Improving static analyses of C programs with conditional predicates

Best paper awardInternational audienceStatic code analysis is increasingly used to guarantee the absence of undesirable behaviors in industrial programs. Designing sound analyses is a continuing trade-off between precision and complexity. Notably, dataflow analyses often perform overly wide approximations when two control-flow paths meet, by merging states from each path. This paper presents a generic abstract interpretation based framework to enhance the precision of such analyses on join points. It relies on predicated domains, that preserve and reuse information valid only inside some branches of the code. Our predicates are derived from conditionals statements, and postpone the loss of information. The work has been integrated into Frama-C, a C source code analysis platform. Experiments on real code show that our approach scales, and improves significantly the precision of the existing analyses of Frama-C

Science, Nature and Beauty: Harmony and Cosmological Perspectives in Islamic Science

This is a brochure to accompany the exhibit: “Science, Nature and Beauty: Harmony and Cosmological Perspectives in Islamic Science” (October 19th, 2022- March 3rd, 2023).This exhibit showcases over 90 manuscripts, instruments and objects from the Muslim World Manuscript collection which are housed in the Rare Book and Manuscript Library (RBML), at the Columbia University Libraries (CUL). This exhibit is a collective curatorial effort that has involved many students, faculty members, librarians and library staff working hand-in-hand to exchange ideas and to select, research, engage with, and mount the items. Keywords: Islamic Science--Exhibits; Manuscripts--Islamic science; Islamic arts and sciences; material culture, codicology, Islamic cultures and societies

Allostery in Its Many Disguises: From Theory to Applications.

Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used here to provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts

Racial and Socioeconomic Disparities in Long Term Survival After Surgery and Radiation for Spinal Cord Hemangioblastoma

Spinal cord hemangioblastomas are rare, benign, intradural tumors that, despite their nonmalignant histopathology, can lead to substantial neurological morbidity. While disparities in outcomes based on race and socioeconomic status have been well-documented in other spinal tumor populations, their role in spinal cord hemangioblastoma remains poorly understood. In this study, we utilize the National Cancer Database (NCDB) to evaluate the influence of race, socioeconomic factors, and healthcare access on survival outcomes in patients with spinal cord hemangioblastoma. Additionally, we explore the utility of machine learning-based survival models to improve individualized risk prediction and to identify key clinical and sociodemographic determinants of long-term survival. Patients diagnosed with spinal cord hemangioblastoma were identified from the National Cancer Database (NCDB) using ICD-O-3 histology and topography codes. Demographic, socioeconomic, and clinical variables were compared across racial groups (White, Black and Asian). Long-term overall survival (OS) was defined as survival beyond 10 years. Kaplan-Meier and multivariable Cox regression analyses were used to evaluate survival outcomes and identify independent predictors of mortality. Tumor size was stratified using the cohort-wide mean (62.2 mm) for interpretability. Temporal trends in racial distribution and surgical technique (open vs. MIS) were assessed using Mann-Kendall trend testing. Gradient Boosting Survival, Cox proportional hazards, and Random Survival Forest models were developed and validated for mortality prediction. The best-performing model was interpreted using SHAP analysis. A total of 716 adult patients with spinal cord hemangioblastoma were analyzed, with the majority being White (83.7%), followed by Black (12.3%) and Asian (4%). Significant differences were observed across racial groups in age, insurance status, income quartiles, and comorbidity scores, though sex distribution and facility type utilization were comparable. Most patients were treated at academic centers, and surgery alone was the predominant treatment modality, with no racial disparities in extent of resection or use of radiation. Kaplan-Meier analysis showed significantly higher 10-year and long-term mortality in White patients; however, race was not an independent predictor in multivariable Cox regression, where increased age, higher CDCC scores, urban residence, and treatment at comprehensive community cancer centers were associated with worse survival. Surgery, with or without radiation, was protective compared to radiation alone. Temporal analysis showed stable racial distribution and minimal uptake of minimally invasive surgery from 2010 to 2017. The Gradient Boosting Survival model achieved the highest predictive performance (AUC = 0.8214; C-index = 0.7817), with age, facility type, and comorbidity burden identified as the strongest predictors of mortality in SHAP analysis. A publicly available web-based calculator was developed based on this model to provide individualized survival estimates. Racial and socioeconomic disparities were associated with differences in clinical outcomes on univariate analysis. However, race and insurance status were not independent predictors of mortality in multivariable-adjusted models. This suggests that the observed survival differences may be explained by confounding factors, such as comorbidity burden, treatment modality, or access to specialized care. Notably, poorer survival was independently associated with treatment at Comprehensive Community Cancer Programs and with higher comorbidity scores, underscoring the importance of ensuring equitable access to high-volume, specialized centers. Lastly, the Gradient Boosting Survival model enhanced mortality risk prediction by incorporating both clinical and socioeconomic variables, supporting its potential utility in guiding targeted interventions to improve long-term outcomes

Intrinsic Determinants of Aβ12–24 pH-Dependent Self-Assembly Revealed by Combined Computational and Experimental Studies

The propensity of amyloid- (A) peptide to self-assemble into highly ordered amyloid structures lies at the core of their accumulation in the brain during Alzheimer's disease. By using all-atom explicit solvent replica exchange molecular dynamics simulations, we elucidated at the atomic level the intrinsic determinants of the pH-dependent dimerization of the central hydrophobic segment A and related these with the propensity to form amyloid fibrils measured by experimental tools such as atomic force microscopy and fluorescence. The process of A dimerization was evaluated in terms of free energy landscape, side-chain two-dimensional contact probability maps, -sheet registries, potential mean force as a function of inter-chain distances, secondary structure development and radial solvation distributions. We showed that dimerization is a key event in A amyloid formation; it is highly prompted in the order of pH 5.02.98.4 and determines further amyloid growth. The dimerization is governed by a dynamic interplay of hydrophobic, electrostatic and solvation interactions permitting some variability of -sheets at each pH. These results provide atomistic insight into the complex process of molecular recognition detrimental for amyloid growth and pave the way for better understanding of the molecular basis of amyloid diseases

Insight into the Stability of Cross-β Amyloid Fibril from VEALYL Short Peptide with Molecular Dynamics Simulation

Amyloid fibrils are found in many fatal neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes, and prion disease. The VEALYL short peptide from insulin has been confirmed to aggregate amyloid-like fibrils. However, the aggregation mechanism of amyloid fibril is poorly understood. Here, we utilized molecular dynamics simulation to analyse the stability of VEALYL hexamer. The statistical results indicate that hydrophobic residues play key roles in stabilizing VEALYL hexamer. Single point and two linkage mutants confirmed that Val1, Leu4, and Tyr5 of VEALYL are key residues. The consistency of the results for the VEALYL oligomer suggests that the intermediate states might be trimer (3-0) and pentamer(3-2). These results can help us to obtain an insight into the aggregation mechanism of amyloid fibril. These methods can be used to study the stability of amyloid fibril from other short peptides

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks