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Background Context: Although anterior cervical discectomy and fusion (ACDF) procedures for cervical spine disease have been increasing amid a growing diabetic patient population, there is a paucity of literature focusing on insulin-dependence as a risk-factor for postoperative ACDF complications., Purpose: To evaluate the differential impact of insulin dependence on perioperative outcomes including total length of stay, surgical, and medical complications within thirty days following ACDF., Study Design/setting: A retrospective cohort, large multicenter database study., Patient Sample: The American College of Surgeons National Surgical Quality Improvement Program database was queried to retrospectively identify patients who had undergone ACDF between 2011 and 2021 using the Current Procedural Terminology code 22551., Outcome Measures: Perioperative surgical and medical complications., Methods: The study population was divided into 3 groups 1) insulin-dependent diabetes mellitus (IDDM), 2) noninsulin-dependent diabetes mellitus (NIDDM), and 3) no diabetes mellitus (non-DM). One-way analysis of variance for continuous variables and chi-square tests for categorical variables were used to identify differences in perioperative variables between the 3 groups. Multivariable logistic regression analysis assessed the effect of diabetes mellitus status on postoperative medical and surgical outcomes., Results: A total of 85,758 ACDF procedures were identified between 2011 and 2021, of which 5,178 were IDDM, 9,652 were NIDDM, and 70,982 were non-DM. The rates of surgical and medical complication varied between the 3 groups. IDDM patients had the highest rates of at least one medical complication (6.1%). Only IDDM increased the risk for medical complications (OR: 1.320, 95% CI [1.144-1.518]) and extended hospital length of stay (LOS) (OR: 1.244, 95% CI [1.071-1.441]) following a multivariate logistic regression analysis., Conclusion: Patients with IDDM were at an increased risk for postoperative medical complications and extended hospital LOS. Personalized postoperative management, guided by risk assessment is indicated for this population. These findings can be used to improve risk stratification and informed consent for DM patients who are insulin dependent., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to understand at what level of the Autonomous Pharmacy Framework facilities are operating, in terms of the current state of data collection and analysis in the medication-use process, and to gather insights about systems integration and automation use., Methods: The Autonomous Pharmacy Advisory Board, a group of chief pharmacy officers and operational leaders, developed a self-assessment instrument based on the previously published Autonomous Pharmacy Framework, made the self-assessment instrument available via the internet, and reviewed respondents' self-reported results. The data collection period for the survey started in March of 2021 and ended in January of 2023., Results: A total of 119 facility-level self-assessments were completed and analyzed. On a scale of 1 to 5, where 1 represented little or no data-driven automation with lots of manual tasks and 5 represented the utmost data-driven automation with few manual tasks, the average overall facility-level score was 2.77 (range, 1.38-4.41). Results revealed slight variance by facility bed capacity. Much more variation was found in the degrees to which individual facilities have automated core processes like inventory management, intravenous medication preparation, and financial reporting., Conclusion: As a baseline, this automation-focused facility self-assessment suggests that for essentially all health-system pharmacy facilities and their larger organizations, a substantial body of work needs to be done to further develop and upgrade technology and practice in tandem, greatly expand data collection and analysis, and thereby achieve better operational, financial, and clinical outcomes. Significant advancements are needed to arrive at the highly reliable, highly automated, data-driven medication-use process involving few repetitive manual tasks envisioned in the Autonomous Pharmacy Framework., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Intrinsically disordered protein regions (IDRs) are highly dynamic sequences that rapidly sample a collection of conformations over time. In the past several decades, IDRs have emerged as a major component of many proteomes, comprising ~30% of all eukaryotic protein sequences. Proteins with IDRs function in a wide range of biological pathways and are notably enriched in signaling cascades that respond to environmental stresses. Here, we identify and characterize intrinsic disorder in the soluble cytoplasmic N-terminal domains of MSL8, MSL9, and MSL10, three members of the MscS-like (MSL) family of mechanosensitive ion channels. In plants, MSL channels are proposed to mediate cell and organelle osmotic homeostasis. Bioinformatic tools unanimously predicted that the cytosolic N-termini of MSL channels are intrinsically disordered. We examined the N-terminus of MSL10 (MSL10 N ) as an exemplar of these IDRs and circular dichroism spectroscopy confirms its disorder. MSL10 N adopted a predominately helical structure when exposed to the helix-inducing compound trifluoroethanol (TFE). Furthermore, in the presence of molecular crowding agents, MSL10 N underwent structural changes and exhibited alterations to its homotypic interaction favorability. Lastly, interrogations of collective behavior via in vitro imaging of condensates indicated that MSL8 N , MSL9 N , and MSL10 N have sharply differing propensities for self-assembly into condensates, both inherently and in response to salt, temperature, and molecular crowding. Taken together, these data establish the N-termini of MSL channels as intrinsically disordered regions with distinct biophysical properties and the potential to respond uniquely to changes in their physiochemical environment., Competing Interests: The Authors did not report any conflict of interest., (© 2023 The Authors. Plant Direct published by American Society of Plant Biologists and the Society for Experimental Biology and John Wiley & Sons Ltd.)

