Sleep is important for survival, and the need for sleep is conserved across species. In the past two decades, the fruit fly Drosophila melanogaster has emerged as a promising system in which to study the genetic, neural, and physiological bases of sleep. Through significant advances in our understanding of the regulation of sleep in flies, the field is poised to address several open questions about sleep, such as how the need for sleep is encoded, how molecular regulators of sleep are situated within brain networks, and what the functions of sleep are. Here, we describe key findings, open questions, and commonly used methods that have been used to inform existing theories and develop new ways of thinking about the function, regulation, and adaptability of sleep behavior.

BackgroundDuring the COVID-19 pandemic, global trends of reduced healthcare-seeking behaviour were observed. This raises concerns about the consequences of healthcare avoidance for population health.AimTo determine the association between healthcare avoidance during the early stages of the COVID-19 pandemic and all-cause mortality.Design and settingThis was a 32-month follow-up within the population-based Rotterdam Study, after sending a COVID-19 questionnaire at the onset of the pandemic in April 2020 to all communty dwelling participants (n = 6241/8732, response rate 71.5%).MethodCox proportional hazards models assessed the risk of all-cause mortality among respondents who avoided health care because of the COVID-19 pandemic. Mortality status was collected through municipality registries and medical records.ResultsOf 5656 respondents, one-fifth avoided health care because of the COVID-19 pandemic (n = 1143). Compared with non-avoiders, those who avoided health care more often reported symptoms of depression (n = 357, 31.2% versus n = 554, 12.3%) and anxiety (n = 340, 29.7% versus n = 549, 12.2%), and more often rated their health as poor to fair (n = 336, 29.4% versus n = 457, 10.1%) . Those who avoided health care had an increased adjusted risk of all-cause mortality (hazard ratio [HR] 1.30, 95% confidence interval [CI] = 1.01 to 1.67), which remained nearly identical after adjustment for history of any non-communicable disease (HR 1.20, 95% CI = 0.93 to 1.54). However, this association attenuated after additional adjustment for mental and physical self-perceived health factors (HR 0.93, 95% CI = 0.71 to 1.20).ConclusionThis study found an increased risk of all-cause mortality among individuals who avoided health care during COVID-19. These individuals were characterised by poor mental and physical self-perceived health. Therefore, interventions should be targeted to these vulnerable individuals to safeguard their access to primary and specialist care to limit health disparities, inside and beyond healthcare crises.

BackgroundOrlistat is recommended as an adjunct to diet and exercise for weight loss in the treatment of type 2 diabetes mellitus (T2DM).AimTo explore associations between patient characteristics and orlistat prescribing, and to determine associations of orlistat with weight loss in T2DM and prediabetes.Design and settingCohort study using anonymised health records from a UK database of general practice.MethodThe UK Clinical Practice Research Datalink (CPRD) Aurum database was searched to compile a cohort of patients aged ≥18 years, first diagnosed with T2DM or prediabetes in 2016 or 2017. Once the data had been collated, multivariable logistic regression models were used to determine associations with starting orlistat and stopping it early (<12 weeks of prescriptions) and orlistat’s associations with weight loss in those who had not been prescribed second-line antidiabetic medications.ResultsOut of 100 552 patients with incident T2DM or prediabetes, 655 (0.8%) patients with T2DM and 128 (0.7%) patients with prediabetes were prescribed orlistat. Younger people, females, those in areas of deprivation, current smokers, those coprescribed metformin, and those recorded as having hypertension were statistically significantly more likely to be prescribed orlistat; higher baseline glycated haemoglobin levels were associated with early stopping. In comparison with patients not on orlistat, those who continued using it for ≥12 weeks were more likely to lose ≥5% weight (adjusted odds ratio [AOR] 1.69, 95% confidence interval [CI] = 1.07 to 2.67) but those who stopped orlistat early were less likely to lose ≥5% weight (AOR 0.56, 95% CI = 0.29 to 1.09).ConclusionOrlistat was significantly associated with weight loss in patients with T2DM and prediabetes when taken for at least 12 weeks; however, it was infrequently prescribed and often taken for <12 weeks. Orlistat may be a useful adjunct to lifestyle modifications for patients with T2DM and prediabetes, but barriers to continued use means it may not be effective for everyone in managing weight loss.

