Risk margin for a non-life insurance run-off

For solvency purposes insurance companies need to calculate so-called best-estimate reserves for outstanding loss liability cash flows and a corresponding risk margin for non-hedgeable insurance-technical risks in these cash flows. In actuarial practice, the calculation of the risk margin is often not based on a sound model but various simplified methods are used. In the present paper we properly define these notions and we introduce insurance-technical probability distortions. We describe how the latter can be used to calculate a risk margin for non-life insurance run-off liabilities in a mathematically consistent way

Sex Does Not Affect Survival: A Propensity Score-Matched Comparison in a Homogenous Contemporary Radical Cystectomy Cohort.

OBJECTIVES To determine whether biological sex affects oncological outcome after extended pelvic lymph node dissection, radical cystectomy, and urinary diversion for muscle-invasive bladder cancer, and to identify risk factors impacting outcome. PATIENTS AND METHODS We performed a single-center, retrospective observational cohort study with prospective data collection with a propensity score matched population. A total of 1165 consecutive patients from 2000 to 2020, (317 women and 848 men) scheduled for open extended pelvic lymph node dissection, radical cystectomy, and urinary diversion for urothelial bladder cancer were included in the final analysis. Overall Survival (OS), Cancer-Specific-Survival (CSS), and Recurrence-Free-survival (RFS) were assessed with multivariable weighted Cox regression analysis as well as with propensity score matched Cox-Regression. RESULTS No significant difference was found between sexes regarding OS (HR 1.18, [0.93-1.49], P = .16), CSS (HR 0.87, [0.64-1.18], P = .38), or RFS (HR 0.80, [0.59-1.07], P = .13). These results were confirmed after propensity score matching: female sex was not associated with inferior OS (HR 1.20, [0.91-1.60], P = .19), CSS (HR 1.01, [0.75-1.35], P = .97) or RFS (HR 0.98, [0.75-1.27], P = .86). CONCLUSIONS We did not find a significant difference in cancer-related outcomes or overall survival after extended pelvic lymph node dissection, open radical cystectomy, and urinary diversion for urothelial cancer between males and females even after adjustment with propensity matching score for multiple factors including oncological parameters, smoking status, and renal function

Opioid-Free Anesthesia for Open Radical Cystectomy Is Feasible and Accelerates Return of Bowel Function: A Matched Cohort Study.

The aim of this study was to evaluate the feasibility of opioid-free anesthesia (OFA) in open radical cystectomy (ORC) with urinary diversion and to assess the impact on recovery of gastrointestinal function. We hypothesized that OFA would lead to earlier recovery of bowel function. A total of 44 patients who underwent standardized ORC were divided into two groups (OFA group vs. control group). In both groups, patients received epidural analgesia (OFA group: bupivacaine 0.25%, control group: bupivacaine 0.1%, fentanyl 2 mcg/mL, and epinephrine 2 mcg/mL). The primary endpoint was time to first defecation. Secondary endpoints were incidence of postoperative ileus (POI) and incidence of postoperative nausea and vomiting (PONV). The median time to first defecation was 62.5 h [45.8-80.8] in the OFA group and 118.5 h [82.6-142.3] (p < 0.001) in the control group. With regard to POI (OFA group: 1/22 patients (4.5%); control group: 2/22 (9.1%)) and PONV (OFA group: 5/22 patients (22.7%); control group: 10/22 (45.5%)), trends but no significant results were found (p = 0.99 and p = 0.203, respectively). OFA appears to be feasible in ORC and to improve postoperative functional gastrointestinal recovery by halving the time to first defecation compared with standard fentanyl-based intraoperative anesthesia

