The crime drop and the security hypothesis

Major crime drops were experienced in the United States and most other industrialised countries for a decade from the early to mid-1990s. Yet there is little agreement over explanation or lessons for policy. Here it is proposed that change in the quantity and quality of security was a key driver of the crime drop. From evidence relating to vehicle theft in two countries it is concluded that electronic immobilisers and central locking were particularly effective. It is suggested that reduced car theft may have induced drops in other crime including violence. From this platform a broader security hypothesis, linked to routine activity and opportunity theory, is outlined

Protein-L-isoaspartate O-methyltransferase is required for <i>in vivo</i> control of oxidative damage in red blood cells

Red blood cells (RBC) have the special challenge of a large amount of reactive oxygen species (from their substantial iron load and Fenton reactions) combined with the inability to synthesize new gene products. Considerable progress has been made in elucidating the multiple pathways by which RBC neutralize reactive oxygen species via NADPH driven redox reactions. However, far less is known about how RBC repair the inevitable damage that does occur when reactive oxygen species break through anti-oxidant defenses. When structural and functional proteins become oxidized, the only remedy available to RBC is direct repair of the damaged molecules, as RBC cannot synthesize new proteins. Amongst the most common amino acid targets of oxidative damage is the conversion of asparagine and aspartate side chains into a succinimidyl group through deamidation or dehydration, respectively. RBC express an L-isoaspartyl methyltransferase (PIMT, gene name PCMT1) that can convert succinimidyl groups back to an aspartate. Herein, we report that deletion of PCMT1 significantly alters RBC metabolism in a healthy state, but does not impair the circulatory lifespan of RBC. Through a combination of genetic ablation, bone marrow transplantation and oxidant stimulation with phenylhydrazine in vivo or blood storage ex vivo, we use omics approaches to show that, when animals are exposed to oxidative stress, RBC from PCMT1 knockout undergo significant metabolic reprogramming and increased hemolysis. This is the first report of an essential role of PCMT1 for normal RBC circulation during oxidative stress

Ask Me! Self-reported features of adolescents experiencing neglect or emotional maltreatment: a rapid systematic review

Neglect is often overlooked in adolescence, due in part to assumptions about autonomy and misinterpretation of behaviors being part of normal adolescent development. Emotional maltreatment (abuse or neglect) has a damaging effect throughout the lifespan, but is rarely recognized amongst adolescents. Our review aims to identify features that adolescents experiencing neglect and/ or emotional maltreatment report. METHOD: A rapid review methodology searched 8 databases (1990-2014), supplemented by hand searching journals, and references, identifying 2,568 abstracts. Two independent reviews were undertaken of 279 articles, by trained reviewers, using standardised critical appraisal. Eligible studies: primary studies of children aged 13-17 years, with substantiated neglect and/ or emotional maltreatment, containing self-reported features. RESULTS: 19 publications from 13 studies were included, demonstrating associations between both neglect and emotional maltreatment with internalising features (9 studies) including depression, post traumatic symptomatology and anxiety; emotional maltreatment was associated with suicidal ideation, while neglect was not (1 study); neglect was associated with alcohol related problems (3 studies), substance misuse (2 studies), delinquency for boys (1 study), teenage pregnancy (1 study), and general victimization for girls (1 study), while emotionally maltreated girls reported more externalising symptoms (1 study). Dating violence victimization was associated with neglect and emotional maltreatment (2 studies), while emotional abuse of boys, but not neglect, was associated with dating violence perpetration (1 study), and neither neglect nor emotional maltreatment had an association with low self-esteem (2 studies). Neither neglect nor emotional maltreatment had an effect on school performance (1 study), but neglected boys showed greater school engagement than neglected girls (1 study). CONCLUSIONS: If asked, neglected or emotionally maltreated adolescents describe significant difficulties with their mental health, social relationships, and alcohol or substance misuse. Practitioners working with youths who exhibit these features should recognize the detrimental impact of maltreatment at this developmental stage, and identify whether maltreatment is a contributory factor that should be addressed

Donor sex, age and ethnicity impact stored red blood cell antioxidant metabolism through mechanisms in part explained by glucose 6-phosphate dehydrogenase levels and activity

