The impact of a multidisciplinary self-care management program on quality of life, self-care, adherence to anti-hypertensive therapy, glycemic control, and renal function in diabetic kidney disease: A Cross-over Study Protocol.

Diabetic kidney disease, a global health issue, remains associated with high morbidity and mortality. Previous research has shown that multidisciplinary management of chronic disease can improve patient outcomes. The effect of multidisciplinary self-care management on quality of life and renal function of patients with diabetic kidney disease has not yet been well established. The aim of this study is to evaluate the impact of a multidisciplinary self-care management program on quality of life, self-care behavior, adherence to anti-hypertensive treatment, glycemic control, and renal function of adults with diabetic kidney disease. A uniform balanced cross-over design is used, with the objective to recruit 40 adult participants with diabetic kidney disease, from public and private out-patient settings in French speaking Switzerland. Participants are randomized in equal number into four study arms. Each participant receives usual care alternating with the multidisciplinary self- care management program. Each treatment period lasts three months and is repeated twice at different time intervals over 12 months depending on the cross-over arm. The multidisciplinary self-care management program is led by an advanced practice nurse and adds nursing and dietary consultations and follow-ups, to the habitual management provided by the general practitioner, the nephrologist and the diabetologist. Data is collected every three months for 12 months. Quality of life is measured using the Audit of Diabetes-Dependent Quality of Life scale, patient self-care behavior is assessed using the Revised Summary of Diabetes Self-Care Activities, and adherence to anti-hypertensive therapy is evaluated using the Medication Events Monitoring System. Blood glucose control is measured by the glycated hemoglobin levels and renal function by serum creatinine, estimated glomerular filtration rate and urinary albumin/creatinine ratio. Data will be analyzed using STATA version 14. The cross-over design will elucidate the responses of individual participant to each treatment, and will allow us to better evaluate the use of such a design in clinical settings and behavioral studies. This study also explores the impact of a theory-based nursing practice and its implementation into a multidisciplinary context. ClinicalTrials.gov identifier: NCT01967901 , registered on the 18th of October 2013

Analysis of the potential of sustainable forest-based bioenergy for climate change mitigation

Current climate mitigation policies are likely to become a strong driver of increased demand for renewable energy sources and particularly for bioenergy. Therefore, it is becoming more and more important to assess the potential amount of biomass that will be available for future energy production and the costs, in terms of greenhouse gas (GHG) emissions, connected to extraction of these potentials. The estimate of emissions produced by different bioenergy sources is important for evaluating the advantages of biomass-based energy compared to fossil fuel use. This allows promotion of energy sources that are the most advantageous for climate mitigation

d-wave superconductivity and Pomeranchuk instability in the two-dimensional Hubbard model

We present a systematic stability analysis for the two-dimensional Hubbard model, which is based on a new renormalization group method for interacting Fermi systems. The flow of effective interactions and susceptibilities confirms the expected existence of a d-wave pairing instability driven by antiferromagnetic spin fluctuations. More unexpectedly, we find that strong forward scattering interactions develop which may lead to a Pomeranchuk instability breaking the tetragonal symmetry of the Fermi surface.Comment: 4 pages (RevTeX), 4 eps figure

Chronic kidney disease in type 2 diabetic patients followed-up by primary care physicians in Switzerland: prevalence and prescription of antidiabetic drugs.

QUESTION UNDER STUDY: The aim of this study was to assess the prevalence of chronic kidney disease (CKD) among type 2 diabetic patients in primary care settings in Switzerland, and to analyse the prescription of antidiabetic drugs in CKD according to the prevailing recommendations. METHODS: In this cross-sectional study, each participating physician was asked to introduce anonymously in a web database the data from up to 15 consecutive diabetic patients attending her/his office between December 2013 and June 2014. Demographic, clinical and biochemical data were analysed. CKD was classified with the KDIGO nomenclature based on estimated glomerular filtration rate (eGFR) and urinary albumin/creatinine ratio. RESULTS: A total of 1 359 patients (mean age 66.5 ± 12.4 years) were included by 109 primary care physicians. CKD stages 3a, 3b and 4 were present in 13.9%, 6.1%, and 2.4% of patients, respectively. Only 30.6% of patients had an entry for urinary albumin/creatinine ratio. Among them, 35.6% were in CKD stage A2, and 4.1% in stage A3. Despite prevailing limitations, metformin and sulfonylureas were prescribed in 53.9% and 16.5%, respectively, of patients with advanced CKD (eGFR <30 ml/min). More than a third of patients were on a dipeptidyl-peptidase-4 inhibitor across all CKD stages. Insulin use increased progressively from 26.8% in CKD stage 1-2 to 50% in stage 4. CONCLUSIONS: CKD is frequent in patients with type 2 diabetes attending Swiss primary care practices, with CKD stage 3 and 4 affecting 22.4% of cases. This emphasizes the importance of routine screening of diabetic nephropathy based on both eGFR and urinary albumin/creatinine ratio, the latter being largely underused by primary care physicians. A careful individual drug risk/benefit balance assessment is mandatory to avoid the frequently observed inappropriate prescription of antidiabetic drugs in CKD patients

