Risk and protective factors in risk assessment: Predicting inpatient aggression in adult males detained in a forensic mental health setting.

Structured clinical risk assessments represent a preferred means of assessing levels of aggression risk at different times and in different individuals. Increasing attention has been given to capturing protective factors, with sound risk assessment critical to high-secure forensic mental health care. The aim was to assess the predictive value of the HCR-20v3 for aggression risk and the long-term care pilot version of the SAPROF (the SAPROF-LC-pilot) in a high-secure forensic mental health inpatient population and to determine the incremental value of protective over risk factors. Participants were adult males detained in a high secure forensic mental health service, with a primary diagnosis of schizophrenia and/or personality disorder. The focus was on examining hospital based aggression (self- and other-directed) at two time points; up to 6 months (T1) and between 7 and 12 months (T2). The HCR-20V3 and SAPROF-LC-pilot demonstrated good predictive validity but with variability across subscales and aggression types/periods. Historical factors of the HCR-20V3 and External factors of the SAPROF-LC-pilot failed to predict, aside from a medium effect at T1 for verbal aggression and self-harm, for Historical factors. There was evidence for protective factors adding to prediction over risk factors alone, with the integration of protective and risk factors into a risk judgement particularly helpful in improving prediction accuracy. Protective factors contributed to risk estimates and particularly if integrated with risk factors. Combining risk and protective factors has clear predictive advantages, ensuring that protective factors are not supplementary but important to the aggression assessment process.

Linked fire activity and climate whiplash in California during the early Holocene.

Recent wildfire activity in semi-arid regions like western North America exceeds the range of historical records. High-resolution paleoclimate archives such as stalagmites could illuminate the link between hydroclimate, vegetation change, and fire activity in pre-anthropogenic climate states beyond the timescale of existing tree-ring records. Here we present an analysis of levoglucosan, a combustion-sensitive anhydrosugar, and lignin oxidation products (LOPs) in a stalagmite, reconstructing fire activity and vegetation composition in the California Coast Range across the 8.2 kyr event. Elevated levoglucosan concentrations suggest increased fire activity while altered LOP compositions indicate a shift toward more woody vegetation during the event. These changes are concurrent with increased hydroclimate volatility as shown by carbon and calcium isotope proxies. Together, these records suggest that climate whiplash (oscillations between extreme wetness and aridity) and fire activity in California, both projected to increase with anthropogenic climate change, were tightly coupled during the early Holocene.

Concentration and origin of lead (Pb) in liver and bone of Eurasian buzzards (Buteo buteo) in the United Kingdom.

Ingestion of lead (Pb) derived from ammunition used in the hunting of game animals is recognised to be a significant potential source of Pb exposure of wild birds, including birds of prey. However, there are only limited data for birds of prey in Europe regarding tissue concentrations and origins of Pb. Eurasian buzzards (Buteo buteo) found dead in the United Kingdom during an 11-year period were collected and the concentrations of Pb in the liver and femur were measured. Concentrations in the liver consistent with acute exposure to Pb were found in 2.7% of birds and concentration in the femur consistent with exposure to lethal levels were found in 4.0% of individuals. Pb concentration in the femur showed no evidence of consistent variation among or within years, but was greater for old than for young birds. The Pb concentration in the liver showed no effect of the birds' age, but varied markedly among years and showed a consistent tendency to increase substantially within years throughout the UK hunting season for gamebirds. The resemblance of the stable isotope composition of Pb from buzzard livers to that of Pb from the types of shotgun ammunition most widely-used in the UK increased markedly with increasing Pb concentration in the liver. Stable isotope results were consistent with 57% of the mass of Pb in livers of all of the buzzards sampled being derived from shotgun pellets, with this proportion being 89% for the birds with concentrations indicating acute exposure to Pb. Hence, most of the Pb acquired by Eurasian buzzards which have liver concentrations likely to be associated with lethal and sublethal effects is probably obtained when they prey upon or scavenge gamebirds and mammals shot using Pb shotgun pellets.

Release kinetics of high-sensitivity cardiac troponins I and T and troponin T upstream open reading frame peptide (TnTuORF) in clinically induced acute myocardial infarction.

CONTEXT: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes. OBJECTIVE: The study examined the early release kinetics of TnTuORF. MATERIALS AND METHODS: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n = 31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH). RESULTS: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18 ng/L versus 27 ng/L; cTnI median: 15 ng/L versus 25 ng/L). TnTuORF showed no variation. DISCUSSION: We observed a significantly greater increase in cTnI compared with cTnT. CONCLUSION: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting.

In Vivo Availability of Pro-Resolving Lipid Mediators in Oxazolone Induced Dermal Inflammation in the Mouse.

The activation and infiltration of polymorphonuclear neutrophils (PMN) are critical key steps in inflammation. PMN-mediated inflammation is limited by anti-inflammatory and pro-resolving mechanisms, including specialized pro-resolving lipid mediators (SPM). We examined the effects of 15-epi-LXA4 on inflammation and the biosynthesis of pro-inflammatory mediators, such as prostaglandins, leukotriene B4 and various hydroxyeicosatetraenoic acids and SPM, in an oxazolone (OXA)-induced hypersensitivity model for dermal inflammation. 15-epi-LXA4 (100 µM, 5 µL subcutaneously injected) significantly (P < 0.05) reduced inflammation in skin, 24 hours after the OXA challenge, as compared to skin treated with vehicle. No significant influence on the biosynthesis of prostaglandins or leukotriene B4 was observed, whereas the level of 15S-hydroxy-eicosatetraenoic acid was significantly (P < 0.05) lower in the skin areas treated with 15-epi-LXA4. In spite of the use of a fully validated analytical procedure, no SPM were detected in the biological samples. To investigate the reason for the lack of analytical signal, we tried to mimic the production of SPM (lipoxins, resolvins, maresin and protectin) by injecting them subcutaneously into the skin of mice and studying the in vivo availability and distribution of the compounds. All analytes showed very little lateral distribution in skin tissue and their levels were markedly decreased (> 95%) 2 hours after injection. However, docosahexaenoic acid derivatives were biologically more stable than SPM derived from arachidonic acid or eicosapentaenoic acid.

