Continuous Synthesis of Artemisinin-Derived Medicines

Described is a continuous, divergent synthesis system which is coupled to continuous purification and is capable of producing four anti-malarial APIs. The system is comprised of three linked reaction modules for photooxidation/cyclization, reduction, and derivatization. A fourth module couples the crude reaction stream with continuous purification to yield pure API

Association rule mining to identify potential under-coding of conditions in the problem list in primary care electronic medical records

Introduction The problem list of a patient’s primary care electronic medical record (EMR) generally reflects their important medical conditions. We will use association rule mining to assess between-provider and between-clinic variation in the coding of select conditions in the EMR problem list, in order to identify possible under-coding outliers. Objectives and Approach EMR data from participating clinics in the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) will be used, with a focus on three commonly-occurring conditions (hypertension, diabetes, and depression). Association rule mining will be used to develop association rules between these conditions and other clinical information available in the EMR, such as other diagnoses in the problem list, billing codes, medications, and laboratory results (e.g., a rule of “diabetic medication→diabetes” indicates that patients prescribed a diabetic medication are likely to have diabetes in the problem list). Under-coding outliers at the provider and clinic levels will be identified by comparing rule enforcement. Results Results from this work in progress will be presented at the conference. An estimated 270 clinics, 1340 providers, and 1.8 million patients will be included from the CPCSSN database. Rule ‘confidence’ will be used to identify outliers; the confidence of a rule X→Y is the proportion of individuals with X who also have Y (Pr(Y|X)). For example, we may find that on average 80% of patients prescribed a diabetic medication will also have a diagnosis of diabetes in the problem list (average confidence of 80%), but an outlier clinic may have a confidence of 40%; this low rule confidence may indicate under-coding of diabetes in the problem list. Confounding by patient demographics (e.g., age, sex, urban/rural) will be assessed and adjusted for, if necessary. Conclusion/Implications This work examines a novel method to identify potential under-coding in the EMR problem list. Providers/clinics could use this information to update patients’ problem list or inform quality improvement interventions. Researchers using primary care EMR data need to be aware of potential under-coding and take steps to mitigate the effects

Impact of the Choosing Wisely Canada recommendations on potentially inappropriate antibiotic prescribing in emergency medicine across Alberta, Canada: An interrupted time-series analysis.

Objectives In Alberta, Canada, we quantified the rate of potentially inappropriate oral antibiotic prescribing in emergency departments for viral infections or conditions not likely requiring antibiotics from 2010-2020 and assessed the impact of two Choosing Wisely Canada (CWC) campaigns (2015/2016 and 2018) discouraging inappropriate antibiotic prescribing in emergency medicine. Approach We linked emergency department adult and pediatric records from the National Ambulatory Care Reporting System and medication dispensations from community-based pharmacies in the Pharmaceutical Information Network. From January 2010 to February 2020, we identified emergency department visits for 5 conditions that were potentially inappropriately treated using antibiotics per CWC recommendations (bronchitis, asthma, bronchiolitis, pharyngitis, and acute otitis media). We used an interrupted time series design to detect changes in antibiotic prescribing by fitting Autoregressive Integrated Moving Average (ARIMA) models to account for secular trends and seasonality, allowing for change in slopes to measure the effect of each CWC intervention. Results Antibiotics were commonly prescribed in emergency departments for bronchitis (proportion of visits with antibiotics: 57%) and asthma (22%) in adults; bronchiolitis in children (43%); pharyngitis (39%) and acute otitis media (54%) in adults and children. Based on visual inspection, the proportion of emergency department visits for each condition where antibiotics were dispensed remained relatively consistent. The ARIMA models demonstrated mixed impacts on potentially inappropriate antibiotic prescribing associated with two interruptions: the 2015/2016 CWC recommendations and subsequent 2018 CWC Using Antibiotics Wisely campaign. Following each interruption, antibiotic prescribing was slightly reduced for bronchitis (-1.0%/year,p=0.03; -4.4%/year,p=0.004, respectively) and bronchiolitis (not significant) (-0.7%/year,p=0.57; -2.5%/year,p=0.34), but unchanged for asthma (-0.6%/year,p=0.30; 0.7%/year,p=0.74) and pharyngitis (0.0%/year,p=0.95; -0.2%/year,p=0.93), and slightly increased for acute otitis media (not significant) (1.4%/year,p=0.07; 5.9%/year,p=0.052). Conclusion Rates of potentially inappropriate antibiotic prescribing remained constant over the past 10 years in Alberta. Campaigns to rethink antibiotic use in emergency medicine may have resulted in small decreases in antibiotic use; however, further initiatives building upon existing campaigns are required to substantially reduce rates of inappropriate antibiotic prescribing

Microtubule dynamics drive enhanced chromatin motion and mobilize telomeres in response to DNA damage

Chromatin exhibits increased mobility on DNA damage, but the biophysical basis for this behavior remains unknown. To explore the mechanisms that drive DNA damage–induced chromosome mobility, we use single-particle tracking of tagged chromosomal loci during interphase in live yeast cells together with polymer models of chromatin chains. Telomeres become mobilized from sites on the nuclear envelope and the pericentromere expands after exposure to DNA-damaging agents. The magnitude of chromatin mobility induced by a single double-strand break requires active microtubule function. These findings reveal how relaxation of external tethers to the nuclear envelope and internal chromatin–chromatin tethers, together with microtubule dynamics, can mobilize the genome in response to DNA damage

RETROSPECTIVE STUDIES Recent Trends in Feline Intestinal Neoplasia: an Epidemiologic Study of 1,129 Cases in the Veterinary Medical Database from 1964 to 2004

