Interventions for drug-using offenders with co-occurring mental illness: : A systematic review and economic appraisal

Background: Drug-using offenders with co-occurring mental health problems are common in the criminal justice system. A combination of drug use and mental health problems makes people more likely to be arrested for criminal involvement after release compared to offenders without a mental health problem. Previous research has evaluated interventions aimed broadly at those with a drug problem but rarely with drug use and mental health problems. This systematic review considers the effectiveness of interventions for drug-using offenders with co-occurring mental health problems. Methods: We searched 14 electronic bibliographic databases up to May 2014 and five Internet resources. The review included randomised controlled trials designed to reduce, eliminate, or prevent relapse of drug use and/or criminal activity. Data were reported on drug and crime outcomes, the identification of mental health problems, diagnoses and resource information using the Drummond checklist. The systematic review used standard methodological procedures as prescribed by the Cochrane collaboration. Results: Eight trials with 2058 participants met the inclusion criteria. These evaluated: case management (RR, 1.05, 95 % CI 0.90 to 1.22, 235 participants), motivational interviewing and cognitive skills, (MD-7.42, 95 % CI-0.20.12 to 5.28, 162 participants) and interpersonal psychotherapy (RR 0.67, 95 % CI 0.3 to 1.5, 38 participants). None of these trials reported significant reductions in self-report drug misuse or crime. Four trials evaluating differing therapeutic community models showed reductions in re-incarceration (RR 0.28, 95 % CI 0.13 to 0.63, 139 participants) but not re-arrest (RR 1.65, 95 % CI 0.83 to 3.28, 370 participants) or self-report drug use (RR 0.73, 95 % CI 0.53 to 1.01, 370 participants). Mental health problems were identified across the eight trials and 17 different diagnoses were described. Two trials reported some resource information suggesting a cost-beneficial saving when comparing therapeutic communities to a prison alternative. Conclusions: Overall, the studies showed a high degree of variation, warranting a degree of caution in the interpretation of the magnitude of effect and direction of benefit for treatment outcomes. Specifically, tailored interventions are required to assess the effectiveness of interventions for drug-using offenders with co-occurring mental health problems

Are Non-Pharmacological Interventions Effective in Reducing Drug Use and Criminality? : A Systematic and Meta-Analytical Review with an Economic Appraisal of These Interventions

Background: The numbers of incarcerated people suffering from drug dependence has steadily risen since the 1980s and only a small proportion of these receive appropriate treatment. A systematic review to evaluate the effectiveness and economic evidence of non-pharmacological interventions for drug using offenders was conducted. Methods: Cochrane Collaboration criteria were used to identify trials across 14 databases between 2004 and 2014. A series of meta-analyses and an economic appraisal were conducted. Results: 43 trials were identified showing to have limited effect in reducing re-arrests RR 0.97 (95% CI 0.89-1.07) and drug use RR 0.90 (95% CI 0.80-1.00) but were found to significantly reduce re-incarceration RR 0.70 (95% CI 0.57-0.85). Therapeutic community programs were found to significantly reduce the number of re-arrests RR 0.70 (95% CI 0.56-0.87). 10 papers contained economic information. One paper presented a cost-benefit analysis and two reported on the cost and cost effectiveness of the intervention. Conclusions: We suggest that therapeutic community interventions have some benefit in reducing subsequent re-arrest. We recommend that economic evaluations should form part of standard trial protocols

Impact of Virtual Reality Simulation in Endodontics on the Learning Experiences of Undergraduate Dental Students

Abstract: We aimed to evaluate the impact of Virtual Reality Dental Simulators (VRDS) on preclinical training in endodontics for undergraduate dental students. Purposive sampling technique was used to target undergraduate dental students at two dental schools: in Qatar and Turkey. After training on endodontic access cavity preparation on upper anterior teeth using acrylic teeth on dental mannequins and virtual reality haptic dental simulator, a questionnaire based on a combination of open- and closed-ended items was distributed to the participants. The sample included 60 dental undergraduate students. The participants reported positive experiences with VRDS and 76% considered it to be helpful in improving their fine motor skills. Endodontic access cavity preparation on VRDS was perceived to be similar to natural and acrylic teeth by 73.34% and 53% of participants, respectively. Overall, 85% of participants supported the use of VRDS training to supplement conventional training on dental mannequins but also recommended the need for improvements in VRDS training in endodontics. The findings of this study underscore the benefits of VRDS in endodontics. Future research involving larger samples from multiple institutions may help to optimize VRDS in undergraduate dental education

