Using oral bioaccessibility measurements to refine risk assessment of potentially toxic elements in topsoils across an urban area.

Elevated concentrations of As, Cr, Cu, Ni, Pb, V and Zn in topsoils in Belfast, Northern Ireland have been found to exceed assessment criteria in the city and therefore may pose a risk to human health. Most generic assessment criteria (GAC) for potentially toxic elements (PTEs) in soils assume PTEs are 100% bioavailable to humans. Here we use in-vitro oral bioaccessibility testing using the Unified BARGE method (UBM) to measure what proportion of soil contamination dissolves in the digestive tract and therefore is available for absorption by the body. This study considers how PTE bioaccessibility in soils varies spatially across urban areas and refines human health risk assessment for these PTEs using site specific oral bioaccessibility results to present the first regional assessment of risk that incorporates bioaccessibility testing. A total of 103 urban soil samples were selected for UBM testing. Results showed low bioaccessible fraction (BAF) for the PTEs from geogenic sources: Cr (0.45-5.9%), Ni (1.1-46.3%) and V (2.2-23.9%). Higher BAF values were registered for PTEs from anthropogenic sources: As (8.0-86.9%), Cu (3.4-67.8%), Pb (9.1-106.2%) and Zn (2.4-77.5%). Graphs of bioaccessibility adjusted assessment criteria (BAAC) were derived for each urban land use type and PTE. These provide a visual representation of the significance of oral bioaccessibility when deriving BAAC and how this is affected by 1) dominant exposure pathways for each land use and 2) relative harm posed from exposure to PTEs via each pathway, allowing oral bioaccessibility research to be targeted to contaminants and pathways that most significantly impact risk assessment. Pb was the most widespread contaminant with 16.5% of sites exceeding the Pb GAC. Applying BAAC did not significantly change risk evaluation for these samples as many had Pb BAF>50%. In contrast, all samples that exceeded the As GAC were found to no longer exceed a minimal level of risk when oral bioaccessibility was considered. Oral bioaccessibility testing resulted in a 45% reduction in the number of sites identified as posing a potential risk to human health.

Examining Predisposing Factors and Program Performance Indicators Associated With Program Completion: A Comparison of Opioid and Non-Opioid-Preferring Participants in Drug Court.

Opioid use and abuse, as well as criminal justice involvement, have increased dramatically in the past two decades. Drug court is a community-based rehabilitation program for individuals with substance abuse issues involved in the criminal justice system. Given unique treatment needs associated with opioids, the current study examined predisposing factors and program performance indicators associated with drug court completion based on individuals' opioid preference. Secondary data (i.e., participant assessment and drug court Management Information System) as well as conviction information from a statewide database were examined for a sample of drug court participants (N = 534). Data analyses compared opioid-preferring (n = 267) and non-opioid-preferring (n = 267) program participants. For non-opioid-preferring participants, a combination of predisposing characteristics, including both social/demographic characteristics and substance use (i.e., education, drug court site, lifetime benzodiazepine use), as well as program performance indicators (i.e., number of days in drug court, number of positive drug tests, and sanctions/therapeutic responses) influenced drug court completion. For opioid-preferring participants, only program performance indicators emerged as important for program completion, specifically number of days in drug court, number of positive drug tests, and sanctions/therapeutic responses. Findings for non-opioid-preferring participants are consistent with past research, suggesting that individual predisposing characteristics and program performance indicators are influential on program completion. However, findings suggesting that only program performance indicators are influential for opioid-preferring participants adds a unique contribution to the literature. This information may help provide more individualized program planning and ultimately more programmatic success.

Examining Individual Characteristics and Program Performance to Understand Two-Year Recidivism Rates Among Drug Court Participants: Comparing Graduates and Terminators.