Motivation: The emergence of high-throughput experiments and high-resolution computational predictions has led to an explosion in the quality and volume of protein sequence annotations at proteomic scales. Unfortunately, sanity checking, integrating, and analyzing complex sequence annotations remains logistically challenging and introduces a major barrier to entry for even superficial integrative bioinformatics., Results: To address this technical burden, we have developed SHEPHARD, a Python framework that trivializes large-scale integrative protein bioinformatics. SHEPHARD combines an object-oriented hierarchical data structure with database-like features, enabling programmatic annotation, integration, and analysis of complex datatypes. Importantly SHEPHARD is easy to use and enables a Pythonic interrogation of largescale protein datasets with millions of unique annotations. We use SHEPHARD to examine three orthogonal proteome-wide questions relating protein sequence to molecular function, illustrating its ability to uncover novel biology., Availability and Implementation: We provided SHEPHARD as both a stand-alone software package (https://github.com/holehouse-lab/shephard), and as a Google Colab notebook with a collection of precomputed proteome-wide annotations (https://github.com/holehouse-lab/shephard-colab)., (© The Author(s) 2023. Published by Oxford University Press.)

Quinol-dependent nitric oxide reductases (qNORs) are considered members of the respiratory heme-copper oxidase superfamily, are unique to bacteria, and are commonly found in pathogenic bacteria where they play a role in combating the host immune response. qNORs are also essential enzymes in the denitrification pathway, catalysing the reduction of nitric oxide to nitrous oxide. Here, we determine a 2.2 Å cryoEM structure of qNOR from Alcaligenes xylosoxidans, an opportunistic pathogen and a denitrifying bacterium of importance in the nitrogen cycle. This high-resolution structure provides insight into electron, substrate, and proton pathways, and provides evidence that the quinol binding site not only contains the conserved His and Asp residues but also possesses a critical Arg (Arg720) observed in cytochrome bo 3 , a respiratory quinol oxidase., (© 2023. The Author(s).)

Repetitive negative thinking (RNT) describes a recursive, unproductive pattern of thought that is commonly observed in individuals who experience anxiety and depression. Past research on RNT has primarily relied on self-report, which fails to capture the potential mechanisms that underlie the persistence of maladaptive thought. We investigated whether RNT may be maintained by a negatively biased semantic network. The present study used a modified free association task to assess state RNT. Following the presentation of a valenced (positive, neutral, negative) cue word, participants generated a series of free associates, which allowed for the dynamic progression of responses. State RNT was conceptualised as the length of consecutive, negatively valenced free associates (i.e. chains). Participants also completed two self-report measures that assessed trait RNT and trait negative affect. Within a structural equation model, negative (but not positive or neutral) response chain length positively predicted trait RNT and negative affect, and this was only the case for positive (but not negative or neutral) cue words. These results suggest that RNT tendencies may be reflected in semantic retrieval and can be assessed without self-report.

Objectives: This paper uses deep (machine) learning techniques to develop and test how motor behaviors, derived from location and movement sensor tracking data, may be associated with falls, delirium, and urinary tract infections (UTIs) in long-term care (LTC) residents., Design: Longitudinal observational study., Setting and Participants: A total of 23 LTC residents (81,323 observations) with cognitive impairment or dementia in 2 northeast Department of Veterans Affairs LTC facilities., Methods: More than 18 months of continuous (24/7) monitoring of motor behavior and activity levels used objective radiofrequency identification sensor data to track and record movement data. Occurrence of acute events was recorded each week. Unsupervised deep learning models were used to classify motor behaviors into 5 clusters; supervised decision tree algorithms used these clusters to predict acute health events (falls, delirium, and UTIs) the week before the week of the event., Results: Motor behaviors were classified into 5 categories (Silhouette score = 0.67), and these were significantly different from each other. Motor behavior classifications were sensitive and specific to falls, delirium, and UTI predictions 1 week before the week of the event (sensitivity range = 0.88-0.91; specificity range = 0.71-0.88)., Conclusion and Implications: Intraindividual changes in motor behaviors predict some of the most common and detrimental acute events in LTC populations. Study findings suggest real-time locating system sensor data and machine learning techniques may be used in clinical applications to effectively prevent falls and lead to the earlier recognition of risk for delirium and UTIs in this vulnerable population., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. All rights reserved.)

