Analysis of Legacy and Novel Neutral Per- and Polyfluoroalkyl Substances in Soils from an Industrial Manufacturing Facility.

Per- and polyfluoroalkyl substances (PFASs) have been detected in an array of environmental media due to their ubiquitous use in industrial and consumer products as well as potential release from fluorochemical manufacturing facilities. During their manufacture, many fluorotelomer (FT) facilities rely on neutral intermediates in polymer production including the FT-alcohols (FTOHs). These PFAS are known to transform to the terminal acids (perfluoro carboxylic acids; PFCAs) at rates that vary with environmental conditions. In the current study on soils from a FT facility, we employed gas chromatography coupled with conventional- and high-resolution mass spectrometry (GC-MS and GC-HRMS) to investigate the profile of these precursor compounds, the intermediary secondary alcohols (sFTOHs), FT-acrylates (FTAcr), and FT-acetates (FTAce) in soils around the former FT-production facility. Of these precursors, the general trend in detection intensity was [FTOHs] > [sFTOHs] > [FTAcrs], while for the FTOHs, homologue intensities generally were [12:2 FTOH] > [14:2 FTOH] > [16:2 FTOH] > [10:2 FTOH] > [18:2 FTOH] > [20:2 FTOH] > [8:2 FTOH] ∼ [6:2 FTOH]. The corresponding terminal acids were also detected in all soil samples and positively correlated with the precursor concentrations. GC-HRMS confirmed the presence of industrial manufacturing byproducts such as FT-ethers and FT-esters and aided in the tentative identification of previously unreported dimers and other compounds. The application of GC-HRMS to the measurement and identification of precursor PFAS is in its infancy, but the methodologies described here will help refine its use in tentatively identifying these compounds in the environment.

Cross-cultural adaptation and psychometric validation of the french version of the "defense and veterans pain rating scale" for acute and chronic pain: A prospective clinical study.

BACKGROUND: Pain assessment and proper evaluation of pain is a prerequisite for treatment of acute and chronic pain. Until now, most evaluations use only resting pain intensity and a unidimensional scale, although multidimensional pain assessment and especially assessment of functional pain impact on activities is recommended. The "Defense and Veterans Pain Rating Scale" (DVPRS) permits this multidimensional assessment, but no validated French translation exists. OBJECTIVES: To validate the French translation of the multidimensional DVPRS, called Functional Pain Scale (FPS) in multiple settings of acute and chronic pain. STUDY DESIGN: Prospective observational study. SETTING: Two large hospitals in the French-speaking region of Switzerland. METHODS: We recruited 232 patients from February 2022 to January 2023. Patients with acute or chronic pain in different settings received a paper questionnaire with both the NRS and the Functional Pain Scale and a customized evaluation questionnaire. Correlation of FPS and NRS, psychometric properties and patient preferences were analysed. RESULTS: For the whole group of 232 patients, correlation of FPS and NRS was high, as well for all subgroups. The multi-item FPS scale showed excellent internal consistency. A large majority of patients, even those >75 years old, preferred FPS over NRS and stated that the FPS was easy to use. CONCLUSIONS: The study confirms that the French translation of the DVPRS (= Functional Pain Scale) is a valid measurement instrument for acute and chronic pain evaluation in a wide range of patient groups, and easy to use by patients.

Generation of Bioactivity-Tailored FK506/FK520 Analogs by CRISPR Editing in Streptomyces tsukubaensis.

For a potential application of FK506 in the treatment of acute kidney failure only the FKBP12 binding capability of the compound is required, while the immunosuppressive activity via calcineurin binding is considered as a likely risk to the patients. The methoxy groups at C13 and C15 are thought to have significant influence on the immunosuppressive activity of the molecule. Consequently, FK506 analogs with different functionalities at C13 and C15 were generated by targeted CRISPR editing of the AT domains in module 7 and 8 of the biosynthetic assembly line in Streptomyces tsukubaensis. In addition, the corresponding FK520 (C21 ethyl derivative of FK506) analogs could be obtained by media adjustments. The compounds were tested for their bioactivity in regards to FKBP12 binding, BMP potentiation and calcineurin sparing. 15-desmethoxy FK506 was superior to the other tested analogs as it did not inhibit calcineurin but retained high potency towards FKBP12 binding and BMP potentiation.

