ABSTRACTIntroduction:Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality. A new clinical intervention (E-MOTIVE) holds the potential to improve early PPH detection and management. We aimed to develop and pilot implementation strategies to support uptake of this intervention in Kenya, Nigeria, South Africa, and Tanzania.Methods:Implementation strategy development: We triangulated findings from qualitative interviews, surveys and a qualitative evidence synthesis to identify current PPH care practices and influences on future intervention implementation. We mapped influences using implementation science frameworks to identify candidate implementation strategies before presenting these at stakeholder consultation and design workshops to discuss feasibility, acceptability, and local adaptations. Piloting: The intervention and implementation strategies were piloted in 12 health facilities (3 per country) over 3 months. Interviews (n=58), case report forms (n=1,269), and direct observations (18 vaginal births, 7 PPHs) were used to assess feasibility, acceptability, and fidelity.Results:Implementation strategy development: Key influences included shortages of drugs, supplies, and staff, limited in-service training, and perceived benefits of the intervention (e.g., more accurate PPH detection and reduced PPH mortality). Proposed implementation strategies included a PPH trolley, on-site simulation-based training, champions, and audit and feedback. Country-specific adaptations included merging the E-MOTIVE intervention with national maternal health trainings, adapting local PPH protocols, and PPH trollies depending on staff needs. Piloting: Intervention and implementation strategy fidelity differed within and across countries. Calibrated drapes resulted in earlier and more accurate PPH detection but were not consistently used at the start. Implementation strategies were feasible to deliver; however, some instances of limited use were observed (e.g., PPH trolley and skills practice after training).Conclusion:Systematic intervention development, piloting, and process evaluation helped identify initial challenges related to intervention fidelity, which were addressed ahead of a larger-scale effectiveness evaluation. This has helped maximize the internal validity of the trial.

ABSTRACTPolitics is one of the critical factors that influence health policy agendas. However, scholarly efforts, especially in low- and middle-income countries, rarely focus on how politics influence health policy agenda-setting. We conducted a qualitative document review to examine the factors that led to developing the free primary health care policy for maternal health in Papua New Guinea. We also discuss mechanisms through which national politics, as an overriding factor, influenced the development of the policy. The review draws on Kingdon’s multiple-stream model for agenda-setting and incorporates theoretical insights from Fox and Reich’s framework for analyzing the politics of health reform for universal health coverage in low- and middle-income countries.

Targeting the endocannabinoid (eCB) signaling system for pain relief is an important treatment option that is only now beginning to be mechanistically explored. In this review, we focus on two recently appreciated cannabinoid-based targeting strategies, treatments with cannabidiol (CBD) and α/β-hydrolase domain containing 6 (ABHD6) inhibitors, which have the exciting potential to produce pain relief through distinct mechanisms of action and without intoxication. We review evidence on plant-derived cannabinoids for pain, with an emphasis on CBD and its multiple molecular targets expressed in pain pathways. We also discuss the function of eCB signaling in regulating pain responses and the therapeutic promises of inhibitors targeting ABHD6, a 2-arachidonoylglycerol (2-AG)-hydrolyzing enzyme. Finally, we discuss how the novel cannabinoid biosensor GRAB_eCB2.0 may be leveraged to enable the discovery of targets modulated by cannabinoids at a circuit-specific level.

Bile acids are the end products of cholesterol catabolism. Hepatic bile acid synthesis accounts for a major fraction of daily cholesterol turnover in humans. Biliary secretion of bile acids generates bile flow and facilitates biliary secretion of lipids, endogenous metabolites, and xenobiotics. In intestine, bile acids facilitate the digestion and absorption of dietary lipids and fat-soluble vitamins. Through activation of nuclear receptors and G protein-coupled receptors and interaction with gut microbiome, bile acids critically regulate host metabolism and innate and adaptive immunity and are involved in the pathogenesis of cholestasis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, type-2 diabetes, and inflammatory bowel diseases. Bile acids and their derivatives have been developed as potential therapeutic agents for treating chronic metabolic and inflammatory liver diseases and gastrointestinal disorders.

