North Carolina has received national attention for its approach to health care payment and delivery reform. Importantly, payment reform alone is not enough to drive systematic changes in care delivery. We highlight the importance of progress in four complementary areas to achieve system-wide payment and care reform.

Endothelial activation and microvascular dysfunction are key pathogenic processes in severe malaria. We evaluated the early role of these processes in experimentally induced Plasmodium falciparum and P. vivax infection. Participants were enrolled in induced blood-stage malaria clinical trials. Plasma osteoprotegerin, angiopoietin-2, and von Willebrand Factor (vWF) levels were measured as biomarkers of endothelial activation. Microvascular function was assessed using peripheral arterial tonometry and near-infrared spectroscopy, and the endothelial glycocalyx was assessed by sublingual videomicroscopy and measurement of biomarkers of degradation. Forty-five healthy, malaria-naive participants were recruited from 5 studies. Osteoprotegerin and vWF levels increased in participants following inoculation with P. vivax (n = 16) or P. falciparum (n = 15), with the angiopoietin-2 level also increasing in participants following inoculation with P. falciparum. For both species, the most pronounced increase was seen in osteoprotegerin. This was particularly marked in participants inoculated with P. vivax, where the osteoprotegerin level correlated with the levels of parasitemia and the malaria clinical score. There were no changes in measures of endothelial glycocalyx or microvascular function. Plasma biomarkers of endothelial activation increased in early P. falciparum and P. vivax infection and preceded changes in the endothelial glycocalyx or microvascular function. The more pronounced increase in osteoprotegerin suggests that this biomarker may play a role in disease pathogenesis.

Background

Canagliflozin reduced renal and cardiovascular events in people with type 2 diabetes in the CREDENCE trial. We assessed efficacy and safety of canagliflozin by initial estimated glomerular filtration rate (eGFR).

Endogenous viral elements (EVEs) are found in many eukaryotic genomes. Despite considerable knowledge about genomic elements such as transposons (TEs) and retroviruses, we still lack information about nonretroviral EVEs. Aedes aegypti mosquitoes have a highly repetitive genome that is covered with EVEs. Here, we identified 129 nonretroviral EVEs in the AaegL5 version of the A. aegypti genome. These EVEs were significantly associated with TEs and preferentially located in repeat-rich clusters within intergenic regions. Genome-wide transcriptome analysis showed that most EVEs generated transcripts although only around 1.4% were sense RNAs. The majority of EVE transcription was antisense and correlated with the generation of EVE-derived small RNAs. A single genomic cluster of EVEs located in a 143 kb repetitive region in chromosome 2 contributed with 42% of antisense transcription and 45% of small RNAs derived from viral elements. This region was enriched for TE-EVE hybrids organized in the same coding strand. These generated a single long antisense transcript that correlated with the generation of phased primary PIWI-interacting RNAs (piRNAs). The putative promoter of this region had a conserved binding site for the transcription factor Cubitus interruptus, a key regulator of the flamenco locus in Drosophila melanogaster. Here, we have identified a single unidirectional piRNA cluster in the A. aegypti genome that is the major source of EVE transcription fueling the generation of antisense small RNAs in mosquitoes. We propose that this region is a flamenco-like locus in A. aegypti due to its relatedness to the major unidirectional piRNA cluster in Drosophila melanogaster.

We document that the undifferentiated chaotic Ligurian Units of the Monferrato–Torino Hill sector (MO-TH) at the Alps–Apennines junction consist of three different units that are comparable with the Cassio, Caio and Sporno Units of the External Ligurian Units of the Northern Apennines. Their internal stratigraphy reflects the character of units deposited in an ocean–continent transition (OCT) zone between the northwestern termination of the Ligurian–Piedmont oceanic basin and the thinned passive margin of Adria microcontinent. The inherited wedge-shaped architecture of this OCT, which gradually closed toward the north in the present-day Canavese Zone, controlled the Late Cretaceous–early Eocene flysch deposition at the trench of the External Ligurian accretionary wedge during the oblique subduction. This favoured the formation of an accretionary wedge increasing in thickness and elevation toward the SE, from the MO-TH to the Emilia Northern Apennines. Our results therefore provide significant information on both the palaeogeographical reconstruction of the northwestern termination of the Ligurian–Piedmont oceanic basin and the role played by inherited along-strike variations (stratigraphy, structural architecture and morphology) of OCT zones in controlling subduction–accretionary processes.