Development and initial validation of the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M): An item bank for evaluating mobility of people who use lower-limb orthoses.

Lower limb orthoses (LLOs) are externally-applied leg braces that are designed to improve or maintain mobility in people with a variety of health conditions that affect lower limb function. Clinicians and researchers are therefore often motivated to measure LLO users' mobility to select or assess the effectiveness of these devices. Patient-reported outcome measures (PROMs) can provide insights into important aspects of a LLO user's mobility for these purposes. However, few PROMs are available to measure mobility of LLO users. Those few that exist have issues that may limit their clinical or scientific utility. The objective of this study was to create a population-specific item bank for measuring mobility of LLO users. Previously-developed candidate items were administered in a cross-sectional study to a large national sample of LLO users. Responses from study participants (n = 1036) were calibrated to a graded response statistical model using Item Response Theory methods. A set of 39 items was found to be unidimensional, locally independent, and function without bias due to characteristics unrelated to mobility. The set of final calibrated items, termed the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M) item bank, was evaluated for initial evidence of convergent, divergent, and known groups construct validity. OPRO-M was strongly correlated with existing PROMs designed to measure aspects of physical function. Conversely, OPRO-M was weakly correlated with PROMs that measured unrelated constructs, like sleep disturbance and depression. OPRO-M also showed an ability to differentiate groups with expected mobility differences. Two fixed-length short forms were created from the OPRO-M item bank. Items on the short forms were selected based on statistical and clinical criteria. Collectively, results from this study indicate that OPRO-M can effectively measure mobility of LLO users, and OPRO-M short forms can now be recommended for use in routine clinical practice and research studies.

A microprocessor stance and swing control orthosis improves balance, risk of falling, mobility, function, and quality of life of individuals dependent on a knee-ankle-foot orthosis for ambulation.

INTRODUCTION: The C-Brace microprocessor stance and swing control orthosis was designed to overcome safety and functional limitations of traditional knee-ankle-foot orthoses (KAFOs) for individuals with lower limb paresis. However, a systematic comparison to established KAFO types has not been performed in a bigger sample. METHODS: International multicenter, randomized, controlled, cross-over clinical trial. Legacy KAFO users at risk of falling were randomized to KAFO/C-Brace or C-Brace/KAFO use for three months with each orthosis. Primary outcome was balance assessed with the Berg Balance Scale (BBS). Secondary outcomes were falls, mobility, function, and quality of life. RESULTS: Intention-to-treat analysis with 102 participants. With the C-Brace, the BBS improved by 3.3 ± 6.3 points (p < 0.0001). Significantly fewer participants presented BBS scores <40 indicative of increased fall risk (16 vs. 36, p = 0.018). Mean falls reduced from 4.0 ± 16.8 to 1.1 ± 3.3 (p = 0.002). Outcomes for function, mobility, and quality of life showed significant improvements with the C-Brace. DISCUSSION: The improvements in fall risk and mobility can be attributed to the stumble recovery and controlled knee flexion during weight bearing of the C-Brace and have a positive impact on the quality of life of users. CONCLUSION: The C-Brace represents an option for KAFO users with increased fall risk and reduced mobility.

When prescribing traditional knee-ankle-foot orthoses (KAFOs), their known limitations, such as limited function and mobility, and the requirement to walk with compensatory mechanisms, especially on non-level terrains, should be considered.For patients with compromised balance and increased risk of falling when using a traditional KAFO, a microprocessor stance and swing control orthosis (MP-SSCO) may be considered as an orthotic option to reduce their fall risk.For patients with mobility restrictions using a traditional KAFO, a MP-SSCO may be considered to improve function, mobility, reintegration into normal living, and quality of life.

Valhidepsin Lipopeptides from Chromobacterium vaccinii: Structures, Biosynthesis, and Coregulation with FR900359 Production.