BackgroundThere has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking.AimTo explore GP and pharmacist views and experiences of in-person, interprofessional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice.Design and settingA mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands, between February 2021 and September 2023.MethodAudio-recordings of IPCDs between GPs and pharmacists, along with individual semi-structured interviews to explore their reflections on these discussions, were used. All recordings were transcribed verbatim and analysed thematically.ResultsA total of 14 practices took part in the process evaluation from February 2022 to September 2023; 17 IPCD meetings were audio-recorded, discussing 30 patients (range 1–6 patients per meeting). In all, six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits, including: strengthening their working relationship; gaining in confidence to manage more complex patients; and learning from each other. It was often challenging, however, to find time for the IPCDs.ConclusionThe model of IPCD used in this study provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for interprofessional liaison and collaboration, and structured interventions may facilitate improved patient care.

Comprehensive maps of neuronal connectivity provide a foundation for understanding the structure of neural circuits. In a circuit, neurons are diverse in morphology, electrophysiology, gene expression, activity, and other neuronal properties. Thus, constructing a comprehensive connectivity map requires associating various properties of neurons, including their connectivity, at cellular resolution. A commonly used approach is to use the gene expression profiles as an anchor to which all other neuronal properties are associated. Recent advances in genomics and anatomical techniques dramatically improved the ability to determine and associate the long-range projections of neurons with their gene expression profiles. These studies revealed unprecedented details of the gene–projection relationship, but also highlighted conceptual challenges in understanding this relationship. In this article, I delve into the findings and the challenges revealed by recent studies using state-of-the-art neuroanatomical and transcriptomic techniques. Building upon these insights, I propose an approach that focuses on understanding the gene–projection relationship through basic features in gene expression profiles and projections, respectively, that associate with underlying cellular processes. I then discuss how the developmental trajectories of projections and gene expression profiles create additional challenges and necessitate interrogating the gene–projection relationship across time. Finally, I explore complementary strategies that, together, can provide a comprehensive view of the gene–projection relationship.

Approximately 8.5%–16.2% of childhood cancers are associated with a pathogenic/likely pathogenic germline variant—a prevalence that is likely to rise with improvements in phenotype recognition, sequencing, and variant validation. One highly informative, classical hereditary cancer predisposition syndrome is Li–Fraumeni syndrome (LFS), associated with germline variants in the TP53 tumor suppressor gene, and a >90% cumulative lifetime cancer risk. In seeking to improve outcomes for young LFS patients, we must improve the specificity and sensitivity of existing cancer surveillance programs and explore how to complement early detection strategies with pharmacology-based risk-reduction interventions. Here, we describe novel precision screening technologies and clinical strategies for cancer risk reduction. In particular, we summarize the biomarkers for early diagnosis and risk stratification of LFS patients from birth, noninvasive and machine learning–based cancer screening, and drugs that have shown the potential to be repurposed for cancer prevention.

The broad application of noninvasive imaging has transformed preclinical cancer research, providing a powerful means to measure dynamic processes in living animals. While imaging technologies are routinely used to monitor tumor growth in model systems, their greatest potential lies in their ability to answer fundamental biological questions. Here we present the broad range of potential imaging applications according to the needs of a cancer biologist with a focus on some of the common biological processes that can be used to visualize and measure. Topics include imaging metastasis; biophysical properties such as perfusion, diffusion, oxygenation, and stiffness; imaging the immune system and tumor microenvironment; and imaging tumor metabolism. We also discuss the general ability of each approach and the level of training needed to both acquire and analyze images. The overall goal is to provide a practical guide for cancer biologists interested in answering biological questions with preclinical imaging technologies.

