HAtt-Flow: Hierarchical Attention-Flow Mechanism for Group-Activity Scene Graph Generation in Videos.

Group-activity scene graph (GASG) generation is a challenging task in computer vision, aiming to anticipate and describe relationships between subjects and objects in video sequences. Traditional video scene graph generation (VidSGG) methods focus on retrospective analysis, limiting their predictive capabilities. To enrich the scene-understanding capabilities, we introduced a GASG dataset extending the JRDB dataset with nuanced annotations involving appearance, interaction, position, relationship, and situation attributes. This work also introduces an innovative approach, a Hierarchical Attention-Flow (HAtt-Flow) mechanism, rooted in flow network theory to enhance GASG performance. Flow-attention incorporates flow conservation principles, fostering competition for sources and allocation for sinks, effectively preventing the generation of trivial attention. Our proposed approach offers a unique perspective on attention mechanisms, where conventional "values" and "keys" are transformed into sources and sinks, respectively, creating a novel framework for attention-based models. Through extensive experiments, we demonstrate the effectiveness of our Hatt-Flow model and the superiority of our proposed flow-attention mechanism. This work represents a significant advancement in predictive video scene understanding, providing valuable insights and techniques for applications that require real-time relationship prediction in video data.

The effect of different types of oral or intravenous corticosteroids on capillary blood glucose levels in hospitalized inpatients with and without diabetes.

PURPOSE: This study investigated: (1) the type of corticosteroid associated with the greatest degree of hyperglycemia, assessed using bedside capillary blood glucose monitoring, in hospitalized patients; and (2) the pattern of hyperglycemia throughout the day with the use of each type of corticosteroid. METHODS: This single-center, retrospective study used data from 964 adult inpatients receiving oral or IV corticosteroids. Data on capillary blood glucose concentrations and time taken over 7 days were collected. A mixed model for repeated measures was applied to investigate changes in glucose concentration over time with the use of four different corticosteroids. An autoregressive covariance structure was used to model correlations between repeated measurements. FINDINGS: Across all 7 days, the mean blood glucose concentration was greater with dexamethasone compared to that with hydrocortisone (mean difference, 16.6 mg/dL [95% CI, 8.1-24.8] [0.92 mmol/L (95% CI, 0.45-1.38)]) or prednisolone (mean difference, 20.0 mg/dL [95% CI, 14.2-25.7] [1.11 mmol/L (95% CI, 0.79-1.43)]). The mean blood glucose concentration was greater with methylprednisolone compared to that with hydrocortisone (mean difference, 23.9 mg/dL [95% CI, 11.3-36.4] [1.33 mmol/L (95% CI, 0.63-2.02)]), and with methylprednisolone versus prednisolone (mean difference, 27.4 mg/dL [95% CI, 16.4-38.3] [1.52 mmol/L (95% CI, 0.91-2.13)]). There were no significant differences in the patterns of hyperglycemia at six time points of the day with each type of corticosteroid. IMPLICATIONS: Treatment with oral or IV dexamethasone or methylprednisolone was associated with greater hyperglycemia in comparison to prednisolone and hydrocortisone. More vigorous monitoring and intervention, when necessary, are suggested in adult inpatients receiving corticosteroids, in particular dexamethasone and methylprednisolone.

How Do Psychosocial Interventions for Adolescents and Young People Living With HIV Improve Adherence and Viral Load? A Realist Review.

PURPOSE: Psychosocial interventions have the potential to support adolescents and young people living with HIV (AYPLHIV) to achieve better HIV outcomes. However, more evidence is needed to understand which interventions are most effective, and the mechanisms driving how they work in practice. METHODS: We used realist methodologies to generate statements based on evidence from intervention studies and linked evidence included in a systematic review of psychosocial interventions for AYPLHIV. Key data were extracted from available sources to generate cases, including context-mechanism-outcome pathways. Higher level themes were refined iteratively to create a mid-range theory of how these interventions may work. RESULTS: From 26 resulting cases, 8 statements were crafted, grouped into 3 overarching categories, to describe how these interventions worked. Interventions were overall found to set off mechanisms to improve adherence when (1) responding to individual-level factors to support AYPLHIV (via incorporating agency and empowerment, personalized and/or contextualized approaches, and self-care skills); (2) tailoring delivery strategies to address specific needs (via diverse strategies, longer duration, and digital delivery); and (3) providing supportive resources (via peer and broader support, and structural support and integration into existing services). DISCUSSION: A collection of diverse mechanisms may individually or collectively drive improved outcomes for AYPLHIV engaged in psychosocial interventions. Recommendations for integrating our findings into practice are discussed.

