Ignorance and moral judgment: Testing the logical priority of the epistemic.

It has recently been argued that a person's moral judgments (about both their own and others' actions) are constrained by the nature and extent of their relevant ignorance and, thus, that such judgments are determined in the first instance by the person's epistemic circumstances. It has been argued, in other words, that the epistemic is logically prior to other normative (e.g., ethical, prudential, pecuniary) considerations in human decision-making, that these other normative considerations figure in decision-making only after (logically and temporally) relevant ignorance has constrained the decision-maker's menu of options. If this is right, then a person's moral judgments in some set of circumstances should vary with their knowledge and ignorance of these circumstances. In this study, we test the hypothesis of the logical priority of the epistemic. We describe two experiments in which subjects' knowledge and ignorance of relevant consequences were manipulated. In the second experiment, we also compared the effect of ignorance on moral judgments with that of personal force, a factor previously shown to influence moral judgments. We found broad empirical support for the armchair arguments that epistemic considerations are logically prior to normative considerations.

Creating an Advanced Practice Registered Nurse Council Within a Regional Hospital Network.

This article describes the development of an advanced practice RN (APRN) council in a large hospital network. Despite obstacles, the council was able to demonstrate positive outcomes, which include standardization of the credentialing and onboarding process, productive networking, and an APRN-oriented education fair. The council has been able to guide workplace culture, establish and support vertical and horizontal interprofessional relationships, provide recommendations to relevant leadership boards, and develop standardized procedures.

Colon diverticulosis is not a risk factor for the detection of adenomatous polyps - results of a prospective study.

BACKGROUND AND AIMS: Colon diverticula (CD) and adenomatous polyps are frequently found during colonoscopy. Data from the literature contains inconsistent information about whether patients with CD have a higher risk for colon adenomas. A positive correlation might influence the current guidelines for screening colonoscopies. The aim of this study was to examine whether presence of CD is associated with endoscopic adenoma detection. MATERIALS AND METHODS: This was a prospective study at 2 centers in Germany. Patients with an indication for colonoscopy were included. The number and localization of diverticula were recorded. Detected polyps were resected, and histopathological results were captured. Logistic regression models were fitted to the data to evaluate the association between CD and adenoma detection. RESULTS: A total of 938 colonoscopies was included. CD occurred in 49.1 % of the colonoscopies. The polyp and adenoma detection rates (PDR, ADR) were 50.3 % and 32.3 %. In 37.5 % of the patients with diverticula, at least 1 adenoma was detected, whereas this was the case in 27.3 % in the absence of diverticula. The presence of diverticula was positively correlated with the detection of adenomas in univariate analysis (p = 0.001), but no significant association could be found in multivariable analysis (p = 0.775). Increasing age (p < 0.001), male sex (p = 0.005), and longer withdrawal time (p < 0.001) were significant predictors for adenoma detection in the multivariable analysis. Similar results were also observed for both the distal and the proximal colon. DISCUSSION: Diverticula and adenomas are frequently found during colonoscopies. However, diverticula disease was not significantly associated with adenoma detection after adjustment for relevant prognostic factors. Older age, male sex, and duration of withdrawal time are predictors for the detection of adenomatous polyps.

Endocuff vision-assisted vs. standard polyp resection in the colorectum (the EVASTA study): a prospective randomized study.

BACKGROUND: Cap-assisted colonoscopy is frequently used to facilitate adenoma detection during endoscopy. However, data on how cap assistance influences polyp resection are scarce. We aimed to evaluate the impact of cap assistance with the Endocuff vision device (EVD) on the resection time for colorectal polyps in patients undergoing colonoscopy. METHODS : A randomized, prospective study was performed in a university hospital in Germany. A total of 250 patients were randomly assigned 1:1 to undergo either colonoscopy with the EVD (EVD arm) or standard colonoscopy without the use of a cap (standard arm). The primary outcome was the average duration of polypectomy. Secondary outcomes included adenoma detection rate, cecal and ileal intubation times, and propofol dosage. RESULTS: The use of EVD led to a significant reduction in the median polypectomy time in the EVD vs. standard arm (54 vs. 80 seconds, respectively; P = 0.02). This effect was strongest for polyps ≥ 6 mm. Compared with the standard group, Endocuff assistance also resulted in a shorter cecal intubation time (6 vs. 8 minutes; P = 0.03) and overall colonoscopy time (23 vs. 27 minutes; P = 0.02). In contrast, no difference in withdrawal time was observed. The polyp and adenoma detection rates did not differ significantly between the two groups. CONCLUSION: Endocuff-assisted colonoscopy reduces the duration of polypectomy, which may be due to a more stable scope position during resection. Further studies are needed to investigate whether comparable effects will be seen for other interventions, such as clipping or biopsy sampling.

