Personalized mood prediction from patterns of behavior collected with smartphones.

Over the last ten years, there has been considerable progress in using digital behavioral phenotypes, captured passively and continuously from smartphones and wearable devices, to infer depressive mood. However, most digital phenotype studies suffer from poor replicability, often fail to detect clinically relevant events, and use measures of depression that are not validated or suitable for collecting large and longitudinal data. Here, we report high-quality longitudinal validated assessments of depressive mood from computerized adaptive testing paired with continuous digital assessments of behavior from smartphone sensors for up to 40 weeks on 183 individuals experiencing mild to severe symptoms of depression. We apply a combination of cubic spline interpolation and idiographic models to generate individualized predictions of future mood from the digital behavioral phenotypes, achieving high prediction accuracy of depression severity up to three weeks in advance (R2 ≥ 80%) and a 65.7% reduction in the prediction error over a baseline model which predicts future mood based on past depression severity alone. Finally, our study verified the feasibility of obtaining high-quality longitudinal assessments of mood from a clinical population and predicting symptom severity weeks in advance using passively collected digital behavioral data. Our results indicate the possibility of expanding the repertoire of patient-specific behavioral measures to enable future psychiatric research.

Dual targeting of mitochondrial Lon peptidase 1 and chymotrypsin-like protease by small molecule BT317, as potential therapeutics in malignant astrocytoma.

Malignant astrocytomas are aggressive glioma tumors characterized by extensive hypoxia-induced, mito-chondria-dependent changes such as altered respiration, increased chymotrypsin-like (CT-L) proteasome activity, decreased apoptosis, drug resistance, stemness and increased invasiveness. Mitochondrial Lon Peptidase I (LonP1) overexpression and increased CT-L proteasome inhibitors activity are the biomarkers of aggressive high grade glioma phenotype, poor prognosis and found to be associated with recurrence and poor patient survival, and drugs targeting either LonP1 or the CT-L activity have anti-glioma activity in pre-clinical models. We here for the first time introduced and evaluated a novel small molecule, BT317, derived from coumarinic compound 4 (CC4) using structure-activity modeling which we found to inhibit both LonP1 and CT-L proteasome activity. Using gain-of-function and loss-of-function genetic models, we dis-covered that BT317 is more effective than the individual LonP1 or CT-L inhibition in increasing reactive oxy-gen species (ROS) generation and inducing apoptosis in high-grade astrocytoma lines. In vitro, BT317 had activity as a single agent but, more importantly, enhanced synergy with the standard of care commonly used chemotherapeutic temozolomide (TMZ). In orthotopic xenograft, patient derived glioma models, BT317 was able to cross the blood-brain barrier, to show selective activity at the tumor site and to demonstrate therapeutic efficacy both as a single agent and in combination with TMZ. BT317 defines an emerging class of dual LonP1, and CT-L proteasome inhibitors exhibited promising anti-tumor activity and could be a promising candidate for clinical translation in the space of malignant astrocytoma therapeutics.

Supporting the Resilience and Mental Health of Missouri Healthcare Workers Through COVID-19 and Beyond: the Gateway2Wellness Program.

The COVID-19 pandemic is over, but US healthcare workers (HCWs) continue to report high levels of work-related exhaustion and burnout but are unlikely to seek help. Digital tools offer a scalable solution. Between February and June 2022, we surveyed Missouri hospital administrators to assess HCW mental health and identify related evidence-based or evidence-informed resources. Simultaneously, we conducted a digital survey and focus groups with HCWs and leaders at Washington University School of Medicine (WUSOM) in St. Louis to evaluate HCW mental health needs, and preferences for digital support. Here, we describe the results and subsequent development of the Gateway to Wellness (G2W) program, a digital precision engagement platform that links HCWs to the most effective tailored resources for their mental health needs.

Elective surgery in ankle and foot disorders-best practices for management of pain: a guideline for clinicians.

