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The main difference between an open-water (regular) flood and an ice jam flood is that it is normally the whole river length that is overtopped whereas an ice jam flood is localized to where the jam is located. Comparatively, the regular flood analysis can use the value of the extreme discharge as the main input parameter for a long river section, an ice jam flood needs to account for the probability of jams of various lengths and intensities occurring at specific locations under significantly variable discharges while having several mechanical ice parameters to be considered. Through the case study of the Chaudière River, the methodology presented in this paper demonstrates how to statistically characterize four significant inputs (jam location, jam length, jam properties and river discharge during jam event) into the widely used numerical river water model (HEC-RAS) and how Monte–Carlo simulations are generated to estimate probable ice jam floods along a whole river reach. The purpose of this article is to propose a robust methodology through a case study and asses the sensitivity that historical and mechanical parameters have as to why specific locations along the reach have higher 1:100 AEP ice-induced water levels as to 1:100 AEP open-water levels. HIGHLIGHTS Comparison of 1:100 AEP open-water flood and ice jam flood.; Historical distribution of input parameters.; Using stochastic modelling with HEC-RAS with external control via Python.; Strength of the Monte–Carlo method.;

The Chaudière River in Quebec, Canada, is well known for its frequent ice jam flooding events. As part of a larger watershed research program, an extensive field campaign has been carried out during the 2018–2019 and 2019–2020 winter seasons to quantify the spatiotemporal characteristics of the break-up processes along the Chaudière River. The results showed that mid-winter ice jams have formed in the Intermediate Chaudière and persisted until spring break-up. Spring break-ups were initiated in the Upper Chaudière, and then, almost simultaneously, in the Intermediate and Lower Chaudière reaches. The break-up in the Intermediate Chaudière usually lasts longer than the rest of the river since the slope is much milder, and the occurrence of mid-winter ice jams has been seen to delay the ice clearing. A reach-by-reach characterization of the cumulative degree day of thawing and discharge thresholds for the onset of break-up has been identified. During the field campaign, 51 ice jams were documented together with their location, length, date of formation, and the morphological feature triggering jam formation. Break-up patterns, hydrometeorological thresholds of ice mobilization, and ice jam sites identified in this study can serve as a basis for the implementation of an early warning system. HIGHLIGHTS Effect of mid-winter jamming and the importance of monitoring the entire ice season has been highlighted.; A reach-by-reach break-up sequence of the entire Chaudière River has been documented.; The dependency of the onset of break-up on threshold levels of cumulative degree day of thawing and discharge was assessed.; Fifty-one ice jams were characterized together with the geomorphological features that initiated their formation.;

Summary: Rats were more frequently used than mice to model human disease before mouse embryonic stem cells (mESCs) revolutionized genetic engineering in mice. Rat ESCs (rESCs) were first reported over 10 years ago, yet they are not as frequently used as mESCs. CRISPR-based gene editing in zygotes is widely used in rats but is limited by the difficulty of inserting or replacing DNA sequences larger than about 10 kb. We report here the generation of germline-competent rESC lines from several rat strains. These rESC lines maintain their potential for germline transmission after serial targeting with bacterial artificial chromosome (BAC)-based targeting vectors, and CRISPR-Cas9 cutting can increase targeting efficiency. Using these methods, we have successfully replaced entire rat genes spanning up to 101 kb with the human ortholog.

The capecitabine/temozolomide regimen has significant activity in pancreatic NETs; however, data are limited in NETs of the small bowel (midgut). A retrospective study of all patients with metastatic midgut NETs seen at Moffitt Cancer Center between January 2008 and June 2019 treated with CAPTEM was conducted. 32 patients with proven or suspected well-differentiated primary small bowel NETs (excluding duodenum) were identified. 6 patients were found to have a radiographic response (19%), 5 of whom had high-grade disease. Only one patient among 23 with low/intermediate-grade disease responded (4%), whereas the response rate for patients with high-grade disease was 56%. Among patients with low/intermediate-grade disease, 44% discontinued due to poor tolerability. The CAPTEM regimen appears to have an activity in patients with high-grade small bowel NETs and is largely inactive in patients with low/intermediate-grade tumors.