Lipoxin and resolvin biosynthesis is dependent on 5-lipoxygenase activating protein.

Resolution of acute inflammation is an active process coordinated by proresolving lipid mediators (SPMs) such as lipoxins (LXs) and resolvins (Rvs), which are formed by the concerted action of 2 lipoxygenases (LOs). Because the exact molecular mechanisms of SPM biosynthesis are not completely understood, we aimed to investigate LX and D-type Rv formation in human leukocytes and HEK293T cells overexpressing leukotriene (LT) pathway enzymes. Activity assays in precursor (15-hydroxyeicosatetraenoic acids, 17-HDoHE)-treated granulocytes [polymorphonuclear leukocytes (PMNLs)] showed a strict dependence of LXA4/RvD1 biosynthesis on cell integrity, and incubation with recombinant human 5-LO did not lead to LX or Rv formation. Pharmacologic inhibition of 5-LO activating protein (FLAP) by MK-886 inhibited LXA4/RvD1 biosynthesis in precursor-treated PMNLs (drug concentration causing 50% inhibition ∼ 0.3/0.2 µM), as did knockdown of the enzyme in MM6 cells, and precursor-treated HEK293T overexpressing 5-LO produced high amounts of LXA4 only in the presence of FLAP. In addition, inhibition of cytosolic phospholipase A2α (cPLA2α) interfered with LXA4/RvD1 formation from exogenous precursors in PMNLs. Furthermore, inhibition of the LT synthases LTA4 hydrolase and LTC4 synthase in PMNL/platelet coincubations augmented LXA4 levels. These findings show that several enzymes known to be involved in the biosynthesis of proinflammatory LTs, such as FLAP and cPLA2α, also contribute to LX and Rv formation.

Chiral chromatography-tandem mass spectrometry applied to the determination of pro-resolving lipid mediators.

Pro-resolving lipid mediators are a class of endogenously synthesized molecules derived from different fatty acids, such as arachidonic, docosahexaenoic or eicosapentaenoic acid, which are derived into four different product families: lipoxins, resolvins, maresins and protectins. For quantitation of these compounds, a sensitive, selective and robust liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantitation of lipoxin A4, 6-epi-lipoxin A4, lipoxin B4 and lipoxin A5, the D-series resolvins D1 and D2 as well as aspirin-triggered lipoxin A4 and resolvin D1, maresin and protectin and the pathway markers 17(S)-hydroxy-docosahexaenoic acid and 17(R)-hydroxy-docosahexaenoic acid in cell culture supernatants. For this purpose, a chiral column was connected in series with a reversed-phase column to achieve efficient analyte separation and high sensitivity. Sample pre-treatment included a fast and simple liquid-liquid extraction procedure. Limits of quantitation in the range of 0.1-0.5ng/mL cell culture media, absolute recoveries between 90 and 115%, intra- and interday precision of less than 13% and an accuracy of less than 11% were obtained. Stability of the samples after 60 days storage at -80°C, three freeze/thaw cycles and 4h at room temperature has been demonstrated for all analytes. Sample extracts can be stored at 7°C for 24h without degradation of the analytes. Deviations of less than 13% in the accuracy, evaluated in terms of relative error, were obtained. The suitability of the method has been demonstrated in cell culture supernatants of human polymorphonuclear leukocytes, stimulated with 15R-hydroxy-eicosatetraenoic acid and in cell culture media of human polymorphonuclear leukocytes co-incubated with human platelets. From all studied analytes, lipoxin A4 and 6-epi-lipoxin A4 were found in cell culture media under both incubation conditions, while 15-epi-lipoxin A4 was additionally detected in cell culture supernatants of polymorphonuclear leukocytes stimulated with 15R-hydroxy-eicosatetraenoic acid.

Lipoxin A4: problems with its determination using reversed phase chromatography-tandem mass spectrometry and confirmation with chiral chromatography.

Lipoxins belong to the family of so-called pro-resolving endogenous lipid mediators which are derived from arachidonic acid and play a key role in the counter-regulation of inflammation. Arachidonic acid is also precursor of multiple pro-inflammatory lipid mediators, such as prostaglandins and leukotrienes, which are simultaneously present in biological compartments. The close structural relationship between several of these lipid mediators and the absence of blank matrix samples enormously complicates the unequivocal identification of these compounds. The determination of lipoxin A4 has been accomplished by chromatographic separation using a C18 reversed phase column and tandem mass spectrometry detection. Samples were liquid-liquid extracted with ethyl acetate before injection. Identification of the analyte was done based on three criteria: retention time, ratio of the m/z transitions and MS/MS spectrum. To avoid false positive results due to endogenous interferences, the extracted samples were re-injected into a chiral Lux Amylose-2 chromatographic column. The authors recommend the use of chiral chromatography in the determination of pro-resolving lipid mediators, together with transition area ratio and fragmentation spectra to improve selectivity for identification and quantitation purposes.