The classification of substance and behavioural addictions: A preliminary investigation

The term addiction has been used to refer to impaired control over substance use for several centuries however recently there has been a shift toward using this term in the context of non-substance use disorders, such as pathological gambling. A preliminary investigation was conducted in an attempt to clarify the most appropriate classification of 'behavioural addictions'. Participants with alcohol dependence (AD, n = 24), pathological gambling (PG, n = 20) and compulsive buying disorder (CBD, n = 14) completed an Addictive Disorder Questionnaire (ADQ); the Symptom Checklist 90 Revised (SCL-90R); Barratt Impulsivity Scale II; and substance specific adaptations of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Although the AD group reported more severe addiction symptoms and had higher levels of depression and anxiety, there were broad similarities across the three disorders in relation to cravings, dyscontrol, impulsivity and obsessions. Despite the small sample size and the different recruitment strategies used across the groups, the findings from this preliminary study provide support for broadening addiction diagnostic definitions to include non-substance related disorders which in turn may contribute to the development of more efficacious treatments

The Lloyd's Register archive: An appraisal

This research note presents the findings of an appraisal of the archives of Lloyd's Register recently undertaken by researchers from Blaydes Maritime Centre at the University of Hull. Funded by the Lloyd's Register Foundation, the aim of this project was to assess the character, extent and evidential quality of a rich yet underutilized assemblage of records relating to shipping and vessel safety from the late eighteenth century. After discussing material generated by the organization's management committees, ship classification process and labour deployment, the research note concludes with a discussion of current and future reader access to this large, historically significant and dynamically evolving collection of primary source materials

Superhumps in Cataclysmic Binaries. XXII. 1RXS J232953.9+062814

We report photometry of 1RXS J232953.9+062814, a recently discovered dwarf nova with a remarkably short 64.2-minute orbital period. In quiescence, the star's light curve is that of a double sinusoid, arising from the "ellipsoidal" distortion of the Roche-lobe-filling secondary. During superoutburst, common superhumps develop with a period 3-4% longer than P_orb. This indicates a mass ratio M_2/M_1=0.19+-0.02, a surprisingly large value in so compact a binary. This implies that the secondary star has a density 2-3 times higher than that of other short-period dwarf novae, suggesting a secondary enriched by H-burning prior to the common-envelope phase of evolution. We estimate i=50+-5 deg, M_1=0.63 (+0.12, -0.09) M_sol, M_2=0.12 (+0.03, -0.02) M_sol, R_2=0.121 (+0.010, -0.007) R_sol, and a distance to the binary of 180+-40 pc.Comment: PDF, 17 pages, 3 tables, 5 figures; accepted, in press, to appear June 2002, PASP; more info at http://cba.phys.columbia.edu

Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital

Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. Conclusion: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies

Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization

Islet transplantation is an efficacious therapy for type 1 diabetes; however, islets from multiple donor pancreata are required, and a gradual attrition in transplant function is seen. Here, we manufactured human umbilical cord perivascular mesenchymal stromal cells (HUCPVCs) to Good Manufacturing Practice (GMP) standards. HUCPVCs showed a stable phenotype while undergoing rapid ex vivo expansion at passage 2 (p2) to passage 4 (p4) and produced proregenerative factors, strongly suppressing T cell responses in the resting state and in response to inflammation. Transplanting an islet equivalent (IEQ):HUCPVC ratio of 1:30 under the kidney capsule in diabetic NSG mice demonstrated the fastest return to normoglycemia by 3 days after transplant: Superior glycemic control was seen at both early (2.7 weeks) and later stages (7, 12, and 16 weeks) versus ratios of 1:0, 1:10, and 1:50, respectively. Syngeneic islet transplantation in immunocompetent mice using the clinically relevant hepatic portal route with a marginal islet mass showed that mice transplanted with an IEQ:HUCPVC ratio of 1:150 had superior glycemic control versus ratios of 1:0, 1:90, and 1:210 up to 6 weeks after transplant. Immunodeficient mice transplanted with human islets (IEQ:HUCPVC ratio of 1:150) exhibited better glycemic control for 7 weeks after transplant versus islet transplant alone, and islets transplanted via the hepatic portal vein in an allogeneic mouse model using a curative islet mass demonstrated delayed rejection of islets when cotransplanted with HUCPVCs (IEQ:HUCPVC ratio of 1:150). The immunosuppressive and proregenerative properties of HUCPVCs demonstrated long-term positive effects on graft function in vivo, indicating that they may improve long-term human islet allotransplantation outcomes

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS