Comparison of multi-state Markov models for cancer progression with different procedures for parameters estimation. An application to breast cancer

Background: the knowledge of sojourn time (the duration of the preclinical screen-detectable period) and screening test sensitivity is crucial for understanding the disease progression and the effectiveness of screening programmes. For this purpose a model of the natural history of the disease is needed. The aim of this work is to provide an illustration of the application of multistate Markov models for breast cancer progression to the data of the Florentine screening programme, in order to estimate the sojourn time and sensitivity for breast cancer screening. Methods: three different multi-state Markov models of increasing complexity were used with three different estimation procedures based on non-linear least squares, maximum likelihood, and on a Bayesian approach. All the models produced estimates for screening sensitivity and mean sojourn time. The data used in our application seem to lead to a non-identifiability problem, since the estimation procedures for both the Maximum Likelihood and Non-Linear Least Squares gave estimates that changed with the parameters’ initial values or difficultly converged. In order to take this problem into account we used the Bayesian Approach by incorporating prior information on all the parameters. Results: the mean sojourn time varied between 2-7 years and 3-5 years for women aged 50-59 and 60-69, respectively. When the model complexity was increased a higher variability in estimates was observed among the estimation procedures. The results of the screening sensitivity estimates were highly variable, both among estimation techniques and models - varying between 63% and 100%, and between 77% and 100% for women aged 50-59 and 60-69, respectively. Conclusions: results are in accord with the literature; those obtained through the Bayesian Approach seem to be more reliable.&nbsp

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 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). 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

Cryogenic Characterization of FBK RGB-HD SiPMs

We report on the cryogenic characterization of Red Green Blue - High Density (RGB-HD) SiPMs developed at Fondazione Bruno Kessler (FBK) as part of the DarkSide program of dark matter searches with liquid argon time projection chambers. A dedicated setup was used to measure the primary dark noise, the correlated noise, and the gain of the SiPMs at varying temperatures. A custom-made data acquisition system and analysis software were used to precisely characterize these parameters. We demonstrate that FBK RGB-HD SiPMs with low quenching resistance (RGB-HD-LR$_q$) can be operated from 40 K to 300 K with gains in the range $10^5$ to $10^6$ and noise rates on the order of a few Hz/mm$^2$