Background

The transition from childhood to adolescence is a uniquely sensitive period for social and emotional learning in the trajectory of human development. This transition is characterized by rapid physical growth, sexual maturation, cognitive and behavioral changes and dynamic changes in social relationships. This pivotal transition provides a window of opportunity for social emotional learning that can shape early adolescent identity formation and gender norms, beliefs and behaviors. The objective of this study is to evaluate the potential of a social emotional learning intervention for very young adolescents (VYAs) to improve social emotional mindsets and skills.

Methods

Discover Learning is a social emotional learning intervention designed for VYAs (10-11 years of age) to support development of social emotional mindsets and skills from four primary schools in Dar es Salaam, Tanzania. The intervention delivered three different packages of learning experiences to three arms of the study. 528 VYAs were randomized to each of the three study arms (A-Content learning, B-Content learning and reflection, and C-Content learning, reflection and experiential practice). A quantitative survey was administered to all participants before and after the intervention to capture changes in social emotional mindsets and skills. A discrete choice experiment measured changes in gender norms, beliefs and behaviors.

Results

528 VYAs were included in the analysis. Participants in all three arms of the study demonstrated significant improvements in social emotional mindsets and skills outcomes (generosity, curiosity, growth mindset, persistence, purpose and teamwork). However, Group C (who received experiential social learning opportunities in small, mixed-gender groups and a parent and community learning components demonstrated larger treatment effects on key outcomes in comparison to Groups A and B. Results indicate Group C participants had greater change in gender equity outcomes (OR = 1.69, p = <0.001) compared to Group A (OR = 1.30, p = <0.001) and Group B (OR = 1.23, p = 0.004).

Conclusion

These findings provide evidence that social emotional learning interventions targeting VYAs can improve social emotional mindsets and skills and gender equity outcomes. The findings indicate the importance of experiential learning activities in mixed-gender groups during the unique developmental window of early adolescence. The study also provides support for the inclusion of parental/caregiver and community engagement in programs designed for VYAs.

Trial registration

Retrospectively registered on July 7^th, 2020. NCT0445807.

Background

Inequitable gender norms, beliefs and behaviors, are shaped by learning experiences during key developmental stages in an individual's life course, and can have negative impacts on health and well-being outcomes. Very early adolescence represents one stage when formative learning experiences about gender inequity can have the potential to support or hinder more equitable gender norms, beliefs and behaviors. The aim of this qualitative study was to evaluate the effect of a gender transformative, social emotional learning intervention for very young adolescents (VYAs) that included experiential learning with peers, parents/caregivers and community members.

Methods

This study examined the effects of an intervention designed to provide social emotional learning opportunities for adolescents ages 10-11 in Dar es Salaam, Tanzania. The qualitative sample included 279 participants. Qualitative methods included 102 in-depth interviews with VYAs, 22 focus groups with 117 VYAs, 60 in-depth interviews with parents/caregivers and 54 participant observations. A grounded theory approach was used to identify emergent themes.

Results

Participants reported growth in targeted areas of social emotional mindsets and skills, including a shift in gender norms, beliefs and behaviors. VYAs reported that experiential learning in mixed gender teams provided opportunities to actively practice and reflect on gender norms, beliefs and behaviors. VYAs also reported active practice of social emotional mindsets and skills with peers, parents/caregivers and the community. Parents/caregivers reported changes in VYAs' social emotional mindsets and skills within the home, with the community and with siblings and peers. Both adolescents and parent/caregivers reported positive change towards more equitable gender norms, beliefs and behaviors through participation in experiential learning activities and reflective discussions.

Conclusions

These findings suggest that an intervention providing social and emotional experiential learning opportunities during the developmental window of very young adolescence can be effective in transforming gender norms, beliefs and behaviors. Involvement of peers, parents/caregivers and community members was effective at supporting learning social emotional mindsets and skills in VYAs. Findings encourage local and global adolescent programming to include gender transformative content paired with social emotional experiential learning with peers, family and the community and can stimulate positive change in gender norms, beliefs and behaviors to promote gender equity.

Background

Variants in multiple genetic loci modify the risk of non-alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis.

Aim

To investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis.

Methods

This is a cross-sectional analysis derived from a well-characterised cohort at risk for NAFLD who underwent genotyping and MRE assessment. Liver stiffness (LS) was estimated using MRE and advanced fibrosis was defined as liver stiffness ≥3.63 kilopascals (kPa). Univariable and multivariable linear and logistic regression analysis, were used to assess the association between genotype and MRE.

