Influence of Different Powder Conditioning Strategies on Metal Binder Jetting with Ti-6Al-4V.

Metal binder jetting shows great potential for medical technology. This potential can be exploited by integrating binder jetting into existing process routes known from metal injection molding. The biggest challenge here is the flowability and packing behavior of the powders used, due to their low size distributions. This paper investigates different powder-drying strategies to improve flowability using a statistical experimental design. Because of its relevance for medical applications, spherical Ti-6Al-4V powder with a size distribution under 25 µm is dried under various parameters using vacuum and gas purging. The investigated parameters, time and temperature, are selected in a central-composite-circumscribed test plan with eleven tests and three center points. The target parameters-water content, flowability and impurity levels (oxygen, nitrogen)-of the powder are analyzed. For validation, practical test trials are carried out on an industrial binder jetting system with unconditioned powder and conditioning with optimized parameters, comparing the manufactured parts and the powder bed. An optimized drying cycle with a duration of 6 h at 200 °C was determined for the investigated powder. Significant improvements in the dimensional accuracy (from ±1.5 to 0.3%) of the components and the visual impression of the powder bed are demonstrated.

Predicting stress in first-year college students using sleep data from wearable devices.

Consumer wearables have been successful at measuring sleep and may be useful in predicting changes in mental health measures such as stress. A key challenge remains in quantifying the relationship between sleep measures associated with physiologic stress and a user's experience of stress. Students from a public university enrolled in the Lived Experiences Measured Using Rings Study (LEMURS) provided continuous biometric data and answered weekly surveys during their first semester of college between October-December 2022. We analyzed weekly associations between estimated sleep measures and perceived stress for participants (N = 525). Through mixed-effects regression models, we identified consistent associations between perceived stress scores and average nightly total sleep time (TST), resting heart rate (RHR), heart rate variability (HRV), and respiratory rate (ARR). These effects persisted after controlling for gender and week of the semester. Specifically, for every additional hour of TST, the odds of experiencing moderate-to-high stress decreased by 0.617 or by 38.3% (p<0.01). For each 1 beat per minute increase in RHR, the odds of experiencing moderate-to-high stress increased by 1.036 or by 3.6% (p<0.01). For each 1 millisecond increase in HRV, the odds of experiencing moderate-to-high stress decreased by 0.988 or by 1.2% (p<0.05). For each additional breath per minute increase in ARR, the odds of experiencing moderate-to-high stress increased by 1.230 or by 23.0% (p<0.01). Consistent with previous research, participants who did not identify as male (i.e., female, nonbinary, and transgender participants) had significantly higher self-reported stress throughout the study. The week of the semester was also a significant predictor of stress. Sleep data from wearable devices may help us understand and to better predict stress, a strong signal of the ongoing mental health epidemic among college students.

Addressing a Pre-Clinical Pipeline Gap: Development of the Pediatric Acute Myeloid Leukemia Patient-Derived Xenograft Program at Texas Children's Hospital at Baylor College of Medicine.

The survival rate of pediatric acute myeloid leukemia (pAML) is currently around 60%. While survival has slowly increased over the past few decades, the development of novel agents likely to further improve survival for this heterogeneous patient population has been limited by gaps in the pAML pre-clinical pipeline. One of the major hurdles in evaluating new agents for pAML is the lack of pAML patient-derived xenograft (PDX) models. Unlike solid tumors and other types of leukemias, AML is notoriously hard to establish in mouse models, likely due in part to the need for specific human microenvironment elements. Our laboratory at TCH/BCM addressed this gap by establishing a systematic PDX workflow, leveraging advanced immunodeficient hosts and capitalizing on our high volume of pAML patients and close coordination between labs and clinical sections. Patients treated at TCH are offered the chance to participate in specimen banking protocols that allow blood and bone marrow collection as well as the collection of relevant clinical data. All patients who consent and have samples available are trialed for PDX development. In addition, samples from the Children's Oncology Group (COG) are also trialed for PDX generation. Serially transplanting PDX models are validated using short tandem repeat (STR) and characterized using both targeted DNA/RNA next generation sequencing and RNAseq. As of March 2023, this systematic approach has resulted in 26 serially transplanting models. Models have been shared with requesting labs to facilitate external pAML pre-clinical studies. Available PDX models can be located through the BCM PDX Portal. We expect our growing PDX resource to make a significant contribution to expediting the testing of promising novel therapeutics for pAML.

