Predicting violent infractions in a Swiss state penitentiary: A replication study of the PCL-R in a population of sex and violent offenders

BACKGROUND: Research conducted with forensic psychiatric patients found moderate correlations between violence in institutions and psychopathy. It is unclear though, whether the PCL-R is an accurate instrument for predicting aggressive behavior in prisons. Results seem to indicate that the instrument is better suited for predicting verbal rather than physical aggression of prison inmates. METHODS: PCL-R scores were assessed for a sample of 113 imprisoned sex and violent offenders in Switzerland. Logistic regression analyses were used to estimate physical and verbal aggression as a function of the PCL-R sum score. Additionally, stratified analyses were conducted for Factor 1 and 2. Infractions were analyzed as to their motives and consequences. RESULTS: The mean score of the PCL-R was 12 points. Neither the relationship between physical aggression and the sum score of the PCL-R, nor the relationship between physical aggression and either of the two factors of the PCL-R were significant. Both the sum score and Factor 1 predicted the occurrence of verbal aggression (AUC=0.70 and 0.69), while Factor 2 did not. CONCLUSION: Possible explanations are discussed for the weak relationship between PCL-R scores and physically aggressive behavior during imprisonment. Some authors have discussed whether the low base rate of violent infractions can be considered an explanation for the non-significant relation between PCL-R-score and violence. The base rate in this study, however, with 27%, was not low. It is proposed that the distinction between reactive and instrumental motives of institutional violence must be considered when examining the usefulness of the PCL-R in predicting in-prison physical aggressive behavior

Timing Calibration and Windowing Technique Comparison for Lightning Mapping Arrays

Since their introduction 22 years ago, lightning mapping arrays (LMA) have played a central role in the investigation of lightning physics. Even in recent years with the proliferation of digital interferometers and the introduction of the LOw Frequency ARray (LOFAR) radio telescope, LMAs still play an important role in lightning science. LMA networks use a simple windowing technique that records the highest pulse in either 80 μs or 10 μs fixed windows in order to apply a time-of-arrival location technique. In this work, we develop an LMA-emulator that uses lightning data recorded by LOFAR to simulate an LMA, and we use it to test three new styles of pulse windowing. We show that they produce very similar results as the more traditional LMA windowing, implying that LMA lightning mapping results are relatively independent of windowing technique. In addition, each LMA station has its GPS-conditioned clock. While the timing accuracy of GPS receivers has improved significantly over the years, they still significantly limit the timing measurements of the LMA. Recently, new time-of-arrival techniques have been introduced that can be used to self-calibrate systematic offsets between different receiving stations. Applying this calibration technique to a set of data with 32 ns uncertainty, observed by the Colorado LMA, improves the timing uncertainty to 19 ns. This technique is not limited to LMAs and could be used to help calibrate future multi-station lightning interferometers

Cotrimoxazole reduces systemic inflammation in HIV infection by altering the gut microbiome and immune activation

Wellcome TrustCanadian Institutes of Health ResearchMedical Research CouncilDepartment for International Development under MRC/DFID Concordat agreement and EDCTP2 programme supported by the European UnionMRC Clinical Trials Unit at UC

β-Hydroxy-β-Methylbutyrate (HMB) Normalizes Dexamethasone-Induced Autophagy-Lysosomal Pathway in Skeletal Muscle

Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.This project has been funded by Abbott Nutrition R&D

Use of 18F-2-Fluorodeoxyglucose to Label Antibody Fragments for Immuno-Positron Emission Tomography of Pancreatic Cancer

We generated 18F-labeled antibody fragments for positron emission tomography (PET) imaging using a sortase-mediated reaction to install a trans-cyclooctene-functionalized short peptide onto proteins of interest, followed by reaction with a tetrazine-labeled-18F-2-deoxyfluoroglucose (FDG). The method is rapid, robust, and site-specific (radiochemical yields > 25%, not decay corrected). The availability of 18F-2-deoxyfluoroglucose avoids the need for more complicated chemistries used to generate carbon–fluorine bonds. We demonstrate the utility of the method by detecting heterotopic pancreatic tumors in mice by PET, using anti-Class II MHC single domain antibodies. We correlate macroscopic PET images with microscopic two-photon visualization of the tumor. Our approach provides easy access to 18F-labeled antibodies and their fragments at a level of molecular specificity that complements conventional 18F-FDG imaging

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

BACKGROUND: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data was donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Psychopathic traits and offender characteristics – a nationwide consecutive sample of homicidal male adolescents

