PURPOSE

Chest pain frequently poses a diagnostic challenge for general practitioners (GPs). Utilizing risk stratification tools might help GPs to rule out acute coronary syndrome (ACS) and make appropriate referral decisions. We conducted a systematic review of studies evaluating risk stratification tools for chest pain in primary care settings, both with and without troponin assays. Our aims were to assess the performance of tools for ruling out ACS and to provide a comprehensive review of the current evidence.

The aim of this work is to test whether the use of a transparent capsule affects the residual capsule weight after inhalation as a surrogate of the inhaled delivered dose for patients with non-reversible chronic airway disease. Researchers conducted an observational cross-sectional study with patients using a single-dose dry powder inhaler. The weight of the capsule was measured with a precision microbalance before and after inhalation. Ninety-one patients were included, of whom 63 (69.2%) used a transparent capsule. Inhalation with a transparent capsule achieved a weight decrease of 30.1% vs 8.6% for devices with an opaque capsule (P <0.001). These data reinforce the need to provide patients with mechanisms that verify the correct inhalation technique.

The strength of reproductive isolation (RI) between two or more lineages during the process of speciation can vary by the ecological conditions. However, most speciation research has been limited to studying how ecologically dependent RI varies among a handful of broadly categorized environments. Very few studies consider the variability of RI and its effects on speciation at finer scales—that is, within each environment due to spatial or temporal environmental heterogeneity. Such variation in RI across time and/or space may inhibit speciation through leaky reproductive barriers or promote speciation by facilitating reinforcement. To investigate this overlooked aspect of speciation research, we conducted a literature review of existing studies of variation in RI in the field and then conducted individual-based simulations to examine how variation in hybrid fitness across time and space affects the degree of gene flow. Our simulations indicate that the presence of variation in hybrid fitness across space and time often leads to an increase in gene flow compared to scenarios where hybrid fitness remains static. This observation can be attributed to the convex relationship between the degree of gene flow and the strength of selection on hybrids. Our simulations also show that the effect of variation in RI on facilitating gene flow is most pronounced when RI, on average, is relatively low. This finding suggests that it could serve as an important mechanism to explain why the completion of speciation is often challenging. While direct empirical evidence documenting variation in extrinsic RI is limited, we contend that it is a prevalent yet underexplored phenomenon. We support this argument by proposing common scenarios in which RI is likely to exhibit variability and thus influence the process of speciation.

Surprisingly little attention has been given to the impact of selfing on speciation, even though selfing reduces gene flow between populations and affects other key population genetics parameters. Here we review recent theoretical work and compile empirical data from crossing experiments and genomic and phylogenetic studies to assess the effect of mating systems on the speciation process. In accordance with theoretical predictions, we find that accumulation of hybrid incompatibilities seems to be accelerated in selfers, but there is so far limited empirical support for a predicted bias toward underdominant loci. Phylogenetic evidence is scarce and contradictory, including studies suggesting that selfing either promotes or hampers speciation rate. Further studies are therefore required, which in addition to measures of reproductive barrier strength and selfing rate should routinely include estimates of demographic history and genetic divergence as a proxy for divergence time.

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.

Vision is initiated by capturing photons in highly specialized sensory cilia known as the photoreceptor outer segment. Because of its lipid and protein composition, the outer segments are prone to photo-oxidation, requiring photoreceptors to have robust antioxidant defenses and high metabolic synthesis rates to regenerate the outer segments every 10 days. Both processes required high levels of glucose uptake and utilization. Retinitis pigmentosa is a prevalent form of inherited retinal degeneration characterized by initial loss of low-light vision caused by the death of rod photoreceptors. In this disease, rods die as a direct effect of an inherited mutation. Following the loss of rods, cones eventually degenerate, resulting in complete blindness. The progression of vision loss in retinitis pigmentosa suggested that rod photoreceptors were necessary to maintain healthy cones. We identified a protein secreted by rods that functions to promote cone survival, and we named it rod-derived cone viability factor (RdCVF). RdCVF is encoded by an alternative splice product of the nucleoredoxin-like 1 (NXNL1) gene, and RdCVF was found to accelerate the uptake of glucose by cones. Without RdCVF, cones eventually die because of compromised glucose uptake and utilization. The NXNL1 gene also encodes for the thioredoxin RdCVFL, which reduces cysteines in photoreceptor proteins that are oxidized, providing a defense against radical oxygen species. We will review here the main steps of discovering this novel intercellular signaling currently under translation as a broad-spectrum treatment for retinitis pigmentosa.