Background: The US Preventive Services Task Force recommends 25 primary preventive services for middle-aged adults, but it can be difficult to do them all., Methods: The Personalized Disease Prevention (PDP) cluster-randomized clinical trial will evaluate whether patients and their providers benefit from an evidence-based decision tool to prioritize preventive services based on their potential to improve quality-adjusted life expectancy. The decision tool will be individualized for patient risk factors and available in the electronic health record. This Phase III trial seeks to enroll 60 primary care providers (clusters) and 600 patients aged 40-75 years. Half of providers will be assigned to an intervention to utilize the decision tool with approximately 10 patients each, and half will be assigned to usual care. Mixed-methods follow-up will include collection of preventive care utilization from electronic health records, patient and physician surveys, and qualitative interviews. We hypothesize that quality-adjusted life expectancy will increase by more in patients who receive the intervention, as compared with controls., Discussion: PDP will test a novel, holistic approach to help patients and providers prioritize the delivery of preventive services, based on patient risk factors in the electronic health record., Trial Registration: ClinicalTrials.gov NCT05463887. Registered on July 19, 2022., (© 2022. The Author(s).)

Objective: To determine the extent of implementation, completeness, and accuracy of Structured and Codified SIG (S&C SIG) directions on electronic prescriptions (e-prescriptions)., Materials and Methods: A retrospective analysis of a random sample of 3.8 million e-prescriptions sent from electronic prescribing (e-prescribing) software to outpatient pharmacies in the United States between 2019 and 2021. Natural language processing was used to identify direction components, including action verb, dose, frequency, route, duration, and indication from free-text directions and were compared to the S&C SIG format. Inductive qualitative analysis of S&C direction identified error types and frequencies for each component., Results: Implementation of the S&C SIG format in e-prescribing software resulted in 32.4% of e-prescriptions transmitted with these standardized directions. Directions using the S&C SIG format contained a greater percentage of each direction component compared to free-text directions, except for the indication component. Structured and codified directions contained quality issues in 10.3% of cases., Discussion: Expanding adoption of more diverse direction terminology for the S&C SIG formats can improve the coverage of directions using the S&C SIG format. Building out e-prescribing software interfaces to include more direction components can improve patient medication use and safety. Quality improvement efforts, such as improving the design of e-prescribing software and auditing for discrepancies, are needed to identify and eliminate implementation-related issues with direction information from the S&C SIG format so that e-prescription directions are always accurately represented., Conclusion: Although directions using the S&C SIG format may result in more complete directions, greater adoption of the format and best practices for preventing its incorrect use are necessary., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To determine the variability of ingredient, strength, and dose form information from drug product descriptions in real-world electronic prescription (e-prescription) data., Materials and Methods: A sample of 10 399 324 e-prescriptions from 2019 to 2021 were obtained. Drug product descriptions were analyzed with a named entity extraction model and National Drug Codes (NDCs) were used to get RxNorm Concept Unique Identifiers (RxCUI) via RxNorm. The number of drug product description variants for each RxCUI was determined. Variants identified were compared to RxNorm to determine the extent of matching terminology used., Results: A total of 353 002 unique pairs of drug product descriptions and NDCs were analyzed. The median (1st-3rd quartile) number of variants extracted for each standardized expression in RxNorm, was 3 (2-7) for ingredients, 4 (2-8) for strength, and 41 (11-122) for dosage forms. Of the pairs, 42.35% of ingredients (n = 328 032), 51.23% of strengths (n = 321 706), and 10.60% of dose forms (n = 326 653) used matching terminology, while 16.31%, 24.85%, and 13.05% contained nonmatching terminology, respectively., Discussion: A wide variety of drug product descriptions makes it difficult to determine whether 2 drug product descriptions describe the same drug product (eg, using abbreviations to describe an active ingredient or using different units to represent a concentration). This results in patient safety risks that lead to incorrect drug products being ordered, dispensed, and used by patients. Implementation and use of standardized terminology may reduce these risks., Conclusion: Drug product descriptions on real-world e-prescriptions exhibit large variation resulting in unnecessary ambiguity and potential patient safety risks., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Posttraumatic stress disorder (PTSD) is one of the most frequently treated behavioral health conditions within the Department of Veterans Affairs and often co-occurs with alcohol or substance use. Past research suggests that alcohol and/or substance use may be used to cope with PTSD symptoms but there are inconsistent findings in how specific PTSD symptom clusters are associated with alcohol use disorder (AUD) or substance use disorder (SUD). Evaluating the relationship between PTSD symptom clusters and craving for individual drug of dependence may help explain these ambiguous results. Methods: Veterans ( N  = 167) recently engaged in mental health residential treatment were recruited to participate in a semi-structured diagnostic interview (Structured Clinical Interview for the DSM-5 , Research Version [SCID-5-RV]) to assess for past 12-month history of AUD/SUD. Participants also completed the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) to assess PTSD symptoms. Results: Covarying for severity of alcohol use, avoidance symptoms were significantly associated with alcohol craving for veterans with alcohol as their drug of dependence. Covarying for severity of stimulant use, no PTSD symptom clusters were associated with stimulant craving for veterans with stimulants as their drug of dependence. Conclusions: Veterans with high levels of PTSD avoidance symptoms may experience alcohol craving symptoms because they believe that alcohol use will eliminate or alleviate thoughts, feelings, or external reminders of the trauma. These results have important clinical implications in the treatment of co-occurring PTSD and AUD.