Automated polyp detection in the colorectum: a prospective study (with videos).

BACKGROUND AND AIMS: Adenoma detection is a highly personalized task that differs markedly among endoscopists. Technical advances are therefore desirable for the improvement of the adenoma detection rate (ADR). An automated computer-driven technology would offer the chance to objectively assess the presence of colorectal polyps during colonoscopy. We present here the application of a real-time automated polyp detection software (APDS) under routine colonoscopy conditions. METHODS: This was a prospective study at a university hospital in Germany. A prototype of a novel APDS ("KoloPol," Fraunhofer IIS, Erlangen, Germany) was used for automated image-based polyp detection. The software functions by highlighting structures of possible polyp lesions in a color-coded manner during real-time colonoscopy procedures. Testing the feasibility of APDS deployment under real-time conditions was the primary goal of the study. APDS polyp detection rates (PDRs) were defined as secondary endpoints provided that endoscopists' detection served as criterion standard. RESULTS: The APDS was applied in 55 routine colonoscopies without the occurrence of any clinically relevant adverse events. Endoscopists' PDRs and ADRs were 56.4% and 30.9%, respectively. The PDRs and ADRs of the APDS were 50.9% and 29.1%, respectively. The APDS detected 55 of 73 polyps (75.3%). Smaller polyp size and flat polyp morphology were correlated with insufficient polyp detection by the APDS. CONCLUSION: Computer-assisted automated low-delay polyp detection is feasible during real-time colonoscopy. Efforts should be undertaken to improve the APDS with respect to smaller and flat shaped polyps. (Clinical trial registration number: NCT02838888.).

Near focus NBI endoscopy plus acetic acid for optical polyp characterization in the colorectum - A proof of principle study.

Background and study aim: Optical polyp characterization (OPC) in the colorectum is an upcoming challenge for endoscopists. Narrow band imanging (NBI) has been proposed to be helpful for OPC. However, data from clinical studies have shown that quality of OPC differs markedly between endoscopists. The aim of this study was to test the value of a combined NBI plus acetic acid (NBI + AA) approach for OPC in the colorectum. Patients and methods: This was a prospective, single-arm study at a tertiary referral center in Germany. The study was designed as a proof of principle study. Initially polyps were characterized using High-definition white light (HDWL) only. Additionally, the same polyps were investigated using NBI + AA (1.5% solution) in order to predict polyp pathology in a real time setting. The near focus function was used for both HDWL and NBI + AA assessment. The primary endpoint was accuracy of colorectal polyp prediction when using NBI + AA. Results: A total of 63 polyps were detected in 55 patients. NBI + AA based accuracy of real-time predictions was 85.5% compared to 80.6% using HDWL (p = .450). Accuracy was 90.2% in the high confidence setting for both NBI + AA and HDWL predictions. A higher share of polyps were assessed with high confidence when using NBI + AA compared to HDWL (p = .006). The use of NBI + AA led to a better identification of polyp margins (p < .001) compared to HDWL. Conclusions: The use of acetic acid led to a high level of accuracy and confidence in the prediction of polyp histology. These data justify further investigation in a randomized controlled study.

Zwitterionic ring-opening polymerization for the synthesis of high molecular weight cyclic polymers.