There is conflicting evidence regarding the use of steroids in severe community-acquired pneumonia (CAP), with previous randomised controlled trials limited by small sample sizes. ESCAPe and CAPE COD are two recently published large trials on steroids in severe CAP. ESCAPe assessed the initiation of methylprednisolone within 72–96 h of hospital admission, while CAPE COD studied the use of hydrocortisone within 24 h of the development of severe CAP. ESCAPe did not show any differences in all-cause 60-day mortality or any of its secondary outcomes. CAPE COD showed that hydrocortisone improved all-cause 28-day mortality and reduced the risk of intubation or vasopressor-dependent shock. Important differences between the trials included the steroid regimens used, timing of steroid administration and baseline characteristics, with more diabetic patients included in ESCAPe. The results of CAPE COD support the initiation of hydrocortisone within 24 h of developing severe CAP, but more research is needed to evaluate long-term outcomes and optimum dosing regimens for steroids in severe CAP.

Central sleep apnoea (CSA) is characterised by recurrent episodes of airway cessation or reduction in the absence of respiratory effort. Although CSA is less common than obstructive sleep apnoea, it shares similar symptoms. CSA can be secondary to various medical conditions, high altitude and medication exposure. CSA can also emerge during obstructive sleep apnoea therapy. There are a range of treatment options and selecting the right therapy requires an understanding of the pathophysiology of CSA. This review explores the aetiology, pathophysiology and clinical management of non-hypercapnic CSA.

Tim Miller hopes Amazon's anthology series will help viewers appreciate the "blood, sweat, and tears" Firewalk Studios put into the scrapped game.

The head of one of the world's largest oil companies has had it with government flip-flopping.

New research shows that bystander CPR can substantially improve a person's odds of surviving a cardiac arrest while avoiding major brain damage, especially if given immediately.

This is not a joke, the subscription to ExpressVPN is at an unprecedented price. We'll tell you everything you need to know so you don't miss out on its Black Friday offer.

The Scotch whisky distiller has announced a major change

A national review of social work in Scotland has been launched in a bid to address ‘systemic racism’ within the sector.

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

You can purchase Steven Camley's cartoons by calling 0141 302 7000 or visiting thepicturedesk.co.uk.

The technology will deliver enhanced day-to-day and major incident response capability

Campaigners in Argyll and Bute are demanding a proposed tourist tax is rejected when it goes to a council vote next month.

The site, on the shores of a famous Scottish loch, has been acquired for a luxury lodge development

Pascal surprises everyone. New challenger Robert appears. Josh makes a triumphant return. Anna Marie leaves to go do important kitten things. Kelley proves she's the best at the Mario's. And Chris still says it's not really an Ys game.

The post RPG Cast – Episode 558: “Never Get on a Boat With Dad” appeared first on RPGamer.

We can't believe we have to say this, but this week Chris tries to understand water vapor. Anna Marie takes a week off to go date some demons. Josh frequents a sex shop to pick up some weapons. Pascal starts vaping in his Xbox. And Robert and Kelley are testing the jiggle physics of sacks in World of Warcraft.

The post RPG Cast – Episode 563: “Isn’t Compile Heart Jail Against the Geneva Convention?” appeared first on RPGamer.

Anna Marie, Chris, and Kelley are joined by special guest Ryan Radcliff! Chris swears every time E3 fails, an angel gets its wings. Anna Marie refuses to play games she's in. Kelley wants to pet the cat cream roll. And Ryan is dragging around Paws's corpse as he spins all the wheels.

The post RPG Cast – Episode 589: “Chaos Never Sleeps” appeared first on RPGamer.

Chris says the quiet things out loud, and challenges Anna Marie to play a gacha game without spending money. Kelley gets distracted by a three-headed monkey, while Josh ponders why the ten rings sounds like Jarvis.

The post RPG Cast – Episode 600: “It’s a HIGH Seven” appeared first on RPGamer.

Kelley puts a price on a good nap. Josh complains about Pokémon (someone has to). And Chris's true Dark Souls adventure begins with his dryer.

The post RPG Cast – Episode 621: “My Elden Ring Fever Dreams” appeared first on RPGamer.

Kelley is creeped out by grown men in diapers. Josh can't name a kaiju that isn't Godzilla or Mothra. And Chris gets an Elden Pacifier since he's never happy.

The post RPG Cast – Episode 647: “Stellar Eve for When You Don’t Feel Fresh” appeared first on RPGamer.

Chris launches his new brand, Elsa coffee. Kelley's Pokémon demand she finds a caramel apple and a teacup. Ryan apparently got left in Seattle and is still at PAX West.

The post RPG Cast – Episode 693: “The Brew Never Bothered Me Anyways” appeared first on RPGamer.

