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Alexandre F DaSilva,1,2,* Dajung J Kim,1,2,* Manyoel Lim,1,2 Thiago D Nascimento,1,2 Peter JH Scott,3 Yolanda R Smith,4 Robert A Koeppe,3 Jon-Kar Zubieta,5 Niko Kaciroti6 1Headache and Orofacial Pain Effort (H.O.P.E.) Laboratory, Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA; 2Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA; 3Department of Radiology, University of Michigan, Ann Arbor, MI, USA; 4Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA; 5Department of Psychiatry, Mass General Brigham, Newton-Wellesley Hospital, Newton, MA, USA; 6Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA*These authors contributed equally to this workCorrespondence: Alexandre F DaSilva, Headache and Orofacial Pain Effort (H.O.P.E.) Laboratory, Michigan Neuroscience Institute, 205 Zina Pitcher PI, Room 1021, Ann Arbor, MI, 48109-5720, USA, Email adasilva@umich.eduObjective: The current understanding of utilizing HD-tDCS as a targeted approach to improve headache attacks and modulate endogenous opioid systems in episodic migraine is relatively limited. This study aimed to determine whether high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) can improve clinical outcomes and endogenous μ-opioid receptor (μOR) availability for episodic migraineurs.Methods: In a randomized, double-blind, and sham-controlled trial, 25 patients completed 10-daily 20-min M1 HD-tDCS, repeated Positron Emission Tomography (PET) scans with a selective agonist for μOR. Twelve age- and sex-matched healthy controls participated in the baseline PET/MRI scan without neuromodulation. The primary endpoints were moderate-to-severe (M/S) headache days and responder rate (≥ 50% reduction on M/S headache days from baseline), and secondary endpoints included the presence of M/S headache intensity and the use of rescue medication over 1-month after treatment.Results: In a one-month follow-up, at initial analysis, both the active and sham groups exhibited no significant differences in their primary outcomes (M/S headache days and responder rates). Similarly, secondary outcomes (M/S headache intensity and the usage of rescue medication) also revealed no significant differences between the two groups. However, subsequent analyses showed that active M1 HD-tDCS, compared to sham, resulted in a more beneficial response predominantly in higher-frequency individuals (> 3 attacks/month), as demonstrated by the interaction between treatment indicator and baseline frequency of migraine attacks on the primary outcomes. These favorable outcomes were also confirmed for the secondary endpoints in higher-frequency patients. Active treatment also resulted in increased μOR concentration compared to sham in the limbic and descending pain modulatory pathway. Our exploratory mediation analysis suggests that the observed clinical efficacy of HD-tDCS in patients with higher-frequency conditions might be potentially mediated through an increase in μOR availability.Conclusion: The 10-daily M1 HD-tDCS can improve clinical outcomes in episodic migraineurs with a higher baseline frequency of migraine attacks (> 3 attacks/month). This improvement may be, in part, facilitated by the increase in the endogenous μOR availability.Clinical Trial Registration: www.ClinicalTrials.gov, identifier - NCT02964741.Keywords: HD-tDCS, neuromodulation, migraine, headache, pain, mu-opioid receptor

Purpose: The purpose of the study was to identify the participation patterns of liver transplant (LT) recipients in valued roles following LT and the relationship of these to quality of life. Design: This was a cross-sectional study of health-related quality of life and role participation in 161 LT recipients, conducted between 27 August 2008 and 1 December 2008. The participants were a mean of 5.25, ±2.5, years post-LT, 75% male, and had a mean age of 59 years, range 37-77 years. Main outcome measures: These were the Role Checklist and the National Institute of Diabetes and Digestive and Kidney Diseases - Quality of Life instrument. Results: Analysis revealed that LT recipients showed a wide disparity in the number of roles currently occupied, range 1-10, mean = 4.9 and SD = 1.8, and normal distribution. There was a significant relationship (p<0.001) between participation in a greater number of valued roles and all five quality of life scales. Conclusion: People who are participating in a smaller number of valued roles have lower levels of life satisfaction. The problem is believed to be related to difficulties in forming new habits. Habit training and monitoring of role return to determine when intervention is needed are required to enable all LT recipients to return to the highest quality of life possible. [ABSTRACT FROM AUTHOR]

