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Novel pathogenic UQCRC2 variants in a female with normal neurodevelopment [RESEARCH REPORT]

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




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De novo TRPM3 missense variant associated with neurodevelopmental delay and manifestations of cerebral palsy [RESEARCH ARTICLE]

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).




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Rapid genome diagnosis of alveolar capillary dysplasia leading to treatment in a child with respiratory and cardiac failure [RESEARCH REPORT]

Alveolar capillary dysplasia (ACD) is a fatal disorder that typically presents in the neonatal period with refractory hypoxemia and pulmonary hypertension. Lung biopsy is traditionally required to establish the diagnosis. We report a 22-mo-old male who presented with anemia, severe pulmonary hypertension, and right heart failure. He had a complicated hospital course resulting in cardiac arrest and requirement for extracorporeal membrane oxygenation. Computed tomography of the chest showed a heterogenous pattern of interlobular septal thickening and pulmonary edema. The etiology of his condition was unknown, lung biopsy was contraindicated because of his medical fragility, and discussions were held to move to palliative care. Rapid whole-genome sequencing (rWGS) was performed. In 2 d it resulted, revealing a novel FOXF1 gene pathogenic variant that led to the presumptive diagnosis of atypical ACD. Cases of atypical ACD have been reported with survival in patients using medical therapy or lung transplantation. Based on the rWGS diagnosis and more favorable potential of atypical ACD, aggressive medical treatment was pursued. The patient was discharged home after 67 d in the hospital; he is currently doing well more than 30 mo after his initial presentation with only one subsequent hospitalization and no requirement for lung transplantation. Our case reveals the potential for use of rWGS in a critically ill child in which the diagnosis is unknown. rWGS and other advanced genetic tests can guide clinical management and expand our understanding of atypical ACD and other conditions.




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Clinical and functional analysis of the germline TP53 p.K164E acetylation site variant [RESEARCH ARTICLE]

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.




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Synchronous T-lymphoblastic lymphoma and neuroblastoma in a 3-yr-old with novel germline SMARCA4 and EZH2 variants [RAPID CANCER COMMUNICATION]

T-lymphoblastic lymphoma (T-LLy) is the most common lymphoblastic lymphoma in children and often presents with a mediastinal mass. Lymphomatous suprarenal masses are possible but rare. Here, we discuss the case of a previously healthy 3-yr-old male who presented with mediastinal T-LLy with bilateral suprarenal masses. Following initial treatment, surgical biopsy of persisting adrenal masses revealed bilateral neuroblastoma (NBL). A clinical genetics panel for germline cancer predisposition did not identify any pathogenic variants. Combination large panel (864 genes) profiling analysis in the context of a precision oncology study revealed two novel likely pathogenic heterozygous variants: SMARCA4 c.1420-1G > T p.? and EZH2 c.1943G > C p.(Ile631Phefs*44). Somatic analysis revealed potential second hits/somatic variants in EZH2 (in the T-LLy) and a segmental loss in Chromosome 19p encompassing SMARCA4 (in the NBL). Synchronous cancers, especially at a young age, warrant genetic evaluation for cancer predisposition; enrollment in a precision oncology program assessing germline and tumor DNA can fulfill that purpose, particularly when standard first-line genetic testing is negative and in the setting of tumors that are not classic for common cancer predisposition syndromes.




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Leukemic presentation and progressive genomic alterations of MCD/C5 diffuse large B-cell lymphoma (DLBCL) [RESEARCH ARTICLE]

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.




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PBRNs: Past, Present, and Future: A NAPCRG Report on the Practice-Based Research Network Conference. [Family Medicine Updates]




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The Odyssey of HOMER: Comparative Effectiveness Research on Medication for Opioid Use Disorder During the COVID-19 Pandemic [Special Report]

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.




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Self-Reported PrEP Use and Risk of Bacterial STIs Among Ontarian Men Who Are Gay or Bisexual or Have Sex With Men [Original Research]

PURPOSE

HIV pre-exposure prophylaxis (PrEP) may increase rates of bacterial sexually transmitted infections (STIs) among gay, bisexual, and other men who have sex with men (GBM) through risk compensation (eg, an increase in condomless sex or number of partners); however, longitudinal studies exploring the time-dependent nature of PrEP uptake and bacterial STIs are limited. We used marginal structural models to estimate the effect of PrEP uptake on STI incidence.