Fetal Thymus Size at 19-22 Weeks of Gestation: A Possible Marker for the Prediction of Low Birth Weight?

INTRODUCTION: The purpose was to compare thymus size measured during second trimester screening of fetuses who were subsequently small for gestational age at birth (weight below 10th percentile, SGA group) with fetuses with normal birth weight (control group). We hypothesized that measuring the fetal thymic-thoracic ratio (TT-ratio) might help predict low birth weight. METHODS: Using three-vessel view echocardiograms from our archives, we measured the anteroposterior thymus size and the intrathoracic mediastinal diameter to derive TT-ratios in the SGA (n = 105) and control groups (n = 533) between 19+0 and 21+6 weeks of gestation. We analyzed the association between TT-ratio and SGA adjusted to the week of gestation using logistic regression. Finally, we determined the possible TT-ratio cut-off point for discrimination between SGA and control groups by means of receiver operating characteristics (ROC) curve analysis. RESULTS: The TT-ratio was significantly higher in the SGA group than in the control group (p < 0.001). An increase of the TT-ratio by 0.1 was associated with a 3.1-fold increase in the odds of diagnosing SGA. We determined that a possible discrimination cut-off point between SGA and healthy controls was achieved using a TT-ratio of 0.390 (area under the ROC curve 0.695). CONCLUSION: An increased TT-ratio may represent an additional prenatal screening parameter that improves the prediction of birth weight below the 10th percentile. Prospective studies are now needed to evaluate the use of fetal thymus size as predictive parameter for adverse fetal outcome.

Identifying Children in Foster Care and Improving Foster Care Documentation in Primary Care.

Background: Children and youth in foster care (CYFC) are a population with special healthcare needs, and the American Academy of Pediatrics has healthcare standards to care for this population, but implementation challenges include identifying clinic patients in foster care (FC). Documentation of FC status in the Electronic Health Record (EHR) can support the identification of CYFC to tailor care delivery. Therefore, we aimed to improve the percentage of CYFC with problem list (PL) documentation of FC status from 20% to 60% within 12 months. Methods: This study used a five-cycle plan-do-study-act quality improvement model in two co-located primary care teaching clinics. The primary outcome was the weekly percentage of patients with FC status on EHR PL. Ishikawa cause and effect analysis and resident survey identified barriers and informed interventions: education, patient list distribution, documentation training, email reminders, and clinic champion. We constructed statistical process control charts of the primary outcome to assess for improvement. Results: Mean weekly percentage of patients with FC status on PL improved from 19.8% to 60.2%. The most extensive improvements occurred after designating a clinic champion and providing email reminders with enhanced patient lists. The sustainability of PL documentation (mean = 71.7%) was demonstrated 3-4 years after the completion of plan-do-study-act cycle interventions. Conclusions: Educating providers, collaborating with child welfare to provide patient lists to providers, standardizing documentation, and designating clinic champions are promising methods of improving EHR documentation of FC status. Identifying and documenting FC status are important initial steps to optimizing care for this vulnerable population in primary care.

A large clinical trial to improve well-being during the transition to college using wearables: The lived experiences measured using rings study.

INTRODUCTION: The transition to college is a period of elevated risk for a range of mental health conditions. Although colleges and universities strive to provide mental health support to their students, the high demand for these services makes it difficult to provide scalable, cost-effective solutions. OBJECTIVE: To address these issues, the present study aims to compare the efficacy of three different treatments using a large cohort of 600 students transitioning to college. Interventions were selected based on their potential for generalizability and cost-effectiveness on college campuses. METHODS: The study is a Phase II parallel-group, four-arm, randomized controlled trial with 1:1 allocation that will assign 600 participants to one (n = 150 per condition) of four arms: 1) group-based therapy, 2) physical activity program, 3) nature experiences, or 4) weekly assessment condition as a control group. Physiological data will be collected from all participants using a wearable device to develop algorithmic mental and physical health functioning predictions. Once recruitment is complete, modeling strategies will be used to evaluate the outcomes and effectiveness of each intervention. DISCUSSION: The findings of this study will provide evidence as to the benefits of implementing scalable and proactive interventions using technology with the goal of improving the well-being and success of new college students.

