Juror Perceptions of Bystander and Victim Intoxication by Different Substances

This study examined the effects of bystander or victim intoxication during a crime on juror perceptions and decision-making. Mock jurors (N = 261) read testimony from a bystander or victim to an assault, who mentioned that they had consumed alcohol, cannabis, amphetamines, or no substances prior to the crime. Participants delivered a verdict, rated the defendant’s guilt, and rated the bystander/victim on their honesty, credibility, and cognitive competence. Witness intoxication and witness role did not influence defendant guilt. However, participants judged any witness intoxicated by amphetamines as less credible and cognitively competent than a sober witness. Furthermore, victims were judged to have lower credibility, cognitive competence, and honesty than bystanders. These findings suggest that jurors’ decision-making about defendant guilt might not be influenced by witness intoxication or witness type. A witness’ testimony, however, might be evaluated as less credible when delivered by a victim or an amphetamine-intoxicated witness

Juror Perceptions of Bystander and Victim Intoxication by Different Substances

This study examined the effects of bystander or victim intoxication during a crime on juror perceptions and decision-making. Mock jurors (N = 261) read testimony from a bystander or victim to an assault, who mentioned that they had consumed alcohol, cannabis, amphetamines, or no substances prior to the crime. Participants delivered a verdict, rated the defendant’s guilt, and rated the bystander/victim on their honesty, credibility, and cognitive competence. Witness intoxication and witness role did not influence defendant guilt. However, participants judged any witness intoxicated by amphetamines as less credible and cognitively competent than a sober witness. Furthermore, victims were judged to have lower credibility, cognitive competence, and honesty than bystanders. These findings suggest that jurors’ decision-making about defendant guilt might not be influenced by witness intoxication or witness type. A witness’ testimony, however, might be evaluated as less credible when delivered by a victim or an amphetamine-intoxicated witness

Utility and Cost-Effectiveness of a Nonendoscopic Approach to Barrett's Esophagus Surveillance After Endoscopic Therapy

BACKGROUND & AIMS: A non-endoscopic approach to Barrett's esophagus (BE) surveillance after radiofrequency ablation (RFA) would offer a less invasive method for monitoring. We assessed the test characteristics and cost-effectiveness of the Cytosponge® in post-RFA patients. METHODS: We performed a multicenter study of dysplastic BE patients after at least one round of RFA. A positive Cytosponge® before endoscopy was defined as intestinal metaplasia (IM) on cytological assessment and/or TFF3 immunohistochemistry. Sensitivity, specificity, and receiver operator characteristic (ROC) curves were calculated. Multivariable regression was used to estimate the odds of a positive Cytosponge® in BE. A microsimulation cost-effectiveness model was performed to assess outcomes of various surveillance strategies: endoscopy-only, Cytosponge®-only, and alternating endoscopy/Cytosponge®. RESULTS: Of 234 patients, Cytosponge® adequately sampled the distal esophagus in 175 (75%). Of the 142 with both endoscopic and histologic data, 19 (13%) had residual/recurrent BE. For detecting any residual Barrett's, Cytosponge® had a sensitivity of 74%, specificity of 85%, accuracy of 84%, and ROC curve showed an area under the curve of 0.74. The adjusted odds of a positive Cytosponge® in BE were 17.1 (95% CI: 5.2-55.9). Cytosponge®-only surveillance dominated all the surveillance strategies, being both less costly and more effective. Cytosponge®-only surveillance required <1/4th the endoscopies, resulting in only 0.69 additional EAC cases/1,000 patients, and no increase in EAC deaths when compared to currently-practiced endoscopy-only surveillance. CONCLUSIONS: A positive Cytosponge® test was strongly associated with residual BE after ablation. While the assay needs further refinement in this context, it could serve as a cost-effective surveillance examination

Clinical population pharmacokinetics and toxicodynamics of linezolid

Thrombocytopenia is a common side effect of linezolid, an oxazolidinone antibiotic often used to treat multidrug-resistant Gram-positive bacterial infections. Various risk factors have been suggested, including linezolid dose and duration of therapy, baseline platelet counts, and renal dysfunction; still, the mechanisms behind this potentially treatment-limiting toxicity are largely unknown. A clinical study was conducted to investigate the relationship between linezolid pharmacokinetics and toxico-dynamics and inform strategies to prevent and manage linezolid-associated toxicity. Forty-one patients received 42 separate treatment courses of linezolid (600 mg every 12 h). A new mechanism-based, population pharmacokinetic/toxicodynamic model was developed to describe the time course of plasma linezolid concentrations and platelets. A linezolid concentration of 8.06 mg/ liter (101% between-patient variability) inhibited the synthesis of platelet precursor cells by 50%. Simulations predicted treatment durations of 5 and 7 days to carry a substantially lower risk than 10- to 28-day therapy for platelet nadirs o

ImaYDiT - Imagining young disabled people's transitions in a time of major societal change: Research project report

ImaYDiT was funded by DRILL – Disability Research for Independent Living and Learning. This is supported by the Big Lottery Fund. WiltsCIL staff, members of WiltsCIL CoproductionGroup and researchers at UWE came up with the original idea for this project. We wanted to support young disabled people to explore and re-imagine their adult lives and have the best future. This involved taking an ‘assets-based’ approach. This is where we focus on what people can do- rather than what they can’t do – which is a ‘deficit approach’. We also thought that there is not enough research about the whole of young disabled people’s lives. Instead a lot of research only concentrates on transitions through the benefits and service system.Wiltshire Social Services and the Wiltshire Parent Council helped steer the project because, where we could, we also wanted to put young disabled people’s hopes and dreams into action.We want to understand how this group of young disabled people can be supported to become the next generation who are aware of their rights, with ambitions for their futures and able to establish meaningful and independent adult lives