Parallel computation of radio listening rates

Obtaining the listening rates of radio stations in function of time is an important instrument for determining the impact of publicity. Since many radio stations are financed by publicity, the exact determination of radio listening rates is vital to their existence and to further development. Existing methods of determining radio listening rates are based on face to face interviews or telephonic interviews made with a sample population. These traditional methods however require the cooperation and compliance of the participants. In order to significantly improve the determination of radio listening rates, special watches were created which incorporate a custom integrated circuit sampling the ambient sound during a few seconds every minutes. Each watch accumulates these compressed sound samples during one full week. Watches are then sent to an evaluation center, where the sound samples are matched with the sound samples recorded from candidate radio stations. The present paper describes the processing steps necessary for computing the radio listening rates, and shows how this application was parallelized on a cluster of PCs using the CAP Computer-aided parallelization framework. Since the application must run in a production environment, the paper describes also the support provided for graceful degradation in case of transient or permanent failure of one of the system's components. The parallel sound matching server offers a linear speedup up to a large number of processing nodes thanks to the fact that disk access operations across the network are done in pipeline with computations

Label-free detection of exosomes using surface plasmon resonance biosensor

The development of a sensitive and specific detection platform for exosomes is highly desirable as they are believed to transmit vital tumour-specific information (mRNAs, microRNAs, and proteins) to remote cells for secondary metastasis. Herein, we report a simple method for the real-time and label-free detection of clinically relevant exosomes using a surface plasmon resonance (SPR) biosensor. Our method shows high specificity in detecting BT474 breast cancer cell-derived exosomes particularly from complex biological samples (e.g. exosome spiked in serum). This approach exhibits high sensitivity by detecting as low as 8280 exosomes/μL which may potentially be suitable for clinical analysis. We believe that this label-free and real-time method along with the high specificity and sensitivity may potentially be useful for clinical settings

Active involvement of nursing staff in reporting and grading complication-intervention events-Protocol and results of the CAMUS Pilot Nurse Delphi Study.

Objectives The aim of this study is to gain experienced nursing perspective on current and future complication reporting and grading in Urology, establish the CAMUS CCI and quality control the use of the Clavien-Dindo Classification (CDC) in nursing staff. Subjects and Methods The 12-part REDCap-based Delphi survey was developed in conjunction with expert nurse, urologist and methodologist input. Certified local and international inpatient and outpatient nurses specialised in urology, perioperative nurses and urology-specific advanced practice nurses/nurse practitioners will be included. A minimum sample size of 250 participants is targeted. The survey assesses participant demographics, nursing experience and opinion on complication reporting and the proposed CAMUS reporting recommendations; grading of intervention events using the existing CDC and the proposed CAMUS Classification; and rating various clinical scenarios. Consensus will be defined as ≥75% agreement. If consensus is not reached, subsequent Delphi rounds will be performed under Steering Committee guidance. Results Twenty participants completed the pilot survey. Median survey completion time was 58 min (IQR 40-67). The survey revealed that 85% of nursing participants believe nurses should be involved in future complication reporting and grading but currently have poor confidence and inadequate relevant background education. Overall, 100% of participants recognise the universal demand for reporting consensus and 75% hold a preference towards the CAMUS System. Limitations include variability in nursing experience, complexity of supplemental grades and survey duration. Conclusion The integration of experienced nursing opinion and participation in complication reporting and grading systems in a modern and evolving hospital infrastructure may facilitate the assimilation of otherwise overlooked safety data. Incorporation of focused teaching into routine nursing education will be essential to ensure quality control and stimulate awareness of complication-related burden. This, in turn, has the potential to improve patient counselling and quality of care

Improved diagnosis by automated macro‐ and micro‐anatomical region mapping of skin photographs