RNA polymerase (RNAP) binding protein A (RbpA) is essential for mycobacterial viability and regulates transcription initiation by increasing the stability of the RNAP-promoter open complex (RP o ). RbpA consists of four domains: an N-terminal tail (NTT), a core domain (CD), a basic linker, and a sigma interaction domain. We have previously shown that truncation of the RbpA NTT and CD increases RP o stabilization by RbpA, implying that these domains inhibit this activity of RbpA. Previously published structural studies showed that the NTT and CD are positioned near multiple RNAP-σ A holoenzyme functional domains and predict that the RbpA NTT contributes specific amino acids to the binding site of the antibiotic fidaxomicin (Fdx), which inhibits the formation of the RP o complex. Furthermore, deletion of the NTT results in decreased Mycobacterium smegmatis sensitivity to Fdx, but whether this is caused by a loss in Fdx binding is unknown. We generated a panel of rbpA mutants and found that the RbpA NTT residues predicted to directly interact with Fdx are partially responsible for RbpA-dependent Fdx activity in vitro, while multiple additional RbpA domains contribute to Fdx activity in vivo. Specifically, our results suggest that the RP o -stabilizing activity of RbpA decreases Fdx activity in vivo. In support of the association between RP o stability and Fdx activity, we find that another factor that promotes RP o stability in bacteria, CarD, also impacts to Fdx sensitivity. Our findings highlight how RbpA and other factors may influence RNAP dynamics to affect Fdx sensitivity., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Membrane proteins are essential for cellular growth, signalling and homeostasis, making up a large proportion of therapeutic targets. However, the necessity for a solubilising agent to extract them from the membrane creates challenges in their structural and functional study. Although amphipols have been very effective for single-particle electron cryo-microscopy (cryoEM) and mass spectrometry, they rely on initial detergent extraction before exchange into the amphipol environment. Therefore, circumventing this pre-requirement would be a big advantage. Here we use an alternative type of amphipol: a cycloalkane-modified amphiphile polymer (CyclAPol) to extract Escherichia coli AcrB directly from the membrane and demonstrate that the protein can be isolated in a one-step purification with the resultant cryoEM structure achieving 3.2 Å resolution. Together this work shows that cycloalkane amphipols provide a powerful approach for the study of membrane proteins, allowing native extraction and high-resolution structure determination by cryoEM., (© 2021. The Author(s).)

This project describes the creation of a single searchable resource during the pandemic, called the COVID-19 Best Evidence Front Door, with a primary goal of providing direct access to high-quality meta-analyses, literature syntheses, and clinical guidelines from a variety of trusted sources. The Front Door makes relevant evidence findable and accessible with a single search to aggregated evidence-based resources, optimizing time, discovery, and improved access to quality scientific evidence while reducing the burden of frontline health care providers and other knowledge-seekers in needing to separately identify, locate, and explore multiple websites., (Copyright © 2021 Nancy J. Allee, Charles P. Friedman, Allen J. Flynn, Chase Masters, Kai Donovan, Jane Ferraro, Roma Patel, Joshua C. Rubin.)

To address the Quintuple Aim of health care improvement, the profession of pharmacy is on the verge of a practice transformation that incorporates continuous learning from medication-related data into existing clinical and dispensing roles. The pharmacists' patient care process (PPCP) enables a learning pharmacy practice through the systematic and standardized collection of real-world medication-related data from pharmacists' patient care activities. A learning pharmacy practice continually generates data-powered discoveries as a byproduct of PPCP interactions. In turn, these discoveries improve our medication knowledge while upgrading our predictive powers, thus helping all people achieve optimal health outcomes. Establishing a practice management system connected to the PPCP means that data are generated from every PPCP interaction, combined with existing data, and analyzed by teams of pharmacists and data scientists. The resulting new knowledge is then incorporated into all future PPCP interactions in the form of predictions coupled to actionable advice. The primary purpose of a learning pharmacy practice is to combine the power of predictive modeling with evidence-based best practices to achieve and sustain population-level health improvements. This purpose is achieved by systematically optimizing individual medication use in an equitable manner on a global scale., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Localized partitioning of amorphous enantioenriched aryl benzyl sulfoxides in the solid state can lead to substantial variation in enantiopurities, even for sulfoxides which do not show detectable levels of self-disproportionation of enantiomers (SDE) during chromatography on an achiral stationary phase. The importance of preparation of representative samples of enantioenriched sulfoxides for chiral HPLC to enable reproducible results is clear.