PURPOSE: Complex elective foot and ankle surgeries are often associated with severe pain pre- and postoperatively. When inadequately managed, chronic postsurgical pain and long-term opioid use can result. As no standards currently exist, we aimed to develop best practice pain management guidelines. METHODS: A local steering committee (n = 16) surveyed 116 North American foot and ankle surgeons to understand the "current state" of practice. A multidisciplinary expert panel (n = 35) was then formed consisting of orthopedic surgeons, anesthesiologists, chronic pain physicians, primary care physicians, pharmacists, registered nurses, physiotherapists, and clinical psychologists. Each expert provided up to three pain management recommendations for each of the presurgery, intraoperative, inpatient postoperative, and postdischarge periods. These preliminary recommendations were reduced, refined, and sent to the expert panel and "current state" survey respondents to create a consensus document using a Delphi process conducted from September to December 2020. RESULTS: One thousand four hundred and five preliminary statements were summarized into 51 statements. Strong consensus (≥ 80% respondent agreement) was achieved in 53% of statements including the following: postsurgical opioid use risk should be assessed preoperatively; opioid-naïve patients should not start opioids preoperatively unless non-opioid multimodal analgesia fails; and if opioids are prescribed at discharge, patients should receive education regarding importance of tapering opioid use. There was no consensus regarding opioid weaning preoperatively. CONCLUSIONS: Using multidisciplinary experts and a Delphi process, strong consensus was achieved in many areas, showing considerable agreement despite limited evidence for standardized pain management in patients undergoing complex elective foot and ankle surgery. No consensus on important issues related to opioid prescribing and cessation highlights the need for research to determine best practice.

RéSUMé: OBJECTIF: Les chirurgies électives complexes du pied et de la cheville sont souvent associées à une douleur intense avant et après l'opération. Lorsque cette douleur est mal prise en charge, elle peut entraîner une douleur postopératoire chronique et une consommation d'opioïdes à long terme. Comme il n'existe actuellement aucune norme, nous avons cherché à élaborer des lignes directrices sur les meilleures pratiques en matière de prise en charge de la douleur. MéTHODE: Un comité directeur local (n = 16) a interrogé 116 chirurgiens nord-américains spécialistes du pied et de la cheville pour comprendre « l'état actuel ¼ de la pratique. Un groupe d'experts multidisciplinaire (n = 35) a ensuite été formé, composé de chirurgiens orthopédistes, d'anesthésiologistes, de médecins spécialistes de la douleur chronique, de médecins de soins primaires, de pharmaciens, d'infirmières autorisées, de physiothérapeutes et de psychologues cliniciens. Chaque expert a fourni jusqu'à trois recommandations de prise en charge de la douleur pour chacune des périodes suivantes : en préchirurgie, en peropératoire, pendant l'hospitalisation postopératoire et après le congé. Ces recommandations préliminaires ont été réduites, affinées et envoyées au groupe d'experts et aux répondants du sondage sur « l'état actuel ¼ afin de créer un document de consensus à l'aide d'une méthode de Delphi réalisée entre septembre et décembre 2020. RéSULTATS: Mille quatre cent cinq déclarations préliminaires ont été résumées en 51 énoncés. Un consensus fort (≥ 80 % des répondants étaient d'accord) a été atteint concernant 53 % des énoncés, notamment les suivants : le risque de consommation postopératoire d'opioïdes devrait être évalué avant l'opération; les patients naïfs aux opioïdes ne devraient pas commencer à prendre des opioïdes avant l'opération, à moins que l'analgésie multimodale non opioïde n'échoue; et si des opioïdes sont prescrits au congé, les patients devraient être informés de l'importance de réduire leur consommation d'opioïdes. Il n'y avait pas de consensus concernant le sevrage des opioïdes en période préopératoire. CONCLUSION: À l'aide d'experts multidisciplinaires et d'une méthode de Delphi, un fort consensus a été atteint dans de nombreux aspects, montrant un accord considérable malgré des données probantes limitées pour une prise en charge standardisée de la douleur chez les patients subissant une chirurgie élective complexe du pied et de la cheville. L'absence de consensus sur des questions importantes liées à la prescription et à l'interruption des opioïdes souligne la nécessité de recherches pour déterminer les pratiques exemplaires.

A prospective observational study of persistent opioid use after complex foot and ankle surgery.

