Repurposing dried blood spot device technology to examine bile acid profiles in human dried fecal spot samples.

Dried blood spot (DBS) analysis has existed for >50 years, but application of this technique to fecal analysis remains limited. To address whether dried fecal spots (DFS) could be used to measure fecal bile acids, we collected feces from five subjects for each of the following cohorts: 1) healthy individuals, 2) individuals with diarrhea, and 3) Clostridioides difficile-infected patients. Homogenized fecal extracts were loaded onto quantitative DBS (qDBS) devices, dried overnight, and shipped to the bioanalytical lab at ambient temperature. For comparison, source fecal extracts were shipped on dry ice and stored frozen. After 4 mo, frozen fecal extracts and ambient DFS samples were processed and subjected to targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics with stable isotope-labeled standards. We observed no differences in the bile acid levels measured between the traditional extraction and the qDBS-based DFS methods. This pilot data demonstrates that DFS-based analysis is feasible and warrants further development for fecal compounds and microbiome applications.NEW & NOTEWORTHY Stool analysis in remote settings can be challenging, as the samples must be stored at -80°C and transported on dry ice for downstream processing. Our work indicates that dried fecal spots (DFS) on Capitainer quantitative DBS (qDBS) devices can be stored and shipped at ambient temperature and yields the same bile acid profiles as traditional samples. This approach has broad applications for patient home testing and sample collection in rural communities or resource-limited countries.

Acute respiratory failure-related excess mortality in pediatric sepsis.

Excess mortality risk imparted by acute respiratory failure in children is unknown. We determined excess mortality risk associated with mechanically ventilated acute respiratory failure in pediatric sepsis. Novel ICD10-based algorithms were derived and validated to identify a surrogate for acute respiratory distress syndrome to calculate excess mortality risk. Algorithm-identified ARDS was identified with specificity of 96.7% (CI 93.0 - 98.9) and sensitivity of 70.5% (CI 44.0 - 89.7). Excess risk of mortality for ARDS was 24.4% (CI 22.9 - 26.2). Development of ARDS requiring mechanical ventilation imparts modest excess risk of mortality in septic children.

Mechanical Power Is Associated With Mortality in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: Mechanical power (MP) transferred from the ventilator to the lungs has been proposed as a summary variable that may impact mortality in children with acute respiratory distress syndrome (ARDS). To date, no study has shown an association between higher MP and mortality in children with ARDS. DESIGN: Secondary analysis of a prospective observational study. SETTING: Single-center, tertiary, academic PICU. PATIENTS: Five hundred forty-six intubated children with ARDS enrolled between January 2013 and December 2019 receiving pressure-controlled ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Higher MP was associated with increased mortality (adjusted hazard ratio [HR] 1.34 per 1 sd increase, 95% CI 1.08-1.65; p = 0.007). When assessing the contribution of individual components of MP, only positive end-expiratory pressure (PEEP) was associated with mortality (HR 1.32; p = 0.007), whereas tidal volume, respiratory rate, and driving pressure (ΔP = [peak inspiratory pressure (PIP)-PEEP]) were not. Finally, we tested whether there remained an association when specific terms were removed from the MP equation by calculating MP from static strain (remove ΔP), MP from dynamic strain (remove PEEP), and mechanical energy (remove respiratory rate). MP from static strain (HR 1.44; p < 0.001), MP from dynamic strain (HR 1.25; p = 0.042), and mechanical energy (HR 1.29; p = 0.009) were all associated with mortality. MP was associated with ventilator-free days only when using MP normalized to predicted body weight, but not when using measured weight. CONCLUSIONS: Higher MP was associated with mortality in pediatric ARDS, and PEEP appears to be the component most consistently driving this association. As higher PEEP is used in sicker patients, the association between MP and mortality may reflect a marker of illness severity rather than MP itself being causal for mortality. However, our results support future trials testing different levels of PEEP in children with ARDS as a potential means to improve outcome.