Results

Two hundred sixty-four patients (63% women) with a mean age 53 (±17) years, and 31% Hispanic ethnicity with genotyping and MRE were included. The odds of advanced fibrosis were 3.1 (95% CI: 1.1-8.9, P = 0.04) for CG and 6.5 (95% CI: 2.2-18.9, P < 0.01) for GG compared to CC PNPLA3 genotype. Each PNPLA3 risk variant copy was associated with 0.40 kPa (95% CI: 0.19-0.61, P < 0.01) increase in LS on MRE in analysis adjusted for age, sex and BMI and there was significant genotype-age interaction (P < 0.01). Conversely, the protective TA allele in HSD17B13 was associated with a -0.41 kPa (95% CI: -0.76 to -0.05, P = 0.03) decrease in liver stiffness on MRE multivariable analysis.

Conclusion

Knowledge of PNPLA3 and HSD17B13 genotype may assist in the non-invasive risk stratification of NAFLD with closer monitoring recommended for those with high genetic risk.

Background: The maturational period from age 10 to 14-often referred to as very young adolescents (VYAs)-represents a dynamic period of learning and neurobehavioral development as individuals transition from childhood to adolescence. This developmental period presents a window of opportunity for strategic investment to improve trajectories of health, education and well-being among young people. More specifically, neurodevelopmental changes during pubertal maturation influence neural circuitry involved in processing emotions, risks, rewards and social relationships. Technology can be leveraged to create social emotional learning experiences for VYAs and provide opportunities for flexible, distance learning in low-income countries. The aim of this study protocol is to detail how insights from developmental science can be used to inform the intervention design, implementation and evaluation of a distance learning, social emotional learning intervention for VYAs. Methods: This study will be delivered to 500 VYAs in Temeke District, Dar es salaam. Study participants will watch culturally-relevant, animated videos on social emotional mindsets and skills and content will be paired with experiential learning activities over a period of 10 weeks. A nested smart-phone based study will practice learning social emotional skills and mindsets through engagement with multi-media material via the WhatsApp messenger application. Surveys and in-depth interviews will be administered to adolescents, their parents/caregivers and teachers before and after the intervention to evaluate the effect of the intervention on study outcomes. Discussion: This study is among the first to provide results on how to effectively design a distance-learning intervention to promote social emotional learning and identity development within a low-resource context. The findings will provide substantial evidence to inform new intervention approaches that are effective in low-resource contexts and strategies to reach scale among similar programs invested in leveraging technology to support adolescent health and development. Clinical Trial registration: Study registered with ClinicalTrials.gov. Identifier number NCT0445807.

Background & aims

Controlled attenuation parameter (CAP) measurements using M probe have been reported to be lower than those of the XL-probe in detection of hepatic steatosis. However, there has been no direct comparison of CAP with the M vs the XL probe in patients with nonalcoholic fatty liver disease (NAFLD). We compared CAP with the M vs the XL probe for quantification of hepatic fat content, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the standard.

Methods

We performed a prospective study of 100 adults (mean body mass index [BMI], 30.6 ± 4.7 kg/m2) with and without NAFLD, assessed by CAP with the M probe and XL probe on the same day, at a single research center, from November 2017 through November 2018. We then measured the MRI-PDFF as the reference standard. Outcomes were presence of hepatic steatosis, defined as MRI-PDFF ≥ 5%, and detection of hepatic fat content ≥ 10%, defined as MRI-PDFF ≥ 10%. We performed area under the receiver operating characteristic curve (AUROC) analyses to assess the diagnostic accuracy of CAP for each probe in detection of hepatic steatosis (MRI-PDFF ≥ 5%) and of hepatic fat content ≥ 10%.

Results

Of the study participants, 68% had an MRI-PDFF of 5% or more and 48% had an MRI-PDFF of 10% or more. The mean CAP measured by the M probe (310 ± 62 db/m) was significantly lower than by the X probe (317 ± 63 db/m) (P = .007). When M probe was used in participants with BMIs <30 kg/m² and XL probe in participants with BMIs ≥30 kg/m², the CAP measured by the M probe (312 ± 51.4 db/m) remained significantly lower than that of the XL probe (345 ± 47.6 db/m) (P = .0035.), when the MRI-PDFF was above 5%. The optimal threshold of CAP for the detection of MRI-PDFF≥5%, was 294 db/m with the M probe and 307 db/m with the XL probe. The optimal threshold of CAP for the detection of MRI-PDFF ≥ 10%, was 311 db/m with the M probe and 322 db/m with the XL probe. For only the XL probe, CAP measurements with an interquartile range below 30 dB/m detected an MRI-PDFF≥5% with a lower AUROC (0.97; 95% CI, 0.80-1.00) than CAP measurements with an interquartile range above 30 dB/m (AUROC, 0.82; 95% CI, 0.71-0.90) (P = .0129).

