The key role of specific DSM-5 diagnostic criteria in the early development of alcohol use disorder: Findings from the RADAR prospective cohort study.

BACKGROUND: Prevention and early intervention of alcohol use disorder (AUD) is a public health priority, yet there are gaps in our understanding of how AUD emerges, which symptoms of AUD come first, and whether there are modifiable risk factors that forecast the development of the disorder. This study investigated potential early-warning-sign symptoms for the development of AUD. METHODS: Data were from the RADAR study, a prospective cohort study of contemporary emerging adults across Australia (n = 565, mean age = 18.9, range = 18-21 at baseline, 48% female). Participants were interviewed five times across a 2.5-year period. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) AUD criteria and diagnoses were assessed by clinical psychologists using the Structured Clinical Interview for DSM-IV (SCID-IV), modified to cover DSM-5 criteria. Hazard analyses modeled the time from first alcoholic drink to the emergence of any AUD criteria and determined which first-emergent AUD criteria were associated with a faster transition to disorder. RESULTS: By the final time point, 54.8% of the sample had experienced at least one DSM-5 AUD criterion and 26.1% met criteria for DSM-5 AUD. The median time from first AUD criterion to a diagnosis of AUD was 4 years. Social problems from drinking (hazard ratio [HR] = 3.24, CI95 = 2.14, 4.92, p < 0.001), major role (HR = 2.53, CI95 = 1.58, 4.06, p < 0.001), and drinking larger amounts/for longer than intended (HR = 2.04, CI95 = 1.20, 3.46, p = 0.008) were first-onset criteria associated with a faster transition to AUD. CONCLUSION: In the context of a prospective general population cohort study of the temporal development of AUD, alcohol-related social problems, major role problems, and using more or for longer than intended are key risk factors that may be targeted for early intervention.

Definition matters: assessment of tolerance to the effects of alcohol in a prospective cohort study of emerging adults.

BACKGROUND AND AIMS: Tolerance to the effects of alcohol is an important element in the diagnosis of alcohol use disorders (AUD); however, there is ongoing debate about its utility in the diagnosis AUD in adolescents and young adults. This study aimed to refine the assessment of tolerance in young adults by testing different definitions of tolerance and their associations with longitudinal AUD outcomes. DESIGN: Prospective cohort study. SETTINGS: Australia. PARTICIPANTS: A contemporary cohort of emerging adults across Australia (n = 565, mean age = 18.9, range = 18-21 at baseline). MEASUREMENTS: Clinician-administered Structured Clinical Interview for DSM-IV Research Version (SCID-IV-RV) assessed for AUD criteria across five interviews, at 6-month intervals over 2.5 years. Tolerance definitions were operationalized using survey-type response (yes/no), clinician judgement (SCID-IV-RV), different initial drinking quantity and percentage increase thresholds and average heavy consumption metrics. AUD persistence was operationalized by the number of times AUD was present across the 2.5-year study period (n = 491), and new-onset AUD was operationalized as any new incidence of AUD during the follow-up period (n = 461). FINDINGS: The (i) SCID-IV-RV clinician judgement [odds ratio (OR) = 2.50, P = 0.005], (ii) an initial drinking quantity threshold of four to five drinks and 50% minimum increase (OR = 2.48, P = 0.007) and (iii) 50% increase only (OR = 2.40, P = 0.005) were the tolerance definitions more strongly associated with any new onset of AUD throughout the four follow-up time-points than other definitions. However, these definitions were not associated with persistent AUD (Ps > 0.05). Average heavy consumption definitions of tolerance were most strongly associated with persistent AUD (OR = 6.66, P = 0.001; OR = 4.65, P = 0.004) but not associated with new-onset AUD (Ps > 0.05). CONCLUSIONS: Initial drink and percentage change thresholds appear to improve the efficacy of change-based tolerance as an indicator for new-onset alcohol use disorder diagnosis in self-report surveys of young adults. When predicting persistent alcohol use disorder, average heavy consumption-based indicators appear to be a better way to measure tolerance than self-reported change-based definitions.

