Purpose:

Radium-223 is approved for metastatic castration-resistant prostate cancer (mCRPC) based on improved overall survival, and delay in skeletal related events. However, it is not associated with PSA or radiographic response, which poses a challenge in real-time assessment of its efficacy. Surrogate markers of treatment outcomes may facilitate tailoring treatment duration with radium-223, by limiting the duration of therapy with radium-223 in these patients. Here, we sought to investigate the utility of bone metabolic markers (BMMs) as surrogate markers of response to radium-223 in mCRPC.

KBP-7072 is a novel third-generation tetracycline (aminomethylcycline) antibacterial that overcomes common efflux and ribosomal protection resistance mechanisms that cause resistance in older-generation tetracyclines. KBP-7072 completed phase 1 clinical development studies for safety, tolerability, and pharmacokinetics (ClinicalTrials.gov identifier NCT02454361) and multiple ascending doses in healthy subjects (ClinicalTrials.gov identifier NCT02654626) in December 2015. Both oral and intravenous formulations of KBP-7072 are being developed. In this study, we evaluated the in vitro activities of KBP-7072 and comparator agents by CLSI document M07 (2018) broth microdilution against 531 recent geographically diverse and/or molecularly characterized Acinetobacter baumannii-A. calcoaceticus species complex (A. baumannii) isolates from the United States, Europe, Asia-Pacific (excluding China), and Latin America. A. baumannii isolates included carbapenem-resistant, colistin-resistant, tetracycline-resistant, and extended-spectrum-β-lactamase (ESBL)- and metallo-β-lactamase (MBL)-producing isolates. Overall, KBP-7072 (MIC_50/90, 0.25/1 mg/liter) was comparable in activity to colistin (92.8%/92.8% susceptible [S] [CLSI/EUCAST]) against A. baumannii isolates, inhibiting 99.2% of isolates at ≤2 mg/liter and 97.6% of isolates at ≤1 mg/liter. KBP-7072 was equally active against A. baumannii isolates, including carbapenem-resistant, colistin-resistant, and tetracycline-resistant isolates, regardless of geographic location, and maintained activity against ESBL- and MBL-producing isolates. KBP-7072 outperformed comparator agents, including ceftazidime (40.3% S [CLSI]), gentamicin (48.2%/48.2% S [CLSI/EUCAST]), levofloxacin (39.5%/37.9% S [CLSI/EUCAST]), meropenem (42.0%/42.0% S [CLSI/EUCAST]), piperacillin-tazobactam (33.3% S [CLSI]), and all tetracycline-class comparator agents, which include doxycycline (67.3% S [CLSI]), minocycline (73.8% S [CLSI]), tetracycline (37.2% S [CLSI]), and tigecycline (79.5% inhibited by ≤2 mg/liter). The potent in vitro activity of KBP-7072 against recent geographically diverse, molecularly characterized, and drug-resistant A. baumannii isolates supports continued clinical development for the treatment of serious infections, including those caused by A. baumannii.

In lung cancer, brain metastasis was associated with somatic amplification of MYC, YAP1, or MMP13.

In the plasmaMATCH trial, researchers performed circulating tumor DNA testing on patients with advanced breast cancer and matched those with ESR1, HER2, or AKT1 alterations to targeted therapies. Patients with HER2 and AKT1 mutations experienced response rates greater than 22% with durable benefit.

An 18-yr-old man with a history of intellectual disability, craniofacial dysmorphism, seizure disorder, and obesity was identified to carry a de novo, pathogenic variant in ASXL1 (c.4198G>T; p.E1400X) associated with the diagnosis of Bohring–Opitz syndrome based on exome sequencing. In addition, he was identified to carry a maternally inherited and likely pathogenic variant in MC4R (c.817C>T; p.Q273X) associated with monogenic obesity. Dual genetic diagnosis occurs in 4%–6% of patients and results in unique clinical phenotypes that are a function of tissue-specific gene expression, involved pathways, clinical expressivity, and penetrance. This case highlights the utility of next-generation sequencing in patients with an unusual combination of clinical presentations for several pillars of precision medicine including (1) diagnosis, (2) prognosis and outcome, (3) management and therapy, and (4) utilization of resources.

Background:

The success of multisite collaborative research relies on effective data collection, harmonization, and aggregation strategies. Data Coordination Centers (DCC) serve to facilitate the implementation of these strategies. The utility of a DCC can be particularly relevant for research on rare diseases where collaboration from multiple sites to amass large aggregate datasets is essential. However, approaches to building a DCC have been scarcely documented.