Microbial secondary metabolites continue to provide a valuable source of both chemical matter and inspiration for drug discovery in a broad range of therapeutic areas. Beyond this, the corresponding microorganisms represent a sustainable modality for biotechnological production of structurally complex molecules at the quantities required for drug development or even commercial manufacturing. Chromobacterium vaccinii, which has recently been reported as a producer of the pharmacologically highly important Gq inhibitor FR900359 (FR), represents such an example. The characterization of an orphan biosynthetic gene cluster (BGC) located directly downstream of the frs BCG led to the discovery of eight new lipopeptides, valhidepsins A-H (1-8), produced by C. vaccinii. Their chemical structures were elucidated through analysis of 1D and 2D NMR data and high-resolution MS/MS fragmentation methods. The valhidepsins did not display significant antibiotic nor cytotoxic activities but showed surfactant properties. The cluster-compound correlation was demonstrated by generation of a knockout mutant, which abolished production of valhidepsins. This knockout mutant yielded a significantly increased isolated yield of FR.

Development of an item bank for measuring prosthetic mobility in people with lower limb amputation: The Prosthetic Limb Users Survey of Mobility (PLUS-M).

BACKGROUND: Achieving mobility with a prosthesis is a common post-amputation rehabilitation goal and primary outcome in prosthetic research studies. Patient-reported outcome measures (PROMs) available to measure prosthetic mobility have practical and psychometric limitations that inhibit their use in clinical care and research. OBJECTIVE: To develop a brief, clinically meaningful, and psychometrically robust PROM to measure prosthetic mobility. DESIGN: A cross-sectional study was conducted to administer previously developed candidate items to a national sample of lower limb prosthesis users. Items were calibrated to an item response theory model and two fixed-length short forms were created. Instruments were assessed for readability, effective range of measurement, agreement with the full item bank, ceiling and floor effects, convergent validity, and known groups validity. SETTING: Participants were recruited using flyers posted in hospitals and prosthetics clinics across the United States, magazine advertisements, notices posted to consumer websites, and direct mailings. PARTICIPANTS: Adult prosthesis users (N = 1091) with unilateral lower limb amputation due to traumatic or dysvascular causes. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Candidate items (N = 105) were administered along with the Patient Reported Outcome Measurement Information System Brief Profile, Prosthesis Evaluation Questionnaire - Mobility Subscale, and Activities-Specific Balance Confidence Scale, and questions created to characterize respondents. RESULTS: A bank of 44 calibrated self-report items, termed the Prosthetic Limb Users Survey of Mobility (PLUS-M), was produced. Clinical and statistical criteria were used to select items for 7- and 12-item short forms. PLUS-M instruments had an 8th grade reading level, measured with precision across a wide range of respondents, exhibited little-to-no ceiling or floor effects, correlated expectedly with scores from existing PROMs, and differentiated between groups of respondents expected to have different levels of mobility. CONCLUSION: The PLUS-M appears to be well suited to measuring prosthetic mobility in people with lower limb amputation. PLUS-M instruments are recommended for use in clinical and research settings.

Spatial and Temporal Characterization of Activity in Public Space, 2019-2020.

The data reported here characterize spatial and temporal variation in the ratio of short-to-long-duration visits in public places (i.e., points of interest) in the United States for each week between January 2019 and December 2020. The underlying data on anonymized and aggregated foot traffic to public places is curated by SafeGraph, a geospatial data provider. In this work, we report the estimated number and duration of "short" (i.e., <4 hours) and "long" (i.e., >4 hours) visits to public places at the US census block group level. Long visits are shown to be a good proxy for workers based on formal economic data. We propose that short visits are more likely to represent nonobligate activities: people visiting a public place for leisure, shopping, entertainment, or civic or cultural engagement. Our work constructs a ratio of short to long visits, which can be used to inform population estimates for nonworker use of public space. These data may be useful for understanding how people's use of public space has changed during the COVID-19 pandemic and, more generally, for understanding activity patterns in public.

Microprocessor feet improve prosthetic mobility and physical function relative to non-microprocessor feet.