METHODS

We analyzed data from the iCruise study, an online longitudinal study of 535 Ontarian GBM from July 2017 to April 2018, to estimate the effects of PrEP uptake on incidence of self-reported bacterial STIs (chlamydia, gonorrhea, and syphilis) collected with 12 weekly diaries. The incidence rate was calculated as the number of infections per 100 person-months, with evaluation of the STIs overall and individually. We used marginal structural models to account for time-varying confounding and quantitative bias analysis to evaluate the sensitivity of estimates to nondifferential outcome misclassification.

RESULTS

Participating GBM were followed up for a total of 1,623.5 person-months. Overall, 70 participants (13.1%) took PrEP during the study period. Relative to no uptake, PrEP uptake was associated with an increased incidence rate of gonorrhea (incidence rate ratio = 4.00; 95% CI, 1.67-9.58), but not of chlamydia or syphilis, and not of any bacterial STI overall. Accounting for misclassification, the median incidence rate ratio for gonorrhea was 2.36 (95% simulation interval, 1.08-5.06).

CONCLUSIONS

We observed an increased incidence rate of gonorrhea associated with PrEP uptake among Ontarian GBM that was robust to misclassification. Although our findings support current guidelines for integrating gonorrhea screening with PrEP services, additional research should consider the long-term impact of PrEP among this population.

Annals Early Access article




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Lack of Knowledge of Antibiotic Risks Contributes to Primary Care Patients Expectations of Antibiotics for Common Symptoms [Research Briefs]

Patient expectations of receiving antibiotics for common symptoms can trigger unnecessary use. We conducted a survey (n = 564) between January 2020 to June 2021 in public and private primary care clinics in Texas to study the prevalence and predictors of patients’ antibiotic expectations for common symptoms/illnesses. We surveyed Black patients (33%) and Hispanic/Latine patients (47%), and over 93% expected to receive an antibiotic for at least 1 of the 5 pre-defined symptoms/illnesses. Public clinic patients were nearly twice as likely to expect antibiotics for sore throat, diarrhea, and cold/flu than private clinic patients. Lack of knowledge of potential risks of antibiotic use was associated with increased antibiotic expectations for diarrhea (odds ratio [OR] = 1.6; 95% CI, 1.1-2.4) and cold/flu symptoms (OR = 2.9; 95% CI, 2.0-4.4). Lower education and inadequate health literacy were predictors of antibiotic expectations for diarrhea. Future antibiotic stewardship interventions should tailor patient education materials to include information on antibiotic risks and guidance on appropriate antibiotic indications.




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Evaluation of the Importance of Capsule Transparency in Dry Powder Inhalation Devices [Research Briefs]

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.




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Digital Innovation to Grow Quality Care Through an Interprofessional Care Team (DIG IT) Among Underserved Patients With Hypertension [Original Research]

PURPOSE

The impact of digital health on medically underserved patients is unclear. This study aimed to determine the early impact of a digital innovation to grow quality care through an interprofessional care team (DIG IT) on the blood pressure (BP) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score of medically underserved patients.

METHODS

This was a 3-month, prospective intervention study that included patients aged 40 years or more with BP of 140/90 mmHg or higher who received care from DIG IT from August through December 2021. Sociodemographic and clinical outcomes of DIG IT were compared with historical controls (controls) whose data were randomly extracted by the University of California Data Warehouse and matched 1:1 based on age, ethnicity, and baseline BP of the DIG IT arm. Multiple linear regression was performed to adjust for potential confounding factors.