Self-extinguishing relay waves enable homeostatic control of human neutrophil swarming.

Neutrophils exhibit self-amplified swarming to sites of injury and infection. How swarming is controlled to ensure the proper level of neutrophil recruitment is unknown. Using an ex vivo model of infection, we find that human neutrophils use active relay to generate multiple pulsatile waves of swarming signals. Unlike classic active relay systems such as action potentials, neutrophil swarming relay waves are self-extinguishing, limiting the spatial range of cell recruitment. We identify an NADPH-oxidase-based negative feedback loop that is needed for this self-extinguishing behavior. Through this circuit, neutrophils adjust the number and size of swarming waves for homeostatic levels of cell recruitment over a wide range of initial cell densities. We link a broken homeostat to neutrophil over-recruitment in the context of human chronic granulomatous disease.

Beliefs, attitudes and experiences of virtual overdose monitoring services from the perspectives of people who use substances in Canada: a qualitative study.

BACKGROUND: Solitary use of substances is a risk factor for substance use-related mortality. Novel e-health harm reduction interventions such as virtual overdose monitoring services (VOMS) have emerged in North America to improve access to emergency overdose support for people who use substances (PWUS). To date, little research has been published, and the perspectives of PWUS are needed to inform evaluation and policy efforts. OBJECTIVE: To explore the beliefs, values and perceptions of PWUS around using and accessing VOMS in Canada. METHODS: A qualitative study following grounded theory methodology was conducted. Using existing peer networks, purposive and snowball sampling was conducted to recruit PWUS (≥ 18 years) with previous experience with VOMS. Thematic analysis was used to analyze twenty-three interviews. Several methods were employed to enhance rigor, such as independent data coding and triangulation. RESULTS: Twenty-three one-on-one telephone interviews of PWUS with previous experience with VOMS were completed and analyzed. The following themes emerged: (1) feelings of optimism around VOMS to save lives; (2) privacy/confidentiality was highly valued due to stigma and fear of arrest; (3) concerns with reliable cell phones negatively impacting VOMS uptake; (4) concerns around emergency response times, specifically in rural/remote communities; (5) desire for trusting relationships with VOMS operators; (6) importance of mental health supports and referrals to psychosocial services; and (7) possible limited uptake due to low public awareness of VOMS. CONCLUSION: This qualitative study provided novel insights about the VOMS from the perspectives of PWUS. PWUS generally felt optimistic about the potential of VOMS as a suitable harm reduction intervention, but several potential barriers around accessing VOMS were identified that may limit uptake. Future research is warranted.

A preliminary assessment of food policy obstacles in California's produce recovery networks.

California is a landmark setting for studying produce recovery efforts and policy implications because of its global relevance in agricultural production, its complex network of food recovery organizations, and its environmental and public health regulations. Through a series of focus groups with organizations involved in produce recovery (gleaning organizations) and emergency food operations (food banks, food pantries), this study aimed to deepen our understanding of the current produce recovery system and determine the major challenges and opportunities related to the produce recovery system. Operational and systematic barriers to produce recovery were highlighted by both gleaning and emergency food operations. Operational barriers, such as the lack of appropriate infrastructure and limited logistical support were found to be a challenge across groups and were directly tied to inadequate funding for these organizations. Systematic barriers, such as regulations related to food safety or reducing food loss and waste, were also found to impact both gleaning and emergency food organizations, but differences were observed in how each type of regulation impacted each stakeholder group. To support the expansion of food recovery efforts, participants expressed need for better coordination within and across food recovery networks and more positive and transparent engagement from regulators to increase understanding of the specifics of their unique operational constraints. The focus group participants also provided critiques on how emergency food assistance and food recovery are inscribed within the current food system and for longer term goals of reducing food insecurity and food loss and waste a systematic change will be required.

Visualization of RNA virus infection in a marine protist with a universal biomarker.