Over the past 20 years reports of sulfonyl migrations have appeared, frequently described as 'unusual' and 'unexpected'. This comprehensive review compiles, for the first time, sulfonyl migrations reported over the last 20 years including formal 1,2-, 1,3-, 1,4-, 1,5-, 1,6- and 1,7-sulfonyl shifts, occurring through either radical or polar processes, either inter- or intramolecularly. Discussion of the sulfonyl migrations is structured according to reaction type, i.e. nitrogen-carbon, nitrogen-oxygen, nitrogen-nitrogen, oxygen-carbon (including anionic and non-anionic thia-Fries rearrangements), oxygen-oxygen and carbon-carbon migrations. Discussion of the underlying mechanisms for the migrations is included, with particular attention afforded to the principal techniques utilised for their elucidation, namely isotopic-labelling, crossover experiments, density functional theory calculations and electron paramagnetic resonance spectroscopy amongst others.

Background: Medication errors are pervasive. Electronic prescriptions (e-prescriptions) convey secure and computer-readable prescriptions from clinics to outpatient pharmacies for dispensing. Once received, pharmacy staff perform a transcription task to select the medications needed to process e-prescriptions within their dispensing software. Later, pharmacists manually double-check medications selected to fulfill e-prescriptions before dispensing to the patient. Although pharmacist double-checks are mostly effective for catching medication selection mistakes, the cognitive process of medication selection in the computer is still prone to error because of heavy workload, inattention, and fatigue. Leveraging health information technology to identify and recover from medication selection errors can improve patient safety., Objective: This study aimed to determine the performance of an automated double-check of pharmacy prescription records to identify potential medication selection errors made in outpatient pharmacies with the RxNorm application programming interface (API)., Methods: We conducted a retrospective observational analysis of 537,710 pairs of e-prescription and dispensing records from a mail-order pharmacy for the period January 2017 to October 2018. National Drug Codes (NDCs) for each pair were obtained from the National Library of Medicine's (NLM's) RxNorm API. The API returned RxNorm concept unique identifier (RxCUI) semantic clinical drug (SCD) identifiers associated with every NDC. The SCD identifiers returned for the e-prescription NDC were matched against the corresponding SCD identifiers from the pharmacy dispensing record NDC. An error matrix was created based on the hand-labeling of mismatched SCD pairs. Performance metrics were calculated for the e-prescription-to-dispensing record matching algorithm for both total pairs and unique pairs of NDCs in these data., Results: We analyzed 527,881 e-prescription and pharmacy dispensing record pairs. Four clinically significant cases of mismatched RxCUI identifiers were detected (ie, three different ingredient selections and one different strength selection). A total of 546 less significant cases of mismatched RxCUIs were found. Nearly all of the NDC pairs had matching RxCUIs (28,787/28,817, 99.90%-525,270/527,009, 99.67%). The RxNorm API had a sensitivity of 1, a false-positive rate of 0.00104 to 0.00312, specificity of 0.99896 to 0.99688, precision of 0.00727 to 0.04255, and F1 score of 0.01444 to 0.08163. We found 872 pairs of records without an RxCUI., Conclusions: The NLM's RxNorm API can perform an independent and automatic double-check of correct medication selection to verify e-prescription processing at outpatient pharmacies. RxNorm has near-comprehensive coverage of prescribed medications and can be used to recover from medication selection errors. In the future, tools such as this may be able to perform automated verification of medication selection accurately enough to free pharmacists from having to perform manual double-checks of the medications selected within pharmacy dispensing software to fulfill e-prescriptions., (©Corey A Lester, Liyun Tu, Yuting Ding, Allen J Flynn. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 11.03.2020.)

A coarse classification of medications into two risk categories, one for high-risk medications and one for all others, allows people to focus safety improvement work on medications that carry the highest risks of harm. However, such coarse categorization does not distinguish the relative risk of harm for the majority of medications. To begin to develop a more fine-grained measurement scale for the relative risk of harm spanning many medications, we performed an experiment with 18 practicing pharmacists. Each pharmacist-participant made 210 paired comparisons of 21 commonly prescribed medications to reveal a subjective scale of perceived medication worrisomeness (PMW). Statistical analyses of their collective judgments of medication pairs differentiated five levels of PMW. This study illuminates one path towards a fine-grained medication risk scale based on PMW. It also shows how the method of paired comparisons can be used to remotely crowdsource expert knowledge in support of learning health systems., (©2019 AMIA - All rights reserved.)