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Latent class evaluation of the performance of serological tests for exposure to Brucella spp. in cattle, sheep, and goats in Tanzania

Background: Brucellosis is a neglected zoonosis endemic in many countries, including regions of sub-Saharan Africa. Evaluated diagnostic tools for the detection of exposure to Brucella spp. are important for disease surveillance and guiding prevention and control activities. Methods and findings: Bayesian latent class analysis was used to evaluate performance of the Rose Bengal plate test (RBT) and a competitive ELISA (cELISA) in detecting Brucella spp. exposure at the individual animal-level for cattle, sheep, and goats in Tanzania. Median posterior estimates of RBT sensitivity were: 0.779 (95% Bayesian credibility interval (BCI): 0.570–0.894), 0.893 (0.636–0.989), and 0.807 (0.575–0.966), and for cELISA were: 0.623 (0.443–0.790), 0.409 (0.241–0.644), and 0.561 (0.376–0.713), for cattle, sheep, and goats, respectively. Sensitivity BCIs were wide, with the widest for cELISA in sheep. RBT and cELISA median posterior estimates of specificity were high across species models: RBT ranged between 0.989 (0.980–0.998) and 0.995 (0.985–0.999), and cELISA between 0.984 (0.974–0.995) and 0.996 (0.988–1). Each species model generated seroprevalence estimates for two livestock subpopulations, pastoralist and non-pastoralist. Pastoralist seroprevalence estimates were: 0.063 (0.045–0.090), 0.033 (0.018–0.049), and 0.051 (0.034–0.076), for cattle, sheep, and goats, respectively. Non-pastoralist seroprevalence estimates were below 0.01 for all species models. Series and parallel diagnostic approaches were evaluated. Parallel outperformed a series approach. Median posterior estimates for parallel testing were ≥0.920 (0.760–0.986) for sensitivity and ≥0.973 (0.955–0.992) for specificity, for all species models. Conclusions: Our findings indicate that Brucella spp. surveillance in Tanzania using RBT and cELISA in parallel at the animal-level would give high test performance. There is a need to evaluate strategies for implementing parallel testing at the herd- and flock-level. Our findings can assist in generating robust Brucella spp. exposure estimates for livestock in Tanzania and wider sub-Saharan Africa. The adoption of locally evaluated robust diagnostic tests in setting-specific surveillance is an important step towards brucellosis prevention and control

UK consensus guidelines for the delivery of unexpected news in obstetric ultrasound: The ASCKS framework

Background: Studies indicate there is a need to improve the delivery of unexpected news via obstetric ultrasound, but there have been few advances in this area. One factor preventing improvement has been a lack of consensus regarding the appropriate phrases and behaviours which sonographers and ultrasound practitioners should use in these situations. Aims: To develop consensus guidelines for unexpected news delivery in Early Pregnancy Unit and Fetal Anomaly Screening Programme NHS settings. Methods: A workshop was conducted to identify priorities and reach consensus on areas of contention. Contributors included interdisciplinary healthcare professionals, policy experts, representatives from third-sector organisations, lay experts and academic researchers (n = 28). Written and verbal feedback was used to draft initial guidance which was then circulated amongst the wider writing group (n = 39). Revisions were undertaken until consensus was reached. Results: Consensus guidelines were developed outlining the behaviours and phrases which should be used during scans where unexpected findings are identified. Specific recommendations included that: honest and clear communication should be prioritised, even with uncertain findings; technical terms should be used, but these should be written down together with their lay interpretations; unless expectant parents use other terminology (e.g. ‘foetus’), the term ‘baby’ should be used as a default, even in early pregnancy; at the initial news disclosure, communication should focus on information provision. Expectant parents should not be asked to make decisions during the scan. Conclusions: These recommendations can be used to develop and improve news delivery interventions in obstetric ultrasound settings. The full guidelines can be accessed online as supplemental material and at https://doi.org/10.5518/100/24

The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance.

The role of autophagy, a lysosomal degradation pathway which prevents cellular damage, in the maintenance of adult mouse hematopoietic stem cells (HSCs) remains unknown. Although normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs leads to leukemia. Therefore, mechanisms protecting HSCs from cellular damage are essential to prevent hematopoietic malignancies. In this study, we crippled autophagy in HSCs by conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system. This resulted in the loss of normal HSC functions, a severe myeloproliferation, and death of the mice within weeks. The hematopoietic stem and progenitor cell compartment displayed an accumulation of mitochondria and reactive oxygen species, as well as increased proliferation and DNA damage. HSCs within the Lin(-)Sca-1(+)c-Kit(+) (LSK) compartment were significantly reduced. Although the overall LSK compartment was expanded, Atg7-deficient LSK cells failed to reconstitute the hematopoietic system of lethally irradiated mice. Consistent with loss of HSC functions, the production of both lymphoid and myeloid progenitors was impaired in the absence of Atg7. Collectively, these data show that Atg7 is an essential regulator of adult HSC maintenance

Cross-Serotype Immunity Induced by Immunization with a Conserved Rhinovirus Capsid Protein

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and COPD exacerbations. There is currently no RV vaccine, largely due to the existence of ∼150 strains. We aimed to define highly conserved areas of the RV proteome and test their usefulness as candidate antigens for a broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0 (VP4+VP2) capsid protein were identified as having high homology across RVs. Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant induced systemic, antigen specific, cross-serotype, cellular and humoral immune responses. Similar cross-reactive responses were observed in the lungs of immunized mice after infection with heterologous RV strains. Immunization enhanced the generation of heterosubtypic neutralizing antibodies and lung memory T cells, and caused more rapid virus clearance. Conserved domains of the RV capsid therefore induce cross-reactive immune responses and represent candidates for a subunit RV vaccine

Latent class evaluation of the performance of serological tests for exposure to Brucella spp. in cattle, sheep, and goats in Tanzania

BACKGROUND : Brucellosis is a neglected zoonosis endemic in many countries, including regions of sub-Saharan Africa. Evaluated diagnostic tools for the detection of exposure to Brucella spp. are important for disease surveillance and guiding prevention and control activities. METHODS AND FINDINGS : Bayesian latent class analysis was used to evaluate performance of the Rose Bengal plate test (RBT) and a competitive ELISA (cELISA) in detecting Brucella spp. exposure at the individual animal-level for cattle, sheep, and goats in Tanzania. Median posterior estimates of RBT sensitivity were: 0.779 (95% Bayesian credibility interval (BCI): 0.570–0.894), 0.893 (0.636–0.989), and 0.807 (0.575–0.966), and for cELISA were: 0.623 (0.443–0.790), 0.409 (0.241–0.644), and 0.561 (0.376–0.713), for cattle, sheep, and goats, respectively. Sensitivity BCIs were wide, with the widest for cELISA in sheep. RBT and cELISA median posterior estimates of specificity were high across species models: RBT ranged between 0.989 (0.980–0.998) and 0.995 (0.985–0.999), and cELISA between 0.984 (0.974–0.995) and 0.996 (0.988–1). Each species model generated seroprevalence estimates for two livestock subpopulations, pastoralist and non-pastoralist. Pastoralist seroprevalence estimates were: 0.063 (0.045–0.090), 0.033 (0.018–0.049), and 0.051 (0.034–0.076), for cattle, sheep, and goats, respectively. Non-pastoralist seroprevalence estimates were below 0.01 for all species models. Series and parallel diagnostic approaches were evaluated. Parallel outperformed a series approach. Median posterior estimates for parallel testing were ≥0.920 (0.760-0.986) for sensitivity and ≥0.973 (0.955-0.992) for specificity, for all species models. CONCLUSIONS : Our findings indicate that Brucella spp. surveillance in Tanzania using RBT and cELISA in parallel at the animal-level would give high test performance. There is a need to evaluate strategies for implementing parallel testing at the herd- and flock-level. Our findings can assist in generating robust Brucella spp. exposure estimates for livestock in Tanzania and wider sub-Saharan Africa. The adoption of locally evaluated robust diagnostic tests in setting-specific surveillance is an important step towards brucellosis prevention and control.The UK Biotechnology and Biological Sciences Research Council (BBSRC), Department for International Development (DFID), the Economic & Social Research Council (ESRC), the Medical Research Council (MRC), the Natural Environment Research Council (NERC) and the Defence Science & Technology Laboratory under the Zoonoses and Emerging Livestock Systems programme, Zoonoses and Emerging Livestock Systems – Associated Studentship programme, US National Institutes of Health-National (NIH) Science Foundation Ecology and Evolution of Infectious Disease program, UK BBSRC , the US NIH, National Institute of Allergy and Infectious Diseases through Investigating Febrile Deaths in Tanzania (INDITe) and the BBSRC Institute Strategic Programme Grants.https://journals.plos.org/plosntdspm2022Veterinary Tropical Disease

Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.

CAPRISA, 2014.Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development