Half of the marine virosphere is hypothesized to be RNA viruses (kingdom Orthornavirae) that infect abundant micro-eukaryotic hosts (e.g. protists). To test this, quantitative approaches that broadly track infections in situ are needed. Here, we describe a technique-dsRNA-Immunofluorescence (dsRIF)-that uses a double-stranded RNA (dsRNA) targeting monoclonal antibody to assess host infection status based on the presence of dsRNA, a replicative intermediate of all Orthornavirae infections. We show that the dinoflagellate Heterocapsa circularisquama produces dsRIF signal ~ 1000 times above background autofluorescence when infected by the + ssRNA virus HcRNAV. dsRNA-positive virocells were detected across > 50% of the 48-h infection cycle and accumulated to represent at least 63% of the population. Photosynthetic and chromosomal integrity remained intact during peak replication, indicating HcRNAV infection does not interrupt these processes. This work validates the use of dsRIF on marine RNA viruses and their hosts, setting the stage for quantitative environmental applications that will accelerate understanding of virus-driven ecosystem impacts.

Cortical thinning in relation to impaired insight into illness in patients with treatment resistant schizophrenia.

Impaired insight into illness is a common element of schizophrenia that contributes to treatment nonadherence and negative clinical outcomes. Previous studies suggest that impaired insight may arise from brain abnormalities. However, interpretations of these findings are limited due to small sample sizes and inclusion of patients with a narrow range of illness severity and insight deficits. In a large sample of patients with schizophrenia, the majority of which were designated as treatment-resistant, we investigated the associations between impaired insight and cortical thickness and subcortical volumes. A total of 94 adult participants with a schizophrenia spectrum disorder were included. Fifty-six patients (60%) had treatment-resistant schizophrenia. The core domains of insight were assessed with the VAGUS insight into psychosis scale. We obtained 3T MRI T1-weighted images, which were analysed using CIVET and MAGeT-Brain. Whole-brain vertex-wise analyses revealed impaired insight, as measured by VAGUS average scores, was related to cortical thinning in left frontotemporoparietal regions. The same analysis in treatment-resistant patients showed thinning in the same regions, even after controlling for age, sex, illness severity, and chlorpromazine antipsychotic dose equivalents. No association was found in non-treatment-resistant patients. Region-of-interest analyses revealed impaired general illness awareness was associated with cortical thinning in the left supramarginal gyrus when controlling for covariates. Reduced right and left thalamic volumes were associated with VAGUS symptom attribution and awareness of negative consequences subscale scores, respectively, but not after correction for multiple testing. Our results suggest impaired insight into illness is related to cortical thinning in left frontotemporoparietal regions in patients with schizophrenia, particularly those with treatment resistance where insight deficits may be more chronic.

USDA Nutrition Evidence Systematic Review's collaborative approach for conducting systematic reviews: Promoting diversity of expertise while managing potential conflicts of interest.

U.S. Department of Agriculture's (USDA) Nutrition Evidence Systematic Review (NESR) Branch develops food-and nutrition-related systematic reviews and other evidence synthesis products. NESR has established itself as a key resource for the Federal government when making evidence-informed decisions related to public health nutrition, such as the development of the Dietary Guidelines for Americans. NESR's systematic review methodology is rigorous, protocol-driven, and highly collaborative. NESR's systematic reviews examine the complex interplay between diet and health with input and support from various collaborators, including Federal stakeholders, expert groups, and public stakeholders. Implementing NESR's rigorous methodology ensures that the appropriate steps are taken to minimize conflict of interest, producing systematic reviews that are high-quality, trustworthy, and useful to end users who make decisions based on their findings. This article describes how NESR's systematic review process leverages a diversity of expertise and experience, while managing potential conflicts of interest. It describes the groups who collaborate to conduct NESR systematic reviews, their expertise, and why their involvement is critical for ensuring the rigor and utility of NESR's work.

Comparison of Perimetric Outcomes from a Tablet Perimeter, Smart Visual Function Analyzer, and Humphrey Field Analyzer.