RESULTS

A total of 140 patients (70 DIG IT, 70 controls) were included. Both arms were similar with an average age (SD) of 62.8 (9.7) years. The population was dominated by Latinx (79.3%) persons, with baseline mean BP of 163/81 mmHg, and mean ASCVD risk score of 23.9%. The mean (SD) reduction in systolic BP at 3 months in the DIG IT arm was twice that of the controls (30.8 [17.3] mmHg vs 15.2 [21.2] mmHg; P <.001). The mean (SD) ASCVD risk score reduction in the DIG IT arm was also twice that of the controls (6.4% [7.4%] vs 3.1% [5.1%]; P = .003).

CONCLUSIONS

The DIG IT was more effective than controls (receiving usual care). Twofold improvement in the BP readings and ASCVD scores in medically underserved patients were achieved with DIG IT.




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Family Medicine Resident Scholarly Activity Infrastructure, Output, and Dissemination: A CERA Survey [Original Research]

PURPOSE

Meeting scholarly activity requirements continues to be a challenge in many family medicine (FM) residency programs. Studies comprehensively describing FM resident scholarship have been limited. We sought to identify institutional factors associated with increased scholarly output and meeting requirements of the Accreditation Council for Graduate Medical Education (ACGME).

OBJECTIVES

Our goals were to: (1) describe scholarly activity experiences among FM residents compared with ACGME requirements; (2) classify experiences by Boyer’s domains of scholarship; and (3) associate experiences with residency program characteristics and scholarly activity infrastructure.

METHODS

This was a cross-sectional survey. The survey questions were part of an omnibus survey to FM residency program directors conducted by the Council of Academic Family Medicine Educational Research Alliance (CERA). All ACGME-accredited US FM residency program directors, identified by the Association of Family Medicine Residency Directors, were sampled.

RESULTS

Of the 691 eligible program directors, 298 (43%) completed the survey. The respondents reported that 25% or more residents exceeded ACGME minimum output, 17% reported that 25% or more residents published their work, and 50% reported that 25% or more residents delivered conference presentations. Programs exceeding ACGME scholarship requirements exhibit robust infrastructure characterized by access to faculty mentorship, scholarly activity curricula, Institutional Review Board, medical librarian, and statistician.

CONCLUSIONS

These findings suggest the need for codified ACGME requirements for scholarly activity infrastructure to ensure access to resources in FM residency programs. By fostering FM resident engagement in scholarly activity, programs help to create a culture of inquiry, and address discrepancies in funding and output among FM residency programs.




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A Cluster-Randomized Study of Technology-Assisted Health Coaching for Weight Management in Primary Care [Original Research]

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.

METHODS

This cluster-randomized controlled trial enrolled 19 primary care teams with 63 clinicians; 9 teams were randomized to GEM and 10 to enhanced usual care (EUC). The GEM intervention included 1 in-person and up to 12 telephone-delivered coaching sessions. Coaches supported goal setting and engagement with weight management programs, facilitated by a software tool. Patients in the EUC arm received educational handouts. We enrolled patients who spoke English or Spanish, were aged 18 to 69 years, and either were overweight (body mass index 25-29 kg/m2) with a weight-related comorbidity or had obesity (body mass index ≥30 kg/m2). The primary outcome (weight change at 12 months) and exploratory outcomes (eg, program attendance, diet, physical activity) were analyzed according to intention to treat.

RESULTS

We enrolled 489 patients (220 in the GEM arm, 269 in the EUC arm). Their mean (SD) age was 49.8 (12.1) years; 44% were male, 41% Hispanic, and 44% non-Hispanic Black. At 12 months, the mean adjusted weight change (standard error) was –1.4 (0.8) kg in the GEM arm vs –0.8 (1.6) kg in the EUC arm, a nonsignificant difference (P = .48). There were no statistically significant differences in secondary outcomes. Exploratory analyses showed that the GEM arm had a greater change than the EUC arm in mean number of weekly minutes of moderate to vigorous physical activity other than walking, a finding that may warrant further exploration.

CONCLUSIONS

The GEM intervention did not achieve clinically important weight loss in primary care. Although this was a negative study possibly affected by health system resource limitations and disruptions, its findings can guide the development of similar interventions. Future studies could explore the efficacy of higher-intensity interventions and interventions that include medication and bariatric surgery options, in addition to lifestyle modification.




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A Few Doctors Will See Some of You: The Critical Role of Underrepresented in Medicine (URiM) Family Physicians in the Care of Medicaid Beneficiaries [Original Research]

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.

METHODS

This descriptive cross-sectional study used 2016 Medicaid claims data from the Transformed Medicaid Statistical Information System and from 2016-2017 American Board of Family Medicine certification questionnaire responses to examine the diversity and Medicaid participation of FPs. We explored the diversity of FP Medicaid patient panels and whether they saw ≥150 beneficiaries in 2016. Using logistic regression models, we controlled for FP demographics, practice characteristics, and characteristics of the communities in which they practiced.

RESULTS

Of 13,096 FPs, Latine, Hispanic, or of Spanish Origin (LHS) FPs and non-LHS Black FPs saw more Medicaid beneficiaries compared with non-LHS White and non-LHS Asian FPs. The patient panels of URiM FPs had a much greater proportion of Medicaid beneficiaries from racial and ethnic minority groups. Overall, non-LHS Black and LHS FPs had greater odds of seeing ≥150 Medicaid beneficiaries in 2016.

CONCLUSIONS

These findings clearly show the critical role URiM FPs play in caring for Medicaid beneficiaries, suggesting physician race and ethnicity are correlated with Medicaid participation. Diversity in the health care workforce is essential for addressing racial health inequities. Policies need to address problems in pathways to medical education, including failures to recruit, nurture, and retain URiM students.




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Family Medicine Presence on Labor and Delivery: Effect on Safety Culture and Cesarean Delivery [Original Research]

PURPOSE

Currently, 40% of counties in the United States do not have an obstetrician or midwife, and in rural areas the likelihood of childbirth being attended to by a family medicine (FM) physician is increasing. We sought to characterize the effect of the FM presence on unit culture and a key perinatal quality metric in Iowa hospital intrapartum units.

METHODS

Using a cross-sectional design, we surveyed Iowa physicians, nurses, and midwives delivering intrapartum care at hospitals participating in a quality improvement initiative to decrease the incidence of cesarean delivery. We linked respondents with their hospital characteristics and outcomes data. The primary outcome was the association between FM physician, obstetrician (OB), or both disciplines’ presence on labor and delivery and hospital low-risk, primary cesarean delivery rate. Unit culture was compared by hospital type (FM-only, OB-only, or Both).

RESULTS

A total of 849 clinicians from 39 hospitals completed the survey; 13 FM-only, 11 OB-only, and 15 hospitals with both. FM-only hospitals were all rural, with <1,000 annual births. Among hospitals with <1,000 annual births, births at FM-only hospitals had an adjusted 34.3% lower risk of cesarean delivery (adjusted incident rate ratio = 0.66; 95% CI, 0.52-.0.98) compared with hospitals with both. Nurses endorsed unit norms more supportive of vaginal birth and stronger safety culture at FM-only hospitals (P <.05).

CONCLUSIONS

Birthing hospitals staffed exclusively by FM physicians were more likely to have lower cesarean rates and stronger nursing-rated safety culture. Both access and quality of care provide strong arguments for reinforcing the pipeline of FM physicians training in intrapartum care.




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Challenges in Receiving Care for Long COVID: A Qualitative Interview Study Among Primary Care Patients About Expectations and Experiences [Original Research]

BACKGROUND

For many patients with post–COVID-19 condition (long COVID), primary care is the first point of interaction with the health care system. In principle, primary care is well situated to manage long COVID. Beyond expressions of disempowerment, however, the patient’s perspective regarding the quality of long COVID care is lacking. Therefore, this study aimed to analyze the expectations and experiences of primary care patients seeking treatment for long COVID.

METHODS

A phenomenological approach guided this analysis. Using purposive sampling, we conducted semistructured interviews with English-speaking, adult primary care patients describing symptoms of long COVID. We deidentified and transcribed the recorded interviews. Transcripts were analyzed using inductive qualitative content analysis.

