BACKGROUND AND PURPOSE:

There has been a distinction made in the 2001 Canadian C-Spine Rule regarding patients 65 and older and younger than 65 years of age as far as indications for cervical spine CT scanning. We sought to determine if there are differences in the symptoms, mechanisms of injury, fracture locations, and types that are still relevant in 2024.

TP53 plays a critical role as a tumor suppressor by controlling cell cycle progression, DNA repair, and apoptosis. Post-translational modifications such as acetylation of specific lysine residues in the DNA binding and carboxy-terminus regulatory domains modulate its tumor suppressor activities. In this study, we addressed the functional consequences of the germline TP53 p.K164E (NM_000546.5: c.490A>G) variant identified in a patient with early-onset breast cancer and a significant family history of cancer. K164 is a conserved residue located in the L2 loop of the p53 DNA binding domain that is post-translationally modified by acetylation. In silico, in vitro, and in vivo analyses demonstrated that the glutamate substitution at K164 marginally destabilizes the p53 protein structure but significantly impairs sequence-specific DNA binding, transactivation, and tumor cell growth inhibition. Although p.K164E is currently considered a variant of unknown significance by different clinical genetic testing laboratories, the clinical and laboratory-based findings presented here provide strong evidence to reclassify TP53 p.K164E as a likely pathogenic variant.

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated and what biological functions it plays. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using beam break counts from Drosophila activity monitors (DAMs). The number of laboratories worldwide studying sleep in Drosophila has grown from only a few 20 years ago to hundreds today. The utility of these studies is limited by the quality of the metrics that can be extracted from the data. Many software options exist to help analyze DAM data; however, these are often expensive or have significant limitations. Therefore, we describe here a method for analyzing DAM-based data using the sleep and circadian analysis MATLAB program (SCAMP). This user-friendly software has an advantage of combining several analyses of both sleep and circadian rhythms in one package and produces graphical outputs as well as spreadsheets of the outputs for further statistical analysis. The version of SCAMP described here is also the first published software package that can analyze data from multibeam DAM5Ms, enabling determination of positional preference over time.

The positional preference of an animal can be very informative regarding the choices it makes about how to interact with its environment. The fruit fly Drosophila melanogaster has been used as a robust system for examining neurobiological mechanisms underlying behavior. Fruit fly positional preference can be gathered from TriKinetics Drosophila activity monitors (DAMs), which contain four infrared beams, allowing for tracking the position of individual flies along the length of a tube. Here, we describe a method for using DAM5Ms to examine food preference. Specifically, we show an example in which circadian changes in food preference are compared between different Drosophila species. More information about the evolution of behavior can be gathered by measuring feeding preference relative to time of day. Noni, fruit from Morinda citrifolia, contains octanoic acid, a chemical toxic to many species of Drosophila. D. melanogaster and D. simulans, both food generalists, show high sensitivity to octanoic acid, whereas D. sechellia, a specialist, can tolerate high concentrations. When two different food substrates are provided at each end of a tube, food preference can be inferred at various times of the day, using the sleep and circadian analysis MATLAB program (SCAMP) to extract and analyze positional data from DAM5Ms. Data gathered from these analyses can be used to compare avoidance or attraction to nutrients, tastants, or odors between species and genotypes or after specific different treatments. Additionally, such data can be examined as a function of time of day.

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.

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.

PURPOSE

We undertook a trial to test the efficacy of a technology-assisted health coaching intervention for weight management, called Goals for Eating and Moving (GEM), within primary care.

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.

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.

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.

Palliative care pertains to the holistic multidimensional concept of "patient-centred" care. It is an interprofessional specialty, primarily aiming to improve quality of care for cancer patients and their families, from the time of diagnosis of malignant disease, over the continuum of cancer care, and extending after the patient's death to the period of bereavement to support the patient's family. There are various complex and frequently unmet needs of lung cancer patients and their families/caregivers, not only physical but also psychological, social, spiritual and cultural. Systematic monitoring of patients’ symptoms using validated questionnaires and patient-reported outcomes (PROs), on a regular basis, is highly encouraged and recommended in recent guidelines on the role of PRO measures in the continuum of cancer clinical care. It improves patient–physician communication, physician awareness of symptoms, symptom control, patient satisfaction, health-related quality of life and cost-effectiveness. This implies that all treating physicians should improve their skills in communication with lung cancer patients/relatives and become more familiar with this multidimensional assessment, repeatedly screening patients for palliative care needs. Therefore, they should receive education and training to develop palliative care knowledge, skills and attitudes. This review is dedicated to lung cancer palliative care essentials that should be within the competences of treating physicians, i.e. pneumologists/thoracic oncologists.