Although the progressive histologic steps leading to endometrial cancer (EndoCA), the most common female reproductive tract malignancy, from endometrial hyperplasia are well-established, the molecular changes accompanying this malignant transformation in a single patient have never been described. We had the unique opportunity to investigate the paired histologic and molecular features associated with the 12-yr development of EndoCA in a postmenopausal female who could not undergo hysterectomy and instead underwent progesterone treatment. Using a specially designed 58-gene next-generation sequencing panel, we analyzed a total of 10 sequential biopsy samples collected over this time frame. A total of eight pathogenic/likely pathogenic mutations in seven genes, APC, ARID1A, CTNNB1, CDKN2A, KRAS, PTEN, and TP53, were identified. A PTEN nonsense mutation p.W111* was present in all samples analyzed except histologically normal endometrium. Apart from this PTEN mutation, the only other recurrent mutation was KRAS G12D, which was present in six biopsy samplings, including histologically normal tissue obtained at the patient's first visit but not detectable in the cancer. The PTEN p.W111* mutant allele fractions were lowest in benign, inactive endometrial glands (0.7%), highest in adenocarcinoma (36.9%), and, notably, were always markedly reduced following progesterone treatment. To our knowledge, this report provides the first molecular characterization of EndoCA development in a single patient. A single PTEN mutation was present throughout the 12 years of cancer development. Importantly, and with potential significance toward medical and nonsurgical management of EndoCA, progesterone treatments were consistently noted to markedly decrease PTEN mutant allele fractions to precancerous levels.

Electron transport chain (ETC) disorders are a group of rare, multisystem diseases caused by impaired oxidative phosphorylation and energy production. Deficiencies in complex III (CIII), also known as ubiquinol–cytochrome c reductase, are particularly rare in humans. Ubiquinol–cytochrome c reductase core protein 2 (UQCRC2) encodes a subunit of CIII that plays a crucial role in dimerization. Several pathogenic UQCRC2 variants have been identified in patients presenting with metabolic abnormalities that include lactic acidosis, hyperammonemia, hypoglycemia, and organic aciduria. Almost all previously reported UQCRC2-deficient patients exhibited neurodevelopmental involvement, including developmental delays and structural brain anomalies. Here, we describe a girl who presented at 3 yr of age with lactic acidosis, hyperammonemia, and hypoglycemia but has not shown any evidence of neurodevelopmental dysfunction by age 15. Whole-exome sequencing revealed compound heterozygosity for two novel variants in UQCRC2: c.1189G>A; p.Gly397Arg and c.437T>C; p.Phe146Ser. Here, we discuss the patient's clinical presentation and the likely pathogenicity of these two missense variants.

We identified a de novo heterozygous transient receptor potential cation channel subfamily M (melastatin) member 3 (TRPM3) missense variant, p.(Asn1126Asp), in a patient with developmental delay and manifestations of cerebral palsy (CP) using phenotype-driven prioritization analysis of whole-genome sequencing data with Exomiser. The variant is localized in the functionally important ion transport domain of the TRPM3 protein and predicted to impact the protein structure. Our report adds TRPM3 to the list of Mendelian disease–associated genes that can be associated with CP and provides further evidence for the pathogenicity of the variant p.(Asn1126Asp).

Over the past decades the zebrafish has emerged as an excellent model organism with which to study the biology of all glial cell types in nervous system development, plasticity, and regeneration. In this review, which builds on the earlier work by Lyons and Talbot in 2015, we will summarize how the relative ease to manipulate the zebrafish genome and its suitability for intravital imaging have helped understand principles of glial cell biology with a focus on oligodendrocytes, microglia, and astrocytes. We will highlight recent findings on the diverse properties and functions of these glial cell types in the central nervous system and discuss open questions and future directions of the field.

