Rethinking Justice in Massachusetts: Public Attitudes Toward Crime and Punishment

Presents results from a public opinion survey about the sharp increase in the incarcerated population in Massachusetts and about current strategies for reintegrating ex-offenders who have been released into the community

Pilot Preference, Compliance, and Performance With an Airborne Conflict Management Toolset

A human-in-the-loop experiment was conducted at the NASA Ames and Langley Research Centers, investigating the En Route Free Maneuvering component of a future air traffic management concept termed Distributed Air/Ground Traffic Management (DAG-TM). NASA Langley test subject pilots used the Autonomous Operations Planner (AOP) airborne toolset to detect and resolve traffic conflicts, interacting with subject pilots and air traffic controllers at NASA Ames. Experimental results are presented, focusing on conflict resolution maneuver choices, AOP resolution guidance acceptability, and performance metrics. Based on these results, suggestions are made to further improve the AOP interface and functionality

A rapid method for the in-field analysis of amphetamines employing the agilent bioanalyzer

This paper reports the first analysis of small molecules on the Agilent bio-analyser. The Bioanalyzer is a commercial lab-on-a-chip instrument designed for the analysis of DNA and proteins. We demonstrate that the instrument is suitable for analyses beyond its design specifications. Amphetamine, methamphetamine and pseudoephedrine were separated with a 50 mM borate and 50 mM sodium dodecyl sulfate (SDS) buffer at pH 9.66. The analytes were derivatised with fluorescein isothiocyanate (FITC) in 3 minutes with a heating block set at 90°C, reducing the typical time of 12 hours required for amine-labelling. Analytes were detected by LED-induced fluorescence (λ = 525 nm and λ = 470 nm). Furthermore, five amphetamine analogues were baseline separated within 1 minute. An average limit of detection of 0.6 mg mL -1 and limit of quantification of 2.2μ mg mL-1 were obtained for all analytes. These rapid analyses in conjunction with a fast and reliable derivatisation method with FITC demonstrate its potential use for the in-field analysis of samples of forensic significance. © 2011 The Royal Society of Chemistry

Development and validation of risk score for predicting positive repeat prostate biopsy in patients with a previous negative biopsy in a UK population.

BACKGROUND: Little evidence is available to determine which patients should undergo repeat biopsy after initial benign extended core biopsy (ECB). Attempts have been made to reduce the frequency of negative repeat biopsies using PSA kinetics, density, free-to-total ratios and Kattan's nomogram, to identify men more likely to harbour cancer but no single tool accurately predicts biopsy outcome. The objective of this study was to develop a predictive nomogram to identify men more likely to have a cancer diagnosed on repeat prostate biopsy. METHODS: Patients with previous benign ECB undergoing repeat biopsy were identified from a database. Association between age, volume, stage, previous histology, PSA kinetics and positive repeat biopsy was analysed. Variables were entered stepwise into logistic regression models. A risk score giving the probability of positive repeat biopsy was estimated. The performance of this score was assessed using receiver characteristic (ROC) analysis. RESULTS: 110 repeat biopsies were performed in this period. Cancer was detected in 31% of repeat biopsies at Hospital (1) and 30% at Hospital (2). The most accurate predictive model combined age, PSA, PSA velocity, free-to-total PSA ratio, prostate volume and digital rectal examination (DRE) findings. The risk model performed well in an independent sample, area under the curve (AUCROC) was 0.818 (95% CI 0.707 to 0.929) for the risk model and 0.696 (95% CI 0.472 to 0.921) for the validation model. It was calculated that using a threshold risk score of > 0.2 to identify high risk individuals would reduce repeat biopsies by 39% while identifying 90% of the men with prostate cancer. CONCLUSION: An accurate multi-variable predictive tool to determine the risk of positive repeat prostate biopsy is presented. This can be used by urologists in an outpatient setting to aid decision-making for men with prior benign histology for whom a repeat biopsy is being considered.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Screening of gunshot residues using desorption electrospray ionisation-mass spectrometry (DESI-MS)

Several studies have indicated that there are potential environmental sources of particles resembling inorganic primer found in gunshot residues (GSR); as a consequence examiners are reluctant to unambiguously assign the origin of inorganic particles. If organic gunshot residues (OGSR) were found in combination with inorganic particles, the possibility of environmental sources could be potentially eliminated, thereby significantly enhancing the strength of the evidence.Methods have been previously described whereby GSR specimens can be analysed for the presence of OGSR or inorganic GRS (IGSR). However, no methods have been reported that allow the analysis of both OGSR and IGSR on the same specimen.Described in this article is a direct method using desorption electrospray ionisation-mass spectrometry (DESI-MS) for the detection of methyl centralite (MC), ethyl centralite (EC) and diphenylamine (DPA) on adhesive tape GSR stubs typically used for scanning electron microscopy-energy-dispersive X-ray (SEM-EDX) analysis. The optimisation of numerous parameters was conducted using an experimental design. The results indicate that direct analysis of these organic components of GSR is possible although some limitations were also identified.This initial investigation has also indicated that subjecting stubs to DESI analysis does not interfere with subsequent SEM-EDX analysis of primer residues; therefore the technique described herein allows a comprehensive examination of GSR that would be highly probative in the event that both OGSR and IGSR are detected in the same specimen. © 2011 Elsevier Ireland Ltd

Conflict Resolution Performance in an Experimental Study of En Route Free Maneuvering Operations