Cyclic polymers are an intriguing class of macromolecules. Because of the constraints of the cyclic topology and the absence of chain ends, the properties of these molecules differ from those of linear polymers in ways that remain poorly understood. Cyclic polymers present formidable synthetic challenges because the entropic penalty of coupling the chain ends grows exponentially with increasing molecular weight. In this Account, we describe recent progress in the application of zwitterionic ring-opening polymerization (ZROP) as a strategy for the synthesis of high molecular weight, cyclic polymers. Zwitterionic ring-opening polymerization involves the addition of neutral organic nucleophiles to strained heterocyclic monomers; under appropriate conditions, cyclization of the resultant macrozwitterions generates cyclic macromolecules. We discuss the mechanistic and kinetic features of these zwitterionic ring-opening reactions and the conditions that influence the efficiency of the initiation, propagation, and cyclization to generate high molecular weight cyclic polymers. N-Heterocyclic carbenes (NHC) are potent nucleophiles and relatively poor leaving groups, two features that are important for the generation of high molecular weight polymers. Investigations of the nature of the monomer and nucleophile have helped researchers understand the factors that govern the reactivity of these systems and their impact on the molecular weight and molecular weight distributions of the resulting cyclic polymers. We focus primarily on ZROP mediated by N-heterocyclic carbene nucleophiles but also discuss zwitterionic polymerizations with amidine, pyridine, and imidazole nucleophiles. The ZROP of N-carboxyanhydrides with N-hetereocyclic carbenes generates a family of functionalized cyclic polypeptoids. We can synthesize gradient lactone copolymers by exploiting differences in relative reactivity present in ZROP that differ from those of traditional metal-mediated polymerizations. These new synthetic methods have allowed us to investigate the influence of topology on the crystallization behavior, stereocomplexation, and solution properties of cyclic macromolecules.

Incentivized collaborative care to disseminate and enhance contingency-management services.

Contingency management is especially effective in supporting medication adherence and drug abstinence among people with opioid use disorder. However, the incorporation of contingency management into clinical practice has been slow. The present study was designed to evaluate the feasibility, acceptability, and usability of incentives for providers as a means of accelerating collaborative care with contingency management. Thirteen buprenorphine prescribers served as participants in a nonexperimental study. The prescribers who referred patients to a contingency-management service received monetary incentives for reviewing patient performance data and describing their use of these data in treatment decisions. The results show that this approach is feasible, acceptable, and easy to use for everyone involved. Self-reports indicate improved prescriber-patient relationships and more informed care. However, prescriber-focused incentives did not appear to greatly enhance access to contingency-management services for patients. Thus, provider incentives may be beneficial but further research is needed to advance adoption of contingency management.

Zwitterionic polymerization to generate high molecular weight cyclic poly(carbosiloxane)s.

The zwitterionic ring-opening of 2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane (TMOSC) with N-heterocyclic carbenes generates high molecular weight cyclic p(TMOSC). The NHC-mediated polymerization of TMOSC with 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes, 1) generates the poly(carbosiloxane) p(TMOSC) with molecular weights from 27,000 < Mn < 80,000 Da (1.4 < Mw/Mn < 2.2) within 30 min at room temp. With the more nucleophilic carbene 1,3,4,5-tetramethyl-imidazol-2-ylidene (4), the ring-opening polymerization occurs within minutes at room temperature to generate cyclic p(TMOSC) with molecular weights up to Mn = 940,000 Da (Mw/Mn = 3.2). The resulting p(TMOSC)s are predominantly cyclic as evidenced by dilute solution viscosity studies and MALDI-TOF MS. DFT calculations provide support for both zwitterionic and neutral, cyclic intermediates.

Conformational restriction in a series of GPR119 agonists: differences in pharmacology between mouse and human.

A series of conformationally restricted GPR119 agonists were prepared based around a 3,8-diazabicyclo[3.2.1]octane scaffold. Examples were found to have markedly different pharmacology in mouse and human despite similar levels of binding to the receptor. This highlights the large effects on GPCR phamacology that can result from small structural changes in the ligand, together with inter-species differences between receptors.

Universal healthcare for all? Maori health inequalities in Aotearoa New Zealand, 1975-2000.

Despite establishing a so-called universal, taxpayer funded health system from 1938, New Zealand's health system has never delivered equitable health outcomes for its indigenous population, the Maori people. This article, using a case study approach focusing on Maori, documents these historic inequalities and discusses policy attempts to address them from the 1970s when the principles of the Treaty of Waitangi were first introduced in legislation. This period is one of increasing self-determination for Maori, but notwithstanding this, Maori continued to have significantly shorter life expectancy than the population as a whole and suffered poor health at much higher rates. Neo-liberal policies were introduced and expanded during the 1980s and 1990s in New Zealand, including in healthcare from the early 1990s. The introduction of the purchaser-provider split in health services and the focus on devolving responsibility to communities provided an opportunity for Maori health providers to be established. However, the neo-liberal economic and social welfare policies implemented during this time also worked against Maori and adversely affected their health. By analysing attempts to reduce inequity in health outcomes for Maori, we explore why these collective attempts, including by Maori themselves, did not result in overall improved health and increased life expectancy for Maori. There was often a significant gap between government rhetoric and action, and we suggest that a predominantly universal healthcare system did not accommodate cultural and ethnic differences, and this is a potential explanation for the failure to reduce inequities. While this is true for all minority ethnic groups it is even more crucial for Maori as New Zealand's tangata whenua (first people) who had been progressively disadvantaged under colonialism. However, the seeds of ideas around Maori-led healthcare were planted in this period and have become part of the current Labour Government's policy on health reform.

Atopic eczema and the barriers to treatment adherence for children: a literature review.

Atopic eczema is a chronic, non-contagious, relapsing inflammatory skin condition commonly seen in children and adults. Children with atopic eczema often endure complex skincare regimens that can keep the condition under control when managed effectively. Nonadherence, particularly to topical treatments, is one of the most common causes of treatment failure in atopic eczema. This literature review aimed to explore the barriers that influence treatment adherence in children and young people with atopic eczema and identify recommendations for practice. Six studies were included in the literature review and three themes were identified: relationships, medicines concerns and information deficits. Healthcare professionals should strive to develop trusting relationships with parents and understand the barriers to treatment adherence. Individualised conversations and education about medicines concerns, understanding the psychosocial effects of atopic eczema on children and families, and providing clear, consistent advice can be beneficial.

Test procedures and positive diagnostic criteria of the upper limb tension tests differ: a systematic review of the DiTA database.

BACKGROUND: The validity of the ULTT is unclear, due to heterogeneity of test procedures and variability in the definition of a positive test OBJECTIVE: To evaluate test procedures and positive diagnostic criteria for the upper limb tension test (ULTT) in diagnostic test accuracy studies. METHODS: A systematic review of diagnostic accuracy studies was performed. We conducted a search of the DiTA (Diagnostic Test Accuracy) database and selected primary studies evaluating the diagnostic accuracy of the ULTT. We assessed risk of bias, performed data extraction on study characteristics, test procedures, and positive diagnostic criteria, and performed a descriptive analysis. RESULTS: We included nine studies (681 participants), four diagnosing people with cervical radiculopathy (CR), four diagnosing people with carpal tunnel syndrome (CTS), and one included both CR and CTS. The risk of bias varied between 2 and 6 out of 6 positive items. Eight studies reported on the ULTT1 (median nerve). Overall, all studies clearly described their test procedures and positive diagnostic criteria although the order of movements and the diagnostic criteria between studies varied. We suggest a more standardised test procedure for the ULTT1 to consist of: 1) stabilising the shoulder in abduction, 2) extending the wrist/fingers, 3) supinating the forearm, 4) externally rotating the shoulder, 5) extending the elbow, and finally 6) performed structural differentiation by side bending (lateral flexion) of the neck. This proposed test procedure should reproduce the symptoms and enables the clinician to evaluate whether symptoms increase/decrease when stressing or relaxing the nerves. CONCLUSION: Based on our findings we proposed a more standardised test procedure for the ULTT1 with accompanying positive diagnostic criteria to facilitate homogeneity in future diagnostic accuracy studies of the ULTT.

Hyperbolic modeling and assessment of hypothetical health behaviors during a viral outbreak using crowdsourced samples.