Kelley gets bored and cleans her bathroom. Memories of the Virtual Boy make Josh's eyes hurt. Robert can't stop singing about Albuquerque. Chris, meanwhile, decides to make his own farming sim with coffee shops and old people.

The post RPG Cast – Episode 719: “Good morning, everybody. Hairball!” appeared first on RPGamer.

Ryan slip 'n slides his health away. Robert lives on the side of danger and poor choices in video games. Meanwhile, Chris makes his own bathtub Geralt.

The post RPG Cast – Episode 725: “Not Every Idea in the Factory Is a Good One” appeared first on RPGamer.

Kelley tells us about her new clawed abomination: the cat-raptor. Chris tries to figure out who cross Ross is and why he's so angry. Robert is "surprised" to find horse girls show up on the sheet. Josh is definitely here for the icons.

The post RPG Cast – Episode 730: “Never Played a JRPG” appeared first on RPGamer.

Devlin takes us inside her new installation, which features as part of The Vinyl Factory: Reverb at 180 Studios.

The post Es Devlin: Screenshare appeared first on Fact Magazine.

Reverb features new works by Es Devlin and Theaster Gates, plus Devon Turnbull's Listening Room.

The post The Vinyl Factory: Reverb exhibition extended until 22 December appeared first on Fact Magazine.

Up to 700 international competitors and crew will flock to Benalla as the event returns to Australia after 30 years.

A 10-year analysis of air accidents reveals good news for most passengers but worrying trends in training and drones.

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/

Nintendo has announced its Black Friday 2024 deals. 

Dozens of games will be discounted including The Legend of Zelda: Tears of the Kingdom, Super Mario Maker 2, Animal Crossing: New Horizons, Pikmin 4, Nintendo Switch Sports, Kirby and the Forgotten Land, Super Mario Odyssey, Pikmin 1 + 2, and more.

The Neon Red and Neon Blue Joy-Con controllers and the Nintendo Switch Pro Controller will be discounted by $20, while the Nintendo Switch Carrying Case & Screen Protector - The Legend of Zelda: Tears of the Kingdom Edition will be discounted by $10.

The Nintendo Switch: Mario Kart 8 Deluxe Bundle will once again return for $299.99, while the new Nintendo Switch – OLED Model: Mario Kart 8 Deluxe Bundle will be available for $349.99. Both bundles include a digital download of Mario Kart 8 Deluxe and a 12-month Nintendo Switch Online Individual Membership.

The Nintendo Switch Lite: Hyrule Edition with Bonus Nintendo Switch Online + Expansion Pack will be available for $209.99. The bundle includes a 12-month Nintendo Switch Online + Expansion Pack Individual Membership.

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/463045/nintendos-black-friday-2024-deals-revealed/

It doesn’t matter how long a play is: sometimes 75 minutes can feel like 3 hours if the play is bad, while a three-hour play may first elicit an inner groan, then flow pleasurably by if the writing and performances are in well-oiled tandem.

Kenneth Lonergan’s Hold on to Me Darling (Lucille Lortel Theatre, to Dec. 22) belongs, mostly, to the latter category: it is long, and it feels long, but that’s OK; not gold-standard wow, but far more than pleasant. This is down to Lonergan’s engaging writing and a collection of differently distinctive, carefully drawn performances, led by Adam Driver as a famous country star called Strings (real name Clarence), wondering if he could/should give up all the trappings of fame for a simpler life after his mother’s death.

It is an off-Broadway treat to see Driver, most recently seen on the big screen as the star of Francis Ford Coppola’s polarizing epic Megalopolis, here bestriding—he is so tall, he is really bestriding—the compact Lucille Lortel stage. Theater fans last saw him on Broadway in Burn This, for which he was nominated for the Tony Award for Best Actor in a Play. He is renowned for playing powder-keg personas. With characters like Adam in Girls, Charlie in Marriage Story, and Pale in Burn This, the question, the bubbling menace, was when will Adam Driver go off? Those characters memorably combusted—thrashing, shouting, snarling and occupying spaces that could barely contain them—and Driver made it so that you recoiled from their crackling fury.

Read more at The Daily Beast.

Relatives of Lyle and Erik Menendez spoke in an interview Wednesday about their long-running fears that the brothers had been abused for years before they killed their parents.

After a press conference in which they’d called for the imprisoned siblings’ freedom, the family members told Chris Cuomo on NewsNation about how their suspicions only deepened as time passed.