Psychosocial interventions for improving engagement in care and health and behavioural outcomes for adolescents and young people living with HIV: a systematic review and meta-analysis.

INTRODUCTION: Adolescents and young people comprise a growing proportion of new HIV infections globally, yet current approaches do not effectively engage this group, and adolescent HIV-related outcomes are the poorest among all age groups. Providing psychosocial interventions incorporating psychological, social, and/or behavioural approaches offer a potential pathway to improve engagement in care and health and behavioural outcomes among adolescents and young people living with HIV (AYPLHIV). METHODS: A systematic search of all peer-reviewed papers published between January 2000 and July 2020 was conducted through four electronic databases (Cochrane Library, PsycINFO, PubMed and Scopus). We included randomized controlled trials evaluating psychosocial interventions aimed at improving engagement in care and health and behavioural outcomes of AYPLHIV aged 10 to 24 years. RESULTS AND DISCUSSION: Thirty relevant studies were identified. Studies took place in the United States (n = 18, 60%), sub-Saharan Africa (Nigeria, South Africa, Uganda, Zambia, Zimbabwe) and Southeast Asia (Thailand). Outcomes of interest included adherence to antiretroviral therapy (ART), ART knowledge, viral load data, sexual risk behaviours, sexual risk knowledge, retention in care and linkage to care. Overall, psychosocial interventions for AYPLHIV showed important, small-to-moderate effects on adherence to ART (SMD = 0.3907, 95% CI: 0.1059 to 0.6754, 21 studies, n = 2647) and viral load (SMD = -0.2607, 95% CI -04518 to -0.0696, 12 studies, n = 1566). The psychosocial interventions reviewed did not demonstrate significant impacts on retention in care (n = 8), sexual risk behaviours and knowledge (n = 13), viral suppression (n = 4), undetectable viral load (n = 5) or linkage to care (n = 1) among AYPLHIV. No studies measured transition to adult services. Effective interventions employed various approaches, including digital and lay health worker delivery, which hold promise for scaling interventions in the context of COVID-19. CONCLUSIONS: This review highlights the potential of psychosocial interventions in improving health outcomes in AYPLHIV. However, more research needs to be conducted on interventions that can effectively reduce sexual risk behaviours of AYPLHIV, as well as those that can strengthen engagement in care. Further investment is needed to ensure that these interventions are cost-effective, sustainable and resilient in the face of resource constraints and global challenges such as the COVID-19 pandemic.

South African adolescents living with spina bifida: contributors and hindrances to well-being.