The COVID-19 pandemic provided an opportunity to investigate factors related to public response to public health measures, which could help better prepare implementation of similar measures for inevitable future pandemics. To understand individual and environmental factors that influence likelihood in engaging in personal and public health measures, three crowdsourced convenience samples from Amazon Mechanical Turk (MTurk) completed likelihood-discounting tasks of engaging in health behaviors given a variety of hypothetical viral outbreak scenarios. Experiment 1 assessed likelihood of mask wearing for a novel virus. Experiment 2 assessed vaccination likelihood based on efficacy and cost. Experiment 3 assessed likelihood of seeking health care based on number of symptoms and cost of treatment. Volume-based measures and three-dimensional modeling were used to analyze hypothetical decision making. Hypothetical public and personal health participation increased as viral fatality increased and generally followed a hyperbolic function. Public health participation was moderated by political orientation and trust in science, whereas treatment-seeking was only moderated by income. Analytic methods used in this cross-sectional study predicted population-level outcomes that occurred later in the pandemic and can be extended to various health behaviors.

Feasibility, Acceptability, and Preliminary Efficacy of a Smartphone-Based Contingency Management Intervention for Buprenorphine Adherence.

Buprenorphine is an important medication for treating opioid use disorder, but medication adherence and treatment retention are key issues that can limit its impact, especially when patients have concurrent stimulant use. Contingency management is efficacious in promoting medication adherence and drug abstinence. Delivering contingency management via smartphones addresses practical barriers to its adoption and improves patient access. A single-group (n = 20) nonexperimental study was conducted to evaluate the feasibility of smartphone-based contingency management to promote adherence to buprenorphine treatment in people with opioid use disorder. Participants were recruited from outpatient treatment clinics. Over 12 weeks participants had access to a smartphone app that provided contingency management supported with peer recovery coaching. Adherence was confirmed daily either by GPS monitoring of clinic medication visits or self-recorded video, and salivary toxicology was conducted weekly. The overall rate of confirmed buprenorphine adherence was 76%, and visual inspection of individual participant outcomes shows consistent medication use for a large majority of participants. All participants were able to successfully use all app features and spend earnings. Participants rated the app and intervention highly on measures of likability, ease of use, and helpfulness. All participants (100%) were retained in buprenorphine treatment throughout the study period. Direct methods for confirming adherence appear superior to confirmation via salivary toxicology. This study shows that smartphone-based contingency management is a feasible means of promoting buprenorphine adherence. The potential efficacy of smartphone-based contingency management as a means of promoting buprenorphine adherence warrants evaluation in a randomized controlled trial.

A multivariate extension to the standard 4σ criterion for comparison of forensic glass evidence.

This manuscript presents a more accurate and easy to implement multivariate generalisation of the international standard 4σ forensic glass comparison technique. Many crimes result in glass breaking, and the broken glass found at a crime scene can be important forensic evidence. The chemical composition of this glass can be measured to establish whether it can be distinguished from glass fragments found on a suspect's clothing. The chemical composition can be measured using laser ablation-inductively coupled plasma mass spectrometry. A commonly used method to compare fragments of glass is the 4σ interval criterion. This method, however, compares each element individually and does not take advantage of the multivariate nature of this data. We introduce a multivariate extension to this method, which makes use of the correlation structure between the elements. We demonstrate that this method results in an improvement in the false positive rate, with only a small compromise in the false negative rate. The improvement in false positive rate is desirable as false positives translate to misleading evidence against a potentially innocent defendant. The multivariate generalisation improves accuracy while retaining a similar interpretation, and so is suitable to present in court.

Discovery, optimisation and in vivo evaluation of novel GPR119 agonists.

GPR119 is increasingly seen as an attractive target for the treatment of type II diabetes and other elements of the metabolic syndrome. During a programme aimed at developing agonists of the GPR119 receptor, we identified compounds that were potent with reduced hERG liabilities, that had good pharmacokinetic properties and that displayed excellent glucose-lowering effects in vivo. However, further profiling in a GPR119 knock-out (KO) mouse model revealed that the biological effects were not exclusively due to GPR119 agonism, highlighting the value of transgenic animals in drug discovery programs.

A Smartphone-Smartcard Platform for Implementing Contingency Management in Buprenorphine Maintenance Patients With Concurrent Stimulant Use Disorder.

