Clinical Outcomes After Definitive Treatment of Soft Tissue Sarcoma of the Hand: A Retrospective Cohort Study of 109 Patients.

PURPOSE: The purpose of this study was to provide updated data on oncologic outcomes following definitive surgical treatment of soft tissue sarcoma of the hand in a cohort of 109 patients, as well as to characterize risk factors for poor oncologic and functional outcomes. METHODS: We analyzed data from 109 consecutive patients who had definitive surgical treatment for soft tissue sarcoma of the hand performed between 1996 and 2019 by a single surgeon at a sarcoma center. Primary outcomes included functional outcome (assessed by Musculoskeletal Tumor Society scores), disease-free survival (DFS), and overall survival (OS). We compiled descriptive data and used a multivariable linear model to identify factors associated with functional outcomes. Kaplan-Meier methods were used to estimate 5- and 10-year DFS and OS. RESULTS: Patients had a median age of 36 years at presentation. Median follow-up was 6.1 years among patients alive at the end of follow-up. The median Musculoskeletal Tumor Society score was 29; functional outcome was worse among patients with high-grade tumors or complications. Among the 107 patients who became disease-free, there were four local recurrences (one with metastasis), six distant recurrences, and one death without recurrence. All local recurrences were deep tumors (two myxofibrosarcoma and two myxoinflammatory fibrosarcoma). Estimated 5- and 10-year DFS rates were 89% (95% confidence interval [CI]: 83% to 96%) and 88% (95% CI: 80% to 95%). There were seven deaths, and the estimated 5- and 10-year OS rates were 95% (95% CI: 90% to 100%) and 92% (95% CI: 84% to 100%). Larger tumor size and higher stage at diagnosis were associated with shorter DFS and OS in univariable analyses; low event rates precluded multivariable analysis of survival. CONCLUSIONS: Aggressive disease-specific surgical and multidisciplinary treatment can yield long DFS and OS, and good functional outcomes. However, complications and high-grade tumors are associated with worse functional scores. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

The impact of climate change and related extreme weather on people with limb loss.

The human health consequences of climate change and extreme weather events are well documented. Published literature details the unique effects and necessary adaptation planning for people with physical disabilities in general; however, the specific impacts and plans for people with limb loss have yet to be explored. In this article, we discuss the impacts related to threats due to heat, cold, severe storms, and power outages. We describe how climate change uniquely affects people with limb loss and underscore the need for rehabilitation care providers and researchers to: (1) study the health impacts of climate change on people with lower limb loss; (2) educate themselves and patients on the climate crisis and climate preparedness; (3) co-develop resiliency strategies with patients, governments, and community organizations to improve adaptive capacity; and (4) advocate for policy changes that will enact protections for this at-risk population.

Clarifying the relationship between mental illness and recidivism using machine learning: A retrospective study.

OBJECTIVE: There is currently inconclusive evidence regarding the relationship between recidivism and mental illness. This retrospective study aimed to use rigorous machine learning methods to understand the unique predictive utility of mental illness for recidivism in a general population (i.e.; not only those with mental illness) prison sample in the United States. METHOD: Participants were adult men (n = 322) and women (n = 72) who were recruited from three prisons in the Midwest region of the United States. Three model comparisons using Bayesian correlated t-tests were conducted to understand the incremental predictive utility of mental illness, substance use, and crime and demographic variables for recidivism prediction. Three classification statistical algorithms were considered while evaluating model configurations for the t-tests: elastic net logistic regression (GLMnet), k-nearest neighbors (KNN), and random forests (RF). RESULTS: Rates of substance use disorders were particularly high in our sample (86.29%). Mental illness variables and substance use variables did not add predictive utility for recidivism prediction over and above crime and demographic variables. Exploratory analyses comparing the crime and demographic, substance use, and mental illness feature sets to null models found that only the crime and demographics model had an increased likelihood of improving recidivism prediction accuracy. CONCLUSIONS: Despite not finding a direct relationship between mental illness and recidivism, treatment of mental illness in incarcerated populations is still essential due to the high rates of mental illnesses, the legal imperative, the possibility of decreasing institutional disciplinary burden, the opportunity to increase the effectiveness of rehabilitation programs in prison, and the potential to improve meaningful outcomes beyond recidivism following release.

