Zur Lehre von dem Indicien-Beweise nach gemeinem und livländischem Rechte : eine mit genehmigung der Hochverordneten Juristen-Fakultät der Kaiserlichen Universität Dorpat zur Erlangung der Würde eines Magisters der Rechte abgefasste und zur öffentlichen Vertheidigung bestimmte Abhandlung

http://tartu.ester.ee/record=b1922673~S1*es

Association of perinatal sentinel events, placental pathology and cerebral MRI in neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia

OBJECTIVE: Placental pathology might provide information on the etiology of hypoxic-ischemic encephalopathy (HIE). To evaluate the association of perinatal sentinel events (PSE), placental pathology and cerebral MRI in cooled neonates with moderate/severe HIE. STUDY DESIGN: Retrospective analysis of 52 neonates with HIE registered in the Swiss National Asphyxia and Cooling Register 2011-2019. PSE and Non-PSE groups were tested for association with placental pathology. Placental pathology categories were correlated with MRI scores. RESULTS: In total, 14/52 neonates (27%) had a PSE, 38 neonates (73%) did not have a PSE. There was no evidence for an association of occurrence of PSE and placental pathologies (p = 0.364). Neonates with high MRI scores tended to have more often chronic pathologies in their placentas than acute pathologies or normal placentas (p = 0.067). CONCLUSION: Independent of the occurrence of PSE, chronic placental pathologies might be associated with more severe brain injury and needs further study

Placental findings are not associated with neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy - an 11-year single-center experience

OBJECTIVES: Although neonates with moderate to severe hypoxic ischemic encephalopathy (HIE) receive therapeutic hypothermia (TH), 40-50% die or have significant neurological disability. The aim of this study is to analyse the association of placental pathology and neurodevelopmental outcome in cooled neonates with HIE at 18-24 months of age. METHODS: Retrospective analysis of prospectively collected data on 120 neonates registered in the Swiss National Asphyxia and Cooling Register born between 2007 and 2017. This descriptive study examines the frequency and range of pathologic findings in placentas of neonates with HIE. Placenta pathology was available of 69/120 neonates, whose results are summarized as placental findings. As neonates with HIE staged Sarnat score 1 (21/69) did not routinely undergo follow-up assessments and of six neonates staged Sarnat Score 2/3 no follow-up assessments were available, 42/48 (88%) neonates remain to assess the association between placental findings and outcome. RESULTS: Of the 42/48 (88%) neonates with available follow up 29% (12/42) neonates died. Major placenta abnormalities occurred in 48% (20/42). Major placenta abnormality was neither associated with outcome at 18-24 months of age (OR 1.75 [95% CI 0.50-6.36, p=0.381]), nor with death by 2 years of age (OR 1.96 [95% CI 0.53-7.78, p=0.320]). CONCLUSIONS: In this study cohort there could not be shown an association between the placenta findings and the neurodevelopmental outcome at 18-24 months of age

Trap efficiency of reservoirs on the Nile River

River morphodynamics and sediment transportSedimentation in reservoir

The use of bat houses as day roosts in macadamia orchards, South Africa

The loss of roost sites is one of the major drivers of the worldwide decline in bat populations and roost site preferences, either natural or artificially provided, are not well known for African bat species specifically. In this study we focus on the preference for different artificial roost sites by insectivorous bats in macadamia orchards in northern South Africa. From June 2016 to July 2017 we monitored 31 bat houses, mounted on poles in six macadamia orchards, for presence of bats or other occupants. Twenty-one multi-chambered bat houses of three different designs were erected in sets of three. Additionally, five Rocket boxes, four bat houses in sets of two (painted black and white) and one colony bat house were erected. Bats were counted and visually identified to family or species level. From December 2016 to the end of March 2017 iButtons were installed to record and analyze temperature variation within one set of three bat houses. We related the occupancy of bat houses to the different types of houses and the environmental variables: distance to water, altitude and height of the bat houses above the ground. Overall bat house occupancy was significantly higher in the central bat house, in the set of three, and the black bat house, in the set of two. Mean temperatures differed between houses in the set of three with the central bat house having a significantly higher mean temperature than the houses flanking it. Our study might confirm previous assumptions that the microclimate of bat houses appears to be an important factor influencing occupancy. In conclusion, from the different bat houses tested in this study the designs we assume the warmest and best insulated attracted the most bats. Further research is needed on the preferred microclimate of different bat species, co-habitation within bat houses and the potential importance of altitude and distance to water. Our study provided little variation in both altitude and the distance to water

The impact of inter‐flood duration on non‐cohesive sediment bed stability

© 2019 John Wiley & Sons, Ltd. Limited field and flume data suggests that both uniform and graded beds appear to progressively stabilize when subjected to inter-flood flows as characterized by the absence of active bedload transport. Previous work has shown that the degree of bed stabilization scales with duration of inter-flood flow, however, the sensitivity of this response to bed surface grain size distribution has not been explored. This article presents the first detailed comparison of the dependence of graded bed stability on inter-flood flow duration. Sixty discrete experiments, including repetitions, were undertaken using three grain size distributions of identical D50 (4.8 mm); near-uniform (σg = 1.13), unimodal (σg = 1.63) and bimodal (σg = 2.08). Each bed was conditioned for between 0 (benchmark) and 960 minutes by an antecedent shear stress below the entrainment threshold of the bed (τ*c50). The degree of bed stabilization was determined by measuring changes to critical entrainment thresholds and bedload flux characteristics. Results show that (i) increasing inter-flood duration from 0 to 960 minutes increases the average threshold shear stress of the D50 by up to 18%; (ii) bedload transport rates were reduced by up to 90% as inter-flood duration increased from 0 to 960 minutes; (iii) the rate of response to changes in inter-flood duration in both critical shear stress and bedload transport rate is non-linear and is inversely proportional to antecedent duration; (iv) there is a grade dependent response to changes in critical shear stress where the magnitude of response in uniform beds is up to twice that of the graded beds; and (v) there is a grade dependent response to changes in bedload transport rate where the bimodal bed is most responsive in terms of the magnitude of change. These advances underpin the development of more accurate predictions of both entrainment thresholds and bedload flux timing and magnitude, as well as having implications for the management of environmental flow design. © 2019 John Wiley & Sons, Ltd. © 2019 John Wiley & Sons, Ltd

