Airborne ultra-wideband radar sounding over the shear margins and along flow lines at the onset region of the Northeast Greenland Ice Stream

We present a high-resolution airborne radar data set (EGRIP-NOR-2018) for the onset region of the Northeast Greenland Ice Stream (NEGIS). The radar data were acquired in May 2018 with the Alfred Wegener Institute\u27s multichannel ultra-wideband (UWB) radar mounted on the Polar 6 aircraft. Radar profiles cover an area of ∼24 000 km2 and extend over the well-defined shear margins of the NEGIS. The survey area is centered at the location of the drill site of the East Greenland Ice-Core Project (EastGRIP), and several radar lines intersect at this location. The survey layout was designed to (i) map the stratigraphic signature of the shear margins with radar profiles aligned perpendicular to ice flow, (ii) trace the radar stratigraphy along several flow lines, and (iii) provide spatial coverage of ice thickness and basal properties. While we are able to resolve radar reflections in the deep stratigraphy, we cannot fully resolve the steeply inclined reflections at the tightly folded shear margins in the lower part of the ice column. The NEGIS is causing the most significant discrepancies between numerically modeled and observed ice surface velocities. Given the high likelihood of future climate and ocean warming, this extensive data set of new high-resolution radar data in combination with the EastGRIP ice core will be a key contribution to understand the past and future dynamics of the NEGIS. The EGRIP-NOR-2018 radar data products can be obtained from the PANGAEA data publisher (https://doi.pangaea.de/10.1594/PANGAEA.928569; Franke et al., 2021a)

Elections and Ethnic Civil War

Existing research on how democratization may influence the risk of civil war tends to consider only changes in the overall level of democracy and rarely examines explicitly the postulated mechanisms relating democratization to incentives for violence. The authors argue that typically highlighted key mechanisms imply that elections should be especially likely to affect ethnic groups’ inclination to resort to violence. Distinguishing between types of conflict and the order of competitive elections, the authors find that ethnic civil wars are more likely to erupt after competitive elections, especially after first and second elections following periods of no polling. When disaggregating to the level of individual ethnic groups and conflicts over territory or government, the authors find some support for the notion that ethno-nationalist mobilization and sore-loser effects provoke postelectoral violence. More specifically, although large groups in general are more likely to engage in governmental conflicts, they are especially likely to do so after noncompetitive elections. Competitive elections, however, strongly reduce the risk of conflict. </jats:p

Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Tissue inhibitor of metalloproteinase 1 (TIMP-1) is a natural inhibitor of the matrix metalloproteinases (MMPs) which are proteolytic enzymes involved in degradation of extracellular matrix thereby favoring tumour cell invasion and metastasis. TIMP-1 activity in tumour tissue may therefore play an essential role in the progression of a malignant tumour.</p> <p>The primary aim of the present study was to evaluate TIMP-1 protein immunoreactivity in tissue from primary ovarian cancer patients and associate these findings with the course of the disease including response to treatment in the individual patient.</p> <p>Methods</p> <p>TIMP-1 was assessed by immunohistochemistry (in tissue micro arrays) in a total of 163 ovarian cancer specimens obtained from primary debulking surgery during 1991-1994 as part of a randomized clinical protocol.</p> <p>Results</p> <p>Positive TIMP-1 immunoreactivity was found in 12.3% of the tumours. The median survival time for the 143 patients with TIMP-1 negative tumours was 23.7 months [19.0-29.4] 95% CI, while the median survival time for the 20 patients with TIMP-1 positive tumours was 15.9 months [12.3-27.4] 95% CI. Although a difference of 7.8 months in median overall survival in favor of the TIMP-1 tumour negative patients was found, this difference did not reach statistical significance (<it>p </it>= 0.28, Kaplan-Meier, log-rank test). Moreover, TIMP-1 immunoreactivity was not associated with CA125 response (p = 0.53) or response at second look surgery (p = 0.72).</p> <p>Conclusion</p> <p>TIMP-1 immunoreactivity in tumour tissue from patients with primary epithelial ovarian cancer did not correlate with patient survival or response to combination platinum/cyclophosphamide therapy.</p

Mutations in GABRB3

Objective: To examine the role of mutations in GABRB3 encoding the b3 subunit of the GABAA receptor in individual patients with epilepsy with regard to causality, the spectrum of genetic variants, their pathophysiology, and associated phenotypes. Methods: We performed massive parallel sequencing of GABRB3 in 416 patients with a range of epileptic encephalopathies and childhood-onset epilepsies and recruited additional patients with epilepsy with GABRB3 mutations from other research and diagnostic programs. Results: We identified 22 patients with heterozygous mutations in GABRB3, including 3 probands frommultiplex families. The phenotypic spectrum of the mutation carriers ranged from simple febrile seizures, genetic epilepsies with febrile seizures plus, and epilepsy withmyoclonic-atonic seizures to West syndrome and other types of severe, early-onset epileptic encephalopathies. Electrophysiologic analysis of 7 mutations in Xenopus laevis oocytes, using coexpression of wild-type or mutant beta(3), together with alpha(5) and gamma(2s) subunits and an automated 2-microelectrode voltage-clamp system, revealed reduced GABA-induced current amplitudes or GABA sensitivity for 5 of 7 mutations. Conclusions: Our results indicate that GABRB3 mutations are associated with a broad phenotypic spectrum of epilepsies and that reduced receptor function causing GABAergic disinhibition represents the relevant disease mechanism

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Post-Processing Posterior Predictive P-values

This article addresses issues of model choice in Bayesian contexts, and focusses on the use of the so-called posterior predictive p-values (ppp values). These involve a general discrepancy or conflict measure and depend on the prior, the model, and the data. They are used in statistical practice to quantify the degree of surprise or conflict in data, and for purposes of comparing different combinations of prior and model. The distribution of such ppp values is however far from uniform, as we demonstrate for different models, making their interpretation and comparison a difficult matter. We propose a natural calibration of the ppp values, where the resulting cppp values are uniform on the unit interval under model conditions. The cppp values, which in general rely on a double simulation scheme for their computation, may then be used to assess and compare different priors and models. Our methods also make it possible to compare parametric with nonparametric model specifications, in that genuine `measures of surprise' are put on the same canonical uniform scale. Our techniques are illustrated for some applications to real data. We also present supplementing theoretical results on various properties of the ppp and cppp