Use Intention and User Expectations of Human-Supported and Self-Help eHealth Interventions: Internet-Based Randomized Controlled Trial.

BACKGROUND: Self-help eHealth interventions provide automated support to change health behaviors without any further human assistance. The main advantage of self-help eHealth interventions is that they have the potential to lower the workload of health care professionals. However, one disadvantage is that they generally have a lower uptake. Possibly, the absence of a relationship with a health care professional (referred to as the working alliance) could lead to negative expectations that hinder the uptake of self-help interventions. The Unified Theory of Acceptance and Use of Technology (UTAUT) identifies which expectations predict use intention. As there has been no previous research exploring how expectations affect the adoption of both self-help and human-supported eHealth interventions, this study is the first to investigate the impact of expectations on the uptake of both kinds of eHealth interventions. OBJECTIVE: This study investigated the intention to use a self-help eHealth intervention compared to a human-supported eHealth intervention and the expectations that moderate this relationship. METHODS: A total of 146 participants were randomly assigned to 1 of 2 conditions (human-supported or self-help eHealth interventions). Participants evaluated screenshots of a human-supported or self-help app-based stress intervention. We measured intention to use the intervention-expected working alliance and the UTAUT constructs: performance expectancy, effort expectancy, and social influence. RESULTS: Use intention did not differ significantly between the 2 conditions (t142=-1.133; P=.26). Performance expectancy (F1,140=69.269; P<.001), effort expectancy (F1,140=3.961; P=.049), social influence (F1,140=90.025; P<.001), and expected working alliance (F1,140=26.435; P<.001) were positively related to use intention regardless of condition. The interaction analysis showed that performance expectancy (F1,140=4.363; P=.04) and effort expectancy (F1,140=4.102; P=.045) more strongly influenced use intention in the self-help condition compared to the human-supported condition. CONCLUSIONS: As we found no difference in use intention, our results suggest that we could expect an equal uptake of self-help eHealth interventions and human-supported ones. However, attention should be paid to people who have doubts about the intervention's helpfulness or ease of use. For those people, providing additional human support would be beneficial to ensure uptake. Screening user expectations could help health care professionals optimize self-help eHealth intervention uptake in practice. TRIAL REGISTRATION: OSF Registries osf.io/n47cz; https://osf.io/n47cz.

Human cues in eHealth to promote lifestyle change: An experimental field study to examine adherence to self-help interventions.

eHealth lifestyle interventions without human support (self-help interventions) are generally less effective, as they suffer from lower adherence levels. To solve this, we investigated whether (1) using a text-based conversational agent (TCA) and applying human cues contribute to a working alliance with the TCA, and whether (2) adding human cues and establishing a positive working alliance increase intervention adherence. Participants (N = 121) followed a TCA-supported app-based physical activity intervention. We manipulated two types of human cues: visual (ie, message appearance) and relational (ie, message content). We employed a 2 (visual cues: yes, no) x 2 (relational cues: yes, no) between-subjects design, resulting in four experimental groups: (1) visual and relational cues, (2) visual cues only, (3) relational cues only, or (4) no human cues. We measured the working alliance with the Working Alliance Inventory Short Revised form and intervention adherence as the number of days participants responded to the TCA's messages. Contrary to expectations, the working alliance was unaffected by using human cues. Working alliance was positively related to adherence (t(78) = 3.606, p = .001). Furthermore, groups who received visual cues showed lower adherence levels compared to those who received relational cues only or no cues (U = 1140.5, z = -3.520, p < .001). We replicated the finding that establishing a working alliance contributes to intervention adherence, independently of the use of human cues in a TCA. However, we were unable to show that adding human cues impacted the working alliance and increased adherence. The results indicate that adding visual cues to a TCA may even negatively affect adherence, possibly because it may create confusion concerning the true nature of the coach, which may prompt unrealistic expectations.