NASA has developed a far-term air traffic management concept, termed Distributed Air/Ground Traffic Management (DAG-TM). One component of DAG-TM, En Route Free Maneuvering, allows properly trained flight crews of equipped autonomous aircraft to assume responsibility for separation from other autonomous aircraft and from Instrument Flight Rules (IFR) aircraft. Ground-based air traffic controllers continue to separate IFR traffic and issue flow management constraints to all aircraft. To examine En Route Free Maneuvering operations, a joint human-in-the-loop experiment was conducted in summer 2004 at the NASA Ames and Langley Research Centers. Test subject pilots used desktop flight simulators to resolve traffic conflicts and adhere to air traffic flow constraints issued by subject controllers. The experimental airspace integrated both autonomous and IFR aircraft at varying traffic densities. This paper presents a subset of the En Route Free Maneuvering experimental results, focusing on airborne and ground-based conflict resolution, and the effects of increased traffic levels on the ability of pilots and air traffic controllers to perform this task. The results show that, in general, increases in autonomous traffic do not significantly impact conflict resolution performance. In addition, pilot acceptability of autonomous operations remains high throughout the range of traffic densities studied. Together with previously reported findings, these results continue to support the feasibility of the En Route Free Maneuvering component of DAG-TM

Detection of gunshot residues using mass spectrometry

In recent years, forensic scientists have become increasingly interested in the detection and interpretation of organic gunshot residues (OGSR) due to the increasing use of lead- and heavy metal-free ammunition. This has also been prompted by the identification of gunshot residue- (GSR-) like particles in environmental and occupational samples. Various techniques have been investigated for their ability to detect OGSR. Mass spectrometry (MS) coupled to a chromatographic system is a powerful tool due to its high selectivity and sensitivity. Further, modern MS instruments can detect and identify a number of explosives and additives which may require different ionization techniques. Finally, MS has been applied to the analysis of both OGSR and inorganic gunshot residue (IGSR), although the "gold standard" for analysis is scanning electron microscopy with energy dispersive X-ray microscopy (SEM-EDX). This review presents an overview of the technical attributes of currently available MS and ionization techniques and their reported applications to GSR analysis. © 2014 Regina Verena Taudte et al

Regulation of peptide import through phosphorylation of Ubr1, the ubiquitin ligase of the N-end rule pathway

Substrates of the N-end rule pathway include proteins with destabilizing N-terminal residues. These residues are recognized by E3 ubiquitin ligases called N-recognins. Ubr1 is the N-recognin of the yeast Saccharomyces cerevisiae. Extracellular amino acids or short peptides up-regulate the peptide transporter gene PTR2, thereby increasing the capacity of a cell to import peptides. Cup9 is a transcriptional repressor that down-regulates PTR2. The induction of PTR2 by peptides or amino acids involves accelerated degradation of Cup9 by the N-end rule pathway. We report here that the Ubr1 N-recognin, which conditionally targets Cup9 for degradation, is phosphorylated in vivo at multiple sites, including Ser300 and Tyr277. We also show that the type-I casein kinases Yck1 and Yck2 phosphorylate Ubr1 on Ser300, and thereby make possible (“prime”) the subsequent (presumably sequential) phosphorylations of Ubr1 on Ser296, Ser292, Thr288, and Tyr277 by Mck1, a kinase of the glycogen synthase kinase 3 (Gsk3) family. Phosphorylation of Ubr1 on Tyr277 by Mck1 is a previously undescribed example of a cascade-based tyrosine phosphorylation by a Gsk3-type kinase outside of autophosphorylation. We show that the Yck1/Yck2-mediated phosphorylation of Ubr1 on Ser300 plays a major role in the control of peptide import by the N-end rule pathway. In contrast to phosphorylation on Ser300, the subsequent (primed) phosphorylations, including the one on Tyr277, have at most minor effects on the known properties of Ubr1, including regulation of peptide import. Thus, a biological role of the rest of Ubr1 phosphorylation cascade remains to be identified

The IL-1 family in relation to psoriasis

Psoriasis is a common chronic inflammatory skin disease which can also affect the joints. Its pathogenesis is still to be fully elucidated and involves a wide range of inflammatory mediators, tissue and immune cells. At present, there is no treatment available to cure psoriasis. Although biologics have considerably improved the treatment of the most severe cases there is still a pressing clinical need to improve therapy for specific disease subtypes (e.g. pustular psoriasis) and the vast majority of patients suffering from psoriasis classified as mild to moderate. In particular, efficient and well tolerated topical approaches are lacking. This work has focused 1) on advancing our understanding of IL-36 cytokines which are recognised for their significance in pustular psoriasis, 2) on identifying endogenous disease limiting mediators such as IL-18 binding protein and how they could be manipulated in a therapeutic approach and 3) on IL-17 neutralising RNA aptamers as tools for topical therapy. Main results include the identification of biologic activity of processed and non-processed IL-36 members. N-terminal cleavage is required to increase activity of all IL-36 members. The protease responsible for IL-36RA processing was elucidated. Neutrophil proteases as well as kallikrein 7 can cleave pro-inflammatory IL-36 members. However, a second processing step seems necessary for full activation and the potentially responsible aminopeptidase remains to be identified. Secondly, it was found that human primary fibroblasts produce significant levels of IL-18BP, which controls pro-inflammatory function of IL-18. Endogenous IL-18BP can be induced by IL-27 which, when given in combination with hydrocortisone does not induce pro-inflammatory responses. Thirdly, an IL-17 specific aptamer was verified to block IL-17A activity in fibroblast and fibroblast Th17 co-cultures but not in keratinocyte cultures. Significant uptake of the RNA aptamer by keratinocytes was identified as potentially responsible for the lack of neutralising capacity