A multi-level developmental approach towards understanding adolescent mental health and behaviour: rationale,design and methods of the LIFECOURSE study in Iceland

Purpose

Identifying and understanding modifiable risk and protective factors that can inform early detection and intervention to prevent adolescent emotional problems and harmful behaviours is among the most pressing modern-day public health challenges. This paper describes the rationale, objectives, methods, and anticipated outcomes of the LIFECOURSE study, a multi-level, bio-psychosocial prospective study designed to advance our understanding of factors that shape adolescent mental health and behaviour.

Methods

Conducted by the Icelandic Centre for Social Research and Analysis at Reykjavik University, LIFECOURSE is a longitudinal population-based developmental study of Icelandic adolescents born in 2004. The study utilizes a comprehensive multi-informant assessment of individual, societal and biological factors measured across the lifespan. Data assembly and collection were conducted from 2016–2020 and utilize both retrospective and prospective data sources: (a) retrospective registry data assembled from seven national databases, (b) prospectively collected social surveys and (c) biomarker samples.

Results

Of the 3914 eligible adolescents, 60.8% (n = 2378) provided informed parental consent and student assent to participate in the study, with approximately half of the participants being female (n = 1175, 49.4%) and the majority being born in the capital area (n = 1455; 61.2%). The coverage of available data from the national databases and participation in the social surveys ranged from 81.7 to 100%.

Conclusions

Major gaps remain in our knowledge of how individual, societal and biological factors across the lifespan—from early life to adolescence—interact and shape the risk for emotional problems and harmful behaviours during adolescence. The LIFECOURSE study was designed to address this knowledge gap.

     

Maximum Tolerated Osmolarity for Peripheral Administration of Parenteral Nutrition in Pediatric Patients

Background: Limited data support a recommended maximum osmolarity for administration of peripheral parenteral nutrition (PPN). In this retrospective, matched‐cohort study, we evaluated the incidence of phlebitis or infiltration associated with administration of PPN with an osmolarity >1000 mOsm/L vs ≤1000 mOsm/L. Materials and Methods: Patients ≤18 years old who received PPN in a 2‐year period were included in the study. Data related to patient demographics, PPN constituents, and adverse effects were analyzed. Results: A total of 352 patients met entry criteria. Overall, 139 (40%) patients experienced phlebitis or infiltration. There were no differences between patients who did or did not develop adverse events in terms of age or weight. Administration of PPN with osmolarity >1000 mOsm/L vs ≤1000 mOsm/L significantly increased infiltration (17% vs 7%; odds ratio [OR, 2.47]; 95% confidence interval [CI], 1.24–4.94; P = .01) and the combined composite end point of phlebitis or infiltration (45% vs 34%; OR, 1.65; 95% CI, 1.07–2.54; P = .02). In multivariate analysis, osmolarity >1000 mOsm/L vs ≤1000 mOsm/L was an independent risk factor for developing complications (OR, 1.67; 95% CI, 1.08–2.52; P = .02). Conclusion: Two of every 5 children experienced phlebitis or infiltration during administration of PPN. These adverse effects were more often observed in those who received PPN with osmolarity >1000 mOsm/L vs ≤1000 mOsm/L. With this high incidence of adverse effects, we recommend that if PPN is used, the osmolarity should not exceed 1000 mOsm/L. More important, PPN should only be used temporarily until central access is obtained.     

The L4F3 antigen is expressed by unipotent and multipotent colony- forming cells but not by their precursors

Antibody L4F3 is a murine monoclonal antibody that recognizes an antigen expressed on in vitro colony-forming cells, including virtually all CFU-GM, CFU-Meg, BFU-E, and CFU-Mix. In the present study we examined whether cells that do not express the L4F3 antigen include precursors of hematopoietic colony-forming cells. Colony-forming cells were depleted from marrow by treatment with L4F3 and complement. The remaining cells generated CFU-GM, BFU-E, and CFU-Mix when cultured in the presence of irradiated adherent cell layers from long-term marrow cultures. Marrow cells not expressing the L4F3 antigen, which were separated by cell-sorting techniques, were depleted of colony-forming cells but nevertheless generated CFU-GM when cultured over irradiated adherent cell layers. These data suggest that there are marrow precursors that do not express the L4F3 antigen and that give rise to colony-forming cells of multiple types. Negative selection techniques should allow the enrichment of these precursors of colony-forming cells, thereby enabling direct studies of these immature stem cells.     

Monoclonal antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors

A monoclonal antibody, 12-8, prepared against KG-1a cells, recognizes an approximately 115-kd cell surface antigen and reacts with 3% to 4% of bone marrow cells, including most of the blast cells. The antigen is not expressed on peripheral blood cells. Marrow cells expressing 12-8 collected by fluorescence-activated cell sorting contained nearly all of the unipotent (CFU-GM, BFU-E) and multipotent (CFU-MIX) colony- forming cells. The isolated 12-8 positive marrow population also contained precursors of these colony-forming cells. In a two-stage long- term marrow culture system employing irradiated allogeneic marrow adherent cells, 12-8 positive cells produced both unipotent and multipotent colony-forming cells for ten weeks. Moreover, the output of colony forming cells substantially exceeded the input. Antibody 12-8 appears useful for analysis and possibly enrichment of hematopoietic progenitor cells that include colony-forming cell precursors.