The development of rating scales to evaluate experiential prosthetic foot preference for people with lower limb amputation.

BACKGROUND: Selection of a foot is an important aspect of prosthetic prescription and vital to maximizing mobility and functional goals after lower limb amputation. Development of a standardized approach to soliciting user experiential preferences is needed to improve evaluation and comparison of prosthetic feet. OBJECTIVE: To develop rating scales to assess prosthetic foot preference and to evaluate use of these scales in people with transtibial amputation after trialing different prosthetic feet. DESIGN: Participant-blinded, repeated measures crossover trial. SETTING: Veterans Affairs and Department of Defense Medical Centers, laboratory setting. PARTICIPANTS: Seventy-two male prosthesis users with unilateral transtibial amputation started, and 68 participants completed this study. INTERVENTIONS: Participants trialed three mobility-level appropriate commercial prosthetic feet briefly in the laboratory. MAIN OUTCOME MEASURES: "Activity-specific" rating scales were developed to assess participants' ability with a given prosthetic foot to perform typical mobility activities (eg, walking at different speeds, on inclines, and stairs) and "global" scales to rate overall perceived energy required to walk, satisfaction, and willingness to regularly use the prosthetic foot. Foot preference was determined by comparing the rating scale scores, after laboratory testing. RESULTS: The greatest within-participant differences in scores among feet were observed in the "incline" activity, where 57% ± 6% of participants reported 2+ point differences. There was a significant association (p < .05) between all "activity-specific" rating scores (except standing) and each "global" rating score. CONCLUSIONS: The standardized rating scales developed in this study could be used to assess prosthetic foot preference in both the research and clinical settings to guide prosthetic foot prescription for people with lower limb amputation capable of a range of mobility levels.

Less stick more carrot? Increasing the uptake of deposit contract financial incentives for physical activity: A randomized controlled trial.

BACKGROUND: Financial incentives are a promising tool to help people increase their physical activity, but they are expensive to provide. Deposit contracts are a type of financial incentive in which participants pledge their own money. However, low uptake is a crucial obstacle to the large-scale implementation of deposit contracts. Therefore, we investigated whether (1) matching the deposit 1:1 (doubling what is deposited) and (2) allowing for customizable deposit amounts increased the uptake and short term effectiveness of a deposit contract for physical activity. METHODS: In this randomized controlled trial, 137 healthy students (age M = 21.6 years) downloaded a smartphone app that provided them with a tailored step goal and then randomized them to one of four experimental conditions. The deposit contract required either a €10 fixed deposit or a customizable deposit with any amount between €1 and €20 upfront. Furthermore, the deposit was either not matched or 1:1 matched (doubled) with a reward provided by the experiment. During 20 intervention days, daily feedback on goal progress and incentive earnings was provided by the app. We investigated effects on the uptake (measured as agreeing to participate and paying the deposit) and effectiveness of behavioral adoption (measured as participant days goal achieved). FINDINGS: Overall, the uptake of deposit contracts was 83.2%, and participants (n = 113) achieved 14.9 out of 20 daily step goals. A binary logistic regression showed that uptake odds were 4.08 times higher when a deposit was matched (p = .010) compared to when it was not matched. Furthermore, uptake odds were 3.53 times higher when a deposit was customizable (p = .022) compared to when it was fixed. Two-way ANCOVA showed that matching (p = .752) and customization (p = .143) did not impact intervention effectiveness. However, we did find a marginally significant interaction effect of deposit matching X deposit customization (p = .063, ηp2 = 0.032). Customization decreased effectiveness when deposits were not matched (p = .033, ηp2 = 0.089), but had no effect when deposits were matched (p = .776, ηp2 = 0.001). CONCLUSIONS: We provide the first experimental evidence that both matching and customization increase the uptake of a deposit contract for physical activity. We recommend considering both matching and customization to overcome lack of uptake, with a preference for customization since matching a deposit imposes significant additional costs. However, since we found indications that customizable deposits might reduce effectiveness (when the deposits are not matched), we urge for more research on the effectiveness of customizable deposit contracts. Finally, future research should investigate which participant characteristics are predictive of deposit contract uptake and effectiveness. PRE-REGISTRATION: OSF Registries, https://osf.io/cgq48.

Reducing low-value ED coags across 11 hospitals in a safety net setting.

BACKGROUND: Prothrombin/international normalized ratio and activated partial thromboplastin time (PT/INR and aPTT) are frequently ordered in emergency departments (EDs), but rarely affect management. They offer limited utility outside of select indications. Several quality improvement initiatives have shown reduction in ED use of PT/INR and aPTT using multifaceted interventions in well-resourced settings. Successful reduction of these low-value tests has not yet been shown using a single intervention across a large hospital system in a safety net setting. This study aims to determine if an intervention of two BPAs is associated with a reduction in PT/INR and aPTT usage across a large safety net system. METHODS: This initiative was set at a large safety net system in the United States with 11 acute care hospitals. Two Best Practice Advisories (BPAs) discouraging inappropriate PT/INR and aPTT use were implemented from March 16, 2022-August 30, 2022. Order rate per 100 ED patients during the pre-intervention period was compared to the post-intervention period on both the system and individual hospital level. Complete blood count (CBC) testing served as a control, and packed red blood cell transfusions served as a balancing measure. An interrupted time series regression analysis was performed to capture immediate and temporal changes in ordering for all tests in the pre and post-intervention periods. RESULTS: PT/INR tests exhibited an absolute decline of 4.11 tests per 100 ED encounters (95% confidence interval -5.17 to -3.05; relative reduction of 18.9%). aPTT tests exhibited absolute decline of 4.03 tests per 100 ED encounters (95% CI -5.10 to -2.97; relative reduction of 19.8%). The control measure, CBC, did not significantly change (-0.43, 95% CI -2.83 to 1.96). Individual hospitals showed variable response, with absolute reductions from 2.02 to 9.6 tests per 100 ED encounters for PT/INR (relative reduction 12.1%-30.5%) and 2.07 to 10.04 for aPTT (relative reduction 12.1%-31.4%). Regression analysis showed that the intervention caused an immediate 25.7% decline in PT/INR and 24.7% decline in aPTT tests compared to the control measure. The slope differences (rate of order increase pre vs post intervention) did not significantly decline compared to the control. CONCLUSIONS: This BPA intervention reduced PT/INR and aPTT use across 11 EDs in a large, urban, safety net system. Further study is needed in implementation to other non-safety net settings.

Effectiveness of Human-Supported and Self-Help eHealth Lifestyle Interventions for Patients With Cardiometabolic Risk Factors: A Meta-Analysis.

OBJECTIVE: eHealth is a useful tool to deliver lifestyle interventions for patients with cardiometabolic diseases. However, there are inconsistent findings about whether these eHealth interventions should be supported by a human professional, or whether self-help interventions are equally effective. METHODS: Databases were searched between January 1995 and October 2021 for randomized controlled trials on cardiometabolic diseases (cardiovascular disease, chronic kidney disease, type 1 and 2 diabetes mellitus) and eHealth lifestyle interventions. A multilevel meta-analysis was used to pool clinical and behavioral health outcomes. Moderator analyses assessed the effect of intervention type (self-help versus human-supported), dose of human support (minor versus major part of intervention), and delivery mode of human support (remote versus blended). One hundred seven articles fulfilled eligibility criteria and 102 unique ( N = 20,781) studies were included. RESULTS: The analysis showed a positive effect of eHealth lifestyle interventions on clinical and behavioral health outcomes ( p < .001). However, these effects were not moderated by intervention type ( p = .169), dose ( p = .698), or delivery mode of human support ( p = .557). CONCLUSIONS: This shows that self-help eHealth interventions are equally effective as human-supported ones in improving health outcomes among patients with cardiometabolic disease. Future studies could investigate whether higher-quality eHealth interventions compensate for a lack of human support.Meta-analysis registration: PROSPERO CRD42021269263 .

Reconstruction of oncologic upper extremity defects with fibula free flaps has high union rates and excellent functional outcomes.

BACKGROUND: Limb salvage has better functional outcomes than amputation in the upper extremity. This can however be challenging after bony tumor resections. METHODS: This is a retrospective case series of patients who underwent humerus, ulna, or radius reconstruction with a fibula free flap. Data were collected on demographics, oncologic history, surgical details, and complications. Functional outcome measures included the patient's ability to perform activities of daily living (ADL), presence of pain, and musculoskeletal tumor society (MSTS) score. RESULTS: Over a 25-year period, 38 reconstructions were performed. The flap success rate was 97.5%. Bony union was obtained in 19 of 19 (100%) forearm reconstructions and in 15 of 19 (79%) humerus reconstructions (p = 0.10). All 19 forearm reconstruction patients and 18/19 humerus reconstruction patients were able to perform ADLs with no pain or only occasional pain. The MSTS scores were not significantly different between the humerus and forearm cohorts (27.1 vs. 27.3, p = 0.68). Functional outcomes were significantly better in limbs that achieved union (p < 0.001). Recipient and donor site complications occurred in 10 (26.3%) and 5 (13%) patients, respectively. CONCLUSIONS: Oncologic upper-extremity reconstruction with fibula free flaps has excellent functional outcomes. Bone union is a predictor of superior limb function.

Repair of a Tractional Retinal Detachment in the Setting of an Idiopathic Vasoproliferative Tumor.

Vasoproliferative tumors (VPT) are benign retinal lesions that may cause epiretinal membrane proliferation and tractional retinal detachments (TRD). We describe a case of a 71-year-old woman who presented with a macula involving TRD in the setting of a VPT. Given the limited number of publications on the management of these cases, we aim to articulate some principles we believe may be helpful in planning a surgical approach that maximizes postoperative anatomic and functional outcomes. We hope that our video provides useful guidance in preparing the vitreoretinal surgeon for managing this uncommon entity. [Ophthalmic Surg Lasers Imaging Retina 2023;54:485-488.].

A National Voter Registration Campaign.

Research suggests that increased voting among adults is associated with improved child health. Despite the benefits of voting, the United States has low voter turnout compared with peer nations. Turnout is especially low among marginalized people in the United States. Voter registration is essential for increasing voter turnout, and registration efforts have been successfully carried out in clinical settings. Working with a nonprofit called Vot-ER, we advocated for nonpartisan voter registration efforts in pediatric settings nationwide preceding the November 2020 US elections. We describe lessons learned from these efforts. Using data obtained from Vot-ER, we also provide the first estimates of participation in a national voter registration campaign in pediatric settings. There was widespread engagement in voter registration efforts among pediatricians in 2020. Many lessons were learned from these efforts, including the benefits of advanced planning because registration deadlines can be up to 1 month in advance of Election Day. Obtaining buy-in from numerous stakeholders (e.g., health center leadership, public relations teams) supports widespread staff participation. Also important is to consider the tradeoffs between active voter registration (in which staff can broach the topic of voting with patients and families) and passive efforts (in which voting is discussed only if patients or families inquire about it). These and other lessons can inform future voter registration efforts in diverse pediatric settings across the country.

Anxiety and Depression Treatment in Primary Care Pediatrics.

