Stratified Static Analysis Based on Variable Dependencies

In static analysis by abstract interpretation, one often uses widening operators in order to enforce convergence within finite time to an inductive invariant. Certain widening operators, including the classical one over finite polyhedra, exhibit an unintuitive behavior: analyzing the program over a subset of its variables may lead a more precise result than analyzing the original program! In this article, we present simple workarounds for such behavior

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

New Aspects of Lung Transplantation: A Narrative Overview Covering Important Aspects of Perioperative Management

The management of lung transplant patients has continued to evolve in recent years. The year 2021 was marked by the publication of the International Consensus Recommendations for Anesthetic and Intensive Care Management of Lung Transplantation. There have been major changes in lung transplant programs over the last few years. This review will summarize the knowledge in anesthesia management of lung transplantation with the most recent data. It will highlight the following aspects which concern anesthesiologists more specifically: (1) impact of COVID-19, (2) future of transplantation for cystic fibrosis patients, (3) hemostasis management, (4) extracorporeal membrane oxygenation management, (5) early prediction of primary graft dysfunction, and (6) pain management

Prevalence, Characteristics and Preoperative Predictors of Chronic Pain After Double-Lung Transplantation: A Prospective Cohort Study

International audienceObjective: Data on chronic pain after lung transplantation are heterogeneous. This study prospectively explored the prevalence, characteristics, consequences, and preoperative predictors of pain in lung transplant recipients. Design: A prospective cohort study. Setting: The Foch University Hospital, Suresnes, France. Participants: Patients registered on the waiting list for double-lung transplantation in the authors’ institution from August 2008 to October 2013 and transplanted. Interventions: Database prospectively completed in real time during consultations with a pain-certified anesthesiologist before lung transplantation and six months after surgery. Measurements and Main Results: The assessments explored pain in three components: physical (intensity, location, neuropathic and sensory qualifications, treatments), mental (anxiety and depression), and quality of life. Seventy-two patients underwent all assessments. The prevalence of six-month postoperative pain was 68.0%. Among patients with pain, 83.3% reported mild average pain and 26.5% had neuropathic pain. All patients who responded to the questionnaire took analgesics frequently, but only 9.1% took opioids. Patients with pain reported higher levels of anxiety (p = 0.02) and depression (p = 0.01). Additionally, they presented with increased difficulty in ambulation (p = 0.03), work (p = 0.02), and sleep (p = 0.02). The maximum level of preoperative pain was an independent risk factor of six-month postoperative pain (p = 0.03). Conclusions: The authors report a high prevalence of chronic pain with concomitant psychosocial repercussions despite a reported mild intensity. Perioperative measures, such as personalized and detailed management plans, could improve patient satisfaction

N"N"C platinum (II) complexes based on phenyl-pyridin-2-ylpyrimidine ligands: synthesis, electrochemical and photophysical properties

International audienceA series of luminescent chloro- and alkynyl-platinum (II) complexes containing various tridentate cyclometalated ligands derived from phenyl-pyridin-2-ylpyrimidine and alkynyl ligands has been successfully synthesized and characterized. Their electrochemical, electronic absorption and luminescence properties have been experimentally investigated and supported by (Time-Dependent) Density Functional Theory ((TD)-DFT) calculations. Electrochemical studies show the presence of a ligand-centered reduction originating from the cyclometalating N"N"C ligands, as well as a major ligand-centered oxidation process (N"N"C or alkynyl) with minor contributions of the metal. Most of the complexes exhibits yellow-to-red luminescence at room-temperature in diluted solutions, in frozen matrices and in the solid state. Electron-withdrawing groups on the alkynyl-ligand induce a red shift of the emission band with increased quantum yield in solution. The emission is also sensitive to the position of the pyridyl fragment on the pyrimidine core: complexes with electron-poorer 4-pyridin-2-ylpyrimidine ligands exhibit red-shifted emission and decreased quantum yield compared to their 2-pyridin-4yl analogues. In solid state, chloro-platinum complexes without tBu bulky group exhibit red-shifted excimer emission

Aggregation-Induced Enhanced Emission of a Dimethylacridan Substituted Pyrimidine Derivative

International audienceA pyrimidine chromophore bearing an acridan fragment was synthesized and its photophysical properties were studied. In solution, this compound is characterized by an important positive emission solvatochromism with a shift of 5800 cm(-1) between nonpolar heptane and dichloromethane (DCM) associated with large Stokes shifts (up to 9100 cm(-1) in DCM). Mono-exponential fluorescence decays are observed in heptane whereas more complicated bi- or three-exponential decays are observed in more polar solvents due to an interplay between locally excited and charge transfer excited state. Additionally, an aggregation-induced enhanced emission process was demonstrated in THF/water mixtures. At low temperature (77 K), in a polymethylmethacrylate (PMMA) thin film, the presence of an accessible triplet state (T1) was demonstrated, which was not observed in solution. Finally, we show that it is possible to protonate the chromophore in thin film leading to panchromatic dual emissio