PURPOSE: The incidence of persistent postsurgical opioid use (PPOU) after complex foot and ankle surgery is unknown. We aimed to determine the incidence and characteristics of PPOU in opioid-naïve, occasional, and regular opioid users at baseline and at six weeks, three months, and six months postoperatively. METHODS: We conducted a prospective observational study in patients undergoing complex foot and ankle surgery over an 18-month period. Daily opioid consumption was recorded at the indicated intervals. Logistic regression models were fit to predict the risk of opioid use at these intervals. The Brief Pain Inventory (BPI) was used to record pain intensity and interference. Correlations were tested between opioid use and BPI interference parameters. RESULTS: Eighty-two out of 139 consecutively approached patients were included in the final analysis. Six percent (98.3% confidence interval [CI], 2 to 20) of patients who were not using opioids preoperatively at baseline were using opioids daily at three and six months after surgery. Fifty percent (98.3% CI, 26 to 73) of patients who were regular opioid users preoperatively continued to use opioids daily six months after surgery. All associations between BPI interference parameters and opioid use were estimated to be positive. CONCLUSION: The probability of using opioid analgesia six months after complex foot and ankle surgery was significantly higher in patients who used opioids preoperatively. Regular preoperative opioid use was associated with a greater risk of PPOU compared with occasional or "as required" opioid use prior to surgery.

RéSUMé: OBJECTIF: L'incidence de consommation persistante d'opioïdes après une chirurgie (CPOC) après une chirurgie complexe du pied et de la cheville est inconnue. Notre objectif était de déterminer l'incidence et les caractéristiques de la CPOC chez les utilisateurs d'opioïdes naïfs, occasionnels et réguliers avant leur opération, puis à six semaines, trois mois et six mois après l'opération. MéTHODE: Nous avons réalisé une étude observationnelle prospective sur une période de 18 mois auprès de patients bénéficiant d'une chirurgie complexe du pied et de la cheville. La consommation quotidienne d'opioïdes a été enregistrée aux intervalles indiqués. Des modèles de régression logistique ont été utilisés pour prédire le risque de consommation d'opioïdes à ces intervalles. Le Questionnaire concis de la douleur (QCD - version française du Brief Pain Inventory, BPI) a été utilisé pour enregistrer l'intensité de la douleur et son interférence. Des corrélations ont été testées entre la consommation d'opioïdes et les paramètres d'interférence du QCD. RéSULTATS: Quatre-vingt-deux des 139 patients approchés consécutivement ont été inclus dans notre analyse finale. Six pour cent (intervalle de confiance [IC] à 98,3 %, 2 à 20) des patients qui ne consommaient pas d'opioïdes avant l'opération utilisaient des opioïdes quotidiennement trois et six mois après la chirurgie. Cinquante pour cent (IC 98,3 %, 26 à 73) des patients qui étaient des consommateurs réguliers d'opioïdes avant l'opération ont continué à utiliser des opioïdes quotidiennement six mois après la chirurgie. Toutes les associations entre les paramètres d'interférence du QCD et la consommation d'opioïdes ont été estimées positives. CONCLUSION: La probabilité d'avoir recours à une analgésie opioïde six mois après une chirurgie complexe du pied et de la cheville était significativement plus élevée chez les patients qui consommaient déjà des opioïdes avant leur opération. La consommation régulière d'opioïdes avant l'opération a été associée à un risque plus élevé de CPOC par rapport à l'utilisation occasionnelle ou « au besoin ¼ d'opioïdes avant la chirurgie.

REEF: Retainable Evaluator Execution Framework.

Resource Managers like Apache YARN have emerged as a critical layer in the cloud computing system stack, but the developer abstractions for leasing cluster resources and instantiating application logic are very low-level. This flexibility comes at a high cost in terms of developer effort, as each application must repeatedly tackle the same challenges (e.g., fault-tolerance, task scheduling and coordination) and re-implement common mechanisms (e.g., caching, bulk-data transfers). This paper presents REEF, a development framework that provides a control-plane for scheduling and coordinating task-level (data-plane) work on cluster resources obtained from a Resource Manager. REEF provides mechanisms that facilitate resource re-use for data caching, and state management abstractions that greatly ease the development of elastic data processing work-flows on cloud platforms that support a Resource Manager service. REEF is being used to develop several commercial offerings such as the Azure Stream Analytics service. Furthermore, we demonstrate REEF development of a distributed shell application, a machine learning algorithm, and a port of the CORFU [4] system. REEF is also currently an Apache Incubator project that has attracted contributors from several instititutions.