1 The disposition of prazosin following oral and intravenous administration has been studied in seven young and seven elderly men, all of whom were in good health and living independently in the community. 2 The elimination half-life (min) of prazosin was 123 +/- 19.4 (s.d.) in the young and 194 +/- 36 in the elderly (P less than 0.01). 3 Clearance (ml min-1 kg-1) was 3.94 +/- 0.73 in the young and 3.53 +/- 1 in the elderly (P greater than 0.1). Volume of distribution at steady state (1 kg-1) was 0.63 +/- 0.14 in the young and 0.89 +/- 0.26 in the elderly (P less than 0.05). 4 The absolute bioavailability of orally administered prazosin was 0.68 +/- 0.17 in the young and 0.48 +/- 0.16 in the elderly (P less than 0.05). 5 The significant increase in prazosin half-life in the elderly results from an increased volume of distribution, not from decreased clearance. 6 Gastrointestinal absorption of prazosin decreases in old age. [ABSTRACT FROM AUTHOR]

Background: The Editorial Board of EJNMMI Radiopharmacy and Chemistry releases a biannual highlight commentary to update the readership on trends in the field of radiopharmaceutical development., Main Body: This selection of highlights provides commentary on 19 different topics selected by each coauthoring Editorial Board member addressing a variety of aspects ranging from novel radiochemistry to first-in-human application of novel radiopharmaceuticals., Conclusion: Trends in radiochemistry and radiopharmacy are highlighted. Hot topics cover the entire scope of EJNMMI Radiopharmacy and Chemistry, demonstrating the progress in the research field in many aspects., (© 2024. The Author(s).)

Evaluating the response to immune checkpoint inhibitors (ICIs) remains an unmet challenge in triple-negative breast cancer (TNBC). The requirement for cholesterol in the activation and function of T cells led us to hypothesize that quantifying cellular accumulation of this molecule could distinguish successful from ineffective checkpoint immunotherapy. To analyze accumulation of cholesterol by T cells in the immune microenvironment of breast cancer, we leveraged the PET radiotracer, eFNP-59. eFNP-59 is an analog of cholesterol that our group validated as an imaging biomarker for cholesterol uptake in preclinical models and initial human studies. In immunocompetent mouse models of TNBC, we found that elevated uptake of exogenous labeled cholesterol analogs functions as a marker for T cell activation. When comparing ICI-responsive and -nonresponsive tumors directly, uptake of fluorescent cholesterol and eFNP-59 increased in T cells from ICI-responsive tumors. We discovered that accumulation of cholesterol by T cells increased in ICI-responding tumors that received anti-PD-1 checkpoint immunotherapy. In patients with TNBC, tumors containing cycling T cells had features of cholesterol uptake and trafficking within those populations. These results suggest that uptake of exogenous cholesterol analogs by tumor-infiltrating T cells allows detection of T cell activation and has potential to assess the success of ICI therapy.

Information systems such as Electronic Health Record (EHR) systems are susceptible to data quality (DQ) issues. Given the growing importance of EHR data, there is an increasing demand for strategies and tools to help ensure that available data are fit for use. However, developing reliable data quality assessment (DQA) tools necessary for guiding and evaluating improvement efforts has remained a fundamental challenge. This review examines the state of research on operationalising EHR DQA, mainly automated tooling, and highlights necessary considerations for future implementations. We reviewed 1841 articles from PubMed, Web of Science, and Scopus published between 2011 and 2021. 23 DQA programs deployed in real-world settings to assess EHR data quality (n = 14), and a few experimental prototypes (n = 9), were identified. Many of these programs investigate completeness (n = 15) and value conformance (n = 12) quality dimensions and are backed by knowledge items gathered from domain experts (n = 9), literature reviews and existing DQ measurements (n = 3). A few DQA programs also explore the feasibility of using data-driven techniques to assess EHR data quality automatically. Overall, the automation of EHR DQA is gaining traction, but current efforts are fragmented and not backed by relevant theory. Existing programs also vary in scope, type of data supported, and how measurements are sourced. There is a need to standardise programs for assessing EHR data quality, as current evidence suggests their quality may be unknown., (© 2023. The Author(s).)

Vat photopolymerization (VP) is a high-throughput additive manufacturing modality that also offers exceptional feature resolution and surface finish; however, the process is constrained by a limited selection of processable photocurable resins. Low resin viscosity (<10 Pa·s) is one of the most stringent process-induced constraints on resin processability, which in turn limits the mechanical performance of printed resin systems. Recently, the authors created a VP-processable photosensitive latex resin, where compartmentalization of the high molecular weight polymer chains into discrete particles resulted in the decoupling of viscosity from molecular weight. However, the monomers used to form the hydrogel green body resulted in decreased ultimate material properties due to the high cross-link density. Herein, we report a novel scaffold that allows for facile UV-based AM and simultaneously enhances the final part's material properties. This is achieved with a chemically labile acetal-containing cross-linker in conjunction with N-vinylpyrrolidone, which forms a glassy polymer after photocuring. Subsequent reactive extraction cleaves the cross-links and liberates the glassy polymer, which provides mechanical reinforcement of the geometrically complex VP-printed elastomer. With only a 0.1 wt % loading of photoinitiator, G '/ G '' crossover times of less than 1 s and green body plateau moduli nearing 10 5 Pa are obtained. In addition, removal of the hydrophilic and thermally labile scaffold results in decreased water uptake and increased thermal stability of the final printed part. Ultimate strain and stress values of over 650% and 8.5 MPa, respectively, are achieved, setting a new benchmark for styrene-butadiene VP elastomers.

