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1.
J Appl Behav Anal ; 2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39004776

ABSTRACT

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.

2.
Braz J Phys Ther ; 27(6): 100558, 2023.
Article in English | MEDLINE | ID: mdl-37967500

ABSTRACT

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.


Subject(s)
Carpal Tunnel Syndrome , Physical Examination , Humans , Upper Extremity/physiology , Wrist , Carpal Tunnel Syndrome/diagnosis , Fingers
3.
Behav Anal Pract ; 16(2): 450-458, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37187840

ABSTRACT

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.

4.
Nurs Child Young People ; 35(6): 21-27, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37066679

ABSTRACT

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.


Subject(s)
Dermatitis, Atopic , Eczema , Adolescent , Child , Humans , Administration, Topical , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/psychology , Eczema/drug therapy , Health Personnel , Parents/psychology , Treatment Adherence and Compliance
5.
Conscious Cogn ; 108: 103472, 2023 02.
Article in English | MEDLINE | ID: mdl-36724707

ABSTRACT

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.


Subject(s)
Judgment , Morals , Humans , Gravitation
6.
J Exp Anal Behav ; 119(2): 300-323, 2023 03.
Article in English | MEDLINE | ID: mdl-36805985

ABSTRACT

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.


Subject(s)
COVID-19 , Crowdsourcing , Humans , Likelihood Functions , Pandemics , Cross-Sectional Studies , Health Behavior
7.
Soc Sci Med ; 319: 115315, 2023 02.
Article in English | MEDLINE | ID: mdl-36089552

ABSTRACT

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.


Subject(s)
Health Care Reform , Universal Health Care , Humans , New Zealand/epidemiology , Maori People
8.
J Nurs Adm ; 52(11): 608-612, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36251967

ABSTRACT

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.


Subject(s)
Advanced Practice Nursing , Nurses , Humans , Advanced Practice Nursing/education , Leadership , Workplace , Hospitals
9.
Forensic Sci Int ; 338: 111386, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35901586

ABSTRACT

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.


Subject(s)
Glass , Laser Therapy , Forensic Medicine , Mass Spectrometry/methods , Spectrum Analysis
10.
Front Psychiatry ; 12: 778992, 2021.
Article in English | MEDLINE | ID: mdl-34950072

ABSTRACT

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.

11.
Z Gastroenterol ; 59(2): 135-142, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33147637

ABSTRACT

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.


Subject(s)
Adenomatous Polyps/diagnosis , Colonic Neoplasms/diagnosis , Colonoscopy/methods , Diverticulum, Colon/diagnostic imaging , Adenomatous Polyps/epidemiology , Aged , Colonic Neoplasms/epidemiology , Germany/epidemiology , Humans , Male , Prospective Studies , Retrospective Studies , Risk Factors
12.
Drug Alcohol Depend ; 216: 108307, 2020 11 01.
Article in English | MEDLINE | ID: mdl-33007699

ABSTRACT

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.


Subject(s)
Amphetamine-Related Disorders/psychology , Amphetamine-Related Disorders/therapy , Methamphetamine/adverse effects , Risk-Taking , Sexual Behavior/psychology , Behavior Therapy/methods , Disease Management , Humans , Randomized Controlled Trials as Topic/methods , Risk Reduction Behavior , Sexual Behavior/physiology , Sexual and Gender Minorities/psychology , Treatment Outcome
13.
Endoscopy ; 52(1): 45-51, 2020 01.
Article in English | MEDLINE | ID: mdl-31614373

ABSTRACT

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.


Subject(s)
Colonic Polyps , Colonoscopy , Cecum , Colonic Polyps/surgery , Germany , Humans , Ileum , Prospective Studies , Reference Standards
14.
Scand J Gastroenterol ; 54(3): 377-383, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30905207

ABSTRACT

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.


Subject(s)
Acetic Acid , Colonic Polyps/diagnostic imaging , Colonic Polyps/pathology , Colonoscopy/methods , Narrow Band Imaging , Aged , Female , Germany , Humans , Image Enhancement , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Tertiary Care Centers
15.
Gastrointest Endosc ; 89(3): 576-582.e1, 2019 03.
Article in English | MEDLINE | ID: mdl-30342029

ABSTRACT

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.).


Subject(s)
Adenomatous Polyps/diagnosis , Carcinoma/diagnosis , Colonic Polyps/diagnosis , Colorectal Neoplasms/diagnosis , Image Processing, Computer-Assisted , Software , Adenoma/diagnosis , Adenoma/pathology , Adenomatous Polyps/pathology , Aged , Automation , Carcinoma/pathology , Cohort Studies , Colonic Polyps/pathology , Colonoscopy , Colorectal Neoplasms/pathology , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Prospective Studies , Tumor Burden
16.
Endosc Int Open ; 5(12): E1289-E1298, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29218322

ABSTRACT

BACKGROUND AND STUDY AIMS: Longer observation times are associated with increased adenoma detection rates (ADR) in the entire colon. However, adenomas in the proximal colon are at risk of being missed during colonoscopy. The aim of this study was to investigate the impact of observation time on detection of adenomatous polyps in the proximal colon. PATIENTS AND METHODS: This was a prospective study at a university hospital in Germany. Colonoscopies were conducted using magnetic endoscope imaging (MEI) in order to determine the exact position of the scope. Exact observation times spent for the detection of polyps in the proximal and distal colon segments were assessed. The primary outcome was adenoma detection in the proximal colon. ROC curves were generated in order to test the correlation between observation time and adenoma detection. Logistic regression analysis was used to check for interfering factors. RESULTS: A total 480 procedures with 538 polyps were available for analysis. The overall adenoma detection rate was 38.5 %. ADR in the proximal colon was 28.0 %. There was a significant association between observation time in the proximal colon and the detection of proximal adenomas ( P  < 0.001). The impact of the time factor on ADR was stronger in the proximal compared to the distal colon ( P  = 0.030). A net period of 4 min 7 sec was found to be the minimum time span for sufficient adenoma detection in the proximal colon. CONCLUSION: Observation time is significant in terms of adenoma detection in the proximal colon. The impact of observation time on ADR is stronger in the proximal compared to the distal colon. In the proximal colon a minimum time span of 4 minutes should be spent in order to ensure adequate adenoma detection.

17.
Forensic Sci Int ; 262: 150-5, 2016 May.
Article in English | MEDLINE | ID: mdl-26990563

ABSTRACT

When considering the impact and value of gunshot residues (GSR) as forensic trace evidence, the likelihood of a suspect producing a positive GSR analysis result without having direct exposure to a firearm is a major consideration. Therefore, the random prevalence of GSR and 'GSR-like' residues in the wider population is a highly pertinent question when considering the probative value of such evidence. The random prevalence of GSR in two Australian jurisdictions - Victoria and South Australia - was assessed through the collection and analysis of GSR samples obtained from randomly selected members of the public. Volunteers were asked to declare any firearms use, hobbies or potential firearms exposure before allowing their hands to be sampled using aluminium GSR sample stubs coated in adhesive tape. A total of 289 samples, 120 from Victoria and 169 from South Australia were collected and analysed using scanning electron microscopy coupled with energy dispersive X-ray microanalysis (SEM-EDS). Across all samples, three 'characteristic' three-component Pb/Ba/Sb particles were detected from a single subject in South Australia, corresponding to an overall prevalence of 0.3%. Two-component 'consistent' particles were more prevalent, with Pb/Sb particles being the most frequently occurring, in 8% of samples, and in South Australia only. A number of samples, approximately 7%, showed populations of single element particles of Pb, Ba and Sb, which has the potential to generate a false positive for GSR if using a bulk analysis technique such as NAA or AAS. The prevalence of GSR or 'GSR like' particles in this study matches closely with similar surveys conducted in other jurisdictions. Such surveys are a useful foundation for the creation of a probabilistic method for the assessment of GSR evidence.


Subject(s)
Antimony/analysis , Barium/analysis , Hand , Lead/analysis , Skin/chemistry , Adolescent , Adult , Australia , False Positive Reactions , Female , Firearms , Forensic Ballistics , Humans , Male , Microscopy, Electron, Scanning , Middle Aged , Sampling Studies , Spectrometry, X-Ray Emission , Young Adult
18.
J Med Chem ; 57(21): 8984-98, 2014 Nov 13.
Article in English | MEDLINE | ID: mdl-25286150

ABSTRACT

Agonism of GPR119 is viewed as a potential therapeutic approach for the treatment of type II diabetes and other elements of metabolic syndrome. During progression of a previously disclosed candidate 1 through mice toxicity studies, we observed tonic-clonic convulsions in several mice at high doses. An in vitro hippocampal brain slice assay was used to assess the seizure liability of subsequent compounds, leading to the identification of an aryl sulfone as a replacement for the 3-cyano pyridyl group. Subsequent optimization to improve the overall profile, specifically with regard to hERG activity, led to alkyl sulfone 16. This compound did not cause tonic-clonic convulsions in mice, had a good pharmacokinetic profile, and displayed in vivo efficacy in murine models. Importantly, it was shown to be effective in wild-type (WT) but not GPR119 knockout (KO) animals, consistent with the pharmacology observed being due to agonism of GPR119.


Subject(s)
Epilepsy, Tonic-Clonic/prevention & control , Oxadiazoles/pharmacokinetics , Pyrimidines/pharmacokinetics , Receptors, G-Protein-Coupled/agonists , Animals , Diabetes Mellitus, Type 2/drug therapy , Dogs , Ether-A-Go-Go Potassium Channels/drug effects , Female , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Male , Mice, Inbred C57BL , Mice, Knockout , Oxadiazoles/chemistry , Oxadiazoles/therapeutic use , Pyrimidines/chemistry , Pyrimidines/therapeutic use , Structure-Activity Relationship
19.
J Am Chem Soc ; 135(50): 18738-41, 2013 Dec 18.
Article in English | MEDLINE | ID: mdl-24308512

ABSTRACT

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.

20.
Acc Chem Res ; 46(11): 2585-96, 2013 Nov 19.
Article in English | MEDLINE | ID: mdl-23789724

ABSTRACT

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.

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