Targeted proteomics using stable isotope labeled protein fragments enables precise and robust determination of total apolipoprotein(a) in human plasma.

Lipoprotein(a), also known as Lp(a), is an LDL-like particle composed of apolipoprotein(a) (apo(a)) bound covalently to apolipoprotein B100. Plasma concentrations of Lp(a) are highly heritable and vary widely between individuals. Elevated plasma concentration of Lp(a) is considered as an independent, causal risk factor of cardiovascular disease (CVD). Targeted mass spectrometry (LC-SRM/MS) combined with stable isotope-labeled recombinant proteins provides robust and precise quantification of proteins in the blood, making LC-SRM/MS assays appealing for monitoring plasma proteins for clinical implications. This study presents a novel quantitative approach, based on proteotypic peptides, to determine the absolute concentration of apo(a) from two microliters of plasma and qualified according to guideline requirements for targeted proteomics assays. After optimization, assay parameters such as linearity, lower limits of quantification (LLOQ), intra-assay variability (CV: 4.7%) and inter-assay repeatability (CV: 7.8%) were determined and the LC-SRM/MS results were benchmarked against a commercially available immunoassay. In summary, the measurements of an apo(a) single copy specific peptide and a kringle 4 specific peptide allow for the determination of molar concentration and relative size of apo(a) in individuals.

The McLean Screening Instrument for Borderline Personality Disorder: What, and why in a clinical cohort?

Borderline Personality Disorder is a severe psychiatric disorder with debilitating consequences. Screening for the disorder is problematic as symptoms overlap with other psychiatric disorders. The McLean Screening Instrument (MSI) assesses endorsement (yes/no) of 10 symptoms, with a cut-off of seven indicating potential caseness. Participants were (N = 68) from an established clinical cohort who completed a structured clinical interview, the MSI, the Childhood Trauma Questionnaire, and the Adolescent and Adult Time Attitudes Scale. A proportion (N = 20) also completed a follow-up interview examining their rationale for endorsing MSI items. Total number of MSI items endorsed was meaningfully related to scores on emotional neglect and negative time attitudes. There was substantive overlap between MSI threshold (≥7 items) and lifetime diagnosis of a mental disorder. The stated rationale for endorsing MSI items, was less indicative of personality trait, and was related more to particular developmental periods, one-off episodes, and life-contexts. Additionally, participants conflated constructs such as emptiness with loneliness, and moodiness with general emotionality. Those meeting MSI threshold recalled more childhood emotional neglect, and were more negative about all time periods. It is apparent that scoring of the MSI is driven by prevailing life circumstances as much as enduring personality traits.

Reference materials for MS-based untargeted metabolomics and lipidomics: a review by the metabolomics quality assurance and quality control consortium (mQACC).

INTRODUCTION: The metabolomics quality assurance and quality control consortium (mQACC) is enabling the identification, development, prioritization, and promotion of suitable reference materials (RMs) to be used in quality assurance (QA) and quality control (QC) for untargeted metabolomics research. OBJECTIVES: This review aims to highlight current RMs, and methodologies used within untargeted metabolomics and lipidomics communities to ensure standardization of results obtained from data analysis, interpretation and cross-study, and cross-laboratory comparisons. The essence of the aims is also applicable to other 'omics areas that generate high dimensional data. RESULTS: The potential for game-changing biochemical discoveries through mass spectrometry-based (MS) untargeted metabolomics and lipidomics are predicated on the evolution of more confident qualitative (and eventually quantitative) results from research laboratories. RMs are thus critical QC tools to be able to assure standardization, comparability, repeatability and reproducibility for untargeted data analysis, interpretation, to compare data within and across studies and across multiple laboratories. Standard operating procedures (SOPs) that promote, describe and exemplify the use of RMs will also improve QC for the metabolomics and lipidomics communities. CONCLUSIONS: The application of RMs described in this review may significantly improve data quality to support metabolomics and lipidomics research. The continued development and deployment of new RMs, together with interlaboratory studies and educational outreach and training, will further promote sound QA practices in the community.