Complementary Therapy Learning in the Setting of Lung Transplantation: A Single-Center Observational Study of Appropriation and Efficacy

International audienceTransplanted patients could benefit from complementary techniques. This prospective single-center, open study, performed in a tertiary university hospital, evaluates the appropriation and efficacy of a toolbox-kit of complementary techniques. Self-hypnosis, sophrology, relaxation, holistic gymnastics, and transcutaneous electric nerve stimulation (TENS) were taught to adult patients scheduled for double-lung transplantation. Patients were asked to use them before and after transplantation, as needed. The primary outcome was appropriation of each technique within the first three postoperative months. Secondary outcomes included efficacy on pain, anxiety, stress, sleep, and quality-of-life. Among the 80 patients included from May 2017 to September 2020, 59 were evaluated at the 4th postoperative month. Over the 4359 sessions performed, the most frequent technique used before surgery was relaxation. After transplantation, the techniques most frequently used were relaxation and TENS. TENS was the best technique in terms of autonomy, usability, adaptation, and compliance. Self-appropriation of relaxation was the easiest, while self-appropriation of holistic gymnastics was difficult but appreciated by patients. In conclusion: the appropriation by patients of complementary therapies such as mind–body therapies, TENS and holistic gymnastics is feasible in lung transplantation. Even after a short training session, patients regularly practiced these therapies, mainly TENS and relaxation.HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés

Styrylpyrimidine chromophores with bulky electron-donating substituents: experimental and theoretical investigation

International audienceStyrylpyrimidine with bulky 9,9-dimethylacridan, phenoxazine and phenothiazine electron-donating fragment were designed. Thermally activated delayed fluorescence (TADF) properties were expected for these structures. These chromophores exhibit peculiar emission properties. For 9,9-dimethylacridan and phenoxazine derivatives, a single emission highly sensitive to the polarity is observed in solution whereas for phenothiazine derivative a dual emission is observed in solution and is attributed to the coexistence of quasi-axial (Qax) and quasi-equatorial (Qeq) conformers. This study intends to understand with theoretical and experimental works, why the studied chromophores do not exhibit TADF properties, contrary to what was expected. The absence of phosphorescence both at room temperature and 77K tends to indicate the impossibility to harvest triplet states in these systems. Wave-function based calculations show that for both conformers of the three chromophores the S1-T1 splitting is significantly larger than 0.2 eV. The second triplet state T2 of Qeq conformers is found very close in energy to the singlet S1 state, but S1 and T2 states possess similar charge transfer characters. This prevents efficient spin-orbit coupling between the states, which is consistent with the absence of TADF

Operating room extubation: A predictive factor for 1-year survival after double-lung transplantation

International audienceBackground: Operating room (OR) extubation has been reported after lung transplantation (LT) in small cohorts. This study aimed to evaluate the prognosis of OR-extubated patients. The secondary objectives were to evaluate the safety of this approach and to identify its predictive factors. Methods: This retrospective single-center cohort study included patients undergoing double lung transplantation (DLT) from January 2012 to June 2019. Patients undergoing multiorgan transplantation, repeat transplantation, or cardiopulmonary bypass during the study period were excluded. OR-extubated patients were compared with intensive care unit (ICU)-extubated patients. Results: Among the 450 patients included in the analysis, 161 (35.8%) were extubated in the OR, and 4 were reintubated within 24 hours. Predictive factors for OR extubation were chronic obstructive pulmonary disease (COPD)/emphysema (p = .002) and cystic fibrosis (p = .005), recipient body mass index (p = .048), and the PaO2/FiO2 ratio 10 minutes after second graft implantation (p < .001). OR-extubated patients had a lower prevalence of grade 3 primary graft dysfunction at day 3 (p < .001). Eight (5.0%) patients died within the first year after OR extubation, and 49 (13.5%) patients died after ICU extubation (log-rank test; p = .005). After adjustment for OR extubation predictive factors, the multivariate Cox regression model showed that OR extubation was associated with greater one-year survival (adjusted hazard ratio = 0.40 [0.16-0.91], p = .028). Conclusions: OR extubation was associated with a favorable prognosis after DLT, but the association should not be interpreted as causality. This fast-track protocol was made possible by a team committed to developing a comprehensive strategy to enhance recovery