RESULTS

This article reports results from 19 interviews (53% female, mean age = 54 years). Patients expected their primary care practitioners (PCPs) to be knowledgeable about long COVID, attentive to their individual condition, and to engage in collaborative processes for treatment. Patients described 2 areas of experiences. First, interactions with clinicians were perceived as positive when clinicians were honest and validating, and negative when patients felt dismissed or discouraged. Second, patients described challenges navigating the fragmented US health care system when coordinating care, treatment and testing, and payment.

CONCLUSION

Primary care patients’ experiences seeking care for long COVID are incongruent with their expectations. Patients must overcome barriers at each level of the health care system and are frustrated by the constant challenges. PCPs and other health care professionals might increase congruence with expectations and experiences through listening, validating, and advocating for patients with long COVID.

Annals Early Access article




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New research to better understand the biological factors of suicidal behaviour

New research to better understand the biological factors of suicidal behaviour Researchers at the University of Glasgow are embarking on two new PhD projects to better understand the impact that biological factors may have on suicidal behaviour.




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MH370 search ends in two weeks

The hunt for missing flight MH370 will end in two weeks, Malaysia’s transport minister said yesterday.




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Rosneft poised for Arctic LNG stake

ENERGY giant Rosneft is poised to take control of a new Arctic Circle LNG project planned for an area of northern Russia fronting the Barents Sea.




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Marcus and Dom Voice Actors to Return for Gears of War: E-Day

Publisher Xbox Game Studios and developer The Coalition have announced John DiMaggio, the voice actor for Marcus Fenix, and Carlos Ferro, the voice actor for Dom Santiago, will reprise their roles for the prequel Gears of War: E-Day.

"On today's 18th anniversary of Gears of War, we're proud to share that John DiMaggio and Carlos Ferro are reprising their roles as the iconic voices of Marcus Fenix and Dominic Santiago in Gears of War: E-Day," announced the developer.

Gears of War: E-Day is in development for the Xbox Series X|S, PC, and Xbox Game Pass.

We are so back. ????????

On today's 18th anniversary of Gears of War, we're proud to share that John DiMaggio and @RealCarlosFerro are reprising their roles as the iconic voices of Marcus Fenix and Dominic Santiago in Gears of War: E-Day. pic.twitter.com/x9uaH9R0sR

— Gears of War (@GearsofWar) November 7, 2024

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/463012/marcus-and-dom-voice-actors-to-return-for-gears-of-war-e-day/




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The Forever Winter devs answer complaints about water scarcity... by adding thieves who invade your HQ and steal your water

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.

Read more



  • Shooter: Third Person
  • The Forever Winter
  • PC
  • Shooter: Loot Shooter
  • Science Fiction
  • Survival & Crafting
  • Fun Dog Studios

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Straftat review: an anarchic First-Person Speed dater you'll fall in love with

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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Warcraft 2: Tides Of Darkness Remastered apparently leaks ahead of the RTS series’ 30th anniversary direct next week

We’re still a week away from Blizzard’s Warcraft 30th Anniversary Direct next Wednesday the 13th of November, but art from an apparent remaster of 1995 real time strategy game Warcraft II: Tides Of Darkness has leaked online, via Xibbly user Stiven. It’s a thin one, as far as leaks go, but does show what looks to be cover, logo art, and a Battle.net icon. Thanks for the spot, Percy Coswald Gamer.

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Offensively good-looking Sims challenger Inzoi hits early access in March 2025

Life simulation game Inzoi will launch on PC via Steam early access on 28th March 2025, publishers Krafton have announced. Billed as a potential Sims 4 usurper, and equipped with syrupy Unreal Engine 5 visuals, it was originally slated for launch this year.