Exact renormalization group flow equations for non-relativistic fermions: scaling towards the Fermi surface

We construct exact functional renormalization group (RG) flow equations for non-relativistic fermions in arbitrary dimensions, taking into account not only mode elimination but also the rescaling of the momenta, frequencies and the fermionic fields. The complete RG flow of all relevant, marginal and irrelevant couplings can be described by a system of coupled flow equations for the irreducible n-point vertices. Introducing suitable dimensionless variables, we obtain flow equations for generalized scaling functions which are continuous functions of the flow parameter, even if we consider quantities which are dominated by momenta close to the Fermi surface, such as the density-density correlation function at long wavelengths. We also show how the problem of constructing the renormalized Fermi surface can be reduced to the problem of finding the RG fixed point of the irreducible two-point vertex at vanishing momentum and frequency. We argue that only if the degrees of freedom are properly rescaled it is possible to reach scale-invariant non-Fermi liquid fixed points within a truncation of the exact RG flow equations.Comment: 20 Revtex pages, with 4 figures; final version to appear in Phys. Rev. B; references and some explanations adde

Aggregation of antibody drug conjugates at room temperature: SAXS and light scattering evidence for colloidal instability of a specific subpopulation

Coupling an hydrophobic drug onto monoclonal antibodies via Lysine residues is a common route to prepare antibody-drug conjugates (ADC), a promising class of biotherapeutics. But a few chemical modifications on protein surface often increases aggregation propensity, without clear understanding of the aggregation mechanisms at stake (loss of colloidal stability, self- assemblies, denaturation...), and the statistical nature of conjugation introduces polydispersity in the ADC population, which raises questions on whether the whole ADC population becomes unstable. To characterize the average interactions between ADC, we monitored small angle X-ray scattering in solutions of monoclonal IgG1 human antibody drug conjugate, with average degree of conjugation of 0, 2, or 3 drug molecules per protein. To characterize stability, we studied kinetics of aggregation at room temperature. Intrinsic Fuchs stability ratio of the ADC was estimated from the variation over time of scattered light intensity and hydrodynamic radius, in buffers of varying pH, and at diverse sucrose (0% or 10%) and NaCl (0 or 100 mM) concentrations. We show that stable ADC stock solutions became unstable upon pH shift, well below the pH of maximum average attraction between IgGs. Data indicates that aggregation can be ascribed to a fraction of ADC population usually representing less than 30 mol% of the sample. In contrast to the case of (monodisperse) monoclonal antibodies, our results suggest that a poor correlation between stability and average interaction parameters should be expected as a corollary of dispersity of ADC conjugation. In practice, the most unstable fraction of the ADC population can be removed by filtrations, which affects remarkably the apparent stability of the samples. Finally, the lack of correlation between the kinetic stability and variations of the average inter-ADC interactions is tentatively attributed to the uneven nature of charge distributions and the presence of patches on the drug-modified antibodies.This work was supported by the French National Research Agency (program Blanc International, grant ANR 2010-INT 1501, and program Investissement d’Avenir ANR-11- LABX-0011-01, and by SANOFI research grant to BFP. Authors are grateful to Javier Perez and Aurélien Thureau for their help and advice in SAXS measurements at SOLEIL. We thank Sophie Norvez from MMC laboratory in ESPCI for her help with circular dichroism.This is the author accepted manuscript. The final version is available from the American Chemical Society via http://dx.doi.org/10.1021/acs.langmuir.6b0065