Red blood cell storage in the blood bank promotes the progressive accumulation of metabolic alterations that may ultimately impact the erythrocyte capacity to cope with oxidant stressors. However, the metabolic underpinnings of the capacity of RBCs to resist oxidant stress and the potential impact of donor biology on this phenotype are not known. Within the framework of the REDS-III RBC-Omics study, RBCs from 8,502 healthy blood donors were stored for 42 days and tested for their propensity to hemolyze following oxidant stress. A subset of extreme hemolyzers donated a second unit of blood, which was stored for 10, 23, and 42 days and profiled again for oxidative hemolysis and metabolomics (599 samples). Alterations of RBC energy and redox homeostasis were noted in donors with high oxidative hemolysis. RBCs from females, donors over 60 years old, donors of Asian/South Asian race-ethnicity, and RBCs stored in additive solution-3 were each independently characterized by improved antioxidant metabolism compared to, respectively, males, donors under 30 years old, Hispanic and African American race ethnicity donors, and RBCs stored in additive solution-1. Merging metabolomics data with results from an independent GWAS study on the same cohort, we identified metabolic markers of hemolysis and G6PD-deficiency, which were associated with extremes in oxidative hemolysis and dysregulation in NADPH and glutathione-dependent detoxification pathways of oxidized lipids. Donor sex, age, ethnicity, additive solution and G6PD status impact the metabolism of the stored erythrocyte and its susceptibility to hemolysis following oxidative insults

Reticulocytes in donor blood units enhance red blood cell alloimmunization

Although red blood cell (RBC) transfusions save lives, some patients develop clinically-significant alloantibodies against donor blood group antigens, which then have adverse effects in multiple clinical settings. Few effective measures exist to prevent RBC alloimmunization and/or eliminate alloantibodies in sensitized patients. Donor-related factors may influence alloimmunization; thus, there is an unmet clinical need to identify which RBC units are immunogenic. Repeat volunteer blood donors and donors on iron supplements have elevated reticulocyte counts compared to healthy non-donors. Early reticulocytes retain mitochondria and other components, which may act as danger signals in immune responses. Herein, we tested whether reticulocytes in donor RBC units could enhance RBC alloimmunization. Using a murine model, we demonstrate that transfusing donor RBC units with increased reticulocyte frequencies dose-dependently increased RBC alloimmunization rates and alloantibody levels. Transfusing reticulocyte-rich RBC units was associated with increased RBC clearance from the circulation and a robust proinflammatory cytokine response. As compared to previously reported post-transfusion RBC consumption patterns, erythrophagocytosis from reticulocyte-rich units was increasingly performed by splenic B cells. These data suggest that reticulocytes in a donated RBC unit impact the quality of blood transfused, are targeted to a distinct compartment, and may be an underappreciated risk factor for RBC alloimmunization

Red blood cell metabolism in Rhesus macaques and humans: comparative biology of blood storage

Macaques are emerging as a critical animal model in transfusion medicine, because of their evolutionary similarity to humans and perceived utility in discovery and translational science. However, little is known about the metabolism of Rhesus macaque red blood cells (RBC) and how this compares to human RBC metabolism under standard blood banking conditions. Metabolomic and lipidomic analyses, and tracing experiments with [1,2,3-13C3]glucose, were performed using fresh and stored RBC (sampled weekly until storage day 42) obtained from Rhesus macaques (n=20) and healthy human volunteers (n=21). These results were further validated with targeted quantification against stable isotope-labeled internal standards. Metabolomic analyses demonstrated inter-species differences in RBC metabolism independent of refrigerated storage. Although similar trends were observed throughout storage for several metabolic pathways, species- and sex-specific differences were also observed. The most notable differences were in glutathione and sulfur metabolites, purine and lipid oxidation metabolites, acylcarnitines, fatty acyl composition of several classes of lipids (including phosphatidylserines), glyoxylate pathway intermediates, and arginine and carboxylic acid metabolites. Species-specific dietary and environmental compounds were also detected. Overall, the results suggest an increased basal and refrigerator-storage-induced propensity for oxidant stress and lipid remodeling in Rhesus macaque RBC cells, as compared to human red cells. The overlap between Rhesus macaque and human RBC metabolic phenotypes suggests the potential utility of a translational model for simple RBC transfusions, although inter-species storage-dependent differences need to be considered when modeling complex disease states, such as transfusion in trauma/hemorrhagic shock models