Most childhood cancers possess distinct clinicopathological profiles from those seen in adulthood, reflecting their divergent mechanisms of carcinogenesis. Rather than depending on the decades-long, stepwise accumulation of changes within a mature cell that defines adult carcinomas, many pediatric malignancies emerge rapidly as the consequence of random errors during development. These errors—whether they be genetic, epigenetic, or microenvironmental—characteristically block maturation, resulting in phenotypically primitive neoplasms. Only an event that falls within a narrow set of spatiotemporal parameters will forge a malignant clone; if it occurs too soon then the event might be lethal, or negatively selected against, while if it is too late or in an incorrectly primed precursor cell then the necessary intracellular conditions for transformation will not be met. The precise characterization of these changes, through the study of normal tissues and tumors from patients and model systems, will be essential if we are to develop new strategies to diagnose, treat, and perhaps even prevent childhood cancer.

Up to 650 houses could be built on land at the golf club

Sega has sold Humankind and Endless developer Amplitude Studios to members of its internal team, announced the developer in a community post. This means the studio is now independent.

"Our studio is backed by strong and meaningful franchises and our team is committed to creating the best games possible," said Amplitude Studios founder Romain de Waubert de Genlis.

"With our extensive experiences in strategy game development and two exciting titles currently in progress, we are confident in our ability to deliver outstanding experience to players. This decision allows us to be more agile in our approach while continuing to shape the vision that has been ours from the very beginning, empowering us to push boundaries and be closer as ever of our community."

Sega in its own statement said: "Sega Europe has today announced the sale of Amplitude Studios following a management buyout from senior leaders and employees at the Parisian studio. The move will see Amplitude go back to its roots as an independent organisation and concludes the structural reforms that have been taking place in Sega’s European business.  

"The decision to part ways follows a period of close consultation between Sega Europe and Amplitude. As an independent studio once more, Amplitude will focus on its in-development projects and growing its own franchises, while Sega will continue to advance its strong and diverse stable of Japanese and Western IP. 

“Sega Europe acquired Amplitude in 2016, and together have released epic strategy titles like Endless Space 2 and Humankind, along with Endless Dungeon, the successor to 2014’s indie hit, Dungeon of the Endless.

"While Amplitude is no longer a part of the Sega family of studios, the two entities will continue to work together on the smooth transition of services and operations, ensuring minimum disruption for Amplitude employees and continuity of service for players of Amplitude games."

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463024/sega-sells-humankind-developer-amplitude-studios/

Neowiz announced it has signed a global publishing rights partnership with Warsaw, Poland-based developer Zakazane to publish the first title from the studio. The game from Zakazane is a single-player noir western RPG.

Zakazane is led by Jan Bartkowicz, Piotr Chomiak, Radosław Gwarek, and Marta Sobek, and features developers who previously worked at central European game companies, including  CD Projekt RED and 11 bit studios.

"Neowiz is committed to delivering remarkable, story-driven games that resonate with gamers worldwide, and we’re actively searching for talented developers with a passion for well-crafted narratives,” said Neowiz co-CEO Seung-Cheol Kim.

"When we first met Zakazane, we felt an immediate kinship around their passion for developing projects that profoundly captivate audiences. Their upcoming neo-western RPG will be a key addition to our portfolio and reflects our ambition to build lasting franchises across PC and consoles. Together, we will create a brand that unites quality and storytelling for gamers to cherish for years to come."

Zakazane CEO and co-founder Jan Barkowicz, "We found a great understanding of our vision with Neowiz, who got excited about our debut title the minute we showed them the demo. In conversations that followed, they never tried to steer us away from our principles but rather to make sure we stick to our guns. It’s clear both sides understand that games can become important to people on a personal level, making them both valuable works of culture and good business."

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463035/neowiz-to-publish-western-rpg-by-poland-based-developer-zakazane/

Tencent Games subsidiary LightSpeed Studios has announced Hideaki Itsuno, who recently left Capcom after 30 years working for the company, will be leading a new video game studio called LightSpeed Japan Studio.