Background

In an evolving landscape of practices and policies, reviewing and incorporating the latest scientific evidence is necessary to ensure optimal clinical management for people with opioid use disorder. We provide a synopsis of the 2024 update of the 2018 National Guideline for the Clinical Management of Opioid Use Disorder, from the Canadian Research Initiative in Substance Matters.

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.

Missing or inaccessible lung function measurements, gathered over time, have the potential to stagnate or impair clinical care decisions being made. This jeopardises patient safety and often contributes to excessive resource utilisation. Data integration is fundamental to clinical decision-making and entails amalgamating lung function data from multiple sources in a user-friendly format. Despite this, current systems for recording lung function data are suboptimal, with copious gaps in the clinical picture arising from missing or inaccessible lung function measurements. This article discusses the importance of data integration for lung function, with a call to action for key stakeholders involved in the performance, management and interpretation of such tests.

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.

Chronic pulmonary aspergillosis has a range of manifestations from indolent nodules to semi-invasive infection. Patients may be asymptomatic or have chronic symptoms such as cough and weight loss or present with life-threatening haemoptysis. The physician can choose from a range of available therapies including medical therapy with antifungals, minimally invasive therapy with intracavitary antifungal therapy and surgery involving open thoracotomy or video-assisted thoracoscopic surgery. The patients with the most severe forms of pulmonary infection may not be surgical candidates due to their underlying pulmonary condition. The management of haemoptysis can include tranexamic acid, bronchial artery embolisation, antifungals or surgery. There are few controlled studies to inform clinicians managing complex cases, so a multidisciplinary approach may be helpful.

For many severe lung diseases, non-invasive biomarkers from imaging could improve early detection of lung injury or disease onset, establish a diagnosis, or help follow-up disease progression and treatment strategies. Imaging of the thorax and lung is challenging due to its size, respiration movement, transferred cardiac pulsation, vast density range and gravitation sensitivity. However, there is extensive ongoing research in this fast-evolving field. Recent improvements in spatial imaging have allowed us to study the three-dimensional structure of the lung, providing both spatial architecture and transcriptomic information at single-cell resolution. This fast progression, however, comes with several challenges, including significant image file storage and network capacity issues, increased costs, data processing and analysis, the role of artificial intelligence and machine learning, and mechanisms to combine several modalities. In this review, we provide an overview of advances and current issues in the field of spatial lung imaging.

A nudibranch from the midnight zone has fingers on its tail, collects food with a hood, and glows.

Jade Ho explains what is possible for university students when they are given opportunities to learn about –and get involved with– social justice and labour issues in their own communities.

The post Students can be agents of change: Talking about activism in universities with Jade Ho appeared first on rabble.ca.

So far, the Israeli leadership seems unmoved by U.S. President Biden’s quiet suggestions for a pause in hostilities in Gaza.

The post Saving Palestinian lives will save Israeli lives appeared first on rabble.ca.

That anyone could witness or directly experience the increasingly frequent and intense heat domes, droughts, floods and record high temperatures and claim we don’t have a problem is insanity!

The post Don’t buy-in to climate science denialism appeared first on rabble.ca.

Watch President Donald Trump and the Greek prime minister’s joint news conference in the player above.

WASHINGTON — President Donald Trump says the U.S. stands with Greece as they recover from their economic crisis. He is speaking with Prime Minister Alexis Tsipras at the White House in a joint news conference.

The U.S. president says the two leaders have discussed defense, energy, commerce and trade.

Trump is praising Greece for its defense spending under NATO and is noting a potential sale to Greece to upgrade its F-16 aircraft, which he says would be worth up to $2.4 billion and generate thousands of U.S. jobs.

Tsipras says his country has made economic strides and is “leaving behind the economic model that led to the crisis.” He says Greece’s relationship with the U.S. is “more important than ever.”

The post WATCH: Trump and Greek prime minister hold joint news conference appeared first on PBS NewsHour.

ROLLING UPDATES: Australia waited eight days for Malcolm Turnbull to claim election victory and now the PM and Bill Shorten have united in their push for online voting.