Intervention impact on alcohol use, alcohol harms, and a combination of both: A latent class, secondary analysis of results from a randomized controlled trial.

BACKGROUND: Alcohol use and alcohol-related harm (ARH) among adolescents places a substantial burden on health, and public services more generally. To date, attempts to intervene at a universal level have yielded results varying from iatrogenic to null, although some skill-enhancing universal interventions have successfully impacted drinking behaviors. One such intervention is SHAHRP. The present study is a secondary analysis of data from the STAMPP Trial, providing new, and more nuanced findings. METHODS: A total of 13,914 adolescents (41.7% female) participated in this cRCT where schools were randomly assigned to a control or intervention group. Growth mixture modelling was used to identify trajectory classes from baseline through third follow-up (+33 months) of adolescents on heavy episodic drinking (HED) and ARH. Extracted classes were related to school intervention participation using multinomial logistic regression. RESULTS: Five trajectory classes of the HED and ARH composite were identified: Low (62%), Late Onset (16%), Early Onset (13%), Delayed Onset (7%), and Unstable (3%). The intervention was most strongly related to Late Onset (OR = 0.50, 95%CI [0.25, 1.01]) and Delayed Onset (OR = 0.55, 95%CI [0.26, 1.16]), although not statistically significant. With classes constructed with ARH only, the Delayed Onset class was significantly related to the intervention (OR = 0.60, 95%CI [0.43, 0.84]). CONCLUSIONS: These results support those previously reported on the STAMPP Trial and provide a more nuanced insight into the effects of the intervention.

One rule for one, and a different rule for another: The case of the Parental Rules about Alcohol Questionnaire.

BACKGROUND: The parental rules about alcohol questionnaire (Van der Vorst et al., 2005, 2006) uses 10 items to assess how strictly adolescents believe the rules set by their parents about drinking are. An increasing body of literature has attested to the importance of rule setting in the prevention of problematic alcohol use among adolescents. A recent study proposed a two-factor solution in place of the hypothesized unidimensional one, with factors assessing non-normative, and normative rules. METHODS: The present study used five waves of data to examine the structure of the scale, and how well it relates to a measure of heavy episodic drinking (HED). Participants in Waves one to four {10,954-9,383} were substantively more numerous than those at wave five (N = 2,332). RESULTS: Confirmatory Factor Analyses did not support either the ten-item hypothesized model, nor the proposed two-factor solution. Results of exploratory factor analyses all pointed to a one factor solution. Using Modification Indices, we obtained a good-fitting, five-item unidimensional model in Waves one to four. At wave five, a good fitting unidimensional model was obtained with the dropping of a further item. Scores on this shortened scale were internally consistent, correlated highly with scores on the original ten-item version, and correlated to a similar degree as the original 10-item measure, with scores on a HED measure. CONCLUSION: Further work is required in assessing the properties of this scale across cultures and samples before definitively determining that two factors best represent parental rules.

Detailed Method for Performing the ExSTA Approach in Quantitative Bottom-Up Plasma Proteomics.

The use of stable isotope-labeled standards (SIS) is an analytically valid means of quantifying proteins in biological samples. The nature of the labeled standards and their point of insertion in a bottom-up proteomic workflow can vary, with quantification methods utilizing curves in analytically sound practices. A promising quantification strategy for low sample amounts is external standard addition (ExSTA). In ExSTA, multipoint calibration curves are generated in buffer using serially diluted natural (NAT) peptides and a fixed concentration of SIS peptides. Equal concentrations of SIS peptides are spiked into experimental sample digests, with all digests (control and experimental) subjected to solid-phase extraction prior to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Endogenous peptide concentrations are then determined using the regression equation of the standard curves. Given the benefits of ExSTA in large-scale analysis, a detailed protocol is provided herein for quantifying a multiplexed panel of 125 high-to-moderate abundance proteins in undepleted and non-enriched human plasma samples. The procedural details and recommendations for successfully executing all phases of this quantification approach are described. As the proteins have been putatively correlated with various noncommunicable diseases, quantifying these by ExSTA in large-scale studies should help rapidly and precisely assess their true biomarker efficacy.