Aggregation of Antibody Drug Conjugates at Room Temperature: SAXS and Light Scattering Evidence for Colloidal Instability of a Specific Subpopulation

Coupling a hydrophobic drug onto monoclonal antibodies via lysine residues is a common route to prepare antibody–drug conjugates (ADC), a promising class of biotherapeutics. But a few chemical modifications on protein surface often increase aggregation propensity, without a clear understanding of the aggregation mechanisms at stake (loss of colloidal stability, self-assemblies, denaturation, etc.), and the statistical nature of conjugation introduces polydispersity in the ADC population, which raises questions on whether the whole ADC population becomes unstable. To characterize the average interactions between ADC, we monitored small-angle X-ray scattering in solutions of monoclonal IgG1 human antibody drug conjugate, with average degree of conjugation of 0, 2, or 3 drug molecules per protein. To characterize stability, we studied the kinetics of aggregation at room temperature. The intrinsic Fuchs stability ratio of the ADC was estimated from the variation over time of scattered light intensity and hydrodynamic radius, in buffers of varying pH, and at diverse sucrose (0% or 10%) and NaCl (0 or 100 mM) concentrations. We show that stable ADC stock solutions became unstable upon pH shift, well below the pH of maximum average attraction between IgGs. Data indicate that aggregation can be ascribed to a fraction of ADC population usually representing less than 30 mol % of the sample. In contrast to the case of (monodisperse) monoclonal antibodies, our results suggest that a poor correlation between stability and average interaction parameters should be expected as a corollary of dispersity of ADC conjugation. In practice, the most unstable fraction of the ADC population can be removed by filtration, which affects remarkably the apparent stability of the samples. Finally, the lack of correlation between the kinetic stability and variations of the average inter-ADC interactions is tentatively attributed to the uneven nature of charge distributions and the presence of patches on the drug-modified antibodies

Orbital quantization in the high magnetic field state of a charge-density-wave system

A superposition of the Pauli and orbital coupling of a high magnetic field to charge carriers in a charge-density-wave (CDW) system is proposed to give rise to transitions between subphases with quantized values of the CDW wavevector. By contrast to the purely orbital field-induced density-wave effects which require a strongly imperfect nesting of the Fermi surface, the new transitions can occur even if the Fermi surface is well nested at zero field. We suggest that such transitions are observed in the organic metal $\alpha$-(BEDT-TTF)$_2$KHg(SCN)$_4$ under a strongly tilted magnetic field.Comment: 14 pages including 4 figure

Re-entrant hidden order at a metamagnetic quantum critical end point

Magnetization measurements of URu2Si2 in pulsed magnetic fields of 44 T reveal that the hidden order phase is destroyed before appearing in the form of a re-entrant phase between ~ 36 and 39 T. Evidence for conventional itinerant electron metamagnetism at higher temperatures suggests that the re-entrant phase is created in the vicinity of a quantum critical end point.Comment: 8 pages, including 3 figures (Physical Review Letters, in press) a systematic error in the field calibration has been fixed since the original submission of this manuscrip

Renormalization group analysis of the 2D Hubbard model

Salmhofer [Commun. Math. Phys. 194, 249 (1998)] has recently developed a new renormalization group method for interacting Fermi systems, where the complete flow from the bare action of a microscopic model to the effective low-energy action, as a function of a continuously decreasing infrared cutoff, is given by a differential flow equation which is local in the flow parameter. We apply this approach to the repulsive two-dimensional Hubbard model with nearest and next-nearest neighbor hopping amplitudes. The flow equation for the effective interaction is evaluated numerically on 1-loop level. The effective interactions diverge at a finite energy scale which is exponentially small for small bare interactions. To analyze the nature of the instabilities signalled by the diverging interactions we extend Salmhofers renormalization group for the calculation of susceptibilities. We compute the singlet superconducting susceptibilities for various pairing symmetries and also charge and spin density susceptibilities. Depending on the choice of the model parameters (hopping amplitudes, interaction strength and band-filling) we find commensurate and incommensurate antiferromagnetic instabilities or d-wave superconductivity as leading instability. We present the resulting phase diagram in the vicinity of half-filling and also results for the density dependence of the critical energy scale.Comment: 16 pages, RevTeX, 16 eps figure