<p>Abstract</p> <p>Background</p> <p>The aim of the study was to evaluate psychopathy-like personality traits in a nationwide consecutive sample of adolescent male homicide offenders and to compare the findings with those of a randomly sampled adult male homicide offender group. A further aim was to investigate associations between psychopathic traits and offender and offence characteristics in adolescent homicides.</p> <p>Methods</p> <p>Forensic psychiatric examination reports and crime reports of all 15 to19- year- old male Finnish offenders who had been subjected to a forensic psychiatric examination and convicted for a homicide during 1995–2004 were collected (n = 57). A random sample of 57 adult male homicide offenders was selected as a comparison group. Offence and offender characteristics were collected from the files and a file-based assessment of psychopathic traits was performed using the Hare Psychopathy Checklist-Revised (PCL-R) by trained raters.</p> <p>Results</p> <p>No significant differences existed between the adolescents and adults in PCL-R total scores, factor 2 (social deviance) scores, or in facets 3 (lifestyle) and 4 (antisocial). Adults scored significantly higher on factor 1 (interpersonal/affective) and facets 1 (interpersonal) and 2 (affective). The adolescent group was divided into two subgroups according to PCL-R total scores. One in five homicidal male adolescents met criteria for psychopathic personality using a PCL-R total score of 26 or higher. These boys significantly more often had a crime history before the index homicide, more frequently used excessive violence during the index homicide, more rarely lived with both parents until 16 years of age, had more institutional or foster home placements in childhood, had more school difficulties, more often had received special education, and, more often had contact with mental health services prior to age 18 years than boys scoring low on the PCL-R. They also more often had parental criminal history as well as homicide history of parents or near relatives than the group scoring low on the PCL-R.</p> <p>Conclusion</p> <p>Homicidal boys behaved as antisocially as the homicidal adults. The adults, however, showed more both affective and interpersonal features of psychopathy. Homicidal adolescents with psychopathy-like personality character form a special subgroup among other homicidal youngsters. Recognizing their characteristics, especially in life course development, would facilitate effective prevention and intervention efforts.</p

Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo

Background: Changes of serum concentrations of glycated, oxidized, and nitrated amino acids and hydroxyproline and anticyclic citrullinated peptide antibody status combined by machine learning techniques in algorithms have recently been found to provide improved diagnosis and typing of early-stage arthritis of the knee, including osteoarthritis (OA), in patients. The association of glycated, oxidized, and nitrated amino acids released from the joint with development and progression of knee OA is unknown. We studied this in an OA animal model as well as interleukin-1β-activated human chondrocytes in vitro and translated key findings to patients with OA. Methods: Sixty male 3-week-old Dunkin-Hartley guinea pigs were studied. Separate groups of 12 animals were killed at age 4, 12, 20, 28 and 36 weeks, and histological severity of knee OA was evaluated, and cartilage rheological properties were assessed. Human chondrocytes cultured in multilayers were treated for 10 days with interleukin-1β. Human patients with early and advanced OA and healthy controls were recruited, blood samples were collected, and serum or plasma was prepared. Serum, plasma, and culture medium were analyzed for glycated, oxidized, and nitrated amino acids. Results: Severity of OA increased progressively in guinea pigs with age. Glycated, oxidized, and nitrated amino acids were increased markedly at week 36, with glucosepane and dityrosine increasing progressively from weeks 20 and 28, respectively. Glucosepane correlated positively with OA histological severity (r = 0.58, p < 0.0001) and instantaneous modulus (r = 0.52–0.56; p < 0.0001), oxidation free adducts correlated positively with OA severity (p < 0.0009–0.0062), and hydroxyproline correlated positively with cartilage thickness (p < 0.0003–0.003). Interleukin-1β increased the release of glycated and nitrated amino acids from chondrocytes in vitro. In clinical translation, plasma glucosepane was increased 38% in early-stage OA (p < 0.05) and sixfold in patients with advanced OA (p < 0.001) compared with healthy controls. Conclusions: These studies further advance the prospective role of glycated, oxidized, and nitrated amino acids as serum biomarkers in diagnostic algorithms for early-stage detection of OA and other arthritic disease. Plasma glucosepane, reported here for the first time to our knowledge, may improve early-stage diagnosis and progression of clinical OA

C. elegans rrf-1 Mutations Maintain RNAi Efficiency in the Soma in Addition to the Germline

Gene inactivation through RNA interference (RNAi) has proven to be a valuable tool for studying gene function in C. elegans. When combined with tissue-specific gene inactivation methods, RNAi has the potential to shed light on the function of a gene in distinct tissues. In this study we characterized C. elegans rrf-1 mutants to determine their ability to process RNAi in various tissues. These mutants have been widely used in RNAi studies to assess the function of genes specifically in the C. elegans germline. Upon closer analysis, we found that two rrf-1 mutants carrying different loss-of-function alleles were capable of processing RNAi targeting several somatically expressed genes. Specifically, we observed that the intestine was able to process RNAi triggers efficiently, whereas cells in the hypodermis showed partial susceptibility to RNAi in rrf-1 mutants. Other somatic tissues in rrf-1 mutants, such as the muscles and the somatic gonad, appeared resistant to RNAi. In addition to these observations, we found that the rrf-1(pk1417) mutation induced the expression of several transgenic arrays, including the FOXO transcription factor DAF-16. Unexpectedly, rrf-1(pk1417) mutants showed increased endogenous expression of the DAF-16 target gene sod-3; however, the lifespan and thermo-tolerance of rrf-1(pk1417) mutants were similar to those of wild-type animals. In sum, these data show that rrf-1 mutants display several phenotypes not previously appreciated, including broader tissue-specific RNAi-processing capabilities, and our results underscore the need for careful characterization of tissue-specific RNAi tools