An Examination of the Longer-Term Impact of a Combined Classroom and Parental Intervention on Alcohol-Related Harms and Heavy Episodic Drinking.

Although fewer adolescents are consuming alcohol than was the case in previous decades, those who are consuming alcohol are still exposed to alcohol-related harms. While the evidence for the effectiveness of universal, school-based interventions is limited, a recent cluster randomised controlled trial (The STAMPP Trial) reported a significant effect at 10 months post-intervention of a combined classroom/parental intervention on heavy episodic drinking (HED) in the previous 30 days, but no significant effect on the number of self-reported alcohol-related harms (ARH) experienced in the previous 6 months. This follow-up study sought to examine intervention effects 24 months after delivery of the intervention (+ 57 months from baseline, or + 34 months post-intervention). Participants were 5029 high school students in STAMPP (38% of 12,738 pupils originally randomised into the trial), from 87 schools (82.3% of schools recruited in the original STAMPP trial). Outcomes were assessed using two-level random intercepts models (logistic regression for HED and negative binomial for number of ARH). Results of the present study show that the intervention effect for HED deteriorated over the following 2 years (OR declined from 0.60 to 0.97), and there was still no difference in ARH. This was due to an increase in the prevalence of intervention students' HED rather than a reduction in prevalence in control students. Results are discussed in the context of prevention initiatives.

Hepatomegaly and short stature in a 14-year-old with type 1 diabetes mellitus: case report.

BACKGROUND: Mauriac syndrome is a rare consequence of poorly controlled insulin-dependent diabetes, characterized by hepatomegaly, growth failure, delayed onset of puberty, and cushingoid features. Case reports of patients with Mauriac syndrome are found infrequently in the literature given historic improvements in diabetes management due to readily available insulin therapy. METHODS: We describe a case of a 14-year-old girl who presented with acute onset abdominal pain, distention, and orthopnea. RESULTS: She had a history of poorly controlled insulin-dependent diabetes as well as short stature. Abdominal imaging revealed impressive hepatomegaly. Laboratory testing showed markedly elevated triglycerides and cholesterol. Mauriac syndrome was suspected and diagnosed by liver biopsy, which demonstrated significant glycogenic hepatopathy. CONCLUSIONS: This case provides an illustrative example of Mauriac syndrome in a child who did not experience delayed onset of puberty and continued to have regular menses unlike what has been previously described. Furthermore, this case highlights the important consideration for significant dyslipidemia in patients with Mauriac syndrome and discusses the challenges of controlling insulin-dependent diabetes in the adolescent population.

Patient-Reported Quality of Life and Convalescence After Minimally Invasive Kidney Cancer Surgery.

OBJECTIVE: To better characterize recovery after minimally invasive kidney surgery, we present a study describing patient-reported health-related quality of life (HRQOL) following minimally invasive radical nephrectomy (RN) and partial nephrectomy (PN). METHODS: Patients who underwent minimally invasive PN or RN for renal cancer were invited to enroll in a prospective, patient-reported HRQOL study using the Convalescence and Recovery Evaluation (CARE) instrument and Short Form-12. Patients completed questionnaires at baseline, 2, 4, 8, and 12 weeks after surgery. Mixed repeated measures model were used to assess time effect on HRQOL scores and predictors of scores within each surgery groups. RESULTS: One hundred seventy-seven patients were included in the study: 50 had RN and 127 had PN. At 2 weeks, both groups had significant decreases in Overall CARE, as well as the Pain, Gastrointestinal, and Activity domain scores which remained slightly below baseline at 4 weeks. At 4 weeks only 50% of patients in both the RN and PN cohorts returned to baseline overall CARE score. By 12 weeks 82% returned to baseline overall CARE score in the RN group while 76% of patients did so in the PN group. CONCLUSION: Convalescence after minimally invasive renal surgery can often extend beyond 4 weeks post-treatment in PN and RN subjects. This information may be used to provide more accurate preoperative counseling in an attempt to improve overall patient satisfaction.