Introduction: The clinical benefits associated with the microprocessor regulation of prosthetic ankle position and resistance have largely been reported through manufacturer conducted research in controlled laboratory environments. Measures with greater ecological validity are needed. This study aimed to understand if there are differences in physical function and mobility outcomes as patients transitioned from a non-Microprocessor to Microprocessor Feet. Method: A retrospective analysis of patient outcomes was performed. Patient-reported benefits associated with the adoption of such prosthetic foot-ankle mechanisms were collected from 23 individuals through the longitudinal use of a custom short form of the Patient-Reported Outcomes Measurement Information System-Physical Function and individual items from the Prosthesis Evaluation Questionnaire. Results: The impact of Microprocessor Feet upon physical function and mobility were observed in a significant increase in physical function (mean increase in t-score of 5.4 ± 1.25; p = .0004) and significant improvements in several mobility items. Conclusions: Collectively, these measures support the beneficial impact of Microprocessor Feet on improving socket comfort, reducing back pain, improving sit to stand transfers and enhancing hill ascent and descent as well as stair negotiation.

Environmental Fate of Cl-PFPECAs: Predicting the Formation of PFAS Transformation Products in New Jersey Soils.

Although next-generation per- and polyfluorinated substances (PFAS) were designed and implemented as safer and environmentally degradable alternatives to "forever" legacy PFAS, there is little evidence to support the actual transformation of these compounds and less evidence of the safety of transformed products in the environment. Multiple congeners of one such PFAS alternative, the chloro-perfluoropolyether carboxylates (Cl-PFPECAs), have been found in New Jersey soils surrounding a manufacturing facility. These compounds are ideal candidates for investigating environmental transformation due to the existence of potential reaction centers including a chlorinated carbon and ether linkages. Transformation products of the chemical structures of this class of compounds were predicted based on analogous PFAS transformation pathways documented in peer-reviewed literature. Potential reaction products were used as the basis for high-resolution mass-spectrometric suspect screening of the soils. Suspected transformation products of multiple congeners, the Cl-PFPECAs, including H-PFPECAs, epox-PFPECAs, and diOH-PFPECAs, were tentatively observed in these screenings. Although ether linkages have been hypothesized as potential reaction centers under environmental conditions, to date, no documentation of ether scission has been identified. Despite exhaustive scrutiny of the high-resolution data for our Cl-PFPECA-laden soils, we found no evidence of ether scission.

Development of a PFAS reaction library: identifying plausible transformation pathways in environmental and biological systems.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are used in many consumer applications due to their stain repellency, surfactant properties, ability to form water-proof coatings and use in fire suppression. The production, application, transport, use and disposal of PFAS and PFAS-treated products have resulted in their wide-spread occurrence in environmental and biological systems. Concern over exposure to PFAS and their transformation products and metabolites has necessitated the development of tools to predict the transformation of PFAS in environmental systems and metabolism in biological systems. We have developed reaction libraries for predicting transformation products and metabolites in a variety of environmental and biological reaction systems. These reaction libraries are based on generalized reaction schemes that encode the process science of PFAS reported in the peer-reviewed literature. The PFAS reaction libraries will be executed through the Chemical Transformation Simulator, a web-based tool that is available to the public. These reaction libraries are intended for predicting the environmental transformation and metabolism of PFAS only.

Per- and polyfluoroalkyl substances in the environment.

Over the past several years, the term PFAS (per- and polyfluoroalkyl substances) has grown to be emblematic of environmental contamination, garnering public, scientific, and regulatory concern. PFAS are synthesized by two processes, direct fluorination (e.g., electrochemical fluorination) and oligomerization (e.g., fluorotelomerization). More than a megatonne of PFAS is produced yearly, and thousands of PFAS wind up in end-use products. Atmospheric and aqueous fugitive releases during manufacturing, use, and disposal have resulted in the global distribution of these compounds. Volatile PFAS facilitate long-range transport, commonly followed by complex transformation schemes to recalcitrant terminal PFAS, which do not degrade under environmental conditions and thus migrate through the environment and accumulate in biota through multiple pathways. Efforts to remediate PFAS-contaminated matrices still are in their infancy, with much current research targeting drinking water.

Promoter-Driven Overexpression in Chromobacterium vaccinii Facilitates Access to FR900359 and Yields Novel Low Abundance Analogs.

