2 but not M1 polarized macrophages. Employing an ultrahigh purified HCMV stock we observed rapamycin-independent viral entry and induction of IFN-b transcripts, but no proinflam- matory cytokines or mitogen-activated protein kinases and mTOR activation early after infection. However, in the late infection phase, sustained mTOR activa- tion was observed in HCMV-infected cells and was required for efficient viral protein synthesis including the viral late phase proteins pUL-44 and pp65. Accord- ingly, rapamycin strongly suppressed CMV replication 3 and 5 days postinfection in macrophages. In conclu- sion, these data indicate that mTOR is essential for virus replication during late phases of the viral cycle in myeloid cells and might explain the potent anti-CMV effects of mTOR inhibitors after organ transplantatio

A controlled study of supplementation with essential amino acids and α-keto acids in the conservative management of patients with chronic renal failure

Art und Zusammensetzung einer optimalen eiweißarmen Ernährung für Patienten mit Niereninsuffizienz sind weiterhin umstritten. Die orale medikamentöse Behandlung mit essentiellen Aminosäuren oder α-Ketosäuren wird häufig empfohlen. Unsere Untersuchungen vergleichen nacheinander bei 15 ambulanten Patienten mit chronischem Nierenversagen (mittlere Kreatinin-Clearance 10,8 ml/min) unter einer eiweißarmen Ernährung von 0,57 g/kg Körpergewicht (40 g/70 kg) die Wirkung einer Substitution mit essentiellen Aminosäuren, danach die Substitution mit α-Ketosäuren gegenüber Plazebo. Der nachgewiesene Proteingehalt in der Nahrung betrug 0,55 g/kg, die Energiezufuhr 27 kcal/kg Körpergewicht, wie mehrfach Ernährungsprotokolle über jeweils 7 Tage bei den Patienten zeigen ließen. Nach einer Vorperiode von 6 Wochen nur unter diätetischen Maßnahmen erhielten alle Patienten zusätzlich 0,112 g essentielle Aminosäuren/kg Körpergewicht über 6 Wochen, danach in einer Doppelblinduntersuchung 0,105 g α-Ketosäuren/kg Körpergewicht im Vergleich gegenüber Plazebo, ebenfalls jeweils über 6 Wochen. Nüchtern-Blutuntersuchungen wurden für ein Standard-Laborwertprogramm, insbesondere für 15 Proteinmangelparameter, alle 3 Wochen durchgeführt, ferner anthropometrische und klinische Kontrollen. Die Laborwerte erbrachten keine Hinweise auf einen manifesten Proteinmangel. Die Therapie mit α-Ketosäuren erniedrigte die Phosphatspiegel signifikant (p<0,05). Dagegen konnten weder unter essentiellen Aminosäuren oder α-Ketosäuren andere für den Patienten wesentliche Effekte nachgewiesen werden. Deshalb erscheint uns eine Substitution mit essentiellen Aminosäuren oder Ketosäuren überflüssig bei Patienten mit einer chronischen Niereninsuffizienz, die sich in einem stabilen Stoffwechselgleichgewicht befinden und mit einer Eiweißzufuhr von 0,55 g/kg Körpergewicht behandelt werden. Oral therapy with essential amino acids (EAA) or α-keto acids (α-KA) has been recommended in patients with renal failure, but quality and quantity of optimal protein intake are still controversial. This study compares sequentially the effect of supplementation with EAA, and with α-KA versus placebo in 15 ambulatory patients with chronic renal failure (average creatinine clearance 10.8 ml/min), maintained on a protein diet of 0.57 g/kg body weight (40 g for a 70-kg patient). The actual dietary intake averaged 0.55 g protein/kg and 27 kcal/kg according to repeated 7-day dietary recordings. After a 6-week baseline period on this diet, all patients received additionally 0.112 g EAA/kg for 6 weeks followed by a double-blind cross-over study of 0.105 g α-KA/kg versus placebo supplementation for 6 weeks each. Fasting blood samples for multiple parameters, including 15 indicators for protein deficiency, as well as anthropometric and clinical data were evaluated every 3 weeks. Laboratory data revealed no indications of protein deficiency. Therapy with α-KA diminished serum phosphate concentration (p<0.05), however no other significant beneficial effects could be demonstrated during supplementation with either EAA or α-KA. Therefore, such supplementation to a 0.55-g/kg-protein diet appears superfluous in stable ambulatory patients with renal insufficiency.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41743/1/394_2005_Article_BF02020747.pd

Dialysis initiation, modality choice, access, and prescription: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied \u201ccountry-specific\u201d factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a \u201cone-size-fits-all\u201d approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions

Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19—Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT)

Background: To date, no oral antiviral drug has proven to be beneficial in hospitalized patients with COVID-19.Methods: In this randomized, controlled, open-label, platform trial, we randomly assigned patients ≥18 years hospitalized with COVID-19 pneumonia to receive either camostat mesylate (CM) (considered standard-of-care) or lopinavir/ritonavir (LPV/RTV). The primary endpoint was time to sustained clinical improvement (≥48 h) of at least one point on the 7-category WHO scale. Secondary endpoints included length of stay (LOS), need for mechanical ventilation (MV) or death, and 29-day mortality.Results: 201 patients were included in the study (101 CM and 100 LPV/RTV) between 20 April 2020 and 14 May 2021. Mean age was 58.7 years, and 67% were male. The median time from symptom onset to randomization was 7 days (IQR 5–9). Patients in the CM group had a significantly shorter time to sustained clinical improvement (HR = 0.67, 95%-CI 0.49–0.90; 9 vs. 11 days, p = 0.008) and demonstrated less progression to MV or death [6/101 (5.9%) vs. 15/100 (15%), p = 0.036] and a shorter LOS (12 vs. 14 days, p = 0.023). A statistically nonsignificant trend toward a lower 29-day mortality in the CM group than the LPV/RTV group [2/101 (2%) vs. 7/100 (7%), p = 0.089] was observed.Conclusion: In patients hospitalized for COVID-19, the use of CM was associated with shorter time to clinical improvement, reduced need for MV or death, and shorter LOS than the use of LPV/RTV. Furthermore, research is needed to confirm the efficacy of CM in larger placebo-controlled trials.Systematic Review Registration: [https://clinicaltrials.gov/ct2/show/NCT04351724, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001302-30/AT], identifier [NCT04351724, EUDRACT-NR: 2020–001302-30]

Which aspects of the open science agenda are most relevant to scientometric research and publishing? An opinion paper

© 2021 The Authors. Published by MIT Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1162/qss_e_00121Open Science is an umbrella term that encompasses many recommendations for possible changes in research practices, management, and publishing with the objective to increase transparency and accessibility. This has become an important science policy issue that all disciplines should consider. Many Open Science recommendations may be valuable for the further development of research and publishing but not all are relevant to all fields. This opinion paper considers the aspects of Open Science that are most relevant for scientometricians, discussing how they can be usefully applied.The work of R.G. was supported by the Flemish Government through its funding of the Flemish Centre for R&D Monitoring (ECOOM