DSM-5 and ICD-11 alcohol use disorder criteria in young adult regular drinkers: Lifetime prevalence and age of onset.

BACKGROUND: Alcohol Use Disorder (AUD) is a significant contributor to global disease burden. AUD has a relatively early onset during young adulthood (Teesson et al., 2010). However, compared to AUD in adults, we have relatively little understanding of AUD in adolescents and emerging adults. METHODS: The RADAR study is a prospective cohort study designed to investigate the emergence of AUD in community-dwelling adolescents and emerging adults across Australia (age range = 18-21 at baseline). At 6 monthly intervals over 2.5 years, participants were interviewed regarding alcohol consumption and alcohol use disorder criteria by clinical psychologists using the SCID-IV-RV. This paper reports the baseline findings of the RADAR cohort. RESULTS: Proportions of lifetime criteria endorsement among regular drinkers varied considerably. Tolerance was the most endorsed criterion (50.3%), followed by Social Problems (10.4%) and Larger/Longer (9.0%). The median age of onset for most individual AUD criteria was 18 years of age. 18.4% of our cohort met DSM-5 AUD diagnosis in their lifetime to date, and 16.8% met ICD-11 dependence. When removing Tolerance from the AUD criteria, DSM-5 AUD lifetime prevalence reduced to 11.0%, and ICD-11 AUD lifetime prevalence fell to 7.1% in our cohort. CONCLUSIONS: Variable rates of criteria endorsement likely reflect both true differences in the experience of AUD criteria and methodological challenges in the assessment of AUD in an emerging adult age group. High rates of tolerance to the effects of alcohol, and relatively low rates of drinking larger/longer than intended are discussed considering methodological challenges in assessing these criteria in young adults.

Variations of the testicular artery and vein: A meta-analysis with proposed classification.

Variations of testicular vessels are more common than supposed. The testicular artery varies because of abnormal regression of the lateral mesonephric arteries in the fetus, whereas variations in the testicular vein are due to abnormalities in the involution of the intersubcardinal anastomosis. Such variations are usually found incidentally during surgical procedures around the renal pedicle and they often lead to complications. Several authors have attempted to classify them. However, these attempts have not been comprehensive. Therefore, the aim of this study is to provide a simple yet comprehensive classification of variations of the testicular vessels. The PubMed database was searched using keywords pertaining to the testicular vessels. The results were subjected to the Anatomical Quality Assessment (AQUA) tool analysis and were screened for appropriateness for inclusion in this study. The screening procedure yielded 31 original articles, 83 case reports, and 1 review article. Both testicular arterial and venous variations were more common on the left side (20.73% and 24.61%) than the right (12.69% and 18.4%, respectively). We classified the testicular arteries on the basis of their number (N), site of origin (O), and course (C). Similarly, the testicular veins were classified on the basis of their number (N) and site of drainage (D). The proposed classification facilitates identification, understanding, and reporting of variations of the testicular vessels by radiologists. It will also help surgeons to enhance the quality of their treatment. Clin. Anat. 31:854-869, 2018. © 2018 Wiley Periodicals, Inc.

Convergence of signaling pathways in the control of differential cell growth in Arabidopsis.

Seedling apical hook development involves a complex interplay of hormones and light in the regulation of differential cell growth. However, the underlying molecular mechanisms that integrate these diverse signals to control bending of the embryonic stem are poorly understood. The Arabidopsis ethylene-regulated HOOKLESS1 (HLS1) gene is essential for apical hook formation. Herein, we identify two auxin response regulators that act downstream of HLS1 to control cell elongation in the hypocotyl. Extragenic suppressors of hls1 were identified as mutations in AUXIN RESPONSE FACTOR 2 (ARF2). The level of ARF2 protein was decreased by ethylene, and this response required HLS1. Exposure to light decreased HLS1 protein levels and evoked a concomitant increase in ARF2 accumulation. These studies demonstrate that both ethylene and light signals affect differential cell growth by acting through HLS1 to modulate the auxin response factors, pinpointing HLS1 as a key integrator of the signaling pathways that control hypocotyl bending.