“Over the years we really did know that there was abuse at gut-level. But as time goes on and we all talked to each other more and more, it validates the fears and the gut-level reactions that we had,” the brothers’ cousin Karen VanderMolen-Copley told Cuomo. “That solidified the knowledge that the sexual abuse actually did occur, because that’s not something you want to believe, and then once you talk to each other it becomes more and more obvious.”

Read more at The Daily Beast.

Stationeers and Icarus developers RocketWerkz are making a spiritual successor to beloved space sim Kerbal Space Program, which is currently titled "Kitten Space Agency" in a flagrant display of adherence to wholesome internet trends. It's based on an actual Kerbal Space Program 2 pitch the studio threw at Take-Two subsidiary Private Division back in the day. RocketWerkz CEO and original DayZ creator Dean Hall has hired several former KSP and KSP2 developers to work on the game, and is describing it on social media as a "KSP killer".

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People have asked me, a Call Of Duty liker, "How's the new COD?" - such is the mass appeal of Call Of Duty that even a lot of my non-industry pals are invested in whether Black Ops 6's shooty really does bang. And every single time my brain clunks into gear and I turn inwards, where I struggle to come up with anything meaningful to say. So much so that a fog develops and out of the fog emerges a figure - it's me. I'm holding an M4A1 with an extended barrel and a vertical foregrip. My brain and body perform a pincer movement of physical response: 1) I shrug 2) I say, "It's like Call Of Duty".

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Like a plague doctor delicately administering another handful of leeches, Ice Pick Lodge have shared a bit more about the recently announced Pathologic 3, explaining how their plans for the cult epidemic-battling series have progressed since the release of Pathologic 2.

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Typing Of The Dead released in arcades 25 years ago remains a masterpiece - funny, absurd, tense, and novel. I am keen on any game that aims to follow in its footsteps, and there are a few. The latest is Blood Typers, a horror game where you tippity-tap on your keyboard to fight montsters in a spooky mansion, but this isn't a rail shooter, so you'll be typing to explore and navigate, too.

It's now got a release of February 2025, and there's a demo you can play now.

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I was excited for Slitterhead, an action adventure game by Bokeh Studio, a studio founded by none other than your boy Keiichiro Toyama: the creator of Silent Hill, Gravity Rush, and the Siren series. And within that first hour, Slitterhead's body-possessing and Hong Kong-inspired streets had me thinking, "Is this it, the sleeper hit of 2024?!"

No, sadly not. It's no doubt built a compelling universe filled with brain-sucking aliens that masquerade as humans, and it attempts plenty else besides: bouncing between bodies as you stealth around dingy apartment blocks, fighting with blood katanas, and gorging on pools of red plasma to refuel skills, many of which require more body-flitting. Thing is, they are ultimately just attempts, attempts that fall victim to an emptiness and jitteriness that quickly reveals Slitterhead's true, irritating form.

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I didn't sleep last night for entirely self-inflicted reasons and my brain feels like that one accursed hoover bag you refuse to empty, because there is no way of doing so that won't turn the neighbourhood into Silent Hill. I need to avoid any complicated write-ups, or my brain will detonate similarly and paint north London grey.

Ah, a minigolf game! I think I can just about hack the concept of minigolf, on this most desperate of Mondays. It is golf but mini. Bonzai golf. Digestible! Intuitive! Why, I've managed to write 100 words without even looking at the Steam page. Let's do so now. Wait a minute, this isn't minigolf. It's Mini Mini Golf Golf. What is Mini Mini Golf Golf? "Destabilize the present and plunge into a neon psychohistory of a bizarre entity in distress," the Steam page explains. "This is not a game about minigolf." It is too late to flee.

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When nightmarish sci-fi extraction shooter The Forever Winter launched into early access in September it was somewhat messy. Bugs and maddening enemy spawns diminished the tension of being a fleshy human scavenger in a mech battlefield. But one feature annoyed some players much more - fresh water. See, you need to keep your headquarters stocked with water, as it gets steadily used by your settlement's inhabitants. The catch being that this water diminishes even while you're not playing the game. If it runs out completely, then everything you've collected gets wiped. The developers have listened to complaints about this most Farmville of mechanics, and they've answered in an interesting way. Water thieves! Now, on top of the usual downward trickle, burglars will come to steal your H2O as well.

It's not as bad as it sounds.

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It’s tempting to frame Straftat as a throwback to an older, better time for the multiplayer FPS, when the lingo was coded in frags and gibs and sucking it down, when satisfaction was drawn entirely from performance rather than some convoluted, artificial system of progression. Not only would this be inaccurate, but it would also do a disservice to what Straftat truly is, namely a wild overcorrection in response to the direction of modern multiplayer gunfests, one that careens straight through retro stations to arrive somewhere new and exciting.

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