Access to the cyclic depsipeptide FR900359 (FR), a selective Gq/11 protein inhibitor of high pharmacological interest and a potential lead molecule for targeted therapy of cancers with oncogenic GNAQ or GNA11 mutations (encoding Gq and G11 respectively), has been challenging ever since its initial discovery more than three decades ago. The recent discovery of Chromobacterium vaccinii as a cultivable FR producer enables the development of approaches leading to a high-yielding, scalable and sustainable biotechnological process for production of FR, thereby removing this bottleneck. Here we characterize different promoters in exchange of the native promoter of the FR assembly line, resulting in an overexpression mutant with significantly increased production of FR. Thereby, the isolation and structure elucidation of novel FR analogs of low abundance is enabled. Further, we explore the antiproliferative activities of fifteen chromodepsins against uveal melanoma cell lines harboring Gq/11 mutations and characterize the major metabolite of FR formed in plasma.

Laboratory-Based SARS-CoV-2 Receptor Binding Domain Serologic Assays Perform with Equivalent Sensitivity and Specificity to Commercial FDA-EUA Approved Tests.

During early phases of the SARS-CoV-2 epidemic, many research laboratories repurposed their efforts towards developing diagnostic testing that could aid public health surveillance while commercial and public diagnostic laboratories developed capacity and validated large scale testing methods. Simultaneously, the rush to produce point-of-care and diagnostic facility testing resulted in FDA Emergency Use Authorization with scarce and poorly validated clinical samples. Here, we review serologic test results from 186 serum samples collected in early phases of the pandemic (May 2020) from skilled nursing facilities tested with six laboratory-based and two commercially available assays. Serum neutralization titers were used to set cut-off values using positive to negative ratio (P/N) analysis to account for batch effects. We found that laboratory-based receptor binding domain (RBD) binding assays had equivalent or superior sensitivity and specificity compared to commercially available tests. We also determined seroconversion rate and compared with qPCR outcomes. Our work suggests that research laboratory assays can contribute reliable surveillance information and should be considered important adjuncts to commercial laboratory testing facilities during early phases of disease outbreaks.

Satisfaction, Usability, and Compliance With the Use of Smartwatches for Ecological Momentary Assessment of Knee Osteoarthritis Symptoms in Older Adults: Usability Study.

BACKGROUND: Smartwatches enable physicians to monitor symptoms in patients with knee osteoarthritis, their behavior, and their environment. Older adults experience fluctuations in their pain and related symptoms (mood, fatigue, and sleep quality) that smartwatches are ideally suited to capture remotely in a convenient manner. OBJECTIVE: The aim of this study was to evaluate satisfaction, usability, and compliance using the real-time, online assessment and mobility monitoring (ROAMM) mobile app designed for smartwatches for individuals with knee osteoarthritis. METHODS: Participants (N=28; mean age 73.2, SD 5.5 years; 70% female) with reported knee osteoarthritis were asked to wear a smartwatch with the ROAMM app installed. They were prompted to report their prior night's sleep quality in the morning, followed by ecological momentary assessments (EMAs) of their pain, fatigue, mood, and activity in the morning, afternoon, and evening. Satisfaction, comfort, and usability were evaluated using a standardized questionnaire. Compliance with regard to answering EMAs was calculated after excluding time when the watch was not being worn for technical reasons (eg, while charging). RESULTS: A majority of participants reported that the text displayed was large enough to read (22/26, 85%), and all participants found it easy to enter ratings using the smartwatch. Approximately half of the participants found the smartwatch to be comfortable (14/26, 54%) and would consider wearing it as their personal watch (11/24, 46%). Most participants were satisfied with its battery charging system (20/26, 77%). A majority of participants (19/26, 73%) expressed their willingness to use the ROAMM app for a 1-year research study. The overall EMA compliance rate was 83% (2505/3036 responses). The compliance rate was lower among those not regularly wearing a wristwatch (10/26, 88% vs 16/26, 71%) and among those who found the text too small to read (4/26, 86% vs 22/26, 60%). CONCLUSIONS: Older adults with knee osteoarthritis positively rated the ROAMM smartwatch app and were generally satisfied with the device. The high compliance rates coupled with the willingness to participate in a long-term study suggest that the ROAMM app is a viable approach to remotely collecting health symptoms and behaviors for both research and clinical endeavors.