"Kate Forbes still has her own leadership ambitions, setting them aside this Spring in the interest of party unity to accept Mr Swinney's offer to become Deputy First Minister."

Kelley graduates from Canada. Josh discovers Tactics Advance is an isekai. Meanwhile Chris calculates the skill check for suplexing a train.

The post RPG Cast – Episode 619: “That One Time I Got Reincarnated as a Canadian Yankee in King Arthur’s Court” appeared first on RPGamer.

It's Extra Life Weekend baby! Phil puts Chris in a closet while Anna states that it's not because she's Canadian, it's because she's a cheap bitch. Meanwhile, the treasure chest looks back at Kelley with an expression that says "...Bruh."

The post RPGCast – Episode 654: “You Canadian” appeared first on RPGamer.

Chris is hunting bears, because of course that's what you do. Kelley hangs out with Chadley and the massively annoying individual. Robert is all about that exquisite fraisier cake.

The post RPG Cast – Episode 716: “Canadian Telephone Game” appeared first on RPGamer.

EA Sports FC 25 has debuted in first place on the Canadian charts for September 2024, according to data from Circana (formerly The NPD Group) reported by the Entertainment Software Association of Canada (ESA).

There were four other new releases in the top 10 with NHL 25 debuting in second place, The Legend of Zelda: Echoes of Wisdom in third place, Astro Bot in fourth place, and NBA 2K25 in 10th place.

Star Wars: Outlaws is in fifth place, Hogwarts Legacy is in sixth place, and Madden NFL 25 is in seventh place. God of War: Ragnarök is in eighth place following the release of the PC version and Elden Ring is in ninth place.

Top 10 best-selling games in Canada:

1. EA Sports FC 25 - NEW
2. NHL 25 - NEW
3. The Legend of Zelda: Echoes of Wisdom* - NEW
4. Astro Bot - NEW
5. Star Wars: Outlaws
6. Hogwarts Legacy
7. Madden NFL 25
8. God of War: Ragnarök
9. Elden Ring
10. NBA 2K25* - NEW

*Digital sales not included

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/463027/ea-sports-fc-25-debuts-in-1st-on-the-canadian-charts/

ublisher Bethesda Softworks and developer MachineGames have released a gameplay deep dive video for Indiana Jones and the Great Circle that is nearly 15 minutes in length.

"From locations and puzzles to gear and combat, MachineGames Audio Director, Pete Ward, takes us on a whirlwind journey through the world of The Great Circle," reads the description to the video. "Get ready for launch with this look at Indy’s grand adventure."

View the gameplay deep dive below:

Indiana Jones and the Great Circle will launch for the Xbox Series X|S, PC via Steam and Microsoft Store, and Xbox Game Pass on December 9.

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/463033/indiana-jones-and-the-great-circle-gets-gameplay-deep-dive/

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.

Read more

"A lot of puzzle games can leave you staring at the same static screen for ages, but here, I’m always pushing you forward," says Mark Brown of Game Maker’s Toolkit. For a decade now, Brown has been releasing accessible deep dives on game design for his popular YouTube channel, like "How Game Designers Protect Players From Themselves" and "The Two Types of Random in Game Design." This week, he’s releasing his own for the first time.

Read more

Astronomers have been spotting strange banana-shaped galaxies and the evidence seems to indicate that filaments of dark matter make them take this shape

A radio signal detected in 1977, sometimes claimed as evidence for aliens, may have been caused by a laser-like beam of microwave radiation

An artificial intelligence model that can identify the calls of eight whale species is helping researchers track the elusive whale behind a perplexing sound in the Pacific

HARRY KANE is now the clear favourite to win the World Cup Golden Boot after his hat-trick against Panama..