BACKGROUND AND OBJECTIVES: Primary care pediatricians (PCP) are often called on to manage child and adolescent anxiety and depression. The objective of this study was to describe PCP care practices around prescription of selective serotonin reuptake inhibitors (SSRI) for patients with anxiety and/or depression by using medical record review. METHODS: We identified 1685 patients who had at least 1 visit with a diagnosis of anxiety and/or depression in a large primary care network and were prescribed an SSRI by a network PCP. We randomly selected 110 for chart review. We reviewed the visit when the SSRI was first prescribed (medication visit), immediately previous visit, and immediately subsequent visit. We abstracted rationale for prescribing medication, subspecialist involvement, referral for psychotherapy, and medication monitoring practices. RESULTS: At the medication visit, in 82% (n = 90) of cases, PCPs documented reasons for starting an SSRI, most commonly clinical change (57%, n = 63). Thirty percent (n = 33) of patients had documented involvement of developmental-behavioral pediatrics or psychiatry subspecialists at 1 of the 3 visits reviewed. Thirty-three percent (n = 37) were referred to unspecified psychotherapy; 4% (n = 4) were referred specifically for cognitive behavioral therapy. Of 69 patients with a subsequent visit, 48% (n = 33) had documentation of monitoring for side effects. CONCLUSIONS: When prescribing SSRIs for children with anxiety and/or depression, PCPs in this network documented appropriate indications for starting medication and prescribed without subspecialist involvement. Continuing medical education for PCPs who care for children with these conditions should include information about evidence-based psychotherapy and strategies for monitoring potential side effects.

Reduction in cycle time for a rapid polymerase chain reaction diagnostic test at the point of care.

Background: Rapid testing facilitates safe and effective diagnosis, but the true speed of the process is the time from collection of a sample to delivery of an accurate and reliable test result - 'end-to-end' time. Transport, unpacking and relaying of information can extend this time considerably beyond the minimum laboratory turnaround times as stipulated by PCR testing protocols. Aim/Objective: This study aimed to minimise time needed to ascertain SARS-CoV-2 status prior to treatment in a UK Dental Hospital using a novel, mobile, direct to polymerase chain reaction (PCR) workflow. Methods: Process flow analysis and PDSA (Plan, Do, Study, Act) cycles for rapid continuous improvement were employed in a service improvement programme. Primerdesign™ q16 rapid PCR instruments and PROmate® COVID-19 direct assays were used for molecular testing. Findings/Results: We showed a reduction in real-world end-to-end time for a diagnostic test from 240 min to 85 min (65% reduction) over a 4-week period. Discussion: New rapid technologies have become available that reduce analytical time to under 90 min, but the real-world clinical implementation of the test requires a fully integrated workflow from clinic to reporting.

Two unique BAP1 pathogenic variants identified in the same family by panel cascade testing.

Germline pathogenic variants in the tumor suppressor gene BAP1 are associated with the hereditary tumor predisposition syndrome with susceptibility to uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other cancers. Germline BAP1 pathogenic variants are rare in the non-cancer general population with an estimated carrier frequency of 1:19,898 but more common in cancer patients with a carrier frequency of 1:1299. In the following we present the first report of a family with two unique BAP1 pathogenic variants. Retrospective case report of a family with two unique pathogenic variants in BAP1. A male (proband) was referred to our ocular oncology clinic for second opinion for his multiple independent uveal melanomas at ages 65, 68 and 71. Given his personal history of squamous cell carcinoma at age 61, renal cell carcinoma at age 63, and family history of atypical meningioma, basal cell carcinoma, pancreatic and prostate cancers he was assessed for germline pathogenic variants in BAP1 through our ongoing research study. Sanger sequencing identified the American founder pathogenic variant, c.1717delC, pL573Wfs*3, that was confirmed in a clinical laboratory. Both the proband's brother and nephew tested negative for the familial variant through single site cascade genetic testing. However, based on the personal history of multiple basal cell carcinoma in the nephew and family history of pancreatic and laryngeal cancers (both not known to be associated with BAP1-TPDS), a large cancer panel testing was recommended for the nephew. His panel testing revealed a different BAP1 pathogenic variant, c.605G>A, p. Trp202*. This variant was not detected in the proband or the proband's brother. Based on the frequency of germline BAP1 variants in the cancer population, the chance of occurrence of two different BAP1 variants in a family with cancer history is 5.9 × 10-7. This case report provides support for the importance of offering large panel cascade genetic testing, rather than single site testing for only the family pathogenic variant, for all at risk family members especially when the family variant cannot explain all the cancers in the family.