PURPOSE: The tablet-based Melbourne Rapid Fields (MRF) visual field (VF) test and the IMOvifa Smart Visual Function Analyzer (SVFA) are portable perimeters that may allow for at-home monitoring and more frequent testing. We compared tablet and SVFA results with outputs from the Humphrey Field Analyzer (HFA) 24-2 Swedish Interactive Threshold Algorithm Standard program. DESIGN: Observational cross-sectional study. SUBJECTS: Adult participants with a diagnosis of glaucoma, suspected glaucoma, or ocular hypertension seen in the Massachusetts Eye and Ear glaucoma clinic were enrolled. All participants were reliable and experienced HFA testers. METHODS: Participants were tested with the SVFA and HFA. The study staff also trained participants on the MRF tablet with instructions to take weekly tests at home for 3 months. Visual field results from the 3 devices were compared. MAIN OUTCOME MEASURES: Mean deviation (MD), pattern standard deviation (PSD), reliability parameters, and point sensitivity. RESULTS: Overall, 79 participants (133 eyes) with a mean age of 61 ± 13 years (range, 26-79 years) were included; 59% of the participants were female, and the mean HFA MD was -2.7 ± 3.9 dB. The global indices of MD and PSD did not significantly vary between HFA and the 2 novel devices, except that the tablet VF reported a 0.6 dB higher PSD compared with HFA. However, tablet and SVFA sensitivities significantly differed from those of the HFA at 36 and 39 locations, respectively, out of 52 locations. Relative to HFA, the tablet overestimated light sensitivity in the nasal field while underestimating the temporal field. The SVFA generally underestimated light sensitivity, but its results were more similar to HFA results compared with the tablet. CONCLUSIONS: Although average MD values from the 2 novel devices suggest that they provide similar results to the HFA, point-by-point comparisons highlight notable deviations. Differences in specific point sensitivity values were significant, especially between the tablet and the other 2 devices. These differences may in part be explained by differences in the devices' normative databases as well as how MD is calculated. However, the tablet had substantial differences based on location, indicating that the tablet design itself may be responsible for differences in local sensitivities. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Visual Field Prediction: Evaluating the Clinical Relevance of Deep Learning Models.

Purpose: Two novel deep learning methods using a convolutional neural network (CNN) and a recurrent neural network (RNN) have recently been developed to forecast future visual fields (VFs). Although the original evaluations of these models focused on overall accuracy, it was not assessed whether they can accurately identify patients with progressive glaucomatous vision loss to aid clinicians in preventing further decline. We evaluated these 2 prediction models for potential biases in overestimating or underestimating VF changes over time. Design: Retrospective observational cohort study. Participants: All available and reliable Swedish Interactive Thresholding Algorithm Standard 24-2 VFs from Massachusetts Eye and Ear Glaucoma Service collected between 1999 and 2020 were extracted. Because of the methods' respective needs, the CNN data set included 54 373 samples from 7472 patients, and the RNN data set included 24 430 samples from 1809 patients. Methods: The CNN and RNN methods were reimplemented. A fivefold cross-validation procedure was performed on each model, and pointwise mean absolute error (PMAE) was used to measure prediction accuracy. Test data were stratified into categories based on the severity of VF progression to investigate the models' performances on predicting worsening cases. The models were additionally compared with a no-change model that uses the baseline VF (for the CNN) and the last-observed VF (for the RNN) for its prediction. Main Outcome Measures: PMAE in predictions. Results: The overall PMAE 95% confidence intervals were 2.21 to 2.24 decibels (dB) for the CNN and 2.56 to 2.61 dB for the RNN, which were close to the original studies' reported values. However, both models exhibited large errors in identifying patients with worsening VFs and often failed to outperform the no-change model. Pointwise mean absolute error values were higher in patients with greater changes in mean sensitivity (for the CNN) and mean total deviation (for the RNN) between baseline and follow-up VFs. Conclusions: Although our evaluation confirms the low overall PMAEs reported in the original studies, our findings also reveal that both models severely underpredict worsening of VF loss. Because the accurate detection and projection of glaucomatous VF decline is crucial in ophthalmic clinical practice, we recommend that this consideration is explicitly taken into account when developing and evaluating future deep learning models.

Resident Perceptions of Continuity Clinic Patient Metrics Differ From EHR Data: Pilot Use of Population Health Dashboards.