BACKGROUND: Spina bifida myelomeningocele is a major cause of disability among adolescents. However, little research is available in low-income nations such as South Africa. Investigating the contributors and hindrances to well-being in adolescents with spina bifida myelomeningocele may yield novel insights. In this study we included both adolescents and their primary caregivers to examine their perspectives on caring for and facilitating improvements in the life of the adolescents living with spina bifida myelomeningocele. OBJECTIVES: To identify and document the perceptions of adolescents with spina bifida myelomeningocele and their primary caregivers on the factors that contribute to and hinder the well-being of adolescents living with spina bifida myelomeningocele in South Africa. METHOD: An explorative qualitative research design was utilized, guided by a positive psychology theoretical framework. Fourteen participants, consisting of seven adolescent-primary caregiver dyads, were interviewed. Data were analyzed using thematic analysis and coded inductively using ATLAS.ti software. RESULTS: We identified eight themes describing participants' perceptions on contributors and hindrances to the well-being of adolescents with spina bifida myelomeningocele. Contributing factors included: family support, social groups, special needs education, sport participation, striving for independence, and finding meaning in life. Hindrances included: structural (lack of resources, medical care and mobility challenges) and social (bullying and harmful friendships, secrecy about the condition, social isolation and unhappiness) hindrances to well-being. CONCLUSION: Acknowledging the contributors and hindrances to the well-being of adolescents with spina bifida myelomeningocele is crucial for guiding informed positive interventions and preventing blind spots. Given the limited number of positive contexts, concentrated effort is required to facilitate opportunities for growth in a range of environments. Primary caregivers lack insight into the positive and negative aspects of the adolescents' lives. We suggest families prioritize bonding time and open communication.Implications for rehabilitationExploring the perspectives of adolescents living with spina bifida and their parents regarding well-being is important to develop appropriate interventions.Adolescents living with spina bifida value social support and social interaction as ways to maintain well-being.Special needs education institutions with curriculums tailored to adolescents with spina bifida promote comfort, acceptance, and personal excellence.Sport contributes to the mental, social and physical well-being of adolescents with spina bifida. Sport inspires and offers opportunities for success, it improves school attendance, increases positive affect, and provides opportunities for close relationships with friends and family.Finding ways to mitigate the stigma around spina bifida is necessary to improve adolescents' well-being within South Africa.

A rare case of emphysematous pancreatitis: managing a killer without the knife.

Emphysematous pancreatitis (EP) is a rare and severe complication of acute pancreatitis carrying a high mortality with only a handful of case reports and small studies reporting these cases and their management. The presence of emphysematous pancreatitis is often indicative of infected pancreatic necrosis with the mainstay of treatment being pancreatic necrosectomy; however there are cases where it may be appropriate to have a trial of conservative management, and there is a small body of evidence to support this. This paper describes a case of an 87-year-old male with acute emphysematous pancreatitis successfully managed with conservative cares.

An incarcerated Spigelian hernia with the appendix in the sac passing though all layers of the abdominal wall: an unusual cause for chronic right iliac fossa pain.

Abdominal wall hernias are a common pathology and source of morbidity including chronic pain. They occur in various anatomical areas; amongst the rarest locations is the Spigelian hernia accounting for <2% of all abdominal hernias. We present a case report of a patient with chronic right iliac fossa pain caused by an incarcerated Spigelian hernia containing her appendix within the hernial defect. Rarer still is that her hernial defect penetrated all three layers of anterior abdominal wall, typically a Spigelian hernia would only pass through transversus abdominis and internal oblique layers.

Injectable nanoclay gels for angiogenesis.

The retention and sustained activity of therapeutic proteins at delivery sites are goals of regenerative medicine. Vascular endothelial growth factor (VEGF) has significant potential in promoting the growth and regeneration of blood vessels but is intrinsically labile. This is exacerbated by the inflammatory microenvironments at sites requiring regeneration. For VEGF to be efficacious, it may require a carrier that stabilises it, protects it from degradation and retains it at the site of interest. In this study, we tested the hypothesis that injectable nanoclay gels comprising Laponite™ XLG (a synthetic hectorite clay) can stabilise VEGF and retain it in the active form for therapeutic delivery. To achieve this, VEGF was incorporated in Laponite gels and its activity tested at a range of concentrations using in vitro cell culture tubulogenesis assays and in vivo angiogenesis assays. We found that VEGF-Laponite gels enhanced tubulogenesis in a dose-dependent manner in vitro. When administered subcutaneously in vivo, Laponite was retained at the injection site for up to a period of three weeks and promoted a 4-fold increase in blood vessel formation compared with that of alginate or vehicle controls as confirmed by CD31 staining. Notably, as compared to alginate, Laponite gels did not release VEGF, indicating a strong interaction between the growth factor and the nanoclay and suggesting that Laponite enhancement of VEGF efficacy is due to its retention at the implantation site for a prolonged period. Our approach provides a robust method for the delivery of bioactive recombinant VEGF without the necessity for complex hydrogel or protein engineering. STATEMENT OF SIGNIFICANCE: In medicine, it is important to deliver drugs to a particular location in the body. Often, however, the drugs are quickly broken down and carried away in the blood before they can exert their effect. In this study, we used a type of synthetic clay, called Laponite™, to preserve a molecule, named VEGF, that stimulates the growth of blood vessels. Previously, we have been able to bind VEGF to the surface of clays, but the clay is not effective when injected or applied as a gel. Herein, we show that we can mix VEGF with the clay and that it strongly stimulates blood vessel growth. We speculate that this would be a useful material for skin wound healing.