Read more




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Search for alien transmissions in promising star system draws a blank

Astronomers listened for radio signals emanating from planets in the TRAPPIST-1 system, but found no evidence of any interplanetary communications




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NASA set to launch Europa probe to search for signs of habitability

A 6000-kilogram spacecraft will embark on a six-year journey to Jupiter to explore whether its icy moon Europa has the conditions to support life




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AI can use tourist photos to help track Antarctica’s penguins

Scientists used AI to transform tourist photos into a 3D digital map of Antarctic penguin colonies – even as researchers debate whether to harness or discourage tourism in this remote region




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Boston Dynamics and Toyota Research Team Up on Robots



Today, Boston Dynamics and the Toyota Research Institute (TRI) announced a new partnership “to accelerate the development of general-purpose humanoid robots utilizing TRI’s Large Behavior Models and Boston Dynamics’ Atlas robot.” Committing to working towards a general purpose robot may make this partnership sound like a every other commercial humanoid company right now, but that’s not at all that’s going on here: BD and TRI are talking about fundamental robotics research, focusing on hard problems, and (most importantly) sharing the results.

The broader context here is that Boston Dynamics has an exceptionally capable humanoid platform capable of advanced and occasionally painful-looking whole-body motion behaviors along with some relatively basic and brute force-y manipulation. Meanwhile, TRI has been working for quite a while on developing AI-based learning techniques to tackle a variety of complicated manipulation challenges. TRI is working toward what they’re calling large behavior models (LBMs), which you can think of as analogous to large language models (LLMs), except for robots doing useful stuff in the physical world. The appeal of this partnership is pretty clear: Boston Dynamics gets new useful capabilities for Atlas, while TRI gets Atlas to explore new useful capabilities on.

Here’s a bit more from the press release:

The project is designed to leverage the strengths and expertise of each partner equally. The physical capabilities of the new electric Atlas robot, coupled with the ability to programmatically command and teleoperate a broad range of whole-body bimanual manipulation behaviors, will allow research teams to deploy the robot across a range of tasks and collect data on its performance. This data will, in turn, be used to support the training of advanced LBMs, utilizing rigorous hardware and simulation evaluation to demonstrate that large, pre-trained models can enable the rapid acquisition of new robust, dexterous, whole-body skills.

The joint team will also conduct research to answer fundamental training questions for humanoid robots, the ability of research models to leverage whole-body sensing, and understanding human-robot interaction and safety/assurance cases to support these new capabilities.

For more details, we spoke with Scott Kuindersma (Senior Director of Robotics Research at Boston Dynamics) and Russ Tedrake (VP of Robotics Research at TRI).

How did this partnership happen?

Russ Tedrake: We have a ton of respect for the Boston Dynamics team and what they’ve done, not only in terms of the hardware, but also the controller on Atlas. They’ve been growing their machine learning effort as we’ve been working more and more on the machine learning side. On TRI’s side, we’re seeing the limits of what you can do in tabletop manipulation, and we want to explore beyond that.

Scott Kuindersma: The combination skills and tools that TRI brings the table with the existing platform capabilities we have at Boston Dynamics, in addition to the machine learning teams we’ve been building up for the last couple years, put us in a really great position to hit the ground running together and do some pretty amazing stuff with Atlas.

What will your approach be to communicating your work, especially in the context of all the craziness around humanoids right now?

Tedrake: There’s a ton of pressure right now to do something new and incredible every six months or so. In some ways, it’s healthy for the field to have that much energy and enthusiasm and ambition. But I also think that there are people in the field that are coming around to appreciate the slightly longer and deeper view of understanding what works and what doesn’t, so we do have to balance that.

The other thing that I’d say is that there’s so much hype out there. I am incredibly excited about the promise of all this new capability; I just want to make sure that as we’re pushing the science forward, we’re being also honest and transparent about how well it’s working.

Kuindersma: It’s not lost on either of our organizations that this is maybe one of the most exciting points in the history of robotics, but there’s still a tremendous amount of work to do.

What are some of the challenges that your partnership will be uniquely capable of solving?

Kuindersma: One of the things that we’re both really excited about is the scope of behaviors that are possible with humanoids—a humanoid robot is much more than a pair of grippers on a mobile base. I think the opportunity to explore the full behavioral capability space of humanoids is probably something that we’re uniquely positioned to do right now because of the historical work that we’ve done at Boston Dynamics. Atlas is a very physically capable robot—the most capable humanoid we’ve ever built. And the platform software that we have allows for things like data collection for whole body manipulation to be about as easy as it is anywhere in the world.

Tedrake: In my mind, we really have opened up a brand new science—there’s a new set of basic questions that need answering. Robotics has come into this era of big science where it takes a big team and a big budget and strong collaborators to basically build the massive data sets and train the models to be in a position to ask these fundamental questions.

Fundamental questions like what?

Tedrake: Nobody has the beginnings of an idea of what the right training mixture is for humanoids. Like, we want to do pre-training with language, that’s way better, but how early do we introduce vision? How early do we introduce actions? Nobody knows. What’s the right curriculum of tasks? Do we want some easy tasks where we get greater than zero performance right out of the box? Probably. Do we also want some really complicated tasks? Probably. We want to be just in the home? Just in the factory? What’s the right mixture? Do we want backflips? I don’t know. We have to figure it out.

There are more questions too, like whether we have enough data on the Internet to train robots, and how we could mix and transfer capabilities from Internet data sets into robotics. Is robot data fundamentally different than other data? Should we expect the same scaling laws? Should we expect the same long-term capabilities?

The other big one that you’ll hear the experts talk about is evaluation, which is a major bottleneck. If you look at some of these papers that show incredible results, the statistical strength of their results section is very weak and consequently we’re making a lot of claims about things that we don’t really have a lot of basis for. It will take a lot of engineering work to carefully build up empirical strength in our results. I think evaluation doesn’t get enough attention.

What has changed in robotics research in the last year or so that you think has enabled the kind of progress that you’re hoping to achieve?

Kuindersma: From my perspective, there are two high-level things that have changed how I’ve thought about work in this space. One is the convergence of the field around repeatable processes for training manipulation skills through demonstrations. The pioneering work of diffusion policy (which TRI was a big part of) is a really powerful thing—it takes the process of generating manipulation skills that previously were basically unfathomable, and turned it into something where you just collect a bunch of data, you train it on an architecture that’s more or less stable at this point, and you get a result.

The second thing is everything that’s happened in robotics-adjacent areas of AI showing that data scale and diversity are really the keys to generalizable behavior. We expect that to also be true for robotics. And so taking these two things together, it makes the path really clear, but I still think there are a ton of open research challenges and questions that we need to answer.

Do you think that simulation is an effective way of scaling data for robotics?

Tedrake: I think generally people underestimate simulation. The work we’ve been doing has made me very optimistic about the capabilities of simulation as long as you use it wisely. Focusing on a specific robot doing a specific task is asking the wrong question; you need to get the distribution of tasks and performance in simulation to be predictive of the distribution of tasks and performance in the real world. There are some things that are still hard to simulate well, but even when it comes to frictional contact and stuff like that, I think we’re getting pretty good at this point.

Is there a commercial future for this partnership that you’re able to talk about?

Kuindersma: For Boston Dynamics, clearly we think there’s long-term commercial value in this work, and that’s one of the main reasons why we want to invest in it. But the purpose of this collaboration is really about fundamental research—making sure that we do the work, advance the science, and do it in a rigorous enough way so that we actually understand and trust the results and we can communicate that out to the world. So yes, we see tremendous value in this commercially. Yes, we are commercializing Atlas, but this project is really about fundamental research.

What happens next?

Tedrake: There are questions at the intersection of things that BD has done and things that TRI has done that we need to do together to start, and that’ll get things going. And then we have big ambitions—getting a generalist capability that we’re calling LBM (large behavior models) running on Atlas is the goal. In the first year we’re trying to focus on these fundamental questions, push boundaries, and write and publish papers.

I want people to be excited about watching for our results, and I want people to trust our results when they see them. For me, that’s the most important message for the robotics community: Through this partnership we’re trying to take a longer view that balances our extreme optimism with being critical in our approach.




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Do Newfoundland's Tablelands hold the answer to life on Mars? This researcher is trying to find out

The Tablelands in Gros Morne National Park, a UNESCO World Heritage Site, is one of the most unique landscapes in the world — and its orange peridotite rocks could hold the secret to finding life on Mars.



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How a researcher hacked ChatGPT's memory to expose a major security flaw

OpenAI recently introduced a new memory feature for ChatGPT that enables it to remember information about people, including age, gender and beliefs.



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Fantastic Arcade 2016

This year’s Fantastic Arcade is happening right now, so if you’re in Austin or a short drive away (n.b., a “short drive” in Texas is anything under 8 hours), you should go. Admission is free, gas is cheap, and Shine Boch actually tastes good if you drink it in the Lone Star State. There’s a […]




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MWC Barcelona 2024 news roundup: Telecom, AI, security and more

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

The post MWC Barcelona 2024 news roundup: Telecom, AI, security and more first appeared on ITBusiness.ca.




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Canadian police need a search warrant to get your IP address: Supreme Court

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 […]

The post Canadian police need a search warrant to get your IP address: Supreme Court first appeared on ITBusiness.ca.




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Hashtag Trending Mar.4- Canadian police need a search warrant to access IP address; Musk sues OpenAI; World Server Throwing Competition too violent?

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 […]

The post Hashtag Trending Mar.4- Canadian police need a search warrant to access IP address; Musk sues OpenAI; World Server Throwing Competition too violent? first appeared on ITBusiness.ca.




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Archaeologists unearth 13,000-year-old mastodon skull in Iowa

Iowa archaeologists have unearthed a 13,600-year-old mastodon skull in pristine condition during a nearly two-week excavation at an eroding creek bank in Wayne County.



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NASA spacecraft to scour Jupiter's icy moon in search of life-supporting conditions

A massive NASA spacecraft is ready to set sail for Jupiter and its moon Europa. The craft, named Europa Clipper, will determine if conditions there could support life.



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Body found in search for missing mum Jane Burton as police launch investigation



Greater Manchester Police launched a public appeal to help find Jane Burton on Tuesday morning but have paused the search after a body was found




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Lion Cavern in Eswatini is World’s Oldest Ochre Mine, Archaeologists Say

Archaeologists say they have discovered the oldest known evidence for intensive ochre mining worldwide, at least 48,000 years ago, in Lion Cavern at Ngwenya in Eswatini, a landlocked country in southern Africa.

The post Lion Cavern in Eswatini is World’s Oldest Ochre Mine, Archaeologists Say appeared first on Sci.News: Breaking Science News.




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Planetary Researchers Examine Tidal Effects on Interiors of Planets and Their Moons

A team of scientists from the Lunar and Planetary Laboratory at the University of Arizona, TU Delft, and Caltech has developed a new method to compute how tides affect the interiors of planets and moons in the Solar System.

The post Planetary Researchers Examine Tidal Effects on Interiors of Planets and Their Moons appeared first on Sci.News: Breaking Science News.




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New Research Questions Standard Theory of How Galaxies Formed in Early Universe

The standard model predicted that the NASA/ESA/CSA James Webb Space Telescope would see dim signals from small, primitive galaxies.

The post New Research Questions Standard Theory of How Galaxies Formed in Early Universe appeared first on Sci.News: Breaking Science News.





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Dazzling images illuminate research on cardiovascular disease

The British Heart Foundation’s Reflections of Research competition showcases beautiful images captured by researchers studying heart and circulatory disease




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The Arctic League kicked off its 2024 Christmas season today




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The Odd Arctic Military Projects Spawned by the Cold War

Many offbeat research efforts were doomed to fail, from atomic subways to a city under the ice.




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NASA Launches Europa Clipper to Search for Signs of Life on Jupiter’s Moon

The huge spacecraft is headed toward the icy moon Europa, where it will use an array of instruments to survey for geologic activity, magnetism and more




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After Decades of Searching, Are Physicists Closing In on Dark Matter?

With no conclusive laboratory results, researchers are turning to other methods to find the elusive substance





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Archbishop of Canterbury under pressure to resign over church abuse scandal

The Archbishop of Canterbury's position is now untenable, according to the Bishop of Newcastle who joined the growing calls for Justin Welby to resign.




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Archbishop of Canterbury resigns over church abuse scandal

Justin Welby's resignation as the Archbishop of Canterbury came after days of mounting pressure following a damning report into the cover-up of horrific abuse.