Arab occupational therapists are in need either to develop their own outcome measures or to translate well-known outcome measures to their culture. The objective of this study was to translate, cross-culturally adapt, and validate preliminarily the Role Checklist Version 3 (RCv3) into Arabic language. The translation and cross-cultural adaptation process of the RCv3 into Arabic language was conducted in four main steps: (a) forward translation, (b) back translation, (c) expert panel review process, and (d) psychometric testing (Validity). The expert panel established the face validity and the content validity of the Arabic RCv3. Pilot testing was conducted, and the utility and content validity of the tool were confirmed. The final version of the Arabic RCv3 is now available for use in the Arab countries. However, further psychometric properties including reliability and responsiveness of this tool is warranted, thus supporting its wide use and proper application.

Objectives: To highlight the role of technology assessment in the management of the COVID-19 pandemic., Method: An overview of existing research and evaluation approaches along with expert perspectives drawn from the International Medical Informatics Association (IMIA) Working Group on Technology Assessment and Quality Development in Health Informatics and the European Federation for Medical Informatics (EFMI) Working Group for Assessment of Health Information Systems., Results: Evaluation of digital health technologies for COVID-19 should be based on their technical maturity as well as the scale of implementation. For mature technologies like telehealth whose efficacy has been previously demonstrated, pragmatic, rapid evaluation using the complex systems paradigm which accounts for multiple sociotechnical factors, might be more suitable to examine their effectiveness and emerging safety concerns in new settings. New technologies, particularly those intended for use on a large scale such as digital contract tracing, will require assessment of their usability as well as performance prior to deployment, after which evaluation should shift to using a complex systems paradigm to examine the value of information provided. The success of a digital health technology is dependent on the value of information it provides relative to the sociotechnical context of the setting where it is implemented., Conclusion: Commitment to evaluation using the evidence-based medicine and complex systems paradigms will be critical to ensuring safe and effective use of digital health technologies for COVID-19 and future pandemics. There is an inherent tension between evaluation and the imperative to urgently deploy solutions that needs to be negotiated., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (IMIA and Thieme. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: Musculoskeletal injury represents the leading cause of medical discharge from the UK Armed Forces. This study evaluates effectiveness of care provision within a large primary care rehabilitation facility (PCRF) against directed defence best practice guidelines (BPGs) METHODS: All new patient electronic records from January to July 16 were interrogated to identify demographics, causation, injury pathology, timelines and outcomes., Results: 393 eligible records (81.9% male) were identified. 17.6% were officers, 32.8% were seniors and 49.6% were juniors. The average age was 35.1 years (mode 30). The average wait to treatment was 8.3 days with 75.6% key performance indicator compliance. 47.3% were repeat injuries. The average care timeline was 117.1 days with 8.7 average treatment sessions needed. 30 remained under care at 2 years. 17.8% accessed hydrotherapy and 44% underwent exercise remedial instructors care. 14.2% of individuals required concurrent DCMH care (15.9% male and 26.8% female). 28.5% required multidisciplinary injury assessment clinic intervention with 74.1% compliance against BPGs. 2.9% used the Defence Medical Rehabilitation Centre. Common pathologies were low back pain (LBP) (n=67), upper limb (UL) soft tissue (n=40) and knee trauma (n=38). LBP had the highest recurrence rates (71.6%). Anterior knee pain took the longest (173.1 days) but had the best outcome on discharge. Ankles and lower limb muscle injuries had the best outcomes. Patella tendinopathy and knee trauma had the poorest outcome on discharge. LBP and patellar tendinopathy had the lowest fully fit rates at 2 years (56.7% and 53.8%, respectively). At 2 years, 58.2% of individuals achieved full fitness (60.7% men and 46.4% women), rising to 64% and 55%, respectively, when including those retained with limitations., Conclusions: The PCRF was generally compliant with BPGs, achieving good functional outcomes on discharge. Women were disproportionally represented, had higher concurrent DCMH attendance and poorer overall long-term outcomes. Repeat injury rates were significantly high., Competing Interests: Competing interests: The author is employed in the study location., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Two weeks' isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization-commissioned review investigated sputum sterilisation dynamics during TB treatment., Methods and Findings: For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness-including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments-was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%-24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%-86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%-14%, N = 2), increasing to 88% at 2 months (95% CI 84%-92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%-16%, N = 1) and 59% (95% CI 47%-70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation., Conclusions: This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment., Trial Registration: Systematic review registration: PROSPERO 85226., Competing Interests: The authors have declared that no competing interests exist.