Herd-level risk for Salmonella culture positive status in slaughtered pigs.

Quantitative definition of risk factors is needed for farms to develop programs and procedures to reduce Salmonella shedding economically and reliably. It is essential that this information be available to producers before full implementation of proposed Salmonella reduction regulations. Producers should then be able to retain market access and choose informed interventions while avoiding unnecessary costs

Translational Studies Using the MALT1 Inhibitor (S)-Mepazine to Induce Treg Fragility and Potentiate Immune Checkpoint Therapy in Cancer

INTRODUCTION: Regulatory T cells (Tregs) play a critical role in the maintenance of immune homeostasis but also protect tumors from immune-mediated growth control or rejection and pose a significant barrier to effective immunotherapy. Inhibition of MALT1 paracaspase activity can selectively reprogram immune-suppressive Tregs in the tumor microenvironment to adopt a proinflammatory fragile state, which offers an opportunity to impede tumor growth and enhance the efficacy of immune checkpoint therapy (ICT). METHODS: We performed preclinical studies with the orally available allosteric MALT1 inhibitor (S)-mepazine as a single-agent and in combination with anti-programmed cell death protein 1 (PD-1) ICT to investigate its pharmacokinetic properties and antitumor effects in several murine tumor models as well as patient-derived organotypic tumor spheroids (PDOTS). RESULTS: (S)-mepazine demonstrated significant antitumor effects and was synergistic with anti-PD-1 therapy in vivo and ex vivo but did not affect circulating Treg frequencies in healthy rats at effective doses. Pharmacokinetic profiling revealed favorable drug accumulation in tumors to concentrations that effectively blocked MALT1 activity, potentially explaining preferential effects on tumor-infiltrating over systemic Tregs. CONCLUSIONS: The MALT1 inhibitor (S)-mepazine showed single-agent anticancer activity and presents a promising opportunity for combination with PD-1 pathway-targeted ICT. Activity in syngeneic tumor models and human PDOTS was likely mediated by induction of tumor-associated Treg fragility. This translational study supports ongoing clinical investigations (ClinicalTrials.gov Identifier: NCT04859777) of MPT-0118, (S)-mepazine succinate, in patients with advanced or metastatic treatment-refractory solid tumors

Reversible magnetic mercury extraction from water

A facile and efficient way to decontaminate mercury(II) polluted water with the aid of magnetic, highly stable and recyclable carbon coated cobalt (Co/C) nanoparticles is reported. Comparing non-functionalised Co/C nanomagnets with particles that were functionalised with amino moieties, the latter one proved to be more effective for scavenging mercury with respect to extraction capacity and recyclability. A novel nanoparticle–poly(ethyleneimine) hybrid (Co/C–PEI) prepared by direct ring opening polymerization of aziridine initiated by an amine functionalised nanoparticle surface led to a high capacity material (10 mmol amino groups per g nanomaterial) and thus proved to be the best material for scavenging toxic mercury at relevant concentrations (mg L−1/μg L−1) for at least 6 consecutive cycles. On a large-scale, 20 L of drinking water with an initial Hg2+ concentration of 30 μg L−1 can be decontaminated to the level acceptable for drinking water (≤2 μg L−1) with just 60 mg of Co/C–PEI particles

Crown ethers: novel permeability enhancers for ocular drug delivery?

Crown ethers are cyclic molecules consisting of a ring containing several ether groups. The most common and important members of this series are 12-crown-4 (12C4), 15-crown-5 (15C5), and 18-crown-6 (18C6). These container molecules have the ability to sequester metal ions and their complexes with drugs are able to traverse cell membranes. This study investigated 12C4, 15C5 and 18C6 for their ability to increase solubility of ocular drugs and enhance their penetration into the cornea. Phase solubility analysis determined crown ethers’ ability to enhance the solubility of riboflavin, a drug used for the therapy of keratoconus, and these solutions were investigated for ocular drug permeation enhancing properties. Atomic absorption spectroscopy demonstrated crown ether solutions ability to sequester Ca2+ from corneal epithelia and crown ether mediated adsorption of riboflavin into the stroma was investigated. Induced corneal opacity studies assessed potential toxicity of crown ethers. Crown ethers enhanced riboflavin’s aqueous solubility and its penetration into in vitro bovine corneas; the smaller sized crown ethers gave greatest enhancement. They were shown to sequester Ca2+ ions from corneal epithelia, doing so loosens cellular membrane tight junctions thus enhancing riboflavin penetration. Induced corneal opacity was similar to that afforded by benzalkonium chloride and less than is produced using polyaminocarboxylic acids. However, in vivo experiments performed in rats with 12C4 did not show any statistically significant permeability enhancement compared to enhancer-free formulation