Inositol 1,4,5-triphosphate receptor type 1 (ITPR1) is an endoplasmic reticulum–bound intracellular inositol triphosphate receptor involved in the regulation of intracellular calcium. Pathogenic variants in ITPR1 are associated with spinocerebellar ataxia (SCA) types 15/16 and 29 and have recently been implicated in a facial microsomia syndrome. In this report, we present a family with three affected individuals found to have a heterozygous missense c.800C > T (predicted p.Thr267Met) who present clinically with a SCA29-like syndrome. All three individuals presented with varying degrees of ataxia, developmental delay, and apparent intellectual disability, as well as craniofacial involvement—an uncommon finding in patients with SCA29. The variant was identified using clinical exome sequencing and validated with Sanger sequencing. It is presumed to be inherited via parental germline mosaicism. We present our findings to provide additional evidence for germline mosaic inheritance of SCA29, as well as to expand the clinical phenotype of the syndrome.

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).

BackgroundLong-term health conditions are major challenges for care systems. Social prescribing link workers have been introduced via primary care networks (PCNs) across England since 2019 to address the wider determinants of health by connecting individuals to activities, groups, or services within their local community.AimTo assess whether the rollout of social prescribing link workers was in areas with the highest need.Design and settingA retrospective study of social prescribing link workers in England from 2019 to 2023.MethodWorkforce, population, survey, and area-level data at the PCN-level from April 2020 to October 2023 were combined. Population need before the rollout of link workers was measured using reported lack of support from local services in the 2019 General Practice Patient Survey. To assess if rollout reflected need, linear regression was used to relate provision of link workers (measured by full-time equivalent [FTE] per 10 000 patients) in each quarter to population need for support.ResultsPopulations in urban, more deprived areas and with higher proportions of people from minority ethnic groups had the highest reported lack of support. Geographically these were in the North West and London. Initially, there was no association between need and provision; then from July 2022, this became negative and significant. By October 2023, a 10-percentage point higher need for support was associated with a 0.035 (95% confidence interval = −0.634 to −0.066) lower FTE per 10 000 patients.ConclusionRollout of link workers has not been sufficiently targeted at areas with the highest need. Future deployments should be targeted at those areas.

The usual challenges of conducting primary care research, including randomized trials, have been exacerbated, and new ones identified, during the COVID-19 pandemic. HOMER (Home versus Office for Medication Enhanced Recovery; subsequently, Comparing Home, Office, and Telehealth Induction for Medication Enhanced Recovery) is a pragmatic, comparative-effectiveness research trial that aims to answer a key question from patients and clinicians: What is the best setting in which to start treatment with buprenorphine for opioid use disorder for this patient at this time? In this article, we describe the difficult journey to find the answer. The HOMER study began as a randomized trial comparing treatment outcomes in patients starting treatment with buprenorphine via induction at home (unobserved) vs in the office (observed, synchronous). The study aimed to enroll 1,000 participants from 100 diverse primary care practices associated with the State Networks of Colorado Ambulatory Practices and Partners and the American Academy of Family Physicians National Research Network. The research team faced unexpected challenges related to the COVID-19 pandemic and dramatic changes in the opioid epidemic. These challenges required changes to the study design, protocol, recruitment intensity, and funding conversations, as well as patience. As this is a participatory research study, we sought, documented, and responded to practice and patient requests for adaptations. Changes included adding a third study arm using telehealth induction (observed via telephone or video, synchronous) and switching to a comprehensive cohort design to answer meaningful patient-centered research questions. Using a narrative approach based on the Greek myth of Homer, we describe here the challenges and adaptations that have provided the opportunity for HOMER to thrive and find the way home. These clinical trial strategies may apply to other studies faced with similar cultural and extreme circumstances.

PURPOSE

Despite being key to better health outcomes for patients from racial and ethnic minority groups, the proportion of underrepresented in medicine (URiM) physicians remains low in the US health care system. This study linked a nationally representative sample of family physicians (FPs) with Medicaid claims data to explore the relative contributions to care of Medicaid populations by FP race and ethnicity.

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.

A new report by the global union Education International shows that AI can degrade the quality of education, worsen working conditions for teachers and provide inferior schooling for students.

The post Artificial Intelligence can cause fake education appeared first on rabble.ca.

The current growth and consumption based economy is not sustainable. The world must move towards a circular economy and sustainability.

The post Degrowth, green energy, social equity, and circular economy appeared first on rabble.ca.

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

As parts of Spain are on alert for new flood warnings, Dominic Hinde meets the volunteers still involved in the aftermath and recovery following the initial disaster

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

Today in "person you already like says something you already agree with, but it’s still good to hear them say it" news, Arkane founder and im-simmy RPG studio WolfEye head Raphael Colantonio has spoken on Microsoft’s decision to shutter Prey (2017) studio Arkane Austin - alongside a handful of others - back in May.

Colantonio, who founded Arkane in 1999 and departed in 2017 to form Weird West studio WolfEye, recently chatted to Jeremy Peel for PC Gamer about Arkane’s closure, saying:

I think if you look a little bit, it's obvious that Arkane Austin was a very special group of people that have made some cool things and that could pull it off again. I think it was a decision that just came down to, 'We need to cut something.' Was it to please the investors, the stock market? They're playing a different game.

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Remedy's Alan Wake 2 has now "recouped most of its development and marketing expenses", CEO Tero Virtala has announced in a business review for January-September 2024. Speaking as somebody who would quite like there to be more Alan Wake games - or at least, moderately weird and pretty decent blockbuster singleplayer horror games - I am both pleased by this news and a little troubled that Remedy's eldritch forest fable (which came out in October 2023) has yet to break even.