Background: Health system decisions to put new technologies into clinical practice require a rapid and trustworthy decision-making process informed by best evidence., Objective: This study aimed to present a rapid evidence review process that can be used to inform health system leaders and clinicians seeking to implement new technology tools to improve patient-clinician decision making and patient-oriented outcomes., Methods: The rapid evidence review process we pioneered involved 5 sequential subprocesses: (1) environmental scan, (2) expert panel recruitment, (3) host evidence review panel, (4) analysis, and (5) local validation panel. We conducted an environmental scan of health information technology (IT) literature to identify relevant digital tools in oncology care. We synthesized the recent literature using current evidence review methods, creating visual summaries for use by a national panel of experts. Panelists were taken through a 6-hour modified Delphi process to prioritize tools for implementation. Findings from the rapid evidence review panel were taken to a local validation panel for further rapid review during a 3-hour session., Results: Our rapid evidence review process shows promise for informing decision making by reducing the amount of time and resources needed to identify and prioritize adoption of IT tools. Despite evidence of improved patient outcomes, panelists had substantial concerns about implementing patient-reported outcome tracking tools, voicing concerns about liability, lack of familiarity with new technology, and additional time and workflow changes such tools would require. Instead, clinicians favored technologies that did not require clinician involvement., Conclusions: Health system leaders can use the rapid evidence review process presented here to usefully inform local technology adoption, implementation, and use in practice., (©Emily R Dibble, Bradley E Iott, Allen J Flynn, Darren P King, Mark P MacEachern, Charles P Friedman, Tanner J Caverly. Originally published in JMIR Cancer (http://cancer.jmir.org), 27.11.2018.)

Objective. To characterize informatics education opportunities in US colleges and schools of pharmacy curricula. Methods. Informatics curricular information online was catalogued via publicly available websites. Website content was searched via domain-specific keywords. Online course descriptions were reviewed. Website searches were also conducted for informatics-related opportunities. Results. Of 132 pharmacy curricula found online, 47 (36%) included an informatics course. Of those, 64% (n=30) were required while 47% (n=22) were elective courses. Additionally, 20% (n=26) provided informatics advanced and/or introductory pharmacy practice experiences, 20% (n=27) offered an informatics residency, and 17% (n=22) listed certificate and/or graduate degree programs in informatics. Conclusion. Over the past 10 years, little observable progress has been made in pharmacy school curricula in response to the increasing importance of informatics to the profession. Pharmacy programs can address this educational gap by internal (eg, course development) and external (eg, open source curriculum) solutions.

Introduction: Health systems are challenged by care underutilization, overutilization, disparities, and related harms. One problem is a multiyear latency between discovery of new best practice knowledge and its widespread adoption. Decreasing this latency requires new capabilities to better manage and more rapidly share biomedical knowledge in computable forms. Knowledge objects package machine-executable knowledge resources in a way that easily enables knowledge as a service. To help improve knowledge management and accelerate knowledge sharing, the Knowledge Object Reference Ontology (KORO) defines what knowledge objects are in a formal way., Methods: Development of KORO began with identification of terms for classes of entities and for properties. Next, we established a taxonomical hierarchy of classes for knowledge objects and their parts. Development continued by relating these parts via formally defined properties. We evaluated the logical consistency of KORO and used it to answer several competency questions about parthood. We also applied it to guide knowledge object implementation., Results: As a realist ontology, KORO defines what knowledge objects are and provides details about the parts they have and the roles they play. KORO provides sufficient logic to answer several basic but important questions about knowledge objects competently. KORO directly supports creators of knowledge objects by providing a formal model for these objects., Conclusion: KORO provides a formal, logically consistent ontology about knowledge objects and their parts. It exists to help make computable biomedical knowledge findable, accessible, interoperable, and reusable. KORO is currently being used to further develop and improve computable knowledge infrastructure for learning health systems.

The Knowledge Grid (KGrid) is a research and development program toward infrastructure capable of greatly decreasing latency between the publication of new biomedical knowledge and its widespread uptake into practice. KGrid comprises digital knowledge objects, an online Library to store them, and an Activator that uses them to provide Knowledge-as-a-Service (KaaS). KGrid's Activator enables computable biomedical knowledge, held in knowledge objects, to be rapidly deployed at Internet-scale in cloud computing environments for improved health. Here we present the Activator, its system architecture and primary functions.

Throughout the world, biomedical knowledge is routinely generated and shared through primary and secondary scientific publications. However, there is too much latency between publication of knowledge and its routine use in practice. To address this latency, what is actionable in scientific publications can be encoded to make it computable. We have created a purpose-built digital library platform to hold, manage, and share actionable, computable knowledge for health called the Knowledge Grid Library. Here we present it with its system architecture.