Absolute Quantification of Apolipoproteins Following Treatment with Omega-3 Carboxylic Acids and Fenofibrate Using a High Precision Stable Isotope-labeled Recombinant Protein Fragments Based SRM Assay.

Stable isotope-labeled standard (SIS) peptides are used as internal standards in targeted proteomics to provide robust protein quantification, which is required in clinical settings. However, SIS peptides are typically added post trypsin digestion and, as the digestion efficiency can vary significantly between peptides within a protein, the accuracy and precision of the assay may be compromised. These drawbacks can be remedied by a new class of internal standards introduced by the Human Protein Atlas project, which are based on SIS recombinant protein fragments called SIS PrESTs. SIS PrESTs are added initially to the sample and SIS peptides are released on trypsin digestion. The SIS PrEST technology is promising for absolute quantification of protein biomarkers but has not previously been evaluated in a clinical setting. An automated and scalable solid phase extraction workflow for desalting and enrichment of plasma digests was established enabling simultaneous preparation of up to 96 samples. Robust high-precision quantification of 13 apolipoproteins was achieved using a novel multiplex SIS PrEST-based LC-SRM/MS Tier 2 assay in non-depleted human plasma. The assay exhibited inter-day coefficients of variation between 1.5% and 14.5% (median = 3.5%) and was subsequently used to investigate the effects of omega-3 carboxylic acids (OM3-CA) and fenofibrate on these 13 apolipoproteins in human plasma samples from a randomized placebo-controlled trial, EFFECT I (NCT02354976). No significant changes were observed in the OM3-CA arm, whereas treatment with fenofibrate significantly increased apoAII and reduced apoB, apoCI, apoE and apoCIV levels. The reduction in apoCIV following fenofibrate treatment is a novel finding. The study demonstrates that SIS PrESTs can facilitate the generation of robust multiplexed biomarker Tier 2 assays for absolute quantification of proteins in clinical studies.

Cost-effectiveness of a combined classroom curriculum and parental intervention: economic evaluation of data from the Steps Towards Alcohol Misuse Prevention Programme cluster randomised controlled trial.

OBJECTIVES: This study aimed to assess the cost-effectiveness of the Steps Towards Alcohol Misuse Prevention Programme (STAMPP) compared with education as normal (EAN) in reducing self-reported heavy episodic drinking (HED) in adolescents. DESIGN: This is a cost-effectiveness analysis from a public sector perspective conducted as part of a cluster randomised trial. SETTING: This study was conducted in 105 high schools in Northern Ireland and in Scotland. PARTICIPANTS: Students in school year 8/S1 (aged 11-12) at baseline were included in the study. INTERVENTIONS: This is a classroom-based alcohol education curricula, combined with a brief alcohol intervention for parents/carers. OUTCOME MEASURES: The outcome of this study is the cost per young person experiencing HED avoided due to STAMPP at 33 months from baseline. RESULTS: The total cost of STAMPP was £85 900, equivalent to £818 per school and £15 per pupil. Due to very low uptake of the parental component, we calculated costs of £692 per school and £13 per pupil without this element. Costs per pupil were reduced further to £426 per school and £8 per pupil when it was assumed there were no additional costs of classroom delivery if STAMPP was delivered as part of activities such as personal, social, health and economic education. STAMPP was associated with a significantly greater proportion of pupils experiencing a heavy drinking episode avoided (0.08/8%) and slightly lower public sector costs (mean difference -£17.19). At a notional willingness-to-pay threshold of £15 (reflecting the cost of STAMPP), the probability of STAMPP being cost-effective was 56%. This level of uncertainty reflected the substantial variability in the cost differences between groups. CONCLUSIONS: STAMPP was relatively low cost and reduced HED. STAMPP was not associated with any clear public sector cost savings, but neither did it increase them or lead to any cost-shifting within the public sector categories. Further research is required to establish if the cost-effectiveness of STAMPP is sustained in the long term. TRIAL REGISTRATION NUMBER: ISRCTN47028486; Results.