Pyridines are ubiquitous aromatic rings used in organic chemistry and are crucial elements of the drug discovery process. Herein we describe a new catalytic method that directly introduces a methyl group onto the aromatic ring; this new reaction is related to hydrogen borrowing, and is notable for its use of the feedstock chemicals methanol and formaldehyde as the key reagents. Conceptually, the C-3/5 methylation of pyridines was accomplished by exploiting the interface between aromatic and non-aromatic compounds, and this allows an oscillating reactivity pattern to emerge whereby normally electrophilic aromatic compounds become nucleophilic in the reaction after activation by reduction. Thus, a set of C-4 functionalised pyridines can be mono or doubly methylated at the C-3/5 positions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

It is a growing concern that outcomes of neuroimaging studies often cannot be replicated. To counteract this, the magnetic resonance (MR) neuroimaging community has promoted acquisition standards and created data sharing platforms, based on a consensus on how to organize and share MR neuroimaging data. Here, we take a similar approach to positron emission tomography (PET) data. To facilitate comparison of findings across studies, we first recommend publication standards for tracer characteristics, image acquisition, image preprocessing, and outcome estimation for PET neuroimaging data. The co-authors of this paper, representing more than 25 PET centers worldwide, voted to classify information as mandatory, recommended, or optional. Second, we describe a framework to facilitate data archiving and data sharing within and across centers. Because of the high cost of PET neuroimaging studies, sample sizes tend to be small and relatively few sites worldwide have the required multidisciplinary expertise to properly conduct and analyze PET studies. Data sharing will make it easier to combine datasets from different centers to achieve larger sample sizes and stronger statistical power to test hypotheses. The combining of datasets from different centers may be enhanced by adoption of a common set of best practices in data acquisition and analysis.

We aimed to develop effective radioligands for quantifying brain O -linked-β- N -acetyl-glucosamine ( O -GlcNAc) hydrolase (OGA) using positron emission tomography in living subjects as tools for evaluating drug target engagement. Posttranslational modifications of tau, a biomarker of Alzheimer's disease, by O -GlcNAc through the enzyme pair OGA and O -GlcNAc transferase (OGT) are inversely related to the amounts of its insoluble hyperphosphorylated form. Increase in tau O -GlcNAcylation by OGA inhibition is believed to reduce tau aggregation. LSN3316612, a highly selective and potent OGA ligand [half-maximal inhibitory concentration (IC 50 ) = 1.9 nM], emerged as a lead ligand after in silico analysis and in vitro evaluations. [ 3 H]LSN3316612 imaged and quantified OGA in postmortem brains of rat, monkey, and human. The presence of fluorine and carbonyl functionality in LSN3316612 enabled labeling with positron-emitting fluorine-18 or carbon-11. Both [ 18 F]LSN3316612 and [ 11 C]LSN3316612 bound reversibly to OGA in vivo, and such binding was blocked by pharmacological doses of thiamet G, an OGA inhibitor of different chemotype, in monkeys. [ 18 F]LSN3316612 entered healthy human brain avidly (~4 SUV) without radiodefluorination or adverse effect from other radiometabolites, as evidenced by stable brain total volume of distribution (V T ) values by 110 min of scanning. Overall, [ 18 F]LSN3316612 is preferred over [ 11 C]LSN3316612 for future human studies, whereas either may be an effective positron emission tomography radioligand for quantifying brain OGA in rodent and monkey., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Vat photopolymerization (VP) additive manufacturing fabricates intricate geometries with excellent resolution; however, high molecular weight polymers are not amenable to VP due to concomitant high solution and melt viscosities. Thus, a challenging paradox arises between printability and mechanical performance. This report describes concurrent photopolymer and VP system design to navigate this paradox with the unprecedented use of polymeric colloids (latexes) that effectively decouple the dependency of viscosity on molecular weight. Photocrosslinking of a continuous-phase scaffold, which surrounds the latex particles, combined with in situ computer-vision print parameter optimization, which compensates for light scattering, enables high-resolution VP of high molecular weight polymer latexes as particle-embedded green bodies. Thermal post-processing promotes coalescence of the dispersed particles throughout the scaffold, forming a semi-interpenetrating polymer network without loss in part resolution. Printing a styrene-butadiene rubber latex, a previously inaccessible elastomer composition for VP, exemplified this approach and yielded printed elastomers with precise geometry and tensile extensibilities exceeding 500%.