Drug courts strive to break the cycle of substance use and crime by providing community-based treatment and rehabilitation. The purpose of the present study was to (a) identify significantly different factors between program participants (i.e., graduates/terminators) that may affect recidivism and (b) examine these significant individual and program performance factors associated with two-year recidivism. Secondary data were examined for a stratified random sample of drug court participants ( N = 534). Examining any two-year post-program recidivism (defined as an arrest, conviction, or incarceration), over one third (37.6%) of graduates and almost all program terminators (95.3%) had two-year post-program recidivism ( p < .001). For the overall sample, age, outpatient treatment, marital status, number of times treated for a psychiatric problem in a hospital, substance use (i.e., past-30-day cocaine use and intravenous opiate use), number of positive drug tests, and receiving any sanction/therapeutic response were associated with two-year post-program recidivism. Further analyses suggested age and outpatient treatment were particularly important for program graduates. Findings provide information for early targeting of resources to drug court participants most at risk of poorer post-program outcomes by identifying factors known at program entry and indicators during program participation.

Examining the Impact of Prior Criminal Justice History on 2-Year Recidivism Rates: A Comparison of Drug Court Participants and Program Referrals.

Drug courts seek to break the cycle of substance use and crime by providing a community-based intervention to individuals with criminal justice involvement and substance-related issues. This study examined recidivism over a 2-year follow-up period as well as factors associated with recidivism for a sample of drug court participants (i.e., graduates and terminators) and a non-equivalent comparison group (i.e., individuals referred/assessed for the program who did not enter). In the 2-year follow-up window, fewer drug court graduates had any convictions compared with program terminators and referrals; specifically, fewer drug court graduates had drug trafficking convictions compared with program terminators and referrals. Fewer graduates were arrested and incarcerated in jail and/or prison in the 2-year follow-up; furthermore, graduates had spent less time incarcerated compared with program terminators and referrals. Demographics (i.e., age, race, marital status) and prior criminal justice system involvement were associated with recidivism; however, these factors had differential impacts for the three groups (i.e., graduates, terminators, and referrals). Drug court shows promise as a community-based intervention that helps keep individuals out of the criminal justice system during a 2-year follow-up period.

Biocultural approaches to well-being and sustainability indicators across scales.

Monitoring and evaluation are central to ensuring that innovative, multi-scale, and interdisciplinary approaches to sustainability are effective. The development of relevant indicators for local sustainable management outcomes, and the ability to link these to broader national and international policy targets, are key challenges for resource managers, policymakers, and scientists. Sets of indicators that capture both ecological and social-cultural factors, and the feedbacks between them, can underpin cross-scale linkages that help bridge local and global scale initiatives to increase resilience of both humans and ecosystems. Here we argue that biocultural approaches, in combination with methods for synthesizing across evidence from multiple sources, are critical to developing metrics that facilitate linkages across scales and dimensions. Biocultural approaches explicitly start with and build on local cultural perspectives - encompassing values, knowledges, and needs - and recognize feedbacks between ecosystems and human well-being. Adoption of these approaches can encourage exchange between local and global actors, and facilitate identification of crucial problems and solutions that are missing from many regional and international framings of sustainability. Resource managers, scientists, and policymakers need to be thoughtful about not only what kinds of indicators are measured, but also how indicators are designed, implemented, measured, and ultimately combined to evaluate resource use and well-being. We conclude by providing suggestions for translating between local and global indicator efforts.

Examining implementation and preliminary performance indicators of veterans treatment courts: The Kentucky experience.

Veterans' Treatment Courts (VTCs) are posited as a solution to offer rehabilitation for veterans involved in the criminal justice system. Despite the pervasive implementation of VTCs, there is little research focused specifically on VTC implementation and outcomes, which are based on other problem-solving court models such as drug court. The current study presents qualitative process evaluation data from key stakeholders (n=21) and veteran participants (n=4) to show accomplishments, challenges, and lessons learned during first-year implementation at two VTC sites. Quantitative performance data is also presented on veteran participants (n=19) served during the first year to show: types of services, monitoring, judicial interaction, sanctions/therapeutic responses, and rewards, as well as preliminary data on recidivism. Qualitative data, from both key stakeholders and veteran participants, suggests that offering rehabilitation via various program components, services/referrals, and accountability are critical to the success of the VTC. Data also provides valuable lessons learned for VTC implementation including communication, collaboration, information/protocols, and resources. Performance data shows that a variety of services are utilized and that frequent judicial interaction, drug testing, and sanctions are cornerstones of the VTC. Implications and future directions for research are discussed.

Implementation of an enhanced probation program: evaluating process and preliminary outcomes.

Supervision, Monitoring, Accountability, Responsibility, and Treatment (SMART) is Kentucky's enhanced probation pilot program modeled after Hawaii's Opportunity Probation with Enforcement (HOPE). SMART is proposed to decrease substance use, new violations, and incarceration-related costs for high-risk probationers by increasing and randomizing drug testing, intensifying supervision, and creating linkages with needed resources (i.e., mental health and substance use). SMART adopts a holistic approach to rehabilitation by addressing mental health and substance abuse needs as well as life skills for fostering deterrence of criminal behavior vs. punitive action only. A mixed methods evaluation was implemented to assess program implementation and effectiveness. Qualitative interviews with key stakeholders (i.e., administration, judges, attorneys, and law enforcement/corrections) suggested successful implementation and collaboration to facilitate the pilot program. Quantitative analyses of secondary Kentucky Offender Management System (KOMS) data (grant Year 1: 07/01/2012-06/30/2013) also suggested program effectiveness. Specifically, SMART probationers showed significantly fewer: violations of probation (1.2 vs. 2.3), positive drug screens (8.6% vs. 29.4%), and days incarcerated (32.5 vs. 118.1) than comparison probationers. Kentucky's SMART enhanced probation shows preliminary success in reducing violations, substance use, and incarceration. Implications for practice and policy will be discussed.

Cleavage at Arg-1689 influences heavy chain cleavages during thrombin-catalyzed activation of factor VIII.

The procofactor, factor VIII, is activated by thrombin or factor Xa-catalyzed cleavage at three P1 residues: Arg-372, Arg-740, and Arg-1689. The catalytic efficiency for thrombin cleavage at Arg-740 is greater than at either Arg-1689 or Arg-372 and influences reaction rates at these sites. Because cleavage at Arg-372 appears rate-limiting and dependent upon initial cleavage at Arg-740, we investigated whether cleavage at Arg-1689 influences catalysis at this step. Recombinant B-domainless factor VIII mutants, R1689H and R1689Q were prepared and stably expressed to slow and eliminate cleavage, respectively. Specific activity values for the His and Gln mutations were approximately 50 and approximately 10%, respectively, that of wild type. Thrombin activation of the R1689H variant showed an approximately 340-fold reduction in the rate of Arg-1689 cleavage, whereas the R1689Q variant was resistant to thrombin cleavage at this site. Examination of heavy chain cleavages showed approximately 4- and 11-fold reductions in A2 subunit generation and approximately 3- and 7-fold reductions in A1 subunit generation for the R1689H and R1689Q mutants, respectively. These results suggest a linkage between light chain cleavage and cleavages in heavy chain. Results obtained evaluating proteolysis of the factor VIII mutants by factor Xa revealed modest rate reductions (<5-fold) in generating A2 and A1 subunits and in cleaving light chain at Arg-1721 from either variant, suggesting little dependence upon prior cleavage at residue 1689 as compared with thrombin. Overall, these results are consistent with a competition between heavy and light chains for thrombin exosite binding and subsequent proteolysis with binding of the former chain preferred.

Light, nutrients, and food-chain length constrain planktonic energy transfer efficiency across multiple trophic levels.

The efficiency of energy transfer through food chains [food chain efficiency (FCE)] is an important ecosystem function. It has been hypothesized that FCE across multiple trophic levels is constrained by the efficiency at which herbivores use plant energy, which depends on plant nutritional quality. Furthermore, the number of trophic levels may also constrain FCE, because herbivores are less efficient in using plant production when they are constrained by carnivores. These hypotheses have not been tested experimentally in food chains with 3 or more trophic levels. In a field experiment manipulating light, nutrients, and food-chain length, we show that FCE is constrained by algal food quality and food-chain length. FCE across 3 trophic levels (phytoplankton to carnivorous fish) was highest under low light and high nutrients, where algal quality was best as indicated by taxonomic composition and nutrient stoichiometry. In 3-level systems, FCE was constrained by the efficiency at which both herbivores and carnivores converted food into production; a strong nutrient effect on carnivore efficiency suggests a carryover effect of algal quality across 3 trophic levels. Energy transfer efficiency from algae to herbivores was also higher in 2-level systems (without carnivores) than in 3-level systems. Our results support the hypothesis that FCE is strongly constrained by light, nutrients, and food-chain length and suggest that carryover effects across multiple trophic levels are important. Because many environmental perturbations affect light, nutrients, and food-chain length, and many ecological services are mediated by FCE, it will be important to apply these findings to various ecosystem types.