Supplementary material: A spreadsheet with X-ray fluorescence spectrometry and inductively coupled plasma mass spectrometry whole-rock major and trace element composition of mantle peridotites, and photomicrographs of mantle peridotites are available at https://doi.org/10.6084/m9.figshare.c.4519643

Approximately 40% of patients with diabetic macular edema (DME) are resistant to anti–vascular endothelial growth factor (VEGF) therapy (rDME). Here, we demonstrate that significant correlations between inflammatory cytokines and VEGF, as observed in naive DME, are lost in patients with rDME. VEGF overexpression in the mouse retina caused delayed inflammatory cytokine upregulation, monocyte/macrophage infiltration (CD11b⁺ Ly6C⁺ CCR2⁺ cells), macrophage/microglia activation (CD11b⁺ CD80⁺ cells), and blood-retinal barrier disruption due to claudin-5 redistribution, which did not recover with VEGF blockade alone. Phosphorylated protein analysis of VEGF-overexpressed retinas revealed rho-associated coiled-coil–containing protein kinase (ROCK) activation. Administration of ripasudil, a selective ROCK inhibitor, attenuated retinal inflammation and claudin-5 redistribution. Ripasudil also contributed to the stability of claudin-5 expression by both transcriptional enhancement and degradation suppression in inflammatory cytokine–stimulated endothelium. Notably, the anti-VEGF agent and the ROCK inhibitor were synergic in suppressing cytokine upregulation, monocyte/macrophage infiltration, macrophage/microglia activation, and claudin-5 redistribution. Furthermore, in vitro analysis confirmed that claudin-5 redistribution depends on ROCK2 but not on ROCK1. This synergistic effect was also confirmed in human rDME cases. Our results suggest that ROCK-mediated claudin-5 redistribution by inflammation is a key mechanism in the anti-VEGF resistance of DME.

Authorities of the Northern province Lang Son has requested VND3.16 trillion ($136 million) from the government to build the Chi Lang-Huu Nghi Expressway.

Real estate insiders and experts said it is essential to develop strict penalties to combat those operating fraudulent property businesses to protect the legitimate rights of consumers and legitimate enterprises.

A gameplay trailer for a Prince of Persia reboot, called Prince of Persia: Redemption, was posted on YouTube in March 2012 and was discovered this week. 

The LinkedIn profile for the former Ubisoft employee Christophe Prelot revealed he worked on a cancelled Prince of Persia title from April 2010 to 2011 as a 3D level artist. The game was in development for the PlayStation 3, Xbox 360 and Windows PC. 

Ubisoft assistant technical director Marc-Andre Belleau in 2018 left a comment on the video asking, "Where did you get that?!"

View the video below:

Thanks ResetEra.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443408/footage-of-cancelled-prince-of-persia-redemption-from-2012-discovered/

Adrian Tchaikovsky's latest novel The Doors of Eden rewrites Earth's evolutionary history, with highlights including fish that upload their minds to supercomputers and cats that rule over primates

This week, new claims about the accuracy of the Garden of Eden story emerged online and in tabloid magazines. Professor Tom Meyer, a scripture expert known as the Bible Memory Man, argues that there are two artifacts—a 4,000-year-old seal and roughly 3,600-year-old stone—that provide evidence both for the location of the Garden of Eden and the Adam and Eve story. But do his claims add up? (Spoiler alert: No)

In a story, reported this week in the Daily Express, Meyer, who teaches at his alma mater Shasta Bible College and University, refers first to a Sumerian king list, an inscribed Middle Bronze aged stone prism currently housed at the Ashmolean Museum in Oxford. The prism dates to between 2100 B.C. and 1650 B.C. and was discovered in 1922 by Herbert Weld-Blundell during his excavations in Kish, the ancient capital of Sumer, in Mesopotamia. It was purchased by the Ashmolean shortly thereafter.

Meyer said, “In addition to enumerating the long reigns of pre-flood rulers, this prism lists Eridu—an ancient site in southern Iraq—as the first city ever built.” This is significant, he says, because “The ancient site of the Garden of Eden… is thought by some to be located at Eridu under a cluster of tels” (Tels are artificial hills).