Background: National Health Service policy suggests that increasing usage of electronic personal health records (PHR) by patients will result in cost savings and improved public health. Medication adherence means that patients take their prescribed medication as agreed with their doctors. Some of the claimed benefits of PHRs are decreasing healthcare costs and improving medication adherence and patient outcomes., Methods: This is a mixed methods convergent study, primarily qualitative. The qualitative and quantitative data collection and analysis will occur in parallel, and then be synthesised. We are interviewing and surveying adults with long-term conditions to identify what are the most important and useful features of their current PHR. The data collection comprises patient demographics, the Medication Adherence Questionnaire, the personality scale Big Five Inventory-2 Extra-Short Form and the WHO Quality of Life-BREF scale. Qualitative data will be analysed using the Framework method., Ethics: We have received a favourable ethical opinion from the Health Research Authority/Research Ethics Committee., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Clinically apparent cerebral oedema during diabetic ketoacidosis (DKA) is rare and more common in children and young adults. Subclinical oedema with mild brain dysfunction is more frequent, with unknown long term effects. Rapid tonicity changes may be a factor although not well studied. Guidelines recommend capping hypertonicity resolution at ≤ 3 mOsmol/kg/h., Objectives: To audit current DKA management in the emergency department (ED) and in the intensive care unit (ICU) for tonicity benchmark compliance, and to determine interactions between plasma tonicity, plasma glucose concentrations and blood haemoglobin concentrations., Methods: Twenty-five adult DKA admissions from ED to ICU were studied retrospectively. Blood gas and electrolyte data were sequenced for 24 hours from first ED blood sample., Results: Sampling was frequent (median, 11 times per day; range, 6-26). Tonicity reduction was largely accomplished by the first ICU blood sample and exceeded 3 mOsmol/ kg/h in 72% of admissions. Correlation with haemoglobin reduction (haemodilution) rates exceeded correlation with glucose rates ( R 2 = 0.52 v 0.38). In benchmark noncompliant admissions, haemodilution was more rapid (6.1 g/L/h v 2.1 g/L/h; P = 0.001). Although also true of glucose reduction (4.5 mmol/L/h v 2.2 mmol/L/h; P = 0.007), there was no interaction between haemodilution and glucose reduction ( R 2 = 0.09)., Conclusions: Major tonicity reductions often exceeding guidelines were common by ICU admission. Correcting DKA-induced hypertonicity at ≤ 3 mOsmol/kg/h requires controlled hyperglycaemia correction and, based on our data, avoidance of high fluid replacement rates; for example, sufficient to reduce haemoglobin concentrations by > 3 g/L/h, unless there is evidence of intravascular hypovolaemia.

Azidoalkyl enol ethers undergo intramolecular 1,3-dipolar cycloaddition to generate stable triazolines; in contrast, the cycloadducts formed by heating analogous azidoalkyl vinyl bromides are unstable with respect to elimination of N 2 and HBr, affording 1-azadienes (2-alkenyl cyclic imines). These primary products may be isolated or treated directly with diphenylketene to produce bi- and tricyclic 3,4-dihydropyridin-2(1 H )-ones; similar ring systems may also be produced from the azadienes by N-acylation and radical cyclization.