ABSTRACT A retrospective epidemiologic study evaluated 1,129 feline intestinal tumor patients via data entered into the Veterinary Medical Database (VMDB) from 1964 to 2004. Cases were analyzed by breed, age, yr of diagnosis, tumor type, and location. The VMDB incidence of all intestinal tumors reported during this 40 yr period was 0.4%, with small intestinal tumors predominating. The most common intestinal tumor was lymphoma, but the most common nonlymphoid tumor was adenocarcinoma. The Siamese breed and increasing age after 7 yr conferred an increased risk. Intact males and females appeared to have a decreased risk compared with neutered patients, but this may be explained by the age difference among these patients as older patients were more likely to be neutered. Prospective studies evaluating neuter status predilection and prognosis are warranted. (J Am Anim Hos

Linking primary care EMR data and administrative data in Alberta, Canada: experiences, challenges, and potential solutions

Introduction Administrative data are commonly used for a variety of secondary purposes. Although they lack clinical detail and risk factor information, linkage to primary care electronic medical records (EMR) could fill this gap. Primary care EMRs are a relatively new data source available in Alberta and thus, EMR-administrative linkages are novel. Objectives and Approach To describe the process undertaken for linking de-identified primary care EMR data from two regional Alberta networks of the Canadian Primary Care Sentinel Surveillance Network (CPCSSN) with administrative data (hospital admissions, emergency department visits, pharmacy information) from Alberta Health Services Analytics, specifically as it relates to a study on patients with complex, chronic diseases. As this linkage process is new in Alberta, we will describe the challenges encountered and possible solutions to inform future data linkage for research studies. Results Linkage steps: 1) approval from research ethics board and individual CPCSSN providers as data custodians; 2) notify Privacy Commissioner on behalf of custodian; 3) send linking key (CPCSSN patient ID, EMR ID) from regional database to Analytics; 4) send linking files (patient personal health number [PHN], EMR ID) from custodian’s EMR system to Analytics; 5) match unique EMR ID from linking key and clinic linking files; 6) PHN from clinic linking file mapped to administrative data; 7) data de-identified before transferring to secure repository; administrative data matched to EMR data using CPCSSN ID. Challenges: obtaining individual provider consent for each study; sampling bias; delays/issues generating clinic linkage file; mismatch between patients in clinic \& regional linking files. Current and potential solutions will be discussed during the presentation. Conclusion/Implications As primary care EMR and administrative data become more routinely linked and accepted, the process will become more efficient and streamlined. These data will contribute to a better understanding of patients and their care in Alberta

Reporting of Model Performance and Statistical Methods in Studies That Use Machine Learning to Develop Clinical Prediction Models: Protocol for a Systematic Review

BACKGROUND: With the growing excitement of the potential benefits of using machine learning and artificial intelligence in medicine, the number of published clinical prediction models that use these approaches has increased. However, there is evidence (albeit limited) that suggests that the reporting of machine learning-specific aspects in these studies is poor. Further, there are no reviews assessing the reporting quality or broadly accepted reporting guidelines for these aspects. OBJECTIVE: This paper presents the protocol for a systematic review that will assess the reporting quality of machine learning-specific aspects in studies that use machine learning to develop clinical prediction models. METHODS: We will include studies that use a supervised machine learning algorithm to develop a prediction model for use in clinical practice (ie, for diagnosis or prognosis of a condition or identification of candidates for health care interventions). We will search MEDLINE for studies published in 2019, pseudorandomly sort the records, and screen until we obtain 100 studies that meet our inclusion criteria. We will assess reporting quality with a novel checklist developed in parallel with this review, which includes content derived from existing reporting guidelines, textbooks, and consultations with experts. The checklist will cover 4 key areas where the reporting of machine learning studies is unique: modelling steps (order and data used for each step), model performance (eg, reporting the performance of each model compared), statistical methods (eg, describing the tuning approach), and presentation of models (eg, specifying the predictors that contributed to the final model). RESULTS: We completed data analysis in August 2021 and are writing the manuscript. We expect to submit the results to a peer-reviewed journal in early 2022. CONCLUSIONS: This review will contribute to more standardized and complete reporting in the field by identifying areas where reporting is poor and can be improved. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020206167; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=206167. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/30956

Sporting embodiment: sports studies and the (continuing) promise of phenomenology

Whilst in recent years sports studies have addressed the calls ‘to bring the body back in’ to theorisations of sport and physical activity, the ‘promise of phenomenology’ remains largely under-realised with regard to sporting embodiment. Relatively few accounts are grounded in the ‘flesh’ of the lived sporting body, and phenomenology offers a powerful framework for such analysis. A wide-ranging, multi-stranded, and interpretatively contested perspective, phenomenology in general has been taken up and utilised in very different ways within different disciplinary fields. The purpose of this article is to consider some selected phenomenological threads, key qualities of the phenomenological method, and the potential for existentialist phenomenology in particular to contribute fresh perspectives to the sociological study of embodiment in sport and exercise. It offers one way to convey the ‘essences’, corporeal immediacy and textured sensuosity of the lived sporting body. The use of Interpretative Phenomenological Analysis (IPA) is also critically addressed. Key words: phenomenology; existentialist phenomenology; interpretative phenomenological analysis (IPA); sporting embodiment; the lived-body; Merleau-Pont

Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer

Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells.National Science Foundation (U.S.) (Grant T32GM007287

Expressions 1983

The 1983 edition of Expressions magazine is the result of the efforts of students from several DMACC programs. Entrants in both the annual Creative Writing Contest and the Campus Chronicle Photography Contest as well as student in the commercial art program contributed material to the magazine. Layout, design and typesetting was done by the summer Publications Production class.https://openspace.dmacc.edu/expressions/1005/thumbnail.jp