Conclusions

In an analysis of the same patients using CAP with the M probe and XL probe, with MRI-PDFF as the standard, we found that the M probe under-quantifies CAP values compared with the XL probe, independent of BMI. The type of probe should be considered when interpreting CAP data from patients with NAFLD.

Background

Controlled attenuation parameter (CAP) is an ultrasound-based point-of-care method to quantify liver fat; however, the optimal threshold for CAP to detect pathologic liver fat among persons living with human immunodeficiency virus (HIV; PLWH) is unknown. Therefore, we aimed to identify the diagnostic accuracy and optimal threshold of CAP for the detection of liver-fat among PLWH with magnetic resonance imaging proton-density fat fraction (MRI-PDFF) as the reference standard.

Methods

Patients from a prospective single-center cohort of PLWH at risk for HIV-associated nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRI-PDFF and CAP assessment were included. Subjects with other forms of liver disease including viral hepatitis and excessive alcohol intake were excluded. Receiver operatic characteristic (ROC) curve analysis were performed to identify the optimal threshold for the detection of HIV-associated NAFLD (liver fat ≥ 5%).

Results

Seventy PLWH (90% men) at risk for NAFLD were included. The mean (± standard deviation) age and body mass index were 48.6 (±10.2) years and 30 (± 5.3) kg/m2, respectively. The prevalence of HIV-associated NAFLD (MRI-PDFF ≥ 5%) was 80%. The M and XL probes were used for 56% and 44% of patients, respectively. The area under the ROC curve of CAP for the detection of MRI-PDFF ≥ 5% was 0.82 (0.69-0.95) at the cut-point of 285 dB/m. The positive predictive value of CAP ≥ 285 dB/m was 93.2% in this cohort with sensitivity of 73% and specificity of 78.6%.

Conclusions

The optimal cut-point of CAP to correctly identify HIV-associated NAFLD was 285 dB/m, is similar to previously published cut-point for primary NAFLD and may be incorporated into routine care to identify patients at risk of HIV-associated NAFLD.

Background & aims

There are limited prospective data on patients with type 2 diabetes mellitus (T2DM) specifically enrolled and systematically assessed for advanced fibrosis or cirrhosis due to non-alcoholic fatty liver disease (NAFLD). Therefore, we aimed to evaluate the prevalence of advanced fibrosis and cirrhosis in a prospectively recruited cohort of adults with T2DM.

Methods

This prospective study enrolled adults aged ≥50 years with T2DM, recruited from primary care or endocrinology clinics. Participants underwent a standardized clinical research visit with MRI-proton density fat fraction (MRI-PDFF), magnetic resonance elastography (MRE), vibration-controlled transient elastography (VCTE) and controlled-attenuation parameter. NAFLD was defined as MRI-PDFF ≥5% after exclusion of other liver diseases. Advanced fibrosis and cirrhosis were defined by established liver stiffness cut-off points on MRE or VCTE if MRE was not available.

Results

Of 524 patients screened, 501 adults (63% female) with T2DM met eligibility. The mean age and BMI were 64.6 (±8.1) years and 31.4 (±5.9) kg/m², respectively. The prevalence of NAFLD, advanced fibrosis and cirrhosis was 65%, 14% and 6%, respectively. In multivariable adjusted models, adjusted for age and sex, obesity and insulin use were associated with increased odds of advanced fibrosis (odds ratio 2.50; 95% CI 1.38-4.54; p = 0.003 and odds ratio 2.71; 95% CI 1.33-5.50; p = 0.006, respectively). Among 29 patients with cirrhosis, two were found to have hepatocellular carcinoma and one patient had gallbladder adenocarcinoma.

Conclusion

Utilizing a uniquely well-phenotyped prospective cohort of patients aged ≥50 years with T2DM, we found that the prevalence of advanced fibrosis was 14% and that of cirrhosis was 6%. These data underscore the high risk of advanced fibrosis/cirrhosis in adults aged ≥50 years with T2DM.