A transition-metal-free reductive hydroxymethylation reaction has been developed, enabling the preparation of tetrahydroisoquinolines bearing C4-quaternary centers from the corresponding isoquinolines. Deuterium labelling studies and control experiments enable a potential mechanism to be elucidated which features a key Cannizzaro-type reduction followed by an Evans-Tishchenko reaction. When isoquinolines featuring a proton at the 4-position are used, a tandem methylation-hydroxymethylation occurs, leading to the formation of 2 new C-C bonds in one pot., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Objective: To assess measurement practice in clinical decision support evaluation studies., Materials and Methods: We identified empirical studies evaluating clinical decision support systems published from 1998 to 2017. We reviewed titles, abstracts, and full paper contents for evidence of attention to measurement validity, reliability, or reuse. We used Friedman and Wyatt's typology to categorize the studies., Results: There were 391 studies that met the inclusion criteria. Study types in this cohort were primarily field user effect studies (n = 210) or problem impact studies (n = 150). Of those, 280 studies (72%) had no evidence of attention to measurement methodology, and 111 (28%) had some evidence with 33 (8%) offering validity evidence; 45 (12%) offering reliability evidence; and 61 (16%) reporting measurement artefact reuse., Discussion: Only 5 studies offered validity assessment within the study. Valid measures were predominantly observed in problem impact studies with the majority of measures being clinical or patient reported outcomes with validity measured elsewhere., Conclusion: Measurement methodology is frequently ignored in empirical studies of clinical decision support systems and particularly so in field user effect studies. Authors may in fact be attending to measurement considerations and not reporting this or employing methods of unknown validity and reliability in their studies. In the latter case, reported study results may be biased and effect sizes misleading. We argue that replication studies to strengthen the evidence base require greater attention to measurement practice in health informatics research., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Two critical tasks in multi-criteria group decision making (MCGDM) are to describe criterion values and to aggregate the described information to generate a ranking of alternatives. A flexible and superior tool for the first task is q-rung orthopair fuzzy number (qROFN) and an effective tool for the second task is aggregation operator. So far, nearly thirty different aggregation operators of qROFNs have been presented. Each operator has its distinctive characteristics and can work well for specific purpose. However, there is not yet an operator which can provide desirable generality and flexibility in aggregating criterion values, dealing with the heterogeneous interrelationships among criteria, and reducing the influence of extreme criterion values. To provide such an aggregation operator, Muirhead mean operator, power average operator, partitioned average operator, and Archimedean T-norm and T-conorm operations are concurrently introduced into q-rung orthopair fuzzy sets, and an Archimedean power partitioned Muirhead mean operator of qROFNs and its weighted form are presented and a MCGDM method based on the weighted operator is proposed in this paper. The generalised expressions of the two operators are firstly defined. Their properties are explored and proved and their specific expressions are constructed. On the basis of the specific expressions, a method for solving the MCGDM problems based on qROFNs is then designed. Finally, the feasibility and effectiveness of the method is demonstrated via a numerical example, a set of experiments, and qualitative and quantitative comparisons., Competing Interests: The authors have declared that no competing interests exist.

Objectives: This paper draws attention to: i) key considerations for evaluating artificial intelligence (AI) enabled clinical decision support; and ii) challenges and practical implications of AI design, development, selection, use, and ongoing surveillance., Method: A narrative review of existing research and evaluation approaches along with expert perspectives drawn from the International Medical Informatics Association (IMIA) Working Group on Technology Assessment and Quality Development in Health Informatics and the European Federation for Medical Informatics (EFMI) Working Group for Assessment of Health Information Systems., Results: There is a rich history and tradition of evaluating AI in healthcare. While evaluators can learn from past efforts, and build on best practice evaluation frameworks and methodologies, questions remain about how to evaluate the safety and effectiveness of AI that dynamically harness vast amounts of genomic, biomarker, phenotype, electronic record, and care delivery data from across health systems. This paper first provides a historical perspective about the evaluation of AI in healthcare. It then examines key challenges of evaluating AI-enabled clinical decision support during design, development, selection, use, and ongoing surveillance. Practical aspects of evaluating AI in healthcare, including approaches to evaluation and indicators to monitor AI are also discussed., Conclusion: Commitment to rigorous initial and ongoing evaluation will be critical to ensuring the safe and effective integration of AI in complex sociotechnical settings. Specific enhancements that are required for the new generation of AI-enabled clinical decision support will emerge through practical application., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart.)

In this chapter, we reflect on the aim and objectives of the textbook and address known gaps in our theory coverage. We reinforce the importance of theory in health informatics and review the varying disciplinary origins of the theories considered in the book. We discuss the question of what makes a good theory and how to know which one is relevant for a given study. We recognize the limitations of the body of theory that we have presented and suggest what might be regarded as "native" theory that is original to health informatics. Finally, we propose topics to form a research agenda for theory in health informatics.