BACKGROUND AND OBJECTIVES: Population health management (PHM) dashboards using electronic health record (EHR) data can teach trainees about the population they serve while also delivering data on their clinical practice. Yet, few studies have demonstrated their use. In this pilot study, we assessed baseline resident perceptions of population health metrics for continuity clinic panels by comparing resident estimates with EHR-reported values delivered by individualized PHM dashboards. METHODS: A descriptive, comparative study was conducted at a primary continuity clinic site for pediatric residents in January 2018. Residents were surveyed about population health metrics for their patient panels, including demographics, utilization, and medical diagnoses. We compared resident estimates to corresponding EHR-reported values using 2-tailed paired t tests. RESULTS: A total of 42 out of 55 eligible residents (76%) completed the survey. Compared with EHR-reported values, residents estimated higher percentages of emergency department utilization (22.1% vs 10.3%, P < .01) and morbidity, including medical complexity (15.6% vs 5.9%, P < .01), overweight (38.1% vs 11.7%, P < .01), obesity (20.5% vs 15.8%, P = .02), and asthma (34.6% vs 21.4%, P < .01). CONCLUSIONS: In this pilot study of PHM dashboards, resident perceptions of continuity clinic population health metrics did not align with EHR data. Estimates were higher for measures of utilization and morbidity. PHM dashboards may help trainees better understand their patient populations and serve as a consistent source of objective practice data. However, further research and investment is needed to evaluate dashboard implementation and impact on trainee and patient outcomes.

Cataract progression after Nd:YAG laser iridotomy in primary angle-closure suspect eyes.

BACKGROUND/AIMS: Prophylactic laser peripheral iridotomy (LPI) is performed in primary angle-closure suspect (PACS) eyes to prevent acute angle-closure attacks. However, accelerated cataractogenesis is a potential risk of the procedure that may result in decreased visual acuity. We aimed to assess the long-term impact of LPI on cataract formation in Chinese PACS. METHODS: In the Zhongshan Angle Closure Prevention Trial, eligible bilateral PACS participants received LPI in one randomly selected eye, while the fellow eye remained untreated. Cataract was graded using the Lens Opacity Classification System III, and progression was defined as an increase in grade by at least two units in any category or cataract surgery. RESULTS: In total, 889 participants were randomly assigned to LPI in one eye only (mean age 59±5 years, 83% female). At 72 months, treated eyes had slightly higher average nuclear grades (p<0.001). However, there were no differences between eyes for predefined cataract progression (cumulative probability at 72 months: 21.2% in LPI vs 19.4% in control, p=0.401) or cataract surgery (1% for both). While LPI-treated eyes had a 10% higher risk of progression over 6 years (HR=1.10 (95% CI 0.88 to 1.36)), this was not statistically significant. Visual acuity at 72 months was similar in treated and untreated eyes (p=0.43). CONCLUSION: Although lenses were graded on average as slightly more opaque in laser-treated eyes, prophylactic neodymium:yttrium-aluminum-garnet LPI did not cause significant cataract progression. Our results suggest that LPI treatment of asymptomatic narrow angles does not increase the risk of developing clinically meaningful cataract worsening over time. TRIAL REGISTRATION NUMBER: ISRCTN45213099.

COVID-19 behavior determinants dataset.

The COVID-19 Behavior Determinants Database (http://covid19-database.com) is a research project that examined the sociodemographic and psychological determinants of COVID-19 related attitudes and behaviors. It is a comprehensive web-based survey that was administered to adults ages 18 or older (total n=8070) from the United States of America (n = 5326), including the four most populous states, specifically New York, California, Florida, and Texas, and Canada (n = 2744), including all provinces, except Quebec. The survey was collected at three timepoints, May 2020 (n=1019), July 2020 (n=4027), and March 2021 (n=3024). Participants provided detailed sociodemographic information and completed a battery of psychological assessments. Participants also provided information about prior testing for COVID-19 and perceived seriousness of COVID-19 and the need for current physical (social) distancing restrictions. The database is helpful to researchers and public health policy decision-makers who are interested in investigating and identifying the determinants of COVID-19 related attitudes and behaviors in North America.