Prevalence and sociodemographic correlates of common mental disorders among first-year university students in post-apartheid South Africa: implications for a public mental health approach to student wellness.

BACKGROUND: There is growing awareness of the need for effective prevention, early detection, and novel treatment approaches for common mental disorders (CMDs) among university students. Reliable epidemiological data on prevalence and correlates are the cornerstones of planning and implementing effective health services and adopting a public health approach to student wellness. Yet, there is a comparative lack of sound psychiatric epidemiological studies on CMDs among university students in low- and middle-income countries, like South Africa (SA). It is also unclear if historically marginalised groups of students are at increased risk for mental health problems in post-apartheid SA. The objective of the study was to investigate the prevalence and sociodemographic correlates of lifetime and 12-month CMDs among university students in SA, with a particular focus on vulnerability among students in historically excluded and marginalised segments of the population. METHODS: Data were collected via self-report measures in an online survey of first-year students registered at two large universities (n = 1402). CMDs were assessed with previously-validated screening scales. Data were weighted and analysed using multivariate statistical methods. RESULTS: A total of 38.5% of respondents reported at least one lifetime CMD, the most common being major depressive disorder (24.7%). Twelve-month prevalence of any CMD was 31.5%, with generalised anxiety disorder being the most common (20.8%). The median age of onset for any disorder was 15 years. The median proportional annual persistence of any disorder was 80.0%. Female students, students who reported an atypical sexual orientation, and students with disabilities were at significantly higher risk of any lifetime or 12-month disorder. Female gender, atypical sexual orientation, and disability were associated with elevated risk of internalising disorders, whereas male gender, identifying as White, and reporting an atypical sexual orientation were associated with elevated risk of externalising disorders. Older age, atypical sexual orientation, and disability were associated with elevated risk of bipolar spectrum disorder. CONCLUSIONS: Despite advances to promote greater social inclusion in post-apartheid SA, students who identify as female, students with atypical sexual orientations, and students with disabilities are nonetheless at increased risk of CMDs, although students who identify as Black and first-generation students are not.

2015 Legislative update of e-cigarette youth access and exposure laws.

BACKGROUND: As of November 15, 2013, 22 states had passed laws explicitly addressing youth access to electronic cigarettes (e-cigarettes); by 2014, this increased to 41 states. Also in 2014, more than 13.4% of youth in the U.S. reported using e-cigarettes, making e-cigarette use more prevalent than conventional cigarette use (9.2%). METHODS: We examined 221 bills addressing youth access and exposure to e-cigarettes between January 1 and November 1, 2015. Text searches on individual state general assembly websites and secondary sources were employed for data collection. Laws were analyzed using seven measures identified to protect adolescents from nicotine initiation and use. RESULTS: Two states (MI, PA) and Washington D.C. do not regulate the sale or distribution of e-cigarettes to youth as of November 1, 2015. Additionally, seventeen states have passed laws requiring e-cigarettes to use child-safety packaging to minimize unintended poisoning. As of July 1, 2016, four states (KS, LA, MN, and NC) will tax e-cigarettes. Oregon prohibits the use of e-cigarettes in cars with children under 18years of age, and Wyoming requires the public health department to develop educational campaigns to better educate the state on the risks of nicotine and tobacco products. CONCLUSION: While states are closing the gap of youth nicotine exposure, there remains a need to protect youth from e-cigarettes access, which can cause adverse health effects of brain development, lung function and potentially lead to addiction. Recommendation for the FDA to regulate e-cigarettes federally would close this regulation gap and protect youth across the U.S.

N-Methyl-3-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamides as a novel class of cannabinoid receptors agonists with low CNS penetration.