The company behind Pornhub and other popular pornographic sites broke Canadian privacy law by allowing intimate images to be shared on its websites without the direct knowledge or consent of everyone depicted, the federal privacy commissioner has ruled. The Office of the Privacy Commissioner’s (OPC) investigation into Aylo (formerly MindGeek), one of the world’s largest […]

How private is your internet address? Very, says the Supreme Court of Canada. Police can’t just walk into a company and demand a suspect’s IP address by saying a Canadian resident doesn’t have an expectation of privacy of that information, the court ruled today. An IP address is vital enough that every resident expects it […]

In Canada, your IP address has the right to remain silent. Elon Musk is suing OpenAI for not being Open. Apple faces a class action not allowing competitive access to backup services and the World Server Throwing Competition in March 2024 is accused of being too violent towards servers.   All this and more on the […]

Canada’s national anti-money laundering agency has been hit by a cyber attack. The Financial Transactions and Reports Analysis Centre of Canada (FINTRAC) said Tuesday that over the last 24 hours it has been managing a cyber incident. “The incident does not involve the centre’s intelligence or classified systems,” it said in a statement. “As a […]

The government of Canada has announced significant investments to improve connectivity in British Columbia and Alberta over the past two days. That includes combined federal and provincial funding of C$112 million to bring high speed internet access to more than 22,500 households in Alta. and another $37 million for 7,500 households in B.C.. The households, […]

Artificial intelligence can be the key to unlocking better relationships with work, HP revealed in its new Work Relationship Index (WRI) report. “AI represents a significant opportunity to transform our work dynamics and unlock a more positive and productive environment for all,” stated Dave Shull, president of HP Workforce Solutions at HP Inc.. “To foster […]

Facing an unprecedented crisis, IT World Canada, a beacon of technology journalism, is on the brink of closure. This poses a critical question: Without IT World Canada, who will narrate Canada’s tech story? After decades of serving the Canadian tech industry, IT World Canada needs help to survive. As of midnight tonight, the company is […]

NASA discovered the cause of a pulsating noise coming from a speaker on the Boeing Starliner spacecraft after astronaut Butch Wilmore reported the sound.

Wonder Brands Inc. is recalling various brands of bread and buns because of pieces of metal in the products. According to the Canadian Food Inspection Agency (CFIA), the recalled products were distributed in Newfoundland and Labrador, Ontario and Quebec, Canada. The brands listed in the recall include Country Harvest, D’Italiano,... Continue Reading

Human bird flu has hospitalized a Canadian teenager at British Columbia Children’s Hospital. He is the first person in Canada to test positive for the bird flu virus. The B.C. teen likely acquired the virus from exposure to a bird or animal. B.C. Health said the infection is a rare... Continue Reading

Montana public health officials are investigating an outbreak of infections caused by Salmonella. The Cascade City-County Health Department in Great Falls is reporting that six students at Sacajawea and Valley View elementary schools have tested positive for the pathogen. A staff member at another school has also tested positive. There... Continue Reading

Listings outpace demand in Toronto and Vancouver

Atlantic Canadians say the region has room to grow, but is facing a shrinking labour pool

Stock and bond markets are already reacting in anticipation of the changes

Canada Post workers might soon be putting down their mailbags and grabbing picket signs

The Canadian women's soccer team was implicated in a drone scandal this past summer. But, an investigation determined drone use against opponents, predated the Paris Olympics.

Have you been on the lookout for ways to improve your trading game? You will come across a number of suggestions and tips, one of which is using sentiment analysis. It has become quite a hot topic in the trading space these days and for a good reason. In today’s fast-paced trading environment, staying ahead […]

The post Integrating Sentiment Analysis with AI Trading Bots: A New Frontier appeared first on Chart Attack.

In today’s complex business environment, organizations rely heavily on external vendors for essential services and resources. Managing these relationships effectively is crucial for operational efficiency, cost control, and risk management. To achieve this, many companies turn to Vendor Management Software to streamline vendor interactions, ensuring that the right processes and tools are in place for […]

The post Optimizing Vendor Portfolio with Vendor Management Software appeared first on Chart Attack.

The new Louisiana requirement that the Ten Commandments be displayed in every public classroom by Jan. 1 was temporarily blocked Tuesday. The judge said the law is "unconstitutional on its face."

Industry Minister François-Philippe Champagne said the decision to dissolve TikTok of its Canadian business is meant to address risks perceived to be related to TikTok's Chinese parent company.

1. Netflix's The Great Indian Kapil Show: Navjot Singh Sidhu is back after 5 years of exit, Archana Puran Singh says, 'He’s taken over my...'  Firstpost
2. Did you know! Navjot Singh Sidhu was ousted from The Kapil Sharma Show for this reason  The Times of India
3. Navjot Singh Sidhu makes a roaring comeback; Archana Puran Singh worried about her The Great Indian Kapil Show throne  Hindustan Times
4. The Great Kapil Sharma Show: Navjot Sidhu shares his fast-track fatherhood plan. Kapil’s response is too f  The Economic Times
5. Navjot Singh Sidhu shares BTS pics from The Great Indian Kapil's show set with Archana Puran Singh and...  Moneycontrol