Background Left circumflex culprit is often missed by the standard 12-lead ECG . Extended lead systems (body surface potential map [ BSPM ]) should improve the diagnosis of culprit left circumflex stenosis with myocardial infarction. Methods and Results Retrospective analysis of a hospital research registry (August 2000-August 2010) comprising consecutive patients with (1) ischemic-type chest pain at rest; (2) 12-lead ECG and 80-lead BSPM at first medical contact; and (3) cardiac troponin-T 12 hours after symptom onset and/or creatine kinase MB fraction, were undertaken. Enrolled in the cohort were patients with culprit left circumflex stenosis (thrombolysis in myocardial infarction flow grade 0/1) at angiography. Acute myocardial infarction AMI was defined as cardiac troponin-T ≥0.1 μg/L and/or creatine kinase MB fraction >2 upper limits of normal. Enrolled were 482 patients: 168 had exclusion criteria. Of the remaining 314 (age 64±11 years; 62% male), 254 (81%) had AMI : of these, 231 had BSPM STE -sensitivity 0.91, specificity 0.72, positive predictive value 0.93, negative predictive value 0.65, and c-statistic 0.803 for AMI ( P<0.001). Of those with BSPM STE and AMI (n=231), STE was most frequently detected in the posterior (n=111, 48%), lateral (n=53, 23%), inferior (n=39, 17%), and right ventricular (n=21, 9%) territories. Conclusions Among patients with 12-lead ECG non-ST-segment-elevation myocardial infarction and culprit left circumflex stenosis, initial BSPM identifies ST-segment elevation beyond the territory of the 12-lead ECG . Greater use of the BSPM may result in earlier identification of AMI , which may lead to more rapid reperfusion.

Aromatic rings are ubiquitous in organic chemistry and form the basis of many commercial products. Despite the numerous routes available for the preparation of aromatic compounds, there remain few methods that allow their conversion into synthetically useful partially saturated derivatives and even fewer that allow new C-C bonds to be formed at the same time. Here we set out to address this problem and uncover a unique catalytic partial reduction reaction that forms partially saturated azaheterocycles from aromatic precursors. In this reaction, methanol and formaldehyde are used for the reductive functionalization of pyridines and quinolines using catalytic iridium; thus, inexpensive and renewable feedstocks are utilized in the formation of complex N-heterocycles. By harnessing the formation of a nucleophilic enamine intermediate, the C-C bond-forming process reverses the normal pattern of reactivity and allows access to the C3 position of the arene. Mechanistic investigations using D-labelling experiments reveal the source of hydride added to the ring and show the reversible nature of the iridium-hydride addition.

The Role Checklist is used by occupational therapists across the globe. Developed in 1981 and consistent with the Model of Human Occupation (MOHO), until recently, the Role Checklist was not updated. This is of concern as the Role Checklist originally was established to measure role performance. In 2008, Kielhofner, in the fourth edition of A Model of Human Occupation, differentiated occupational performance in 10 roles which clearly fall into occupational participation in the Role Checklist Version 3. The objective of the study was to describe changes and establish utility, feasibility, and reliability of the Role Checklist Version 3. The Role Checklist Version 3 was administered electronically to N = 114 occupational therapists and students. A short time span was used due to sensitivity to history bias. Test-retest reliability using Cohen's Kappa and Cronbach's alpha mirrored analysis done on the original version. Qualitatively, nine themes emerged regarding utility and feasibility. Test-retest reliability is acceptable to excellent for present role incumbency (κ = 0.74-1.00), desired future role engagement (κ = 0.44-1.00), and satisfaction with performance (α = 0.77-0.98). Participants (91%) found it useful for treatment planning and 75% would recommend Version 3 over the original Role Checklist. Data support the Role Checklist Version 3 as a reliable, electronic instrument feasible for occupational therapists to measure participation.

Objective:: To empirically test the hypothesis that the 10 roles on the Revised Role Checklist are represented in the International Classification of Functioning, Disability and Health participation areas., Design:: Cross-sectional survey., Subjects:: Investigators from Japan, Norway, Sweden, Switzerland, the United Kingdom and the United States recruited a total of 295 adults from the general population. There were 103 (34.9%) male and 191 (64.7%) female participants with one participant not indicating gender. The age distribution of participants was from <25 ( n = 68) to 75+ with a mode of 25-34 years., Main Measure:: The Revised Role Checklist Part 1 was used to assess perceived incumbency in 10 roles. In addition, subjects were asked to provide role examples., Results:: Of the 7087 examples provided by participants, 6578 (92.8%) fit the original hypothesis that the roles in the Revised Role Checklist were covered in participation areas. Fit was determined when the role example was either named in the associated International Classification of Functioning, Disability and Health participation area or when the criteria of: "does this example conceivably fit in the respective area as 'a person's involvement in life situations' fit relative to each role." Slight modification of the scope of three roles of the original hypothesis resulted in a 97.6% match., Conclusion:: The roles in the Revised Role Checklist are well represented in the International Classification of Functioning, Disability and Health categories of participation.

