805 research outputs found

    State Public Nuisance Claims and Climate Change Adaptation

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    This Article explores the potential for state public nuisance claims to facilitate adaptation, resource protection, and other climate change responses by coastal communities in California. The California public nuisance actions represent just the latest chapter in efforts to spur responses to climate change and attribute responsibility for climate change through the common law. Part II of this Article describes the California public nuisance lawsuits and situates them in the context of common law actions directed against climate change. Part III considers the preliminary defenses that defendants have raised and could raise in the California public nuisance lawsuits, including the existence of state common law in this context, separation of powers and the political question doctrine, displacement and preemption, and standing. Part IV considers the potential merits of the plaintiffs’ public nuisance claims under California law

    The thermal QCD transition with two flavours of twisted mass fermions

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    We investigate the thermal QCD transition with two flavors of maximally twisted mass fermions for a set of pion masses, 300 MeV \textless mπm_\pi \textless 500 MeV, and lattice spacings aa \textless 0.09 fm. We determine the pseudo-critical temperatures and discuss their extrapolation to the chiral limit using scaling forms for different universality classes, as well as the scaling form for the magnetic equation of state. For all pion masses considered we find resonable consistency with O(4) scaling plus leading corrections. However, a true distinction between the O(4) scenario and a first order scenario in the chiral limit requires lighter pions than are currently in use in simulations of Wilson fermions.Comment: 11 pages, 11 figure

    Antagonism of the mammalian target of rapamycin selectively mediates metabolic effects of epidermal growth factor receptor inhibition and protects human malignant glioma cells from hypoxia-induced cell death

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    Although inhibition of the epidermal growth factor receptor is a plausible therapy for malignant gliomas that, in vitro, enhances apoptosis, the results of clinical trials have been disappointing. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates starvation signals and generates adaptive responses that aim at the maintenance of energy homeostasis. Antagonism of mTOR has been suggested as a strategy to augment the efficacy of epidermal growth factor receptor inhibition by interfering with deregulated signalling cascades downstream of Akt. Here we compared effects of antagonism of mTOR utilizing rapamycin or a small hairpin RNA-mediated gene silencing to those of epidermal growth factor receptor inhibition or combined inhibition of epidermal growth factor receptor and mTOR in human malignant glioma cells. In contrast to epidermal growth factor receptor inhibition, mTOR antagonism neither induced cell death nor enhanced apoptosis induced by CD95 ligand or chemotherapeutic drugs. However, mTOR inhibition mimicked the hypoxia-protective effects of epidermal growth factor receptor inhibition by maintaining adenosine triphosphate levels. These in vitro experiments thus challenge the current view of mTOR as a downstream target of Akt that mediates antiapoptotic stimuli. Under the conditions of the tumour microenvironment, metabolic effects of inhibition of epidermal growth factor receptor, Akt and mTOR may adversely affect outcome by protecting the hypoxic tumour cell fractio

    Using Raccoons as an Indicator Species for Metal Accumulation Across Trophic Accumulation across Trophic Levels: A Stable Isotope Approach

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    : The fact that raccoons (Procyon lotor) are an opportunistic omnivore has severely complicated interpreta- tions of contaminant uptake patterns due to the inability to determine the trophic position an individual occupies. Moreover, few studies have examined the relationships between heavy metal bioaccumulation and trophic struc- ture, especially in the terrestrial environment. In this study, the stable isotopes of nitrogen were used to charac- terize the feeding habits of the raccoon at the population level and to determine whether metal burden was relat- ed to trophic feeding structure within a welldefined ecosystem. Raccoon populations were isotopically distinct, and significant positive relationships existed between some trace element contents and 6 1 5 ~of muscle when site was used as a covariable in a statistical model. Although the transfer of metals through terrestrial ecosystems is com- plex, our study showed that some of the variation in contaminant body burdens in raccoon populations can be attributed to trophic feeding position and that 1 5 ~ / 1 4 ~ ratios of muscle tissue provide a quantitative measure of this process. The potential for using omnivores such as the raccoon, as a sentinel species for contaminant studies, should be explored further since the ambiguity of the relative trophlc level an animal occupies can be directly esti- mated. This provides a more extensive sampling across trophic levels using a single species, which can have broad consequences for ecological risk assessment

    Raccoons as potential vectors of radionuclide contamination to human food chains from a nuclear industrial site

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    Although the raccoon (Procyon lotor) is commonly harvested and consumed throughout the southeastern United States, little is known regarding the fate and effects of environmental pollutants to this species, and the potential for it to act as a contaminant vector to humans or other predators. Muscle and liver tissues were collected from 76 raccoons from locations on and near the Department of Energy\u27s Savannah River Site (SRS) in South Carolina and analyzed for radiocesium (137Cs). Raccoons were trapped from areas near a former reactor cooling reservoir known to be contaminated from former nuclear production activities, a stream drainage system also known to have received 137Cs contamination from low level releases, and 4 on-site reference areas that have been unimpacted by nuclear production activities. Raccoons from 3 hunting areas 3-15 km of SRS were used as off-site reference samples. 137Cs levels differed between the 3 treatment groups (contaminated, on-site reference, off-site reference) for both muscle and liver tissues. Muscle and liver samples from raccoons from on-site reference areas were higher in 137Cs than those from off-site reference animals. 137Cs in raccoon tissues from contaminated habitats exceeded levels in the pooled reference animals. The 2 contaminated areas differed in 137Cs tissue levels. Only 1 of 20 raccoons from contaminated sites on the SRS exceeded the European Economic Community (EEC) limit for 137Cs in edible muscle tissue of 0.6 Bq 137Cs/g fresh-weight edible muscle. Further, none of the raccoons from the on-site reference areas exceeded EEC limits for muscle. It is unlikely that the hunting public faces any significant risk from exposure to raccoons from the SRS. Although some raccoons might stray off the SRS which is closed to public access, most of the heavily contaminated areas are not adjacent to the edges of the site, decreasing the potential for off-site movement of contaminated animals