Read more at The Daily Beast.

An exclusive look at the world’s most dynamic robots

The idea of an in-game Travis Scott concert might seem a little silly — particularly if, like me, you’re not really a Fortnite player. Yes, the popular multiplayer game has hosted other promotional events for movies and music. But even if all this COVID-19 imposed isolation has left you hungry for live performances, why not […]

ROGER FEDERER has explained why he gets injured less than rivals Rafael Nadal and Novak Djokovic..

Coronavirus illnesses to date may touch as little as 4 percent of meat and poultry employment, but it been enough to roil the industry over how much protection the plants need to be safe. Actions taken in tight proximity to one another by U.S. Secretary of Agriculture Sonny Perdue and U.S. District Court Judge Greg... Continue Reading

STOCKHOLM (AP) - The flight from Italy was one of the last arrivals that day at the Stockholm airport. A Swedish couple in their 50s walked up and loaded their skis into Razzak Khalaf's taxi.

It was early March and concerns over the coronavirus were already present, but the couple, ...

The NFL Players Coalition and other athletes and coaches called on the Justice Department and the FBI to launch a federal investigation into the shooting death of Ahmaud Arbery in a letter Friday.

Follow our live coronavirus updates HERE Coronavirus: the symptoms

Follow our live coronavirus updates HERE Coronavirus: The symptoms

Coronavirus: the symptoms Read live Covid-19 updates here

A pedestrian has died after being hit by a black BMW as he crossed a road in south London.

Coronavirus: the symptoms Follow our live updates here

A group of parents who were challenged by police over a trip to the beach during the coronavirus lockdown claimed their children needed a "change of air".

MPs will investigate the potential consequences of allowing electric scooters to be used on the road.

Record-breaking daredevil pensioner Jack Reynolds has died aged 108, his family have said.

Heartfelt appeal on behalf of families and vulnerable during coronavirus crisis You can donate here virginmoneygiving.com/fund/FoodforLondonNOW

A Swedish city plans to cover its main park with a tonne of chicken manure to discourage people from going there during the coronavirus outbreak.

Anxiety levels soared to unprecedented heights around the time lockdown was announced in late March, according to the Government's official "happiness index".

Thousands of firms today rushed to get "bounce back" loans of up to £50,000 to avoid going bust within weeks as the coronavirus crisis wreaked havoc in the economy.

Teenager's parents criticise Foreign Secretary Dominic Raab's comments on son's death as "misleading"

The flight from Italy was one of the last arrivals that day at the Stockholm airport. A Swedish couple in their 50s walked up and loaded their skis into Razzak Khalaf's taxi. It was early March and concerns over the coronavirus were already present, but the couple, both coughing for the entire 45-minute journey, assured Khalaf they were healthy and just suffering from a change in the weather.

Imaging specialist produces clearest pictures yet from dramatic Nasa mission

'It has become too difficult to make the 12-acre project financially viable'

Gov. Tim Walz is hesitant to reopen businesses until his state's daily testing rate dramatically increases. "You can't flip it like a switch and say you're open if you don't have testing," he says.

Prime Minister Justin Trudeau described Canada’s current economic situation as a recession on Friday, and that should come as no surprise, says Finance Minister Bill Morneau, as the latest economic figures show two consecutive months of major job losses.

The Canadian Olympic Committee CEO talks about state of Canadian sport during COVID-19 and how funding will help keep sport organizations afloat.

The federal government will provide relief funding to the country's sport sector that has seen myriad events cancelled because of the COVID-19 pandemic.

And let's move beyond the tiresome ideological battle lines of “private bad, public good.” It's not that simple.

Alberta's use of a smartphone app to help slow the spread of the coronavirus may provide other provinces with insight on what to do — and what to avoid — as Canada begins easing restrictions, heightening the need for effective contact tracing.

'If I'm not acting, I'm not sure who I am,' the True Blood star said

Mayim Bialik, Debra Messing, Finn Wolfhard and many others joined

People have noted a certain timeliness in a clip from the 1993 episode 'Marge in Chains'

Is it all moot because of the deadly virus infecting Australia and no I don’t mean the National party ahahaha

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