Acidic residues C-terminal to the A2 domain facilitate thrombin-catalyzed activation of factor VIII.

Factor VIII is activated by thrombin through proteolysis at Arg740, Arg372, and Arg1689. One region implicated in this exosite-dependent interaction is the factor VIII a2 segment (residues 711-740) separating the A2 and B domains. Residues 717-725 (DYYEDSYED) within this region consist of five acidic residues and three sulfo-Tyr residues, thus representing a high density of negative charge potential. The contributions of these residues to thrombin-catalyzed activation of factor VIII were assessed following mutagenesis of acidic residues to Ala or Tyr residues to Phe and expression and purification of the B-domainless proteins from stable-expressing cell lines. All mutations showed reduced specific activity from approximately 30% to approximately 70% of the wild-type value. While replacement of the Tyr residues showed little, if any, effect on rates of thrombin-catalyzed proteolysis of factor VIII and consequent activation, the acidic to Ala mutations Glu720Ala, Asp721Ala, Glu724Ala, and Asp725Ala showed decreased rates of proteolysis at each of the three P1 residues. Mutations at residues Glu724 and Asp725 were most affected with double mutations at these sites showing approximately 10-fold and approximately 30-fold reduced rates of cleavage at Arg372 and Arg1689, respectively. Factor VIII activation profiles paralleled the results assessing rates of proteolysis. Kinetic analyses revealed these mutations minimally affected apparent V max for thrombin-catalyzed cleavage but variably increased the K m for procofactor up to 7-fold, suggesting the latter parameter was dominant in reducing catalytic efficiency. These results suggest that residues Glu720, Asp721, Glu724, and Asp725 likely constitute an exosite-interactive region in factor VIII facilitating cleavages for procofactor activation.

Proteolysis at Arg740 facilitates subsequent bond cleavages during thrombin-catalyzed activation of factor VIII.

Thrombin activates factor VIII by proteolysis at three P1 residues: Arg372, Arg740, and Arg1689. Cleavage at Arg372 and Arg1689 are essential for procofactor activation; however cleavage at Arg740 has not been rigorously studied. To evaluate the role for cleavage at Arg740, we prepared and stably expressed two recombinant B-domainless factor VIII mutants, R740H and R740Q to slow and eliminate, respectively, cleavage at this site. Specific activity values for the variants were approximately 50 and 20%, respectively, that of wild-type factor VIII. Activation of factor VIII R740H by thrombin showed an approximately 40-fold reduction in the rate of A2 subunit generation, which reflected an approximately 20-fold reduction in cleavage rate at Arg372. Similarly, a approximately 40-fold rate reduction in cleavage at Arg1689 and consequent generation of the A3-C1-C2 subunit were observed. Rate values for A2 and A3-C1-C2 subunit generation were reduced by >700-fold and approximately 140-fold, respectively, in the R740Q variant. These results suggest that initial cleavage at Arg740 affects cleavage at both Arg372 and Arg1689 sites. Results obtained evaluating proteolysis of the factor VIII mutants by factor Xa revealed more modest rate reductions (<10-fold) in generating A2 and A3-C1-C2 subunits from either variant, suggesting that factor Xa-catalyzed activation of factor VIII was significantly less dependent upon prior cleavage at residue 740 than thrombin. Overall, these results support a model whereby cleavage of factor VIII by thrombin is an ordered pathway with cleavage at Arg740 facilitating cleavages at Arg372 and Arg1689, which result in procofactor activation.