Publisher Correction: Protein expression changes caused by spaceflight as measured for 18 Russian cosmonauts.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

The molecular mechanisms driving physiological changes after long duration space flights revealed by quantitative analysis of human blood proteins.

BACKGROUND: The conditions of space flight have a significant effect on the physiological processes in the human body, yet the molecular mechanisms driving physiological changes remain unknown. METHODS: Blood samples of 18 Russian cosmonauts who had conducted long-duration missions to the International Space Station were collected 30 days before launch and on the first and seventh days after landing. RESULTS: A panel of 125 proteins in the blood plasma was quantitated by a well-established and highly regarded targeted mass spectrometry approach. This method involves the monitoring of multiple reactions in conjunction with stable isotope-labeled standards at the University of Victoria - Genome BC Proteomics Centre. CONCLUSIONS: Reduction of circulating plasma volume during space flight and activation of fluid retention at the final stage of the flight affect the changes in plasma protein concentrations present in the first days after landing. Using an ANOVA approach, it was revealed that only 1 protein (S100A9) reliably responded to space flight conditions. This protein plays an important role in the functioning of the endothelium and can serve as a marker for activation of inflammatory reactions. Concentrations of the proteins of complement, coagulation cascades, and acute phase reactants increase in the blood of cosmonauts as measured the first day after landing. Most of these proteins' concentrations continue to increase by the 7th day after space flight. Similar dynamics are observed for proteases and their inhibitors. Thus, there is a shift in proteolytic blood systems, which is necessary for the restoration of muscle tissue and maintenance of oncotic homeostasis.

Recanting of Previous Reports of Alcohol Consumption within a Large-Scale Clustered Randomised Control Trial.

The aim of this study was to examine the extent of recanting (inconsistencies in reporting of lifetime alcohol use) and its impact on the assessment of primary outcomes within a large-scale alcohol prevention trial. One hundred and five post-primary schools in were randomised to receive either the intervention or education as normal. Participants (N = 12,738) were secondary school students in year 8/S1 (mean age 12.5) at baseline. Self-report questionnaires were administered at baseline (T0) and at T1 (+ 12 months post-baseline), T2 (+ 24 months) and T3 (+ 33 months). The primary outcomes were (i) heavy episodic drinking (consumption of ≥ 6 units in a single episode in the previous 30 days for males and ≥ 4.5 units for females) assessed at T3 and (ii) the number of alcohol-related harms experienced in the last 6 months assessed at T3. Recanting was defined as a negative report of lifetime alcohol consumption that contradicted a prior positive report. Between T1 and T3, 9.9% of students recanted earlier alcohol consumption. Recanting ranged from 4.5 to 5.3% across individual data sweeps. While recanting was significantly associated (negatively) with both primary outcomes, the difference in the rate of recanting across trial arms was small, and adjusting for recanting within the primary outcome models did not impact on the primary outcome effects. Males were observed to recant at a greater rate than females, with a borderline small-sized effect (V = .09). While differential rates of recanting have the potential to undermine the analysis of prevention trial outcomes, recanting is easy to identify and control for within trial primary outcome analyses. Adjusting for recanting should be considered as an additional sensitivity test within prevention trials.Trial Registration: ISRCTN47028486 ( http://www.isrctn.com/ISRCTN47028486 ). The date of trial registration was 23/09/2011, and school recruitment began 01/11/2011.

