ty of modelling assumptions. This review was commissioned by WHO and supported by Danube-University-Krems. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.Sacrificing body parts is one of many behaviors that animals use to escape predation. This trait, termed autotomy, is classically associated with lizards. However, several other taxa also autotomize, and this trait has independently evolved multiple times throughout Animalia. Despite having multiple origins and being an iconic antipredatory trait, much remains unknown about the evolution of autotomy. Here, we combine morphological, behavioral, and genomic data to investigate the evolution of autotomy within leaf-footed bugs and allies (Insecta Hemiptera Coreidae + Alydidae). We found that the ancestor of leaf-footed bugs autotomized and did so slowly; rapid autotomy ( less then 2 min) then arose multiple times. The ancestor likely used slow autotomy to reduce the cost of injury or to escape nonpredatory entrapment but could not use autotomy to escape predation. This result suggests that autotomy to escape predation is a co-opted benefit (i.e., exaptation), revealing one way that sacrificing a limb to escape predation may arise. In addition to identifying the origins of rapid autotomy, we also show that across species variation in the rates of autotomy can be explained by body size, distance from the equator, and enlargement of the autotomizable appendage. © 2020 The Authors. Evolution published by Wiley Periodicals LLC on behalf of The Society for the Study of Evolution.A ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for determination of homocysteine (HCY) in human plasma. HCY in human plasma was derivatized with 2-chloro-1-methylquinolinium tetrafluoroborate (CMQT), and isolated through solid phase extraction (SPE). Derivatization, isolation and detection procedures were optimized. Satisfactory linearity was obtained with determination coefficients (r2 ) > 0.999. The intra- and inter-day precisions were in the interval of 1.2-5.1% and accuracy was within ± 7%. Mean recoveries were closed to 100%. The limit of detection (LOD) and the limit of quantification (LOQ) were 0.46 and 1.38 μmol/L, respectively. The method was then applied to investigate the relationship between plasma HCY and whole blood 5-methyltetrahydrofolate (5-MTHF) levels in healthy volunteers. The results revealed that plasma level of HCY was significantly negatively correlated to whole blood 5-MTHF in volunteers. This article is protected by copyright. All rights reserved.A 25-year-old male was referred to hepatology clinic for abnormal liver enzymes AST 242 IU/L, ALT 507 IU/L, alkaline phosphatase 139 IU/L, INR 1.1, bilirubin 1.3 mg/dl, and albumin 4.2 g/dL. His hemoglobin was 13.3 g/dl and platelet count 130 x109 /L. The patient reported heavy alcohol use in teenage years but quit 1 year prior to presentation. Serologic testing was negative for viral hepatitis, autoimmune markers, Wilson disease, schistosomiasis, and alpha-1-antitrypsin deficiency. Transferrin saturation was 3%, ferritin 21 ng/ml, and 25-OH-vitamin D 14.1 ng/ml. A liver biopsy showed bilirubinostasis, portal inflammation, and bridging fibrosis. This article is protected by copyright. All rights reserved.In the present study, a rapid derivatization liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to evaluate phenylephrine in human plasma. The plasma samples were processed to precipitate the proteins, followed by derivatization of the phenylephrine in the plasma with dansyl-chloride solution and extraction with methyl tert-butyl ethern-hexane (21; (v/v)). The treated samples were analyzed on a Gemini C18 column with 3-min gradient elution, and sensitive detection was achieved with a Waters TQ-s. The method gave linear results over a concentration range from 0.020 to 10.0 ng/mL. The lower limit of quantification was 0.020 ng/mL. Intra- and inter-day precision was less then 15%, and accuracy was 95.0-105.3%. The validated LC-MS/MS method was successfully applied in the pharmacokinetic analysis of phenylephrine in Chinese subjects with common cold after a single-dose administration of 5, 10, or 20 mg phenylephrine. This pre-column derivatization method may also be applied in the analysis of endogenous hormones such as norepinephrine and adrenaline in a biological matrix. This article is protected by copyright. All rights reserved.The aim of this study was to demonstrate the altered metabolic infrastructure of pregnant women with methylenetetrahydrofolate reductase (MTHFR) polymorphisms at first trimester and during delivery. Eight singleton pregnant women with MTHFR polymorphisms were compared with 10 normal pregnant women. Maternal blood samples were obtained twice during their pregnancy period (between the 11th and 14th gestational weeks and during delivery). Metabolomic analysis was performed using GC-MS. The GC-MS based metabolomic profile helped identify 95 metabolites in the plasma samples. In the MTHFR group, the levels of 1-monohexadecanoylglycerol, pyrophosphate, benzoin, and linoleic acid significantly decreased (P ˂ 0.05 for all), whereas the levels of glyceric acid, l-tryptophan, l-alanine, l-proline, norvaline, l-threonine, and myo-inositol significantly increased (P ˂ 0.01 for the first two metabolites, P ˂ 0.05 for the others) at 11-14 gestational weeks. Conversely, the levels of benzoin, 1-monohexadecanoylglycerol, pyruvic acid, l-proline, phosphoric acid, epsilon-caprolactam, and pipecolic acid significantly decreased in the MTHFR group, whereas metabolites such as hexadecanoic acid and 2-hydroxybutyric acid increased significantly in the study group during delivery. An impaired energy metabolism pathway, vitamin B complex disorders, tendency for metabolic acidosis (oxidative stress), and the need for cell/tissue support seem prevalent in pregnancies with MTHFR polymorphisms. © 2020 John Wiley & Sons, Ltd.This policy brief sets forth American Geriatrics Society (AGS) recommendations to guide federal, state, and local governments when making decisions about care for patients with COVID-19 in nursing homes (NHs) and other long-term care facilities (LTCFs). The AGS continues to review guidance set forth in peer-reviewed articles and editorials, as well as ongoing and updated guidance from the Centers for Medicare and Medicaid Services (CMS), the Centers for Disease Control and Prevention (CDC), and other key agencies. This brief is based on the situation and any federal guidance/actions as of April 4, 2020. It is focused on NHs and other LTCFs, given their essential role in addressing the COVID-19 pandemic. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.KEY POINTS Lymphatic valve defects are one of the major causes of lymph transport dysfunction; however, there are no accessible methods for quantitatively assessing valve function. This manuscript provides a novel technique for quantifying lymphatic valve back-leak. Postnatal endothelial-specific deletion of Cx43 in Cx37-/- mice results in rapid regression of valve leaflets and severe valve dysfunction. This method can also be used for assessing the function of lymphatic valves from various species, including humans. ABSTRACT The lymphatic system relies on robust, spontaneous contractions of collecting lymphatic vessels and one-way secondary lymphatic valves to efficiently move lymph forward. Secondary valves prevent reflux and allow for the generation of propulsive pressure during each contraction cycle. Lymphatic valve defects are one of the major causes of lymph transport dysfunction. Genetic mutations in multiple genes have been associated with the development of primary lymphedema in humans and many of tes displaying a wide range of dysfunction, from fully-competent to completely incompetent. Our results were validated by simultaneous direct measurement of pressure back-leak using a servo-null micropressure system. Our diameter-based technique can be used to quantify valve function in isolated lymphatic valves from a variety of species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.PURPOSE The goal was to develop and test a large diameter parallel plate ionization chamber capable of intercepting at least 98% of the proton beamlets tested with the system. METHODS A commercial synchrotron proton therapy system was used for the study (Hitachi, Ltd, Hitachi City, Japan; Model Probeat-V). The energies investigated were in the range of 100 to 192 MeV. 3 beam spot options available from the system were used. A PTW Bragg peak IC of diameter 84 mm (BP84) (Model PTW34070) was employed for comparison in a scanning water phantom. A prototype of 150 mm diameter was produced (PTW, Freiburg, Germany; model T34089) and used for the testing. Monte Carlo calculations were also performed with FLUKA to guide the BP150 design and for comparison to the radiological measurements. For comparison, a 40 cm diameter ideal virtual detector was included in the Monte Carlo model. RESULTS The measured proton range R90 agrees between the BP84 and BP150 ionization chambers within +0.06/-0.27 mm across the energies 100 – 192 MeV, which is less than the daily experimental setup uncertainty of 0.4 mm. The differences in the absolute integral depth dose curves (IDDs) between the BP84 and BP150 ranged from 0.3% to 1.0% for the spot sizes and beam energies tested. As predicted by the Monte Carlo modeling, the greatest differences were found in the plateau region of the IDDs. Also, the IDDs measured with the BP150 were very similar to those of the ideal 40 cm diameter detector Monte Carlo simulations. CONCLUSIONS We conclude that the BP150 offers a small, but a useful reduction in uncertainty from the nuclear halo effect for the system under test. This article is protected by copyright. All rights reserved.PURPOSE To introduce the definite target volume (DTV) and evaluate dosimetric consequences of boosting dose to this region of high CTV- and low OAR- probability. METHODS This work defines the DTV via occupancy probability and via contraction of the CTV by margin M less any PRV volumes. The equivalence to within varying occupancy probability of the two methods is established for spherical target volumes. We estimate a margin for four radiation treatment sites based on modern IGRT-literature utilizing repeat volumetric imaging. Based on margins and patient-specific DTV targets, the ability to dose-escalate the DTV including the effects of spatial uncertainty was evaluated. We simulate delivery assuming violation of the underlying spatial uncertainty of 130%. RESULTS Contracting the PTV by M and excluding PRV volumes, the DTV ranged from 7.3 cc – 93.6 cc. In a brain treatment, DTV-Dmax increased to 66.8 Gy (145% of prescription isodose); in advanced lung DTV-Dmax increased to 122.2 Gy (204% of prescription isodose), in a pancreatic case DTV-Dmax was boosted up to 87.3 Gy (173% or prescription isodose), and in retroperitoneal sarcoma to 74.6 Gy (249% of prescription isodose). The high point doses were not associated with increased dose to OARs, even when considering the effects of spatial uncertainty. Simulated delivery at 130% of assumed spatial uncertainties revealed DTV-based planning can result in minor increases in OAR Dmean / Dmax of 2.7±2.1 Gy / 1.8±2.2Gy with duodenum Dmax >110% of prescription isodose in the pancreatic case. These dose increases were consistent with simulation of clinical, homogenous PTV-dose distributions. CONCLUSION We have proposed and tested a method to deliver extremely high doses to sub-volumes of PTVs in multiple treatment sites by defining a new target volume, the DTV. Based on simulated delivery, the method does not result in significant increases in dose to OARs if spatial uncertainty can be estimated. This article is protected by copyright. All rights reserved.