The Herald understands that former first minister Nicola Sturgeon has made no decisions on whether she will stand for election in 2026.

Human rights campaigners are calling on SNP ministers to do all they can to “mitigate” Prevent, the UK Government's controversial anti-terror strategy.

3D Scotland are an innovative, Glasgow-based company who specialise in the design and manufacture of unique chess sets. Their sets have proved extremely popular as Christmas gifts, graduation gifts, fathers’ day gifts and everything in between.

A Scottish distillery has hailed the opening of a new 'dining destination' amid an expansion push.

Health Secretary Neil Gray will address concerns around his use of a ministerial car to attend football games at Hampden.

A film about a campaign to ban greyhound racing in Scotland has won an animal welfare award at a ceremony in London.

Shetland Library and the National Library of Scotland have been praised for "providing optimist for the future."

On this week's show, Chris is going through his failed Kickstarters; Anna Marie is off banging a ghost, which was fun; Kelley is collecting wheels of cheese in Skyrim; Josh is lookin' fly in his Yakuza shoes; and Alex wonders why he didn't just skip this week and write more E3 stories.

The post RPG Cast – Episode 588: “Nintendo Leaked Themselves” appeared first on RPGamer.

Chris snuggles his Teddy body pillow. Kelley signs up for rare Pokémon. Josh sacrifices children (what?!). Meanwhile Anna Marie is off celebrating her birthday by spreading the hork.

The post RPG Cast – Episode 593: “Banished to the Prince Dimension” appeared first on RPGamer.

Josh has a decently sized angry cat burrito. Kelley butters the wolf in Rune Factory. Chris wonders if people have phones. But we all agree the new trend in game graphics should be soulshading.

The post RPG Cast – Episode 628: “Air Conditioning for Your Feet” appeared first on RPGamer.

Kelley is the master of the hunting horn. Chris is too old to play Solid Snake. Robert only steals from old people. And Ryan stuffs all the kids into the cannon.

The post RPG Cast – Episode 667: “Nintendo Has an Animal Crossing Jail?” appeared first on RPGamer.

Phil laughs at stupid Diablo IV hardcore deaths. Kelley goes for the all cannon ending. Jason is depressed and wants to play Dirge of Cerberus. Ryan doesn't have enough turn based RPGs in his life. Also, happy 100th birthday to Paw's grandfather!

The post RPG Cast – Episode 680: “Warning: Spicy Sausage” appeared first on RPGamer.

Robert finds out what Godzilla sushi tastes like. Josh pimps his Segway. Phil has a pictomancer at home. The awards all Chris's fault, because he didn't vote. Also, PoE is to Chris, as CoH is to Phil.

The post RPG Cast – Episode 710: “Xenoblade Chronicles X Doesn’t Love You Back” 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.

Chris realizes WoW is the new Diablo. Phil bakes a potato into two. Kelley becomes a cat in a frog suit. And we're dressing beds with old t-shirts.

The post RPG Cast – Episode 726: “Princes of the Mew-niverse” appeared first on RPGamer.

Chris goes and touches grass in WoW. Matt brings about the apocalypse through dating. Phil is striking from Persona 5. Now let me tell you all the uses for earwax...

The post RPG Cast – Episode 738: “Golf Innit” appeared first on RPGamer.

Chris's lamp wasn't lamping. Kelley complains about alchemy themed high heels. Phil just shoots arrows.

The post RPG Cast – Episode 739: “It’s a Cat Union” appeared first on RPGamer.

Paul Cousins presents a multi-channel installation in which the listener becomes the performer.

The post Patch Notes: Atomised Listening appeared first on Fact Magazine.

Sony Interactive Entertainment in its financial results announced it has shipped 65.5 million PlayStation 5 consoles as of September 30, 2024.

With 65.5 million PlayStation 5 consoles shipped through the end of June that means 3.8 million units were shipped from July to September. This is down 1.1 million (-22.45%) from the same quarter in 2023 when 4.9 million units were shipped.