PURPOSEThe purpose of this study was to determine the safety and efficacy of liver-directed therapies in patients with unresectable metastatic leiomyosarcoma to the liver. Liver-directed therapies included in this study were transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE), yttrium-90 (Y90) radioembolization, and percutaneous microwave ablation.METHODSThis is a single institution retrospective study of unresectable metastatic leiomyosarcoma to the liver treated with DEB-TACE, radioembolization, or microwave ablation. DEB-TACE was performed using 70–150 or 100–300 µ doxorubicin-loaded drug-eluting LC beads. Radioembolization was performed using Y90 glass microspheres. Electronic medical records were retrospectively reviewed to evaluate clinical and biochemical toxicities, tumor response on imaging, overall survival (OS), and liver progression-free survival (PFS).RESULTSA total of 24 patients with metastatic leiomyosarcoma to the liver who underwent liver-directed treatment were identified (8 males, 16 females; average age, 62.8±11.4 years). Of these patients, 13 underwent DEB-TACE, 6 underwent Y90, and 5 underwent ablation. Three patients received a combination of treatments: one received Y90 followed by DEB-TACE, one received ablation followed by DEB-TACE, and one received ablation followed by Y90. Of the 24 patients, 19 received prior chemotherapy. At 3-month follow-up, grade 1 or 2 lab toxicities were found in 20 patients; 3 patients had grade 3 toxicities. A grade 3 clinical toxicity was reported in one patient. MELD score was 7.5±1.89 at baseline and 8.8±4.2 at 3 months. Median OS was 59 months (95% CI, 39.8–78.2) from diagnosis, 27 months (95% CI, 22.9–31.0) from development of liver metastasis, and 9 months (95% CI, 0–21.4) from first liver-directed treatment. Median liver PFS was 9 months (95% CI, 1.4–16.6).CONCLUSIONTreatment with liver-directed therapies for patients with unresectable metastatic leiomyosarcoma to the liver is safe and can improve overall survival, with OS after liver-directed therapy being similar to patients who underwent surgical resection.

A 76-year-old male with a small bowel neuroendocrine tumor with hepatic metastases presented with new onset lower extremity swelling, bloating, and weight gain which ultimately lead to cardiac magnetic resonance (CMR) to evaluate for cardiac involvement of disease. CMR showed right and left ventricular myocardial metastases along with findings suggestive of carcinoid heart disease. The patient had severe tricuspid valve regurgitation necessitating surgical valve repair. The patient underwent bioprosthetic tricuspid valve replacement and debulking of the metastases with surgical pathology confirming neuroendocrine tumor metastases. Follow-up clinical evaluations at 3, 6, and 9 months postoperatively showed improvement in cardiac function and stable hepatic tumor burden. This case demonstrates the utility of CMR to diagnose myocardial metastases and carcinoid heart disease complicated by severe tricuspid regurgitation, which guided surgical management.

In the period 1999 to 2003, river ice has continued to have important socio-economic impacts in Canada and other Nordic countries. Concurrently, there have been many important advances in all areas of Canadian research into river ice engineering and hydrology. For example: (1) River ice processes were highlighted in two special journal issues (Canadian Journal of Civil Engineering in 2003 and Hydrological Processes in 2002) and at five conferences (Canadian Committee on River Ice Processes and the Environment in 1999, 2001 and 2003, and International Association of Hydraulic Research in 2000 and 2002). (2) A number of workers have clearly advanced our understanding of river ice processes by bringing together disparate information in comprehensive review articles. (3) There have been significant advances in river ice modelling. For example, both one-dimensional (e.g. RIVICE, RIVJAM, ICEJAM, HEC-RAS, etc.) and two-dimensional (2-D; www.river2d.ca) public-domain ice-jam models are now available. Work is ongoing to improve RIVER2D, and a commercial 2-D ice-process model is being developed. (4) The 19992003 period is notable for the number of distinctly hydrological and ecological studies. On the quantitative side, many are making efforts to determine streamflow during the winter period. On the ecological side, some new publications have addressed the link to water quality (temperature, dissolved oxygen, nutrients and pollutants), and others have dealt with sediment transport and geomorphology (particularly as it relates to break-up), stream ecology (plants, food cycle, etc.) and fish habitat.There is the growing recognition, that these types of study require collaborative efforts. In our view, the main areas requiring further work are: (1) to interface geomorphological and habitat models with quantitative river ice hydrodynamic models; (2) to develop a manager''s toolbox (database management, remote sensing, forecasting, intervention methodologies, etc.) to enable agencies to intervene better at the time of ice-jam-induced floods; and (3) finalize ice-jam prevention methods on the St Lawrence River to safeguard its $2 billion commercial navigation industry. Copyright 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]