This protocol is used to determine the concentration of DNase-resistant vector genomes (i.e., packaged in the capsid) in purified recombinant adeno-associated virus (rAAV) preparations. The protocol begins with treatment of the vector stock with DNase I to eliminate unencapsidated AAV DNA or contaminating plasmid DNA. This is followed by a heat treatment to heat-inactivate DNase I, to disrupt the viral capsid, and to release the packaged vector genomes for quantification by real-time polymerase chain reaction (PCR) using a set of standards (linearized plasmid used for vector production) containing known copy numbers. To accomplish high-throughput titration, the primer and probe sets used in real-time PCR are usually designed to target common elements present in most rAAV genomes, such as promoters and poly(A) signals. This strategy significantly reduces the number of PCRs, controls, and turnaround time. Several important controls should be included in the assay as follows: The first two controls should have a known copy number of the rAAV genome plasmid treated or not treated with DNase I. This control tests the effectiveness of DNase treatment. To control for potential cross-contamination between samples during the preparation process, a blank control containing nuclease-free water only should be processed and tested in parallel. A validation vector sample with a known titer should be included in every assay to monitor interassay variability. Finally, for the PCR run, a no-template control (NTC) is included to indicate cross-contamination during PCR setup.

“Dear Designer” is a blog series on orienting novice practitioners to the discipline of instructional design and learning experience design.

The post Dear Designer: 3 Considerations for Length When Shifting to VILT appeared first on e-Learning Feeds.

It’s time to start planning our return to the workplace. Adjustments made during the pandemic will extend into and impact our return to the office. […]

The post 5 L&D considerations for returning to the workplace appeared first on e-Learning Feeds.

Publisher Private Division and developer V1 Interactive announced Disintegration will launch for the PlayStation 4, Xbox One and Windows PC via Steam on June 16 for $49.99.

View the story trailer below:

Here is an overview of the game:

Disintegration is a sci-fi, first-person shooter that blends real-time tactical elements to create an entirely new experience. Set in a world ripped apart by famine, scarce resources, and the planet on the brink of destruction, humanity has developed a process to survive its harsh reality known as Integration, in which a human brain is transferred to a robotic armature. From the ensuing chaos, an aggressive, militaristic legion, known as the Rayonne, gain control and begins to impose the once optional process of Integration onto the rest of humanity to consolidate their power.

Players command Romer Shoal, an incredibly-skilled Gravcycle pilot, who leads a small band of outlaws to fight back against an overwhelming Rayonne force. Over the course of a thrilling single-player campaign, players will control a Gravcycle loaded with weaponry, leading Romer and his team across a series of diverse missions packed with action, explosions, and plot twists, to beat back the Rayonne forces and give the last vestiges of humanity hope to prevail.

In addition to the full single-player campaign, Disintegration features frenetic player-versus-player multiplayer where pilots and their crews compete in three game modes and six distinct maps. Players can select from nine highly-stylized “Crews” which lend themselves to different playstyles.

Multiplayer provides a host of cosmetic customizations that can be purchased or earned in-game, including pilot and crew skins, cosmetic Gravcycle customizations, and a variety of banners. In addition to the multiplayer content at release, the team at V1 will be supporting the game post-launch with seasonal content drops.

Key Features:

• Tactical Gravcycle Combat – Pilot a heavily armed Gravcycle featuring a variety of firepower, maneuverability, and abilities.
• Riveting Single-player Campaign – From Marcus Lehto, the co-creator of Halo and creative director of Halo: Reach, comes an all-new sci-fi saga. Play as Romer Shoal and confront the Rayonne, a rising global army set on eliminating what remains of humanity.
• Frenetic Multiplayer Action – Battle across a variety of maps in three intense, team-based five-versus-five multiplayer modes. Choose your favorite Gravcycle and lead your crew alongside your teammates, competing against opposing pilots to win objective-based matches.

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/443412/disintegration-launches-june-16-for-ps4-xbox-one-and-steam/

In light of the newly declassified documents, it is clear that understanding what happened in that January 5 Oval Office meeting is essential to understanding the corrupt operation against the Trump administration.

Job postings from a NASA contractor suggest that a new humanoid robot is under development

Michael Kratsios, the fourth U.S. Chief Technology Officer, explains administration policies at the Fall Conference of the Stanford Institute for Human-Centered Artificial Intelligence

Shannon's said: “OCRO HLI RGWR NMIELWIS”

It’s four two two on 4/22. Can you feel the synergy? No? Listen, it’s a slow news week so we need you to work with...