LightSpeed Japan Studio will have two locations in Tokyo and Osaka and is focused on developing original AAA games.

"Joining LightSpeed Studios is an exciting new chapter for me," said Hideaki Itsuno. "With LightSpeed’s strong development capability and global network, I look forward to creating original AAA action game titles together with the amazing team and building aesthetic and innovative experiences for the global player community. We welcome all talented and passionate game creators from the world over to join our vision."

LightSpeed Studios president Jerry Chen added, "It is our great honor to have Hideaki Itsuno join LightSpeed Studios. The establishment of LightSpeed Japan Studio is a significant step in LightSpeed Studios’ expansion and demonstrates our commitment to bringing the best possible games to our players."

Itsuno directed entries in the Rival Schools, Power Stone, Capcom VS. SNK, Devil May Cry, and Dragon’s Dogma franchises.

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 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463041/hideaki-itsuno-to-lead-new-aaa-developer-lightspeed-japan-studio/

The largest and most ambitious Martian drone yet could carry kilograms of scientific equipment over great distances and set itself down on the Red Planet unassisted

Autonomous taxis are already operating on US streets, while Elon Musk has spent years promising a self-driving car and failing to deliver. The newly announced Tesla Cybercab is unlikely to change that

While quantum computers are still in their infancy, more and more people are training to become quantum software developers

“It’s not funny,” he told her while hosting Saturday Night Live.

Gary is up to his usual schtick with Dani. Will he or the new stews ever learn? (Don’t answer that.)

After a dismal start, the UN is hosting a "halftime summit" about its 15-year plan to meet a series of human-development targets by 2030. Delegates will try to focus on problems like extreme poverty and gender equality while watching for sparks between the representatives of Ukraine and Russia.

MWC Barcelona 2024 comes to a close today. Here’s a look at some of the announcements that the event brought to light, from industry leaders like Cisco, Google, Intel and others, spanning artificial intelligence, telecom, security and sustainability. Telecom Cisco has partnered with Telus to launch new 5G capabilities for IoT use cases across industry […]

In an interview with IT World Canada, consulting giant Deloitte highlighted the importance of an ecosystem-based approach to tackle issues around digital equity in Canada and service delivery challenges in the public sector. “Our strong view is that the people of Canada benefit when there’s effective collaboration between public and private organizations, including on critical […]

Andy delves deep into the caverns of this chassis. Worth £130?

The design is portable, modular and boasts of 5G connectivity.

The Renaissance artist Michelangelo had carried out human dissections, which may have led him to include women with breast cancer in some of his pieces

President-elect Trump announced that billionaire Elon Musk and former GOP presidential candidate Vivek Ramaswamy will lead the Department of Government Efficiency.

The appointment of a political outsider like Musk could help Trump cut regulations and rein in government bureaucracy, even if the moves are unpopular

The storm decimated a region rich with dozens of species already struggling with habitat loss and disease

President-elect Donald Trump announced he has picked Tesla CEO and X owner Elon Musk and entrepreneur and former Republican presidential candidate Vivek Ramaswamy to "lead the Department of Government Efficiency."

The post Donald Trump Selects Elon Musk, Vivek Ramaswamy to ‘Lead the Department of Government Efficiency’ appeared first on Breitbart.

With the vision of a billion developers, AI is evolving from a specialized tool to a platform that democratizes coding. As AI’s

The post Preparing for a Billion Developers appeared first on Gigaom.

A Brief History of DevOps To understand the future of DevOps, it’s worth understanding its past—which I can recall with a level

The post DevOps, LLMs, and the Software Development Singularity appeared first on Gigaom.

The billionaire businessman has spent weeks campaigning relentlessly for Donald Trump. That dedication could lead to major benefits for him and his companies.

