Modeling and experimental investigations of the stress-softening behavior of soft collagenous tissues

This paper deals with the formulation of a micro-mechanically based dam-age model for soft collagenous tissues. The model is motivated by (i) a sliding filament model proposed in the literature [1] and (ii) by experimental observations from electron microscopy (EM) images of human abdominal aorta specimens, see [2]. Specifically, we derive a continuum damage model that takes into account statistically distributed pro- teoglycan (PG) bridges. The damage model is embedded into the constitutive framework proposed by Balzani et al. [3] and adjusted to cyclic uniaxial tension tests of a hu- man carotid artery. Furthermore, the resulting damage distribution of the model after a circumferential overstretch of a simplified arterial section is analyzed in a finite element calculation

Integrated zone picking and vehicle routing operations with restricted intermediate storage

The competitiveness of a retailer is highly dependent on an efficient distribution system. This is especially true for the supply of stores from distribution centers. Stores ask for high flexibility when it comes to their supply. This means that fast order processing is essential. Order processing affects different subsystems at the distribution center: Orders are picked in multiple picking zones, transferred to intermediate storage, and delivered via dedicated tours. These processing steps are highly interdependent. The schedule for picking needs to be synchronized with the routing decisions to ensure availability of the delivery orders at the DC’s loading docks when their associated tours are scheduled. Concurrently, intermediate storage represents a bottleneck as capacities for order storage are limited. The simultaneous planning of picking and routing operations with restricted intermediate storage is therefore relevant for retail practice but has not so far been considered within an integrated planning approach. Our work addresses this task and discusses an integrated zone picking and vehicle routing problem with restricted intermediate storage. We present a comprehensive model formulation and introduce a general variable neighborhood search for simultaneous consideration of the given planning stages. We also present two alternative sequential approaches that are motivated by the prevailing planning situation in industry. Numerical experiments that we have conducted show the need for an integrated planning approach to obtain practicable results. Further, we identify the impact of the main problem characteristics on the overall planning problem and provide valuable insights for the application of this approach in industry

Atrophy patterns in isolated subscapularis lesions

Background!#!While supraspinatus atrophy can be described according to the system of Zanetti or Thomazeau there is still a lack of characterization of isolated subscapularis muscle atrophy. The aim of this study was to describe patterns of muscle atrophy following repair of isolated subscapularis (SSC) tendon.!##!Methods!#!Forty-nine control shoulder MRI scans, without rotator cuff pathology, atrophy or fatty infiltration, were prospectively evaluated and subscapularis diameters as well as cross sectional areas (complete and upper half) were assessed in a standardized oblique sagittal plane. Calculation of the ratio between the upper half of the cross sectional area (CSA) and the total CSA was performed. Eleven MRI scans of patients with subscapularis atrophy following isolated subscapularis tendon tears were analysed and cross sectional area ratio (upper half /total) determined. To guarantee reliable measurement of the CSA and its ratio, bony landmarks were also defined. All parameters were statistically compared for inter-rater reliability, reproducibility and capacity to quantify subscapularis atrophy.!##!Results!#!The mean age in the control group was 49.7 years (± 15.0). The mean cross sectional area (CSA) was 2367.0 mm!##!Conclusion!#!Analysis of typical atrophy patterns of the subscapularis muscle demonstrates that the CSA ratio represents a reliable and reproducible assessment tool in quantifying subscapularis atrophy. We propose the classification of subscapularis atrophy as Stage I (mild atrophy) in case of reduction of the cross sectional area ratio < 0.4, Stage II (moderate atrophy) in case of < 0.35 and Stage III (severe atrophy) if < 0.3

Case Report: Unilateral Sixth Cranial Nerve Palsy Associated With COVID-19 in a 2-year-old Child

Children have been described to show neurological symptoms in acute coronavirus disease 2019 (COVID-19) and multisystemic inflammatory syndrome in children (MIS-C). We present a 2-year-old boy's clinical course of unilateral acute sixth nerve palsy in the context of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Onset of the palsy in the otherwise healthy boy occurred seven days after symptoms attributed to acute infection had subsided respectively 3 weeks after onset of respiratory symptoms. SARS-CoV-2 specific IgG was detected in serum as well as in cerebrospinal fluid. The patient showed a prolonged but self-limiting course with a full recovery after three and a half months. This case illustrates in a detailed chronological sequence that sixth cranial nerve involvement may occur as post-infectious, self-limiting complication of pediatric SARS-CoV-2-infection thus expanding the neurological spectrum of symptoms for children with COVID-19. Clinicians should be aware of the possibility of post-infectious sixth nerve palsy related to SARS-CoV-2-infection particularly in view of recent respiratory tract infection or confirmed cases of SARS-CoV-2-infection amongst the patient's close contacts