The notoriously independent-minded federal judge who once said he was disgusted by the conduct of Michael Flynn could block the administration's bid to drop criminal charges against the former adviser to President Donald Trump, legal experts said.

The last Formula One season was a disappointing one for Daniel Ricciardo, who retains a burning desire to win the world title.

President Donald Trump said on Thursday his administration is talking to Republican senators about work visa issues, amid the coronavirus outbreak that has wreaked havoc on the U.S. economy.

This generation saw a boom in quality horror games and we're counting down the 25 scariest.

It's quite the refresh

BRITONS flocked outside to celebrate the 75th anniversary of VE Day yesterday, which caused major backlash online, especially against the BBC.

The House's special panel policing coronavirus spending demanded Friday that five large corporations return rescue money that was intended for small businesses.

The letters to the five companies were the first official action of the newly formed Select Subcommittee on the Coronavirus Crisis.

"Since your company is a public entity ...

SEATTLE (AP) - Officials on Friday confirmed the first positive COVID-19 test at the Northwest detention center in Tacoma, in a detainee who had previously tested positive at another detention center and was being medically screened on arrival at the immigration jail. The development came just as immigrant rights advocates ...

Russia proceeded with Victory Day celebrations despite a rapidly deteriorating situation in the face of the pandemic.

Conservation groups are fighting the creation of 3,500 gas wells in Wyoming that threaten a 170-mile path

The Path of the Pronghorn is a 170-mile migration route that the antelope-like creatures have traveled annually for 6,000 years. It is one of North America’s last remaining long-distance terrestrial migration corridors.

And it is at risk. This week conservation groups filed a legal petition challenging the Trump administration’s plan to allow 3,500 new gas wells in south-western Wyoming that would block the route.

Once again, Intel's banking on a high clock speed to drum up excitement.

Consumer Gmail users are seeing a "Google Meet" section in the sidebar.

Future Navy SEALs will conduct combat scenarios six-feet apart, emulate high-risk combat scenarios, study in smaller classrooms and be directed by megaphones at farther distances, because more candidates for the special operations unit are again competing, training and preparing for war following temporary delays caused by COVID 19.

The Trump administration is drafting a legal blueprint for mining on the moon under a new U.S.-sponsored international agreement called the Artemis Accords, people familiar with the proposed pact told Reuters.

Read our live coronavirus updates HERE

Read our live updates on coronavirus HERE Coronavirus: The symptoms

Fashion chains Oasis and Warehouse have fallen into administration, affecting some 2,300 workers.

Follow our live Covid-19 updates HERE Coronavirus: The symptoms

NHS staff and Carrie Symonds are among those who have thanked "inspirational" war veteran Captain Tom Moore during the weekly clap for carers.

The first coronavirus patients to be successfully treated at London's new NHS Nightingale London are returning home to their loved ones.

Hospital leaders have criticised the Government after a shipment which contained vital equipment for NHS staff was delayed.

Defiant US healthcare workers have been praised after silently blocking cars during coronavirus anti-lockdown demonstrations in Colorado.

The Duke and Duchess of Sussex have told four new newspaper groups – The Mirror, The Sun, The Daily Mail and Daily Express – they are no longer co-operating with them.

The move, which the US leader announced in a tweet in the early hours of Tuesday, effectively achieves a long-term policy goal of the president to curb immigration, making use of the crisis to do so.

Virgin Australia has gone into voluntary administration after failing to secure a government bailout due to impacts of the coronavirus pandemic.

Donald Trump has said his new US immigration ban would last for 60 days and apply to those seeking "green cards" for permanent residency.

Police have arrested six people and seized about £1m in assets from brothels in Westminster as part of a major crackdown operation.

Donald Trump has signed an executive order temporarily suspending immigration into the US during the coronavirus pandemic.

Matt Hancock has praised Muslims across the UK for making changes to how they mark Ramadan due to the coronavirus lockdown.

Boris Johnson and Carrie Symonds have welcomed the arrival of their first child together.

A cuckoo named Carlton II has smashed the record books by flying more than 4,000 miles in just seven days on his annual migration to the UK from Africa.

A nurse who stayed at work despite having been diagnosed with cancer and an inspirational teacher are among the latest Londoners to die with Covid-19.