Cannabinoid CB(1) receptor agonists exhibit potent analgesic effects in rodents and humans, but their clinical utility as analgesic drugs is often limited by centrally mediated side effects. We report herein the preparation of N-methyl-3-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamides as a novel class of hCB(1)/hCB(2) dual agonists with attractive physicochemical properties. More specifically, (R)-N,9-dimethyl-N-(4-(methylamino)-4-oxobutyl)-3-(tetrahydro-2H-pyran-4-yl)-2,3,4,9-tetrahydro-1H-carbazole-6-carboxamide, displayed an extremely low level of CNS penetration (Rat Cbr/Cplasma=0.005 or 0.5%) and was devoid of CNS side effects during pharmaco-dynamic testing.

Novel benzimidazole derivatives as selective CB2 agonists.

The preparation and evaluation of a novel class of CB2 agonists based on a benzimidazole moiety are reported. They showed binding affinities up to 1nM towards the CB2 receptor with partial to full agonist potencies. They also demonstrated good to excellent selectivity (>1000-fold) over the CB1 receptor.

New 1,2,3,4-tetrahydropyrrolo[3,4-b]indole derivatives as selective CB2 receptor agonists.

The preparation and evaluation of a novel class of CB2 agonists based on a 1,2,3,4-tetrahydropyrrolo[3,4-b]indole moiety are reported. They showed binding affinities up to 4.2 nM toward CB2 with sub-nanomolar EC(50) values. They also showed moderate to good (>350-fold) selectivity over the CB1 receptor.

Thermodynamic, kinetic, and electron microscopy studies of concanavalin A and Dioclea grandiflora lectin cross-linked with synthetic divalent carbohydrates.

The jack bean lectin concanavalin A (ConA) and the Dioclea grandiflora lectin (DGL) are highly homologous Man/Glc-specific members of the Diocleinae subtribe. Both lectins bind, cross-link, and precipitate with carbohydrates possessing multiple terminal nonreducing Man residues. The present study investigates the binding and cross-linking interactions of ConA and DGL with a series of synthetic divalent carbohydrates that possess spacer groups with increasing flexibility and length between terminal alpha-mannopyranoside residues. Isothermal titration microcalorimetry was used to determine the thermodynamics of binding of the two lectins to the divalent analogs, and kinetic light scattering and electron microscopy studies were used to characterize the cross-linking interactions of the lectins with the carbohydrates. The results demonstrated that divalent analogs with flexible spacer groups between the two terminal Man residues possess higher affinities for the two lectins as compared with those with inflexible spacer groups. Furthermore, despite their high degree of homology, ConA and DGL exhibit differences in their kinetics of cross-linking and precipitation with the divalent analogs. Electron microscopy shows the loss of organized cross-linked lattices of the two lectins with analogs possessing increased distance between the terminal Man residues. The loss of lattice patterns with the analogs is distinct for each lectin. These results have important implications for the interactions of lectins with multivalent carbohydrate receptors in biological systems.

New scaffolds in the development of mu opioid-receptor ligands.

A new class of mu selective receptor antagonists has been developed using a combinatorial approach based on previously reported Dmt-Tic dipeptide ligands. Modified tetrahydroisoquinoline (Tiq) residues were reacted with different electrophiles in order to create novel molecules that would mimic the original dipeptide. A specific class of thioureas bearing basic pyrrolidine residues were shown to give good binding affinities. Further alkylation of the pyrrolidine ring with benzyl derivatives also proved to increase the mu binding affinity. In addition, it was demonstrated that mu binding was enhanced by the presence of polar groups around the benzyl ring having hydrogen-bonding character (donor/acceptor). This new class of ligands represents a novel scaffold in the development of opioid analogues.

Inhibition of adhesion of type 1 fimbriated Escherichia coli to highly mannosylated ligands.