Ultrasound-based "CEUS-Bosniak"classification for cystic renal lesions: an 8-year clinical experience

Purpose Renal cysts comprise benign and malignant entities. Risk assessment profts from CT/MRI imaging using the Bosniak classifcation. While Bosniak-IIF, -III, and -IV cover complex cyst variants, Bosniak-IIF and -III stand out due to notorious overestimation. Contrast-enhanced ultrasound (CEUS) is promising to overcome this defcit but warrants standardization. This study addresses the benefts of a combined CEUS and CT/MRI evaluation of renal cysts. The study provides a realistic account of kidney tumor boards' intricacies in trying to validate renal cysts. Methods 247 patients were examined over 8 years. CEUS lesions were graded according to CEUS-Bosniak (IIF, III, IV). 55 lesions were resected, CEUS-Bosniak- and CT/MRI-Bosniak-classifcation were correlated with histopathological diagnosis. Interobserver agreement between the classifcations was evaluated statistically. 105 lesions were followed by ultrasound, and change in CEUS-Bosniak-types and lesion size were documented. Results 146 patients (156 lesions) were included. CEUS classifed 67 lesions as CEUS-Bosniak-IIF, 44 as CEUS-BosniakIII, and 45 as CEUS-Bosniak-IV. Histopathology of 55 resected lesions revealed benign cysts in all CEUS-Bosniak-IIF lesions (2/2), 40% of CEUS-Bosniak-III and 8% of CEUS-Bosniak-IV, whereas malignancy was uncovered in 60% of CEUS-Bosniak-III and 92% of CEUS-Bosniak-IV. Overall, CEUS-Bosniak-types matched CT/MRI-Bosniak types in 58% (fair agreement, κ=0.28). CEUS-Bosniak resulted in higher stages than CT/MRI-Bosniak (40%). Ultrasound follow-up of 105 lesions detected no relevant diferences between CEUS-Bosniak-types concerning cysts size. 99% of lesions showed the same CEUS-Bosniak-type. Conclusion The CEUS-Bosniak classifcation is an essential tool in clinical practice to diferentiate and monitor renal cystic lesions and empowers diagnostic work-up and patient care

Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

Background In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. Methods To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in 2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. Results In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing;while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. Conclusions The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group

STRAW-b (STRings for Absorption length in Water-b): the second pathfinder mission for the Pacific Ocean Neutrino Experiment

Since 2018, the potential for a high-energy neutrino telescope, named the Pacific Ocean Neutrino Experiment (P-ONE), has been thoroughly examined by two pathfinder missions, STRAW and STRAW-b, short for short for Strings for Absorption Length in Water. The P-ONE project seeks to install a neutrino detector with a one cubic kilometer volume in the Cascadia Basin's deep marine surroundings, situated near the western shores of Vancouver Island, Canada. To assess the environmental conditions and feasibility of constructing a neutrino detector of that scale, the pathfinder missions, STRAW and STRAW-b, have been deployed at a depth of 2.7 km within the designated site for P-ONE and were connected to the NEPTUNE observatory, operated by Ocean Networks Canada (ONC). While STRAW focused on analyzing the optical properties of water in the Cascadia Basin, \ac{strawb} employed cameras and spectrometers to investigate the characteristics of bioluminescence in the deep-sea environment. This report introduces the STRAW-b concept, covering its scientific objectives and the instrumentation used. Furthermore, it discusses the design considerations implemented to guarantee a secure and dependable deployment process of STRAW-b. Additionally, it showcases the data collected by battery-powered loggers, which monitored the mechanical stress on the equipment throughout the deployment. The report also offers an overview of STRAW-b's operation, with a specific emphasis on the notable advancements achieved in the data acquisition (DAQ) system and its successful integration with the server infrastructure of ONC.Comment: 20 pages, 11 figures, 2 table

Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database

*Shared first authorship (Dominguez-V M, Sampson J, Seppälä T)PURPOSE: Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. METHODS: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. RESULTS: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. CONCLUSION: Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.Peer reviewe