Commercial 68 Ge/ 68 Ga generators provide a means to produce positron emission tomography agents on site without use of a cyclotron. This development has led to a rapid growth of academic literature and patents ongallium-68 ( 68 Ga). As 68 Ga positron emission tomography agents usually involve a targeting moiety attached to a metal chelator, the development lends itself to the investigation of theragnostic applications; the 68 Ga-based diagnostic is utilized to determine if the biological target is present and, if so, a therapeutic isotope (e.g., 177 Lu, 225 Ac) can be complexed with the same scaffold to generate a corresponding radiotherapeutic. This review considers patents issued between 2012 and 2017 that contain a 68 Ga-labeled molecule indexed by Chemical Abstract Services (a division of the American Chemical Society).

Objectives:  The paper draws attention to: i) key considerations involving the confidentiality, privacy, and security of shared data; and ii) the requirements needed to build collaborative arrangements encompassing all stakeholders with the goal of ensuring safe, secure, and quality use of shared data., Method:  A narrative review of existing research and policy approaches along with expert perspectives drawn from the International Medical Informatics Association (IMIA) Working Group on Technology Assessment and Quality Development in Health Care and the European Federation for Medical Informatics (EFMI) Working Group for Assessment of Health Information Systems., Results:  The technological ability to merge, link, re-use, and exchange data has outpaced the establishment of policies, procedures, and processes to monitor the ethics and legality of shared use of data. Questions remain about how to guarantee the security of shared data, and how to establish and maintain public trust across large-scale shared data enterprises. This paper identifies the importance of data governance frameworks (incorporating engagement with all stakeholders) to underpin the management of the ethics and legality of shared data use. The paper also provides some key considerations for the establishment of national approaches and measures to monitor compliance with best practice., Conclusion: Data sharing endeavours can help to underpin new collaborative models of health care which provide shared information, engagement, and accountability amongst all stakeholders. We believe that commitment to rigorous evaluation and stakeholder engagement will be critical to delivering health data benefits and the establishment of collaborative models of health care into the future., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart.)

Background: The National Health Service (NHS) England spent £15.5 billion on medication in 2015. More than a third of patients affected by at least one long-term condition do not adhere to their drug regime. Many interventions have been trialed to improve medication adherence. One promising innovation is the electronic personal health record., Objective: This systematic literature review aims to identify the important design features of personal health records to improve medication adherence for patients with long-term conditions., Methods: This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P 2015) statement. The following databases will be searched for relevant articles: PubMed, Science Direct, BioMed Central, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials. Studies published in the last fifteen years, in English, will be included if the participants are adults who were treated outside the hospital, have the ability to self-administer their medication, and have at least one long-term condition. The review will exclude commercial or political sources and papers without references. Papers that research pediatrics, pregnant, or terminally ill patients will also be excluded, since their medication management is typically more complex., Results: One reviewer will screen the included studies, extract the relevant data, and assess the quality of evidence utilizing the Grading of Recommendations Assessment, Development, and Evaluation system and the risk of bias using the Cochrane RevMan tool. The second reviewer will assess the quality of 25% of the included studies to assess interrater agreement. Any disagreement will be solved by a third reviewer. Only studies of high and moderate quality will be included for narrative synthesis., Conclusions: NHS policy assumes that increasing usage of personal health records by citizens will reduce demand on health care services. There is limited evidence, however, that the use of health apps can improve patient outcomes, and, to our knowledge, this is the first systematic literature review aiming to identify important design features of the personal health record which may improve medication adherence in the adult population with long-term conditions., Trial Registration: PROSPERO CRD42017060542; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=60542 (Archived by WebCite at http://www.webcitation.org/6zeuWXxVh)., Registered Report Identifier: RR1-10.2196/9778., (©Elisavet Andrikopoulou, Philip James Scott, Helena Herrera. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 28.06.2018.)

Healthcare interoperability depends upon sound semantic models to support safe and reliable exchange of information. We argue that clinical information modelling requires a collaborative team of healthcare professionals, process and content analysts and terminologists and that 'separation of concerns' is unhelpful. We present six fundamental concepts that participants must understand to collaborate meaningfully in technology-agnostic information modelling.

Introduction: Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI)., Methods: Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L., Results: Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/m 2 . Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90%). EP STE occurred in 165 patients using TVCM (sensitivity 88%, specificity 95%; p < 0.001) and in 206 patients using PSTM (sensitivity 98%, specificity 79%; p < 0.001). Of those with AMI by cTnT and EPs ⩽0.3 mV using TVCM ( n = 22), 18 (82%) patients had EPs >0.3 mV when an individualised PSTM was used., Conclusion: Among patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis.