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Background The desire of medical students to eventually work with underserved and vulnerable populations (hereafter ‘service interest’), has been shown to be shaped by individual factors including job satisfaction and financial considerations. School-level factors such as required longitudinal primary care experiences and the availability of extracurricular opportunities to work with underserved patients also affect service interest, but little is known about the impact of student volunteer activities. Methods This cross-sectional study gathered data from preclinical medical students via an online questionnaire. The data were linked to academic records, deidentified, and analysed using an ordinal logistic regression model with interest in caring ‘primarily for underserved or vulnerable populations’ as the outcome variable. Results Of 121 respondents (33% response rate), 24.8% expressed a definite interest, 55.3% expressed possible interest, and 19.9% expressed no service interest. Intent to work with the underserved was not related to age, sex, race/ethnicity, being from a rural hometown, academic qualifications prior to medical school, or anticipated debt at medical school graduation. Students with no service interest had a higher average academic performance in medical school and plans of subspecialising. When considering volunteerism prior to medical school, students in the highest and middle volunteerism tertiles had 5.68 (95% CI: 1.63, 19.81) and 4.34 (1.32, 14.32) times the odds, respectively, of having definite or possible service interest relative to those who were in the lowest volunteerism tertile, after adjusting for potential confounders. Volunteerism in a student-run clinic for the underserved during medical school was not correlated with service interest. Conclusions Medical schools looking to enroll more students interested in working with underserved or vulnerable populations may choose to emphasise applicant premedical volunteerism record in their admissions decisions.

The International Ocean Discovery Programme (IODP) and its predecessors generated a treasure trove of Cenozoic climate and carbon cycle dynamics. Yet, it remains unclear how climate and carbon cycle interacted under changing geologic boundary conditions. Here, we present the carbon isotope (δ 13 C) megasplice, documenting deep-ocean δ 13 C evolution since 35 million years ago (Ma). We juxtapose the δ 13 C megasplice with its δ 18 O counterpart and determine their phase-difference on ~100-kyr eccentricity timescales. This analysis reveals that 2.4-Myr eccentricity cycles modulate the δ 13 C-δ 18 O phase relationship throughout the Oligo-Miocene (34-6 Ma), potentially through changes in continental weathering. At 6 Ma, a striking switch from in-phase to anti-phase behaviour occurs, signalling a reorganization of the climate-carbon cycle system. We hypothesize that this transition is consistent with Arctic cooling: Prior to 6 Ma, low-latitude continental carbon reservoirs expanded during astronomically-forced cool spells. After 6 Ma, however, continental carbon reservoirs contract rather than expand during cold periods due to competing effects between Arctic biomes (ice, tundra, taiga). We conclude that, on geologic timescales, System Earth experienced state-dependent modes of climate–carbon cycle interaction. Climate and carbon cycle interactions during major Earth system changes through the Cenozoic remain unclear. Here, the authors present a combined δ 13 C-δ 18 O megasplice for the last 35 Ma which allows them to identify three marked intervals of distinct climate–carbon cycle interactions.

Background: Mental health and substance use disorders among youth continue to be of critical public health concern in Canada, and urgent action is required within the health system to better respond to the evolving health and wellness needs of youth. Foundry, an integrated youth services (IYS) initiative in British Columbia (BC), is piloting a learning health system (LHS) framework at two (out of 7) operational IYS centres. The goal of Foundry LHS is to optimize the flow of data to knowledge to practice, supporting rapid adaptation and the continuous improvement of service delivery, experiences, and wellness outcomes for youth. The objective of this study was to elucidate learnings from the pilot experience and identify the barriers and facilitators to LHS implementation in an IYS context. Approach: This study was co-designed with the IYS initiative and incorporated an integrated knowledge translation approach. Participants (n=2) were purposively recruited from the LHS implementation team and Foundry Central Office (i.e., the backbone organization supporting the community-based IYS centres). Individual interviews were conducted at the pre- and post-implementation stages of the pilot LHS project and followed a semi-structured guide to broadly capture knowledge and perceptions of the LHS framework, barrier and facilitators to its implementation, and the potential impact on the IYS and its community. Data were analyzed using directed content analysis, guided by the Theoretical Domains Framework and COM-B model. Overarching themes and subthemes were generated, and findings were further interpreted to determine the barriers and facilitators to implementing the LHS in an IYS context, as well as other key learnings from the pilot implementation process. Results: This real-world case study highlights the importance of ensuring that LHS values and structures are incorporated into the overall organizational culture of an IYS initiative. Key themes in participant perception of barriers to the pilot implementation included a lack of clarity, shared vision, change management, and meaningful engagement, leading to limited buy-in and motivation for change. Strong governance, leadership, operational support, and dedicated resourcing over time emerged as strong themes critical to the successful implementation of the LHS in an IYS context. Participants saw the pilot LHS project as an invaluable learning experience and perceived early barriers to be future facilitators of the LHS in this context. Importantly, participants felt that the IYS organizational values, people, and infrastructures were highly aligned with an LHS way of working. These ideas reflected major facilitators and were thought to have created optimism and motivation to continue the work of implementing an LHS across the initiative. Implications: Learnings from this project reveal important challenges and opportunities related to the implementation of an LHS within a dynamic and evolving IYS initiative. Results will be integral to informing the continued development, implementation, and scale-up of the LHS within the IYS context in BC and beyond.

Background TikTok is a global social media platform with over 1 billion active users. Presently, there are few data on how TikTok users navigate the platform for mental health purposes and the content they view. Objective This study aims to understand the patterns of mental health-related content on TikTok and assesses the accuracy and quality of the advice and information provided. Methods We performed a summative content analysis on the top 1000 TikTok videos with the hashtag #mentalhealth between October 12 and 16, 2021. Six content themes were developed to code the data: (1) a personal story, perspective, or confessional, (2) advice and information, (3) emoting, (4) references to death, (5) references to science or research, and (6) a product or service for sale. Advice and information were further assessed by clinical experts. Results A total of 970 mental health-related videos were pulled for our analysis (n = 30 removed due to non-English content). The most prevalent content themes included a personal story, perspective, or confessional (n = 574), advice and information (n = 319), emoting (n = 198), references to death (n = 128). Advice and information were considered misleading in 33.0% of videos (n = 106), with misleading content performing better. Few videos included references to scientific evidence or research (n = 37). Conclusion Healthcare practitioners and researchers may consider increasing their presence on the platform to promote the dissemination of evidence-based information to a wider and more youth-targeted population. Interventions to reduce the amount of misinformation on the platform and increase people's ability to discern between anecdotal and evidence-based information are also warranted.

We estimated effects of maternal depressive symptoms, utilizing the Patient Health Questionnaire-8 (PHQ-8), on women’s HIV prevention behaviors in Migori County, Kenya. Pregnant women ≥ 18 years old, with gestational age of < 37 weeks, were randomized into standard care or three home visits (2 during pregnancy, 1 postpartum) promoting couple HIV testing and counseling (CHTC) and HIV prevention. Of 105 female participants, 37 (35.24%) reported depressive symptoms and 50 (47.62%) were HIV-positive. Three Poisson regressions with robust variance (univariable, multivariable, and multivariable with depressive symptoms/study arm interaction) were modeled for three outcomes: CHTC, infant HIV testing, health-seeking postpartum. In multivariable analysis with interaction, a moderating trend for the interaction between depressive symptoms and individual health-seeking was observed (p-value = 0.067). Women scoring ≤ 9 (n = 68) on the PHQ-8 and participating in home visits were 1.76 times more likely to participate in individual health-seeking compared to participants in standard care (ARR 1.76, 95% CI 1.17–2.66).

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21827-8

The growth factor receptor/PI3K/AKT pathway is an important drug target in many cancers including Glioblastoma. AKT, a key node in the pathway, has 3 isoforms, AKT1, AKT2 and AKT3. Here we investigate their role in GBM. We find each activated, ser473 phosphorylated isoform is present in some GBMs but expression patterns vary. There is a direct relationship between human GBM patient outcome and both AKT1 and AKT2 mRNA levels, but an inverse relationship with AKT3 mRNA. Furthermore, AKT3 mRNA levels were high in a less aggressive GBM subtype. Overexpressing AKT3 improves survival in a rodent model of GBM and decreases colony forming efficiency, but not growth rate, in glioma cells. Silencing AKT3 slows cell cycle progression in one cell line and increases apoptosis in another. Our studies of AKT3 substrates indicate (1) silencing both AKT2 and AKT3 reduces GSK3 phosphorylation (2) only AKT2 silencing reduces S6 phosphorylation. Since S6 phosphorylation is a marker of mTORC1 activity this indicates that AKT2 activates mTORC1, but AKT3 does not. Our results indicate AKT isoforms have different roles and downstream substrates in GBM. Unexpectedly, they indicate AKT3 delays tumor progression. Therefore strategies that inhibit AKT3 may be unhelpful in some GBM patients.

Violence against sex workers can heighten their vulnerability to HIV and other sexually transmitted infections (STIs). Evidence suggests the risk of acquiring STI/HIV infections among female sex workers (FSWs) who have experienced violence to be almost three-times higher than FSWs, who have not experienced violence. Moreover, an experience of physical and sexual violence makes it difficult for them to negotiate safer sex with their partners and often act as a barrier to utilization of prevention services. This study utilizes data from 2785 FSWs aged 18 years and above who participated in a cross-sectional behavioural study conducted during 2013-14 in Thane district, Maharashtra. A probability-based two-stage cluster sampling method was used for data collection. This study assesses the effect of physical violence on self-reported STI symptoms (any STI and multiple STIs) and treatment seeking for the last STI symptom using propensity score matching method. About 18% of sampled FSWs reported physical violence at the time of the survey. The likelihood of experiencing such violence was significantly higher among FSWs who solicited clients at public places, engaged in other economic activities apart from sex work, had savings, and reported high client volume per week. FSWs experiencing violence were also inconsistent condom users while engaging in sex with regular partners and clients. The average adjusted effect of violence clearly depicted an increase in the risk of any STI (11%, p<0.05) and multiple STIs (8%, p<0.10) and reduction in treatment seeking (10%, p<0.05). This study demonstrates a significant effect of physical violence on reporting of any STI symptom and treatment seeking. Findings call for the immediate inclusion of strategies aimed to address violence related challenges in HIV prevention program currently being provided at Thane district. Such strategies would further help in enhancing the access to tailored STI prevention and care services among FSWs in the district.

Purpose: To synthesise evidence on the effectiveness of online learning platforms for facilitating knowledge translation in allied health professionals. Approach: A systematic review of the literature searched three databases (Medline-OVID, CINAHL, Embase) in November 2023 for studies measuring outcomes of knowledge translation initiatives targeting allied health professionals delivered using online learning platforms. Papers were eligible if allied health professionals made up at least 50% of the sample, most of the learning component was online, and comparative data was reported. Data were extracted using a customised form. Quality of studies was appraised using the Downs and Black checklist. Meta-analyses were conducted where sufficient homogenous data were available. Findings: Twenty-three studies published over a 13-year period were included in this review primarily using pre-post study designs. All reported improvements in either knowledge, skill and/or confidence, with an metaanalysis (n=9 studies) showing a significant increase in knowledge gain after exposure to online learning (SMD 1.39; 95% CI = 0.96-1.83). However, there is little evidence that participation in online learning is associated with a change in clinical practice. Research implications: This study supports previous research that online learning can improve knowledge but highlights a need for more rigorous studies addressing the impacts on behaviour change. Practical Implications: Online learning is an effective way of improving knowledge, skill and/or confidence but additional knowledge translation strategies may be needed to lead to a behaviour change. Originality/value: Synthesis of current knowledge of the value and limitations of online learning as a tool to facilitate the implementation of evidence into practice in the allied health professions. Limitations: This review was limited to studies published in the English language only. The quality of studies in this field is low. Few studies measure behaviour change. Funding: Funding support was provided by the National Health and Medical Research Council. The protocol was registered with PROSPERO (CRD42020147013). Conflict of Interest: No authors report a conflict of interest for this study. Acknowledgements: We acknowledge funding support from the National Health and Medical Research Council (NHMRC) of Australia Partnership grant (GNT1134495) and NHMRC Ideas grant (GNT2004443) awarded to LMC.

Introduction HIV infection is frequently transmitted within stable couple partnerships. In order to prevent HIV acquisition in HIV‐negative couples, as well as improve coping in couples with an HIV‐positive diagnosis, it has been suggested that interventions be aimed at strengthening couple relationships, in addition to addressing individual behaviours. However, little is known about factors that influence relationships to impact joint decision‐making related to HIV. Methods We conducted qualitative in‐depth interviews with 40 pregnant women and 40 male partners in southwestern Kenya, an area of high HIV prevalence. Drawing from the interdependence model of communal coping and health behaviour change, we employed thematic analysis methods to analyze interview transcripts in Dedoose software with the aim of identifying key relationship factors that could contribute to the development of a couples‐based intervention to improve health outcomes for pregnant women and their male partners. Results In accordance with the interdependence model, we found that couples with greater relationship‐centred motivations described jointly engaging in more health‐enhancing behaviours, such as couples HIV testing, disclosure of HIV status, and cooperation to improve medication and clinic appointment adherence. These couples often had predisposing factors such as stronger communication skills and shared children, and were less likely to face potential challenges such as polygamous marriages, wife inheritance, living separately, or financial difficulties. For HIV‐negative couples, joint decision‐making helped them face the health threat of acquiring HIV together. For couples with an HIV‐positive diagnosis, communal coping helped reduce risk of interspousal transmission and improve long‐term health prospects. Conversely, participants felt that self‐centred motivations led to more concurrent sexual partnerships, reduced relationship satisfaction, and mistrust. Couples who lacked interdependence were more likely to mention experiencing violence or relationship dissolution, or having difficulty coping with HIV‐related stigma. Conclusions We found that interdependence theory may provide key insights into health‐related attitudes and behaviours adopted by pregnant couples. Interventions that invest in strengthening relationships, such as couple counselling during pregnancy, may improve adoption of beneficial HIV‐related health behaviours. Future research should explore adaptation of existing evidence‐based couple counselling interventions to local contexts, in order to address modifiable relationship characteristics that can increase interdependence and improve HIV‐related health outcomes.