Interplay Between Sensation Seeking and Parental Rules in the Emergence of Heavy Episodic Drinking.

This study examined the parallel mediational processes between sensation seeking and parental rules on alcohol, in the emergence of heavy episodic drinking (HED) in adolescents. Data were drawn from a U.K. clustered randomized control trial (control arm only, N ≈ 6,300, Mage at baseline = 12.5). Using parallel process latent growth curve analysis, stricter parental rules at baseline were found to be associated with greater declines in sensation seeking over time and a lower risk of HED at follow-up (+33 months). Higher initial levels of sensation seeking predicted a faster relaxation of parental rules and a greater risk of HED. By maintaining strict rules about alcohol, parents may promote a positive reduction in sensation seeking and a lower risk of HED.

Designing Prison-Based Parenting Programs to Maximize Their Outcomes.

Parenting programs are increasingly being offered in prison as governments seek to reduce the negative consequences of parental imprisonment and encourage desistance from crime. However, little is known about the design and delivery of such programs and how this may shape program effectiveness. This article seeks to address this gap by examining how the design and delivery of the Families Matter program for imprisoned adult fathers in Northern Ireland affected its ability to achieve its goals of improving family relationships and fathers' parenting skills. Examples of good practice are offered, as well as challenges that remain to be overcome. It is argued that more attention needs to be paid to the design and delivery of these programs if their ability to achieve long-term improvements in family relationships and parenting skills are to be improved.

The Belfast Youth Development Study (BYDS): A prospective cohort study of the initiation, persistence and desistance of substance use from adolescence to adulthood in Northern Ireland.

BACKGROUND: Substance misuse persists as a major public health issue worldwide with significant costs for society. The development of interventions requires methodologically sound studies to explore substance misuse causes and consequences. This Cohort description paper outlines the design of the Belfast Youth Development (BYDS), one of the largest cohort studies of its kind in the UK. The study was established to address the need for a long-term prospective cohort study to investigate the initiation, persistence and desistance of substance use, alongside life course processes in adolescence and adulthood. The paper provides an overview of BYDS as a longitudinal data source for investigating substance misuse and outlines the study measures, sample retention and characteristics. We also outline how the BYDS data have been used to date and highlight areas ripe for future work by interested researchers. METHODS: The study began in 2000/1 when participants (n = 3,834) were pupils in their first year of post-primary education (age 10/11 years, school year 8) from over 40 schools in Northern Ireland. Children were followed during the school years: Year 9 (in 2002; aged 12; n = 4,343), Year 10 (in 2003; aged 13; n = 4,522), Year 11 (in 2004; aged 14; n = 3,965) and Year 12 (in 2005; aged 15; n = 3,830) and on two more occasions: 2006/07 (aged 16/17; n = 2,335) and 2010/11 (aged 20/21; n = 2,087). Data were collected on substance use, family, schools, neighbourhoods, offending behaviour and mental health. The most novel aspect of the study was the collection of detailed social network data via friendship nominations allowing the investigation of the spread of substance use via friendship networks. In 2004 (school year 11; respondents aged 14), a sub-sample of participants' parents (n = 1,097) and siblings (n = 211) also completed measures on substance use and family dynamics. RESULTS: The most recent wave (in 2010/2011; respondents aged 20/21 years) indicated lifetime use of alcohol, tobacco and cannabis among the cohort was 94, 70 and 45 per cent, respectively. The paper charts the development of drug use behaviour and some of the key results to date are presented. We have also identified a number of key areas ripe for analysis by interested researchers including sexual health and education. CONCLUSIONS: We have established a cohort with detailed data from adolescence to young adulthood, supplemented with parent and sibling reports and peer network data. The dataset, allowing for investigation of trajectories of adolescent substance use, associated factors and subsequent long-term outcomes, constitutes an important resource for longitudinal substance misuse research. A planned further wave as the cohort enter their late twenties and potential to link to administrative data sources, will further enrich the datasets.