Background: The exact location of skin lesions is key in clinical dermatology. On one hand, it supports differential diagnosis (DD) since most skin conditions have specific predilection sites. On the other hand, location matters for dermatosurgical interventions. In practice, lesion evaluation is not well standardized and anatomical descriptions vary or lack altogether. Automated determination of anatomical location could benefit both situations. Objective: Establish an automated method to determine anatomical regions in clinical patient pictures and evaluate the gain in DD performance of a deep learning model (DLM) when trained with lesion locations and images. Methods: Retrospective study based on three datasets: macro-anatomy for the main body regions with 6000 patient pictures partially labelled by a student, micro-anatomy for the ear region with 182 pictures labelled by a student and DD with 3347 pictures of 16 diseases determined by dermatologists in clinical settings. For each dataset, a DLM was trained and evaluated on an independent test set. The primary outcome measures were the precision and sensitivity with 95% CI. For DD, we compared the performance of a DLM trained with lesion pictures only with a DLM trained with both pictures and locations. Results: The average precision and sensitivity were 85% (CI 84-86), 84% (CI 83-85) for macro-anatomy, 81% (CI 80-83), 80% (CI 77-83) for micro-anatomy and 82% (CI 78-85), 81% (CI 77-84) for DD. We observed an improvement in DD performance of 6% (McNemar test P-value 0.0009) for both average precision and sensitivity when training with both lesion pictures and locations. Conclusion: Including location can be beneficial for DD DLM performance. The proposed method can generate body region maps from patient pictures and even reach surgery relevant anatomical precision, e.g. the ear region. Our method enables automated search of large clinical databases and make targeted anatomical image retrieval possible

Development of EndoScreen chip, a microfluidic pre-endoscopy triage test for esophageal adenocarcinoma

The current endoscopy and biopsy diagnosis of esophageal adenocarcinoma (EAC) and its premalignant condition Barrett’s esophagus (BE) is not cost-effective. To enable EAC screening and patient triaging for endoscopy, we developed a microfluidic lectin immunoassay, the EndoScreen Chip, which allows sensitive multiplex serum biomarker measurements. Here, we report the proof-of-concept deployment for the EAC biomarker Jacalin lectin binding complement C9 (JAC-C9), which we previously discovered and validated by mass spectrometry. A monoclonal C9 antibody (m26 3C9) was generated and validated in microplate ELISA, and then deployed for JAC-C9 measurement on EndoScreen Chip. Cohort evaluation (n = 46) confirmed the expected elevation of serum JAC-C9 in EAC, along with elevated total serum C9 level. Next, we asked if the small panel of serum biomarkers improves detection of EAC in this cohort when used in conjunction with patient risk factors (age, body mass index and heartburn history). Using logistic regression modeling, we found that serum C9 and JAC-C9 significantly improved EAC prediction from AUROC of 0.838 to 0.931, with JAC-C9 strongly predictive of EAC (vs. BE OR = 4.6, 95% CI: 1.6–15.6, p = 0.014; vs. Healthy OR = 4.1, 95% CI: 1.2–13.7, p = 0.024). This proof-of-concept study confirms the microfluidic EndoScreen Chip technology and supports the potential utility of blood biomarkers in improving triaging for diagnostic endoscopy. Future work will expand the number of markers on EndoScreen Chip from our list of validated EAC biomarkers

Global gene disruption in human cells to assign genes to phenotypes

Insertional mutagenesis in a haploid background can disrupt gene function[superscript 1]. We extend our earlier work by using a retroviral gene-trap vector to generate insertions in >98% of the genes expressed in a human cancer cell line that is haploid for all but one of its chromosomes. We apply phenotypic interrogation via tag sequencing (PhITSeq) to examine millions of mutant alleles through selection and parallel sequencing. Analysis of pools of cells, rather than individual clones[superscript 1] enables rapid assessment of the spectrum of genes involved in the phenotypes under study. This facilitates comparative screens as illustrated here for the family of cytolethal distending toxins (CDTs). CDTs are virulence factors secreted by a variety of pathogenic Gram-negative bacteria responsible for tissue damage at distinct anatomical sites[superscript 2]. We identify 743 mutations distributed over 12 human genes important for intoxication by four different CDTs. Although related CDTs may share host factors, they also exploit unique host factors to yield a profile characteristic for each CDT