1. Top Roles For Elon Musk, Vivek Ramaswamy In Donald Trump's Cabinet  NDTV
2. Trump’s 'Manhattan Project' of government reform: Musk and Ramaswamy to lead efficiency crusade  The Times of India
3. Donald Trump Picks Elon Musk, Vivek Ramaswamy For Cabinet: Internet Has This To Say  News18
4. A dope for DOGE (and Dogecoin): Trump taps Musk in efficiency team, crypto fans rejoice  The Economic Times
5. Video | Elon Musk In Trump's New Cabinet, UK Church Abuse Scandal, Saudi Megacity in Trouble  NDTV

The show originally aired on Doordarshan in 1997, became one of India’s most beloved superhero shows, running for over 450 episodes

It didn't take long to see what makes 16-year-old Shola Jimoh a prospect for Canada's men's soccer team. In a frenzied training session on Wednesday, he was always on the attack, always on the balls of his feet, leaving coach Jesse Marsch impressed.

Netflix recently announced more games coming to its service in the coming months, but an unannounced (as far as I’m …

Continue reading "‘SpongeBob: Bubble Pop’ Is a New Bust-a-Move-Like Coming to iOS and Android Through Tic Toc Games, Nickelodeon, and Netflix"

Following developer TRAGsoft bringing monster collecting game Coromon to mobile after it debuted on PC and Switch, we are getting …

Continue reading "Roguelite ‘Coromon: Rogue Planet’ in Development for Release on iOS, Android, Switch, and Steam in 2025"

President-elect Donald Trump announced Tesla CEO Elon Musk and Republican primary candidate Vivek Ramaswamy will lead a new agency he's calling the "Department of Government Efficiency."

Sacramento-based Zennify, a tech consulting firm for financial service companies, has acquired Terazo, a digital engineering firm based in Richmond, Virginia.

The free virtual event is hosted by SolluCIO Partners, a Seattle-based company with a presence in Hawaii.

Top Democrats on Tuesday evening filed a compromise economic development bill containing state support for the life sciences and climate technology industries, ticket sales regulations, a new live theater tax credit, educator diversity reforms and more.

‘I’m gonna come out and say it at long last,’ sketch show star said

The Tesla CEO hosted ‘SNL’ in 2021

The United States has a wide range of climate zones, from the subtropical to the arctic. On the low end of the thermometer, there are plenty of options for a deep winter chill. Here, we look at a couple different ways to determine the coldest state in the U.S. — and by both definitions, there's one winner.

Fujifilm is developing a medium-format, 102-megapixel cinema camera, the company said in a surprise announcement. Due next year, the GFX Eterna will carry a boxy, modular design reminiscent of Sony's FX6 or the new Blackmagic Pyxis and will likely be launched with a top handle, electronic viewfinder and other optional accessories.

The new camera will have a medium format GFX 102-megapixel (MP) CMOS II HS sensor, the same one used on the GFX100 II. That sensor is 43.8mm x 32.9 mm in size, or 1.7 times larger than the full-frame sensor found on the aforementioned FX or Pyxis. That will be one of the largest cinema camera sensors available, even bigger than RED's V-Raptor XL sensor.

The benefits will be extra dynamic range, potentially high resolution and a very shallow depth of field that should allow for cinematic shots when paired with the right lens. That does bring up the fact that Fujifilm currently has no GFX glass designed specifically for film production. However, the company said it's developing a 32-90mm power zoom lens (24-70mm full-frame equivalent) and will have a mount adapter for GFX to PL lenses, which are widely used in cinema. 

One other concern might be rolling shutter distortion. RED's V-Raptor XL uses a global shutter that has zero distortion, but the sensor Fujifilm will employ has a fair bit of it . In addition, the GFX100 II captures 8K with a 1.53x crop, negating many of the benefits of a medium format sensor — so, hopefully Fujifilm will resolve those issues with its cinema camera. 

Fujifilm will show off the GFX Eterna starting tomorrow at the InterBEE 2024 media exhibition in Chiba City, Japan. It's set to be released sometime in 2025, with an exact date and pricing yet to be announced.