Impact and implications

Non-alcoholic fatty liver disease (NAFLD) is common in patients with type 2 diabetes (T2DM), however, there are limited prospective data characterizing the prevalence of advanced fibrosis and cirrhosis using the most accurate non-invasive biomarkers of liver fat and fibrosis. We show that 14% of older adults with T2DM have advanced fibrosis and 6% have cirrhosis, which places them at risk for liver failure and liver cancer. Accurate prevalence rates and comparative analysis regarding the diagnostic accuracy of non-invasive tests in this population will guide the optimal screening strategy and future cost-effectiveness analyses. These results will inform future Hepatology and Endocrinology practice guidelines regarding NAFLD screening programs in older adults with T2DM.

Background & aims

Controlled attenuation parameter (CAP) measurements using M probe have been reported to be lower than those of the XL-probe in detection of hepatic steatosis. However, there has been no direct comparison of CAP with the M vs the XL probe in patients with nonalcoholic fatty liver disease (NAFLD). We compared CAP with the M vs the XL probe for quantification of hepatic fat content, using magnetic resonance imaging proton density fat fraction (MRI-PDFF) as the standard.

Methods

We performed a prospective study of 100 adults (mean body mass index [BMI], 30.6 ± 4.7 kg/m2) with and without NAFLD, assessed by CAP with the M probe and XL probe on the same day, at a single research center, from November 2017 through November 2018. We then measured the MRI-PDFF as the reference standard. Outcomes were presence of hepatic steatosis, defined as MRI-PDFF ≥ 5%, and detection of hepatic fat content ≥ 10%, defined as MRI-PDFF ≥ 10%. We performed area under the receiver operating characteristic curve (AUROC) analyses to assess the diagnostic accuracy of CAP for each probe in detection of hepatic steatosis (MRI-PDFF ≥ 5%) and of hepatic fat content ≥ 10%.

Results

Of the study participants, 68% had an MRI-PDFF of 5% or more and 48% had an MRI-PDFF of 10% or more. The mean CAP measured by the M probe (310 ± 62 db/m) was significantly lower than by the X probe (317 ± 63 db/m) (P = .007). When M probe was used in participants with BMIs <30 kg/m² and XL probe in participants with BMIs ≥30 kg/m², the CAP measured by the M probe (312 ± 51.4 db/m) remained significantly lower than that of the XL probe (345 ± 47.6 db/m) (P = .0035.), when the MRI-PDFF was above 5%. The optimal threshold of CAP for the detection of MRI-PDFF≥5%, was 294 db/m with the M probe and 307 db/m with the XL probe. The optimal threshold of CAP for the detection of MRI-PDFF ≥ 10%, was 311 db/m with the M probe and 322 db/m with the XL probe. For only the XL probe, CAP measurements with an interquartile range below 30 dB/m detected an MRI-PDFF≥5% with a lower AUROC (0.97; 95% CI, 0.80-1.00) than CAP measurements with an interquartile range above 30 dB/m (AUROC, 0.82; 95% CI, 0.71-0.90) (P = .0129).

Conclusions

In an analysis of the same patients using CAP with the M probe and XL probe, with MRI-PDFF as the standard, we found that the M probe under-quantifies CAP values compared with the XL probe, independent of BMI. The type of probe should be considered when interpreting CAP data from patients with NAFLD.

Cardiovascular disease (CVD) is the leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (DM2).¹ Accurately assessing CVD risk in NAFLD patients is critical to improving clinical outcomes.¹ Use of liver stiffness measurements to noninvasively assess for liver fibrosis is broadening, and magnetic resonance elastography (MRE) is the most accurate modality in NAFLD.² However, the association between fibrosis severity on MRE and the degree of CVD risk is unknown. The aim of this study was to determine whether MRE-assessed liver fibrosis stage is associated with CVD risk determined by Framingham risk score (FRS) and coronary artery calcium (CAC).

Cardiovascular disease (CVD) is the leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (DM2).¹ Accurately assessing CVD risk in NAFLD patients is critical to improving clinical outcomes.¹ Use of liver stiffness measurements to noninvasively assess for liver fibrosis is broadening, and magnetic resonance elastography (MRE) is the most accurate modality in NAFLD.² However, the association between fibrosis severity on MRE and the degree of CVD risk is unknown. The aim of this study was to determine whether MRE-assessed liver fibrosis stage is associated with CVD risk determined by Framingham risk score (FRS) and coronary artery calcium (CAC).