Hyperpigmented epiretinal membrane in macular telangiectasia type 2: imaging characteristics and correlation with transretinal pigment migration.

OBJECTIVES: To explore the features of black hyperpigmentation in macular telangiectasia (MacTel) type 2 and correlate these findings with the characteristics of hyperpigmented epiretinal membranes (ERMs) using multimodal imaging. METHODS: A case series of three patients with MacTel type 2 and hyperpigmented ERMs imaged with colour fundus photography, fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT) and swept-source OCT angiography. Registration of different types of imaging was done using ImageJ v1.53f51 (National Institutes of Health, USA). RESULTS: Three female patients with late-stage MacTel type 2 presented with unilateral hyperpigmented ERMs in the absence of peripheral retinal breaks. In one patient, an extensive ERM occurred along with a full-thickness macular hole (FTMH); in 2 patients, smaller ERMs were seen adjacent to superficial retinal veins. Serial imaging demonstrated that transretinal pigment migration preceded epiretinal proliferation of the hyperpigmented ERM towards superficial retinal veins. CONCLUSION: Hyperpigmented ERMs may occur in the late phases of MacTel type 2 following a FTMH or transretinal migration of pigmented cells to the retinal surface. Once on the retinal surface, black pigment cells seem to proliferate centripetally toward superficial retinal veins.

Immunometabolic Analysis of Synovial Fluid from Juvenile Idiopathic Arthritis Patients.

Juvenile idiopathic arthritis (JIA) is an inflammatory rheumatic disorder. Polymorphonuclear neutrophils (PMNs) are present in JIA synovial fluid (SF), but with variable frequency. SF PMNs in JIA were previously shown to display high exocytic but low phagocytic and immunoregulatory activities. To further assess whether the degree of SF neutrophilia associated with altered immune responses in JIA, we collected SF and blood from 16 adolescent JIA patients. SF and blood leukocytes were analyzed by flow cytometry. SF and plasma were used for immune mediator quantification and metabolomics. Healthy donor blood T cells were cultured in SF to evaluate its immunoregulatory activities. PMN and T cell frequencies were bimodal in JIA SF, delineating PMN high/T cell low (PMNHigh) and PMN low/T cell high (PMNLow) samples. Proinflammatory mediators were increased in SF compared with plasma across patients, and pro- and anti-inflammatory mediators were further elevated in PMNHigh SF. Compared to blood, SF PMNs showed increased exocytosis and programmed death-1/programmed death ligand-1 expression, and SF PMNs and monocytes/macrophages had increased surface-bound arginase-1. SPADE analysis revealed SF monocyte/macrophage subpopulations coexpressing programmed death-1 and programmed death ligand-1, with higher expression in PMNHigh SF. Healthy donor T cells showed reduced coreceptor expression when stimulated in PMNHigh versus PMNLow SF. However, amino acid metabolites related to the arginase-1 and IDO-1 pathways did not differ between the two groups. Hence, PMN predominance in the SF of a subset of JIA patients is associated with elevated immune mediator concentration and may alter SF monocyte/macrophage phenotype and T cell activation, without altering immunoregulatory amino acids.

Investigating Rewards and Deposit Contract Financial Incentives for Physical Activity Behavior Change Using a Smartphone App: Randomized Controlled Trial.