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Twitch have introduced a new "Politics and Sensitive Social Issues" label for streams that "focus" on topics like "elections, civic integrity, and war or military conflict". As with the streaming giant's existing labels for M-rated material, sexual themes or depictions of gambling, the idea is that viewers can filter out such streams in advance by altering their settings.

Advertisers, similarly, can "make better choices about the content they want to advertise next to" - in other words, pull their ads from a whole swathe of material if they don't want to be associated with anything controversial. Twitch's hope is that "the labels will allow advertisers to have more context to inform which types of streams they show their ads alongside, which we expect to increase brands’ confidence in running ads on Twitch, and could bring new advertisers to our service."

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Roblox is making changes in an attempt to keep younger players safe in the online platform. Beginning later this month, children under the age of 13 will no longer be able to search, discover or play unrated experiences within Roblox, and will be unable to access social hangout experiences.

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Between 2005 and 2021, Facebook, Twitter and YouTube were more likely to make policy changes in the weeks after negative stories in the media

Artificial intelligence has more in common with ants than humans, says Neil Lawrence. Only by taking a more nuanced view of intelligence can we see how machines will truly transform society

A US standards agency has issued new guidance saying organisations shouldn’t require users to change their passwords periodically – advice that is backed up by decades of research

Emma Raducanu struck a deal to return to one of her favourite tournaments.

Unknown host Charlie Stone analyzes Trump's unprecedented victory with Obama Homeland Security Secretary, Jeh Johnson

Black Ops 6 is here, and it's Black Ops 2's anniversary, so what better time than to rank the Call of Duty Black Ops titles? Here's our ranking of every mainline version.

As artificial intelligence becomes more common in university classrooms, some professors are weighing the benefits — and downsides — of students using it for research projects.

People keep predicting that each wave of new technology will mean humans can put their feet up. It hasn't happened yet. Some economists and anthropologists who study the subject say even with the arrival of artificial intelligence, humans will remain integral to making the world go round.

A pediatrician, author and co-inventor of a low-cost COVID-19 vaccine warns that the anti-vaccine movement has morphed into a political force that threatens the world's gains against deadly childhood infections like measles.

Local officials are beginning to certify the results of this year's presidential election in a process that, so far, has been playing out quietly, in stark contrast to the tumultuous certification period four years ago that followed then-President Donald Trump's loss.

President-elect Donald Trump has tapped Steven Witkoff to be special envoy to the Middle East, marking another key position for his incoming administration.

President-elect Donald Trump announced Tuesday that John Ratcliffe, a former Texas congressman and director of national intelligence, will serve as the director of the Central Intelligence Agency in his administration.

President-elect Donald Trump announced a flurry of appointments Tuesday for key posts in his new administration, including former Director of National Intelligence John Ratcliffe to lead the CIA and the expected nomination of South Dakota Gov. Kristi Noem to head the Department of Homeland Security.

Tech expert Kurt “CyberGuy" Knutsson reveals four signs of compromised Social Security numbers and offers five steps to protect yourself.

A virtual private network is a service that encrypts your internet connection, ensuring your online activity remains private and secure.

Doubled number of specialists should make up for the switch from the classic class system.

People who went from using social media for at least 2 hours a day to just 30 minutes a day reported no improvement to their sleep or emotional well-being

Social media commentators claimed Jill Biden refused to look at Vice President Harris as they were seated together at Arlington Cemetery for a Veterans' Day Remembrance.

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

John Ratcliffe, who previously served as President-elect Trump's principal intelligence advisor, has now been picked by Trump to serve as director of the CIA.

Dallas Mavericks minority owner Mark Cuban returned to the Bluesky social media platform with a post after weeks of contentious X posts.

From the busy cities to ocean waters, our need to illuminate the world has had some strange and tragic consequences

The Puerto Rican singer covers the latest issue of 'Out' magazine.

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Brianna Ghey's mother, Esther Ghey, is now campaigning to raise awareness about the dangers of social media and the "toxic" online world which her daughter came to inhabit. She wants tighter regulation on internet access and more parental controls.

It has just the right mix of spreadability, stickiness, and friction to give pitchers a better grip on the ball.

President-elect Donald Trump announced that he has picked businessman and real estate investor Steven Witkoff to serve as Special Envoy to the Middle East.

The post President-Elect Donald Trump Picks Businessman Steven Witkoff to Be Special Envoy to Middle East appeared first on Breitbart.

President-elect Donald Trump has made many selections to lead his administration as his transition gets underway, ranging from chief of staff to head of the Environmental Protection Agency (EPA). At the same time, a number of crucial positions have yet to be filled just one week removed from the landslide election.

The post Donald Trump’s Administration Takes Shape After 15 Official or Expected Picks appeared first on Breitbart.

Patriots are regaining control over this country in January. However, we all need to prepare for what’s to come because the road ahead won't be easy. And that’s why we need to play the long game.

The post Trump Won. Woke Lost. Here’s Your Financial Battle Plan appeared first on Breitbart.

President-elect Donald Trump on Wednesday announced that former Rep. John Ratcliffe (R-TX) will serve as his director of the Central Intelligence Agency (CIA).

The post President-Elect Donald Trump Names Former Rep. John Ratcliffe as CIA Director appeared first on Breitbart.

A teenager who tested positive for avian flu is in critical condition with acute respiratory distress according to Provincial Health Officer Dr. Bonnie Henry.