For those with high blood pressure, diabetes, or high cholesterol, adherence to a home medication regimen is important for health. Reductions in the number of daily medication-taking events or daily pill burden improve adherence. A novel advice-giving computer application was developed using the SMART platform to generate advice on how to potentially simplify home medication regimens. MedMinify generated advice for 41.3% of 1,500 home medication regimens for adults age 60 years and older with chronic medical conditions. If the advice given by MedMinify were implemented, 320 regimen changes would have reduced daily medication-taking events while an additional 295 changes would have decreased the daily pill burden. The application identified four serious drug-drug interactions and so advised against taking two pairs of medications simultaneously. MedMinify can give advice to change home medication regimens that could result in simpler home medication-taking schedules.

The specificity of medication-related alerts must be improved to overcome the pernicious effects of alert fatigue. A systematic comparison of new drug orders to historical orders could improve alert specificity and relevance. Using historical order data from a computerized provider order entry system, we alerted physicians to atypical orders during the prescribing of five medications: calcium, clopidogrel, heparin, magnesium, and potassium. The percentage of atypical orders placed for these five medications decreased during the 92 days the alerts were active when compared to the same period in the previous year (from 0.81% to 0.53%; p=0.015). Some atypical orders were appropriate. Fifty of the 68 atypical order alerts were over-ridden (74%). However, the over-ride rate is misleading because 28 of the atypical medication orders (41%) were changed. Atypical order alerts were relatively few, identified problems with frequencies as well as doses, and had a higher specificity than dose check alerts.

In this first attempt to model the distributions of a mesopelagic fish family at this scale in the eastern Australian region (10°S to 57°S), lanternfish species occurrence data spanning a period from 1928 to 2010 were modelled against environmental covariates. This involved: (1) data collation and taxonomic quality checking, (2) classification of trawls into "horizontal" (presence-absence) and "oblique" (presence-only) types, and classification of vertical migration patterns using existing literature and the species occurrence database, (3) binomial GAMs using presence-absence data for representative temperate, subtropical and tropical species to examine depth interactions with environmental covariates and refine the selection of environmental layers for presence-only MAXENT models, (4) Presence-only MAXENT modelling using data from all trawls and the reduced environmental layers, and (5) Multivariate analysis (area-wise and species-wise) of the resulting matrix of logistic score by geographic pixel. We test the hypothesis that major fronts in the region (Tasman Front, Subtropical Convergence, Subantarctic Front) represent zoogeographic boundaries. A four-region zoogeographic scheme is hypothesised: Coral Sea region, Subtropical Lower Water region, Subtropical Convergence/South Tasman region and Subantarctic region. The Tasman Front, Subtropical Convergence and Subantarctic Front represented zoogeographic boundaries. An additional boundary at ∼25°S (coined the 'Capricorn' boundary) was adopted to delineate the Coral Sea from Subtropical Lower Water regions. Lanternfish zoogeographic regions are congruent with some aspects of two prevailing physicochemical biogeographic schema in the region, but neither of these schema alone accurately predicts lanternfish distributions. As lanternfishes integrate vertical ocean processes, the hypothesised lanternfish zoogeography may represent a useful model for a generalised pelagic biogeography that should be tested for other oceanic groups.

Pharmacy has an established history of technology use to support business processes. Pharmacy informatics education within doctor of pharmacy programs, however, is inconsistent, despite its inclusion as a requirement in the 2007 Accreditation Council for Pharmacy Education Standards and Guidelines. This manuscript describes pharmacy informatics knowledge and skills that all graduating pharmacy students should possess, conceptualized within the framework of the medication use process. Additionally, we suggest core source materials and specific learning activities to support pharmacy informatics education. We conclude with a brief discussion of emerging changes in the practice model. These changes are facilitated by pharmacy informatics and will inevitably become commonplace in our graduates' practice environment.

All known guanidino kinases contain a conserved cysteine residue that interacts with the non-nucleophilic eta1-nitrogen of the guanidino substrate. Site-directed mutagenesis studies have shown that this cysteine is important, but not essential for activity. In human muscle creatine kinase (HMCK) this residue, Cys283, forms part of a conserved cysteine-proline-serine (CPS) motif and has a pKa about 3 pH units below that of a regular cysteine residue. Here we employ a computational approach to predict the contribution of residues in this motif to the unusually low cysteine pKa. We calculate that hydrogen bonds to the hydroxyl and to the backbone amide of Ser285 would both contribute approximately 1 pH unit, while the presence of Pro284 in the motif lowers the pKa of Cys283 by a further 1.2 pH units. Using UV difference spectroscopy the pKa of the active site cysteine in WT HMCK and in the P284A, S285A, and C283S/S285C mutants was determined experimentally. The pKa values, although consistently about 0.5 pH unit lower, were in broad agreement with those predicted. The effect of each of these mutations on the pH-rate profile was also examined. The results show conclusively that, contrary to a previous report (Wang et al. (2001) Biochemistry 40, 11698-11705), Cys283 is not responsible for the pKa of 5.4 observed in the WT V/K(creatine) pH profile. Finally we use molecular dynamics simulations to demonstrate that, in order to maintain the linear alignment necessary for associative inline transfer of a phosphoryl group, Cys283 needs to be ionized.