    Deep-Learning-Based Segmentation of the Shoulder from MRI with Inference Accuracy Prediction

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    Three-dimensional (3D)-image-based anatomical analysis of rotator cuff tear patients has been proposed as a way to improve repair prognosis analysis to reduce the incidence of postoperative retear. However, for application in clinics, an efficient and robust method for the segmentation of anatomy from MRI is required. We present the use of a deep learning network for automatic segmentation of the humerus, scapula, and rotator cuff muscles with integrated automatic result verification. Trained on N = 111 and tested on N = 60 diagnostic T1-weighted MRI of 76 rotator cuff tear patients acquired from 19 centers, a nnU-Net segmented the anatomy with an average Dice coefficient of 0.91 ± 0.06. For the automatic identification of inaccurate segmentations during the inference procedure, the nnU-Net framework was adapted to allow for the estimation of label-specific network uncertainty directly from its subnetworks. The average Dice coefficient of segmentation results from the subnetworks identified labels requiring segmentation correction with an average sensitivity of 1.0 and a specificity of 0.94. The presented automatic methods facilitate the use of 3D diagnosis in clinical routine by eliminating the need for time-consuming manual segmentation and slice-by-slice segmentation verification

    Positive impact of pre-stroke surgery on survival following transient focal ischemia in hypertensive rats

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    We describe a positive influence of pre-stroke surgery on recovery and survival in a commonly used experimental stroke model. Two groups of male, stroke-prone spontaneously hypertensive rats (SHRSPs) underwent transient middle cerebral artery occlusion (tMCAO). Group 1 underwent the procedure without any prior intervention whilst group 2 had an additional general anaesthetic 6 days prior to tMCAO for a cranial burrhole and durotomy. Post-stroke recovery was assessed using a 32 point neurological deficit score and tapered beam walk and infarct volume determined from haematoxylin–eosin stained sections. In group 2 survival was 92% (n = 12) versus 67% in group 1 (n = 18). In addition, post-tMCAO associated weight loss was significantly reduced in group 2. There was no significant difference between the two groups in experimental outcomes: infarct volume (Group 1 317 ± 18.6 mm<sup>3</sup> versus Group 2 332 ± 20.4 mm<sup>3</sup>), and serial (day 0–14 post-tMCAO) neurological deficit scores and tapered-beam walk test. Drilling a cranial burrhole under general anaesthesia prior to tMCAO in SHRSP reduced mortality and gave rise to infarct volumes and neurological deficits similar to those recorded in surviving Group 1 animals. This methodological refinement has significant implications for animal welfare and group sizes required for intervention studies

    DNA Extraction Method Development for Ocular Tissues

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    Purpose: DNA extraction kits are traditionally developed to work with liquid tissues such as blood, saliva, and swabs, but some have been proposed to work with solid tissues. Somatic variation in cancers can be important for tumor subtyping and treatment guidance, including ocular tumors. Additionally, epigenetic marks such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are tissue-specific and change in disease states, particularly evident in diabetic retinopathy and age-related macular degeneration. Commercial DNA extraction kits are available from several vendors, but the various kits have different strengths and weaknesses, and the removal of PCR inhibitors will vary with each kit. This project investigates the yield and purity of DNA from ocular tissues using commercial DNA extraction kits. Methods: Cornea, neural retina, RPE/choroid layer, optic nerve, and capsular bag were collected and aliquoted into 15 mg aliquots. Extractions were performed using the following kits: DNEasy Blood and Tissue Kit (Qiagen;), GeneJET Genomic DNA Purification Kit (ThermoFisher Scientific), Monarch HMW DNA Extraction Kit for Tissue (New England Biosciences), and genomicPrep Mini Spin Kit (Cytiva). DNA was quantified using the Qubit Fluorometer and molecular weight was checked by agarose gel. Several more kits are currently being tested. Results: All four kits yielded high molecular weight DNA (above 20 kbp). The Monarch HMW kit yielded DNA with significantly higher molecular weights. The DNA yields per milligram of tissue were highest using the DNEasy Blood and Tissue Kit for optic nerve, neural retina, and RPE/choroid. The yield was highest for the cornea using the genomicPrep Mini Spin Kit. Only the genomicPrep Mini Spin Kit yielded sufficient DNA for quantification from the capsular bag, and total yields were minimal (600 ng or less). Additional kits are currently being tested, but initial results indicate that several commercial kits will be sufficient for DNA extraction of ocular tissues. Further work is needed to purify epithelial cells and stem cells from the intraocular lens. Conclusions: Of the kits tested, all are sufficient to obtain significant amounts of DNA from all ocular tissues aside from the capsular bag. The Monarch HMW yielded the highest molecular weight, but significantly lower quantities of DNA than the other kits, indicating that it may not be ideal for most purposes. Protocol development for the capsular bag is still underway

    Increased plasma zonulin in patients with sepsis

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    Introduction: Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae’s zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. Materials and methods: Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). Results: Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). Conclusion: We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS
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