BACKGROUND: Financial incentive interventions for improving physical activity have proven to be effective but costly. Deposit contracts (in which participants pledge their own money) could be an affordable alternative. In addition, deposit contracts may have superior effects by exploiting the power of loss aversion. Previous research has often operationalized deposit contracts through loss framing a financial reward (without requiring a deposit) to mimic the feelings of loss involved in a deposit contract. OBJECTIVE: This study aimed to disentangle the effects of incurring actual losses (through self-funding a deposit contract) and loss framing. We investigated whether incentive conditions are more effective than a no-incentive control condition, whether deposit contracts have a lower uptake than financial rewards, whether deposit contracts are more effective than financial rewards, and whether loss frames are more effective than gain frames. METHODS: Healthy participants (N=126) with an average age of 22.7 (SD 2.84) years participated in a 20-day physical activity intervention. They downloaded a smartphone app that provided them with a personalized physical activity goal and either required a €10 (at the time of writing: €1=US $0.98) deposit up front (which could be lost) or provided €10 as a reward, contingent on performance. Daily feedback on incentive earnings was provided and framed as either a loss or gain. We used a 2 (incentive type: deposit or reward) × 2 (feedback frame: gain or loss) between-subjects factorial design with a no-incentive control condition. Our primary outcome was the number of days participants achieved their goals. The uptake of the intervention was a secondary outcome. RESULTS: Overall, financial incentive conditions (mean 13.10, SD 6.33 days goal achieved) had higher effectiveness than the control condition (mean 8.00, SD 5.65 days goal achieved; P=.002; ηp2=0.147). Deposit contracts had lower uptake (29/47, 62%) than rewards (50/50, 100%; P<.001; Cramer V=0.492). Furthermore, 2-way analysis of covariance showed that deposit contracts (mean 14.88, SD 6.40 days goal achieved) were not significantly more effective than rewards (mean 12.13, SD 6.17 days goal achieved; P=.17). Unexpectedly, loss frames (mean 10.50, SD 6.22 days goal achieved) were significantly less effective than gain frames (mean 14.67, SD 5.95 days goal achieved; P=.007; ηp2=0.155). CONCLUSIONS: Financial incentives help increase physical activity, but deposit contracts were not more effective than rewards. Although self-funded deposit contracts can be offered at low cost, low uptake is an important obstacle to large-scale implementation. Unexpectedly, loss framing was less effective than gain framing. Therefore, we urge further research on their boundary conditions before using loss-framed incentives in practice. Because of limited statistical power regarding some research questions, the results of this study should be interpreted with caution, and future work should be done to confirm these findings. TRIAL REGISTRATION: Open Science Framework Registries osf.io/34ygt; https://osf.io/34ygt.

Bioaccumulation Screening of Neutral Hydrophobic Organic Chemicals in Air-Breathing Organisms Using In Vitro Rat Liver S9 Biotransformation Assays.

To advance methods for bioaccumulation assessment of organic substances in air-breathing organisms, the present study developed an in vitro approach for screening neutral hydrophobic organic substances for their bioaccumulation potential in air-breathing organisms consisting of (1) depletion assays for chemicals in rat liver S9 subcellular fractions, (2) in vitro-in vivo extrapolation, and (3) whole-organism bioaccumulation modeling to assess the biomagnification potential of neutral organic substances in the rat. Testing of the in vitro method on 14 test chemicals of potentially biomagnifying substances showed that the bioassays could be conducted with a high level of reproducibility and that in vitro-derived elimination rate constants were in good agreement with in vivo-determined elimination rate constants in the rat. Exploring the potential of the in vitro approach for screening organic chemicals for bioaccumulation in air-breathing organisms indicated that chemical substances that exhibit a depletion rate constant in the S9 in vitro bioassay ≥0.3 h-1 are not expected to biomagnify in rats independent of their octanol-water partitioning coefficient (KOW ) or octanol-air partitioning coefficient (KOA ). The high level of reproducibility achieved in the test, combined with the good agreement between in vitro-derived and in vivo-determined depuration rates, suggests that the in vitro approach in combination with a KOA - and KOW -based screening approach has good potential for screening chemicals in commerce for their bioaccumulation potential in air-breathing organisms in a cost-effective and expedient manner, especially if the bioassay can be automated. Environ Toxicol Chem 2022;41:2565-2579. © 2022 SETAC.