Recently the crystal structure of creatine kinase from Torpedocalifornica was determined to 2.1 A. The dimeric structure revealed two different forms in the unit cell: one monomer was bound to a substrate, MgADP, and the other monomer was bound to a transition-state analogue complex composed of MgADP, nitrate and creatine. The most striking difference between the structures is the movement of two loops (comprising residues 60-70 and residues 323-333) into the active site in the transition state structure. This loop movement effectively occludes the active site from solvent, and the loops appear to be locked into place by a salt bridge formed between His66 and Asp326. His66 is of particular interest as it is located within a PGHP motif conserved in all creatine kinases but not found in other guanidino kinases. We have carried out alanine-scanning mutagenesis of each of the residues in the PGHP motif and determined that only the His66 plays a significant role in the creatine kinase reaction. Although neither residue interacts directly with the substrate, the interaction His66 and Asp326 appears to be important in providing the precise alignment of substrates necessary for phosphoryl group transfer. Finally, it is clear that neither His66 nor Asp326 are responsible for the pKs observed in the pH-rate profile for HMCK.

Skin surface temperature (SST) changes measured on live hairless mice are presented as a simple means of following wound healing. SST is generally determined by 3 factors which are the ambient temperature, the rate of water loss from the surface of the skin and the diffusion of thermal energy from the body's core. The SST increase immediately after a burn injury reflects the amount of thermal energy absorbed by the skin surface. For burns and other injuries, the drop in SST following injury, but after thermal equilibrium has been established, provides an early indication of the degree of impairment of the skin's barrier. Three kinds of mouse skin wounds, mechanical (tape stripping), thermal and chemical (phenol application), were investigated. SST nadirs ranged from 2.1 to 4.4 degrees C with mild to full-thickness burns, respectively. Except for the earliest moments after wounding, striking parallels were noted between SST and transepidermal water loss profiles for these injuries. The SST profile over the full course of wound healing clearly indicates the severity of the injury, the stages of wound maturation and the time to complete skin healing., (Copyright 2003 S. Karger AG, Basel)

Ovariectomized, castrated, and sham-castrated rats pretreated with oil or testosterone were intra-arterially infused with saline and three doses of angiotensin II while blood pressure and cochlear blood flow were measured. The results indicated a positive dose-response relationship for blood pressure and cochlear blood flow. Sham-castrated males had higher mean blood pressure responses than castrated males, followed by ovariectomized females. Cochlear blood flow responses were higher in the sham-castrated males than the ovariectomized females, followed by the castrated males. In comparison to the male groups, the ovariectomized females evidenced the lowest, middle, and highest cochlear blood flow responses to the three increasing doses of angiotensin II. Testosterone pretreatment facilitated angiotensin-induced cochlear blood flow elevations in all three angiotensin doses. These results suggest that endogenous and exogenous androgens may alter blood pressure and/or cochlear blood flow responses to angiotensin II via different mechanisms.

Guinea pigs and Sprague-Dawley rats were intracerebroventricularly (icv) infused with various doses of angiotensin II (AII) in order to investigate central control of and species differences in cochlear blood flow (CBF) and blood pressure (BP). The results indicated a positive dose-response relationship between icv infusions of AII for BP and CBF in members of both species. This relationship was more predictable in the guinea pig than in the rat. In addition, responses to similar AII doses between species indicated that: a) BP elevations were significantly greater in the rat than in the guinea pig, b) CBF elevations were not significantly different between the rats and guinea pigs, and c) CBF was more highly correlated with BP in the guinea pig than in the rat. These results suggest that different relationships may exist between BP and CBF in rats and guinea pigs.

This study investigated blood pressure in guinea pigs while they were 1) alert and free moving, 2) anesthetized with different anesthetics, and 3) exposed to continuous, 115 dB SPL white noise under anesthesia. The animals were prepared with a carotid artery catheter and permitted to recover for 48 h before blood pressure levels were measured. Mean arterial blood pressure in the resting, unrestrained guinea pig was 64 mmHg (+/- 1.38 S.E.). Ketamine Hydrochloride (Ketamine) significantly decreased, and Fentanyl-Citrate significantly increased, blood pressure. Fentanyl-Droperidol produced no substantial blood pressure change. Guinea pigs anesthetized with Fentanyl-Citrate and Fentanyl-Droperidol demonstrated significant blood pressure increases when exposed to noise, with the Fentanyl-Citrate group showing a greater response. Animals anesthetized with Ketamine Hydrochloride exhibited no significant blood pressure changes when exposed to the noise.