Background and Objectives: Opioid agonist pharmacotherapies are effective in the treatment of opioid use disorder (OUD) but concurrent stimulant use is common and can lead to relapse and treatment drop out. Contingency management in combination with opioid agonist pharmacotherapy has broad beneficial effects in polysubstance users, including promoting drug abstinence and treatment retention, but clinic-based implementation can be burdensome. The present study was conducted to evaluate a contingency management intervention delivered via a smartphone-smartcard platform in OUD patients who had concurrent stimulant use disorder. Methods: Retrospective comparison of (n = 124) patients; half received the contingency management intervention and half were matched controls. Drug use and clinic attendance outcomes over four consecutive 30-day periods were analyzed with regression. Results: The intervention group showed consistently higher rates of drug abstinence and clinic attendance which were significant at the latter two timepoints. Discussion: Smartphone-smartcard platforms can facilitate dissemination of contingency management by surmounting or obviating key barriers to adoption. They appear to be convenient for all stakeholders, are easy to use, and facilitate high-fidelity implementation. Delivering contingency management via a smartphone-smartcard platform produces effects consistent with those observed when the intervention is delivered with substantially costlier and more burdensome in-person procedures.

Comparative use of isolated hepatocytes and hepatic microsomes for cytochrome P450 inhibition studies: transporter-enzyme interplay.

Accurate assignment of the concentration of victim drug/inhibitor available at the enzyme active site, both in vivo and within an in vitro incubation, is an essential requirement in rationalizing and predicting drug-drug interactions. Inhibitor accumulation within the liver, whether as a result of active transport processes or intracellular binding, may best be accounted for using hepatocytes rather than hepatic microsomes to estimate in vitro inhibitory potency. The aims of this study were to compare K(i) values determined in rat liver microsomes and freshly isolated rat hepatocytes of four cytochrome P450 (P450) inhibitors (clarithromycin, enoxacin, nelfinavir, and saquinavir) with known hepatic transporter involvement and a range of uptake (cell/medium concentration ratios 20-3000) and clearance (10-1200 µl/min/10(6) cells) properties. Inhibition studies were performed using two well established P450 probe substrates (theophylline and midazolam). Comparison of unbound K(i) values showed marked differences between the two in vitro systems for inhibition of metabolism. In two cases (clarithromycin and enoxacin, both low-clearance drugs), inhibitory potency in hepatocytes markedly exceeded that in microsomes (10- to 20-fold), and this result was consistent with their high cell/medium concentration ratios. For nelfinavir and saquinavir (high-clearance, extensively metabolized drugs), the opposite trend was seen in the K(i) values: despite very high cell/medium concentration ratios, stronger inhibition was evident within microsomal preparations. Hence, the consequences of hepatic accumulation resulting from uptake transporters vary according to the clearance of the inhibitor. This study demonstrates that transporter-enzyme interplay can result in differences in inhibitory potency between microsomes and hepatocytes and hence drug-drug interaction predictions that are not always intuitive.

Contingency management for the treatment of methamphetamine use disorder: A systematic review.

Methamphetamine use continues to be an important public health problem. Contingency management is among the most effective interventions for reducing methamphetamine use. It has been more than ten years since the last systematic review of contingency management for methamphetamine use disorder. Since then, an additional ten randomized controlled trials and a variety of other studies have been completed. The present systematic review includes 27 studies. Several factors, most notably problem severity, appear to predict treatment outcome. However, the effectiveness of CM has been demonstrated in studies restricted to MSM, studies restricted to implementation in community programs, and in studies of the general population of methamphetamine users conducted in research treatment programs. There appear to be broad benefits of contingency management intervention, including greater drug abstinence, higher utilization of other treatments and medical services, and reductions in risky sexual behavior. Twenty of the twenty-one studies that reported abstinence outcomes showed an effect of contingency management on abstinence, and seven of the nine studies that reported sexual risk behavior outcomes showed an effect of contingency management in reducing risky sexual behavior. Taken together, recent evidence suggests strongly that outpatient programs that offer treatment for methamphetamine use disorder should prioritize adoption and implementation of contingency management intervention.