Prioritizing Direct Photolysis Products Predicted by the Chemical Transformation Simulator: Relative Reasoning and Absolute Ranking.

The United States Environmental Protection Agency's Chemical Transformation Simulator (CTS) platform implemented the first freely available reaction library to predict direct photolysis products of organic contaminants in aquatic systems. However, the initial version of the reaction library did not differentiate the formation likelihood of each predicted product, and therefore, the number of predicted products that are not observed tended to exponentially increase with the prediction generation. To alleviate this problem, we first employed relative reasoning algorithms to remove unlikely products. We then ranked different reaction schemes according to their transformation kinetics and removed slowly forming products. Applying the two strategies improved the precision (the percentage of correctly predicted products over all predicted products) by 34% and 53% for the internal evaluation set and the external evaluation set, respectively, when products from three generations were considered. This improved library also revealed new research directions to improve predictions of the dominant phototransformation products.

Quantitative structure activity relationships (QSARs) and machine learning models for abiotic reduction of organic compounds by an aqueous Fe(II) complex.

Due to the increasing diversity of organic contaminants discharged into anoxic water environments, reactivity prediction is necessary for chemical persistence evaluation for water treatment and risk assessment purposes. Almost all quantitative structure activity relationships (QSARs) that describe rates of contaminant transformation apply only to narrowly-defined, relatively homogenous families of reactants (e.g., dechlorination of alkyl halides). In this work, we develop predictive models for abiotic reduction of 60 organic compounds with diverse reducible functional groups, including nitroaromatic compounds (NACs), aliphatic nitro-compounds (ANCs), aromatic N-oxides (ANOs), isoxazoles (ISXs), polyhalogenated alkanes (PHAs), sulfoxides and sulfones (SOs), and others. Rate constants for their reduction were measured using a model reductant system, Fe(II)-tiron. Qualitatively, the rates followed the order NACs > ANOs ≈ ISXs ≈ PHAs > ANCs > SOs. To develop QSARs, both conventional chemical descriptor-based and machine learning (ML)-based approaches were investigated. Conventional univariate QSARs based on a molecular descriptor ELUMO (energy of the lowest-unoccupied molecular orbital) gave good correlations within classes. Multivariate QSARs combining ELUMO with Abraham descriptors for physico-chemical properties gave slightly improved correlations within classes for NCs and NACs, but little improvement in correlation within other classes or among classes. The ML model obtained covers reduction rates for all classes of compounds and all of the conditions studied with the prediction accuracy similar to those of the conventional QSARs for individual classes (r2 = 0.41-0.98 for univariate QSARs, 0.71-0.94 for multivariate QSARs, and 0.83 for the ML model). Both approaches required a scheme for a priori classification of the compounds for model training. This work offers two alternative modeling approaches to comprehensive abiotic reactivity prediction for persistence evaluation of organic compounds in anoxic water environments.

The Temporal Relationship Between Ecological Pain and Life-Space Mobility in Older Adults With Knee Osteoarthritis: A Smartwatch-Based Demonstration Study.