Identification of a potent and selective LAPTc inhibitor by RapidFire-Mass Spectrometry, with antichagasic activity

Background: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and leads to ~10,000 deaths each year. Nifurtimox and benznidazole are the only two drugs available but have significant adverse effects and limited efficacy. New chemotherapeutic agents are urgently required. Here we identified inhibitors of the acidic M17 leucyl-aminopeptidase from T. cruzi (LAPTc) that show promise as novel starting points for Chagas disease drug discovery.Methodology/Principal findings: A RapidFire-MS screen with a protease-focused compound library identified novel LAPTc inhibitors. Twenty-eight hits were progressed to the dose-response studies, from which 12 molecules inhibited LAPTc with IC50 &lt; 34 μM. Of these, compound 4 was the most potent hit and mode of inhibition studies indicate that compound 4 is a competitive LAPTc inhibitor, with Ki 0.27 μM. Compound 4 is selective with respect to human LAP3, showing a selectivity index of &gt;500. Compound 4 exhibited sub-micromolar activity against intracellular T. cruzi amastigotes, and while the selectivity-window against the host cells was narrow, no toxicity was observed for un-infected HepG2 cells. In silico modelling of the LAPTc-compound 4 interaction is consistent with the competitive mode of inhibition. Molecular dynamics simulations reproduce the experimental binding strength (-8.95 kcal/mol), and indicate a binding mode based mainly on hydrophobic interactions with active site residues without metal cation coordination.Conclusions/Significance: Our data indicates that these new LAPTc inhibitors should be considered for further development as antiparasitic agents for the treatment of Chagas disease.</p

international Epidemiology of Carbapenemase-Producing Escherichia Coli

BACKGROUND: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. METHODS: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. RESULTS: Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. CONCLUSIONS: Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations

"The extreme penalty of the law": mercy and the death penalty as aspects of state power in colonial Nyasaland, c. 1903-47

Open access article.Capital punishment was the pinnacle of the colonial judicial system and its use of state violence, but has previously been neglected as a topic of historical research in Africa. This article is based on the case files and legal records of over 800 capital trials – predominantly for murder – dating between 1900 and 1947. It outlines the functioning of the legal system in Nyasaland and the tensions between “violence” and “humanitarianism” in the use and reform of the death penalty. Capital punishment was a political penalty as much as a judicial punishment, with both didactic and deterrent functions: it operated through mercy and the sparing of condemned lives as well as through executions. Mercy in Nyasaland was consistent with colonial political objectives and cultural values: it was decided not only on the facts of cases, but according to British conceptions of “justice”, “order”, “criminality”, and “African” behaviour. This article analyses the use of mercy in Nyasaland to provide a lens on the nature of colonial governance, and the tensions between African and colonial understandings of violence.Arts and Humanities Research Council (UK) and the Beit Fund, University of Oxfor

Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): a prospective cohort study

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a global threat, but the distribution and clinical significance of carbapenemases are unclear. The aim of this study was to define characteristics and outcomes of CRPA infections and the global frequency and clinical impact of carbapenemases harboured by CRPA. METHODS: We conducted an observational, prospective cohort study of CRPA isolated from bloodstream, respiratory, urine, or wound cultures of patients at 44 hospitals (10 countries) between Dec 1, 2018, and Nov 30, 2019. Clinical data were abstracted from health records and CRPA isolates were whole-genome sequenced. The primary outcome was 30-day mortality from the day the index culture was collected. We compared outcomes of patients with CRPA infections by infection type and across geographic regions and performed an inverse probability weighted analysis to assess the association between carbapenemase production and 30-day mortality. FINDINGS: We enrolled 972 patients (USA n=527, China n=171, south and central America n=127, Middle East n=91, Australia and Singapore n=56), of whom 581 (60%) had CRPA infections. 30-day mortality differed by infection type (bloodstream 21 [30%] of 69, respiratory 69 [19%] of 358, wound nine [14%] of 66, urine six [7%] of 88; p=0·0012) and geographical region (Middle East 15 [29%] of 52, south and central America 20 [27%] of 73, USA 60 [19%] of 308, Australia and Singapore three [11%] of 28, China seven [6%] of 120; p=0·0002). Prevalence of carbapenemase genes among CRPA isolates also varied by region (south and central America 88 [69%] of 127, Australia and Singapore 32 [57%] of 56, China 54 [32%] of 171, Middle East 27 [30%] of 91, USA ten [2%] of 527; p\u3c0·0001). KPC-2 (n=103 [49%]) and VIM-2 (n=75 [36%]) were the most common carbapenemases in 211 carbapenemase-producing isolates. After excluding USA patients, because few US isolates had carbapenemases, patients with carbapenemase-producing CRPA infections had higher 30-day mortality than those with non-carbapenemase-producing CRPA infections in both unadjusted (26 [22%] of 120 vs 19 [12%] of 153; difference 9%, 95% CI 3-16) and adjusted (difference 7%, 95% CI 1-14) analyses. INTERPRETATION: The emergence of different carbapenemases among CRPA isolates in different geographical regions and the increased mortality associated with carbapenemase-producing CRPA infections highlight the therapeutic challenges posed by these organisms. FUNDING: National Institutes of Health