The inhibitory potencies of a number of mannosides, di- and trivalent mannosides, a set of mannose-terminating dendrimers, and five types of mannose-bearing neoglycoproteins were determined by using a binding assay that measures the binding of (125)I-labeled, highly mannosylated neoglycoprotein to a type 1 fimbriated Escherichia coli (K12) strain in suspension. The IC(50) values (the concentration of inhibitor that causes 50 % reduction in the bound (125)I-ligand to E. coli) obtained by this method were much lower than the equivalent values obtained by hemagglutination or in assays that involve microplate immobilization. Two important factors that strongly influence the affinity to E. coli adhesin are: 1) the presence of an alpha-oriented aglycon that has a long aliphatic chain or an aromatic group immediately next to the glycosyl oxygen, and 2) the presence of multiple mannosyl residues that can span a distance of 20 nm or longer on a relatively inflexible structure. The two best inhibitors, which are a highly mannosylated neoglycoprotein with the longest linking arm between a mannose and protein amino group and the largest mannosylated dendrimer (fourth generation), exhibited sub-nM IC(50) values.

Negative cooperativity associated with binding of multivalent carbohydrates to lectins. Thermodynamic analysis of the "multivalency effect".

Our previous study demonstrated that isothermal titration microcalorimetry (ITC) could be used to determine the thermodynamics of binding of a series of synthetic multivalent carbohydrates to the Man/Glc-specific lectins concanavalin A (ConA) and Dioclea grandiflora lectin (DGL) [Dam, T. K., Roy, R., Das, S. K., Oscarson, S. and Brewer, C. F. (2000) J. Biol. Chem. 275, 14223-14230]. The higher affinities of the multivalent carbohydrates for the two lectins were shown to be due to their greater positive entropy of binding contributions relative to monovalent analogues. In the present study, ITC data from our previous report for binding of di-, tri-, and tetravalent carbohydrate analogues possessing terminal 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside residues to ConA and DGL were subjected to Hill plot analysis. Hill plots of the binding of monovalent methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside to ConA and DGL are linear with slopes near 1.0, demonstrating a lack of binding cooperativity and allosteric transitions in the proteins. However, Hill plots for the binding of the di-, tri-, and tetravalent trimannoside analogues to both lectins are curvilinear with decreasing tangent slopes below 1.0, indicating increasing negative cooperativity upon binding of the analogues to the lectins. The curvilinear Hill plots are consistent with decreasing affinity and functional valencies of the multivalent analogues upon sequential binding of lectin molecules to the carbohydrate epitopes of the analogues. The following paper [Dam, T. K., Roy, R., Pagé, D., and Brewer, C. F. (2002) Biochemistry 41, 1359-1363] provides direct evidence of the decreasing affinity constants of multivalent carbohydrates upon sequential binding of lectin molecules.

Thermodynamic binding parameters of individual epitopes of multivalent carbohydrates to concanavalin a as determined by "reverse" isothermal titration microcalorimetry.

The preceding paper [Dam, T. K., Roy, R., Pagé, D., and Brewer, C. F. (2002) Biochemistry 41, 1351-1358] demonstrated that Hill plots of isothermal titration microcalorimetry (ITC) data for the binding of di-, tri-, and tetravalent carbohydrate analogues possessing terminal 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside residues to the lectin concanavalin A (ConA) show increasing negative cooperativity upon binding of the analogues to the lectin. The present study demonstrates "reverse" ITC experiments in which the lectin is titrated into solutions of di- and trivalent analogues. The results provide direct determinations of the thermodynamics of binding of ConA to the individual epitopes of the two multivalent analogues. The n values (number of binding sites per carbohydrate molecule) derived from reverse ITC demonstrate two functional binding epitopes on both the di- and trivalent analogues, confirming previous "normal" ITC results with the two carbohydrates [Dam, T. K., Roy, R., Das, S. K., Oscarson, S., and Brewer, C. F. (2000) J. Biol. Chem. 275, 14223-14230]. The reverse ITC measurements show an 18-fold greater microscopic affinity constant of ConA for the first epitope of the divalent analogue versus its second epitope and a 53-fold greater microscopic affinity constant of ConA binding to the first epitope of the trivalent analogue versus its second epitope. The data also demonstrate that the microscopic enthalpies of binding of the two epitopes on the di- and trivalent analogues are essentially the same and that differences in the microscopic K(a) values of the epitopes are due to their different microscopic entropies of binding values. These findings are consistent with the increasing negative Hill coefficients of these analogues binding to ConA in the previous paper.