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Along the way, it seeks to derive broader lessons for innovation policy scholarship as well as recommendations for institutional reform. The opioid crisis challenges the conventional understanding of IP law as a trade-off between allocative efficiency and dynamic efficiency; it highlights the potentially pernicious role of IP protection for addictive and habit-forming products; and it exposes deep flaws in the structure of federal subsidies for and regulation of prescription drugs. It also draws attention to the political and cultural factors that contribute to innovation policy failures. Ultimately, the opioid crisis underscores both the urgency and the limits of institutional change in the innovation policy domain.COVID-19 is a major, urgent, and ongoing threat to global health. Globally more than 24 million have been infected and the disease has claimed more than a million lives as of November 2020. Predicting which patients will need respiratory support is important to guiding individual patient treatment and also to ensuring sufficient resources are available. The ability of six common Early Warning Scores (EWS) to identify respiratory deterioration defined as the need for advanced respiratory support (high-flow nasal oxygen, continuous positive airways pressure, non-invasive ventilation, intubation) within a prediction window of 24 h is evaluated. It is shown that these scores perform sub-optimally at this specific task. Therefore, an alternative EWS based on the Gradient Boosting Trees (GBT) algorithm is developed that is able to predict deterioration within the next 24 h with high AUROC 94% and an accuracy, sensitivity, and specificity of 70%, 96%, 70%, respectively. The GBT model outperformed the best EWS (LDTEWSNEWS), increasing the AUROC by 14%. Our GBT model makes the prediction based on the current and baseline measures of routinely available vital signs and blood tests.

Patients with severe coronavirus disease 2019 (COVID-19) pneumonia often have complications of coagulopathy and thrombotic phenomena, which lead to high mortality. Whether administering systematic anticoagulant therapy is beneficial remains unclear. We report our experience using systemic anticoagulation with unfractionated heparin to treat severe COVID-19.

We conducted a retrospective historical control study of severe COVID-19 patients requiring mechanical ventilation who received prophylactic-dose anticoagulation (April 1-May 25) or therapeutic-dose anticoagulation (May 26-August 31) in the intensive care unit (ICU) of a tertiary emergency critical care medical center in Japan. The primary endpoints were in-hospital mortality and anticoagulation therapy-related adverse events. Ilginatinib solubility dmso The secondary endpoints included thromboembolic events, administration of venovenous extracorporeal membrane oxygenation (ECMO), ventilator-free days (VFDs), ICU-free days, and the development of multiple organ dysfunction syndrome.

A total of 29 and 33 patients were in the prophylactic-dose and therapeutic-dose groups, respectively. Background characteristics between the groups were not significantly different, although the therapeutic-dose group had a significantly lower in-hospital mortality rate [5 (17.2%) patients versus 0 (0.0%) patients;

=0.033] and longer ICU-free days (median [interquartile range] 15days [13-18] versus 5days [0-13];

=0.008). Hemorrhagic-events did not occur during the study period. Compared with the prophylactic-dose group, the therapeutic-dose group tended to have longer VFDs, was not treated with ECMO, and did not experience thromboembolic events and multiple organ dysfunction syndrome; however, the difference was not statistically significant.

Therapeutic-dose anticoagulation may be beneficial for patients with severe COVID-19 pneumonia requiring mechanical ventilation.

Therapeutic-dose anticoagulation may be beneficial for patients with severe COVID-19 pneumonia requiring mechanical ventilation.

The diagnosis of nonocclusive mesenteric ischemia (NOMI) is always challenging in critically ill patients. Herein, we aimed to report a case of NOMI associated with a hyperosmolar hyperglycemic state (HHS). A small amount of hepatic portal venous gas (HPVG) triggered the diagnosis of NOMI.

A 77-year-old man was transferred due to shock and disorder of consciousness. He was diagnosed with an HHS. We suspected intestinal ischemia due to a small amount of HPVG revealed by computed tomography (CT). Peritoneal signs were revealed after treatment for the HHS. Computed tomography was carried out again 5h after admission, which showed a large amount of HPVG, remarkable bowel dilatation, and pneumatosis intestinalis. We performed an emergency laparotomy and resected the small bowel necrosis resulting from NOMI.

An HHS can cause NOMI, and the presence of HPVG on CT is an important finding that suggests mesenteric ischemia, even in small amounts.

An HHS can cause NOMI, and the presence of HPVG on CT is an important finding that suggests mesenteric ischemia, even in small amounts.Because of the difficulty of measuring nanoplastics (NP), the use of NPs doped with trace metals has been proposed as a promising approach to detect NP in environmental media and biota. In the present study, the freshwater amphipod Gammarus pulex were exposed to palladium (Pd)-doped NP via natural sediment at six spiking concentrations (0, 0.3, 1, 3, 10 and 30 g plastic per kg of sediment dry weight) with the aim of assessing their uptake and chronic effects using 28 days standardized single species toxicity tests. NP concentrations were quantified based on Pd concentrations measured by ICP-MS on digests of the exposed organisms and faecal pellets excreted during a post-exposure 24 hour depuration period. Additionally, NP concentrations were measured in sediments and water to demonstrate accuracy of NP dosing and to quantify the resuspension of NP from the sediment caused by the organisms. A significant positive linear relationship between the uptake of NP by G. pulex and the concentration of NP in the sediments was observed, yet no statistically significant effects were found on the survival or growth of G. pulex. A biodynamic model fitted well to the data and suggested bioaccumulation would occur in two kinetic compartments, the major one being reversible with rapid depuration to clean medium. Model fitting yielded a mass based trophic transfer factor (TTF), conceptually similar to the traditional biota sediment accumulation factor, for NP in the gut of 0.031. This value is close to a TTF value of 0.025 that was obtained for much larger microplastic particles in a similar experiment performed previously. Mechanistically, this suggests that ingestion of plastic is limited by the total volume of ingested particles. We demonstrated that using metal-doped plastics provides opportunities for precise quantification of NP accumulation and exposure in fate and effect studies, which can be a clear benefit for NP risk assessment.

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