BACKGROUND: Older adults who experience pain are more likely to reduce their community and life-space mobility (ie, the usual range of places in an environment in which a person engages). However, there is significant day-to-day variability in pain experiences that offer unique insights into the consequences on life-space mobility, which are not well understood. This variability is complex and cannot be captured with traditional recall-based pain surveys. As a solution, ecological momentary assessments record repeated pain experiences throughout the day in the natural environment. OBJECTIVE: The aim of this study was to examine the temporal association between ecological momentary assessments of pain and GPS metrics in older adults with symptomatic knee osteoarthritis by using a smartwatch platform called Real-time Online Assessment and Mobility Monitor. METHODS: Participants (n=19, mean 73.1 years, SD 4.8; female: 13/19, 68%; male: 6/19, 32%) wore a smartwatch for a mean period of 13.16 days (SD 2.94). Participants were prompted in their natural environment about their pain intensity (range 0-10) at random time windows in the morning, afternoon, and evening. GPS coordinates were collected at 15-minute intervals and aggregated each day into excursion, ellipsoid, clustering, and trip frequency features. Pain intensity ratings were averaged across time windows for each day. A random effects model was used to investigate the within and between-person effects. RESULTS: The daily mean pain intensities reported by participants ranged between 0 and 8 with 40% reporting intensities ≥2. The within-person associations between pain intensity and GPS features were more likely to be statistically significant than those observed between persons. Within-person pain intensity was significantly associated with excursion size, and others (excursion span, total distance, and ellipse major axis) showed a statistical trend (excursion span: P=.08; total distance: P=.07; ellipse major axis: P=.07). Each point increase in the mean pain intensity was associated with a 3.06 km decrease in excursion size, 2.89 km decrease in excursion span, 5.71 km decrease total distance travelled per day, 31.4 km2 decrease in ellipse area, 0.47 km decrease ellipse minor axis, and 3.64 km decrease in ellipse major axis. While not statistically significant, the point estimates for number of clusters (P=.73), frequency of trips (P=.81), and homestay (P=.15) were positively associated with pain intensity, and entropy (P=.99) was negatively associated with pain intensity. CONCLUSIONS: In this demonstration study, higher intensity knee pain in older adults was associated with lower life-space mobility. Results demonstrate that a custom-designed smartwatch platform is effective at simultaneously collecting rich information about ecological pain and life-space mobility. Such smart tools are expected to be important for remote health interventions that harness the variability in pain symptoms while understanding their impact on life-space mobility.

Resolving Conflict in Real Time: Operationalizing Culture Transformation in Deployments.

Preparation is the key to performance. The Army invests substantially in team and unit preparation prior to deployments. However, despite the time and training to build camaraderie and confidence in one another, conflict still arises within units. Most training does not address the underlying mindset that is the source of conflict. Army medicine has utilized training material that addresses the mindset source of conflict to improve team and organizational collaboration and outcomes in hospital settings. We adapted this current Army training to conditions in a deployment environment and improved the culture and reduced the conflict in the unit.

Sustained Impact of Real-time Continuous Glucose Monitoring in Adults With Type 1 Diabetes on Insulin Pump Therapy: Results After the 24-Month RESCUE Study.

OBJECTIVE: In recent years, a growing number of people with type 1 diabetes gained access to real-time continuous glucose monitoring (rtCGM). Long-term benefits of rtCGM are unclear because of a lack of large studies of long duration. We evaluated whether real-world rtCGM use up to 24 months offered benefits, particularly in those living with impaired awareness of hypoglycemia (IAH). RESEARCH DESIGN AND METHODS: This 24-month, prospective, observational cohort study followed 441 adults with insulin pumps receiving full reimbursement for rtCGM. Forty-two percent had IAH. The primary end point was evolution of HbA1c, with secondary end points change in acute hypoglycemia complications, diabetes-related work absenteeism, and quality of life scores. Additionally, we evaluated whether people could achieve glycemic consensus targets during follow-up. RESULTS: After 24 months, HbA1c remained significantly lower compared with baseline (7.64% [60 mmol/mol] vs. 7.37% [57 mmol/mol], P < 0.0001). Sustained benefits were also observed for the score on the hypoglycemia fear survey and hypoglycemia-related acute complications irrespective of hypoglycemia awareness level. People with IAH had the strongest improvement, especially for severe hypoglycemia (862 events in the year before vs. 119 events per 100 patient-years in the 2nd year, P < 0.0001). Over 24 months, more people were able to meet hypoglycemia consensus targets at the expense of slightly fewer people achieving hyperglycemia consensus targets. Furthermore, the number of people with HbA1c <7% (<53 mmol/mol) without severe hypoglycemia events more than doubled (11.0% vs. 25.4%, P < 0.0001). CONCLUSIONS: Use of rtCGM led to sustained improvements in hypoglycemia-related glucose control over 24 months. Lower fear of hypoglycemia, fewer acute hypoglycemia-related events, and fewer diabetes-related days off from work were observed, particularly in those with IAH.