For reference, the PlayStation 4 had shipped 4.2 million units in the same quarter for a lifetime total of 67.7 million units shipped as of September 30, 2017. This puts the PS5 behind shipped PS4 units by 2.2 million units.

There were a total of 77.7 million games sold on the PlayStation 5 and PlayStation 4 for the quarter. This is up 10.1 million from 67.6 million during the same period a year earlier. Digital sales accounted for 70 percent of software sales.

There were 5.3 million first-party games sold across the PlayStation 5 and PlayStation 4. This is up 0.6 million from 4.7 million a year ago.

There were 116 million monthly active users on the PlayStation Network, an increase of nine million from 107 million a year ago. Sony did not disclose the number of PlayStation Plus subscribers. It was at 47.4 million at the end of March 2023.

Sony's Game & Network Services Segment for the quarter ending September 30, 2024, reported revenue increased 244.5 billion yen ($1.60 billion) year-over-year to 2,973.4 billion yen ($19.46 billion), while operating income increased 142.0 billion yen ($0.93 billion) to 389.3 billion yen ($2.55 billion).

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/463014/ps5-ships-655-million-units-as-of-september-2024/

Publisher Sony Interactive Entertainment and developer Team Asobi in Sony's latest earnings report have announced Astro Bot has sold over 1.5 million units as of November 3, 2024.

Astro Bot released for the PlayStation 5 on September 6.

Our own Lee Mehr gave the game an 8.5 out of 10 in his review and said "As an ode to PlayStation, Astro Bot succeeds at meaningfully infusing its history; as an all-ages theme park, it succeeds by infusing each location with an overwhelming sense of joyous wonder most often felt in Nintendo platformers, but with a level of technical sophistication not yet seen from its hardware."

Read details on the game below:

Join ASTRO on a supersized space adventure.

When the PlayStation 5 mothership is attacked by ASTRO’s long-standing galactic nemesis, scrambling its wires and scattering the crew throughout space, only ASTRO can make things right! Setting off on his biggest mission yet, he needs your help to rescue the stranded crew and rebuild the mothership.

Make the most of ASTRO’s new power-ups, handcrafted to level up your immersion: from springy punches and rockets all the way to a giant sponge!

Buckle up for some epic PlayStation camaraderie, join forces with your favorite PlayStation icons and show the universe that small is mighty in this fresh new ASTRO adventure, exclusive to PlayStation 5 consoles!

Features:

• Embark on a galactic quest and explore more than 50 planets in search of ASTRO’s lost crew.
• Dash, swing, and rocket-punch your way through this journey, with all-new power-ups.
• Feel the world come to life via your DualSense wireless controller.
• Team up with iconic PlayStation heroes to save the galaxy!

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/463015/astro-bot-sales-top-15-million-units/

Nintendo and The Pokémon Company in September filed a patent infringement lawsuit against Palworld developer Pocketpair. 

At the time Nintendo did not share which patents Palworld infringed on, however, Pocketpair has now revealed what patents Nintendo are claiming were infringed on.

"As announced on September 19, 2024, The Pokémon Company and Nintendo Co Ltd (hereinafter referred to as the Plaintiffs) have filed a patent infringement lawsuit against us," said Pocketpair. "We have received inquiries from various media outlets regarding the status of the lawsuit, and we would like to report the details and current status of this case as follows.

"The Plaintiffs claim that Palworld, released by us on January 19, 2024, infringes upon the following three patents held by the Plaintiffs, and are seeking an injunction against the game and compensation for a portion of the damages incurred between the date of registration of the patents and the date of filing of this lawsuit."

Nintendo and The Pokémon Company are each seeking an injunction and damages of five million yen plus late payment damages.

Pocketpair added, "We will continue to assert our position in this case through future legal proceedings. Please note that we will refrain from responding individually to inquiries regarding this case. If any matters arise that require public notice, we will announce them on our website, etc."

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/463022/nintendo-and-the-pokemon-company-seeking-injunction-and-damages-from-pocketpair/