Seattle University

Biotherapy offers a promising approach for treating a variety of diseases. However, the lack of advanced delivery systems remains a significant barrier to improve the efficacy, safety, and cost‐effectiveness of biotherapeutics. The microneedle, as a minimally invasive drug delivery tool, has demonstrated considerable potential in biotherapeutic applications. Despite this promise, challenges remain in fabricating microneedles that effectively preserve the bioactivity of biotherapeutics. Emerging as a novel solution, cryomicroneedles (cryoMNs) employ cryogenically molded ice matrices that exploit phase‐transition thermodynamics. The metabolic stasis induced by cryoimmobilization preserves biomolecular conformation and cellular viability. Moreover, the ice‐reinforced architectures achieve an optimal balance between mechanical penetration capacity and post‐insertion dissolution kinetics, overcoming the rigidity‐flexibility trade‐off in traditional dissolving microneedles. Current research prioritizes three breakthrough directions: material innovation for cryocompatible polymer‐ice interfaces, cold‐chain optimization strategies to enhance payload viability, and innovations in medical application scenarios. Notably, preclinical successes in regenerative tissue engineering and thermostable vaccine platforms highlight cryoMNs’ potential to bridge precision medicine and global health equity. This review provides an overview of recent advancements in cryoMNs and discusses the potential challenges and future directions for the development of cryoMNs‐mediated biotherapeutics delivery.

Objective Administrative claims are used to evaluate oral glucocorticoid use in rheumatoid arthritis (RA), despite limited evidence to support accuracy. We aimed to evaluate the performance of claims‐based algorithms for glucocorticoid use compared to self‐report in an RA population. Methods Participants with RA enrolled at 7 VA Rheumatoid Arthritis (VARA) registry sites were asked six questions as part of clinical care assessing current prednisone use and dose, recent use, “stockpiling”, and receiving prednisone outside VA. Algorithms using VA prescription claims operationalized current use (active prescription on date of self‐report assessment), current dose (that prescription's mean dose), and recent use (active course overlapping the prior 30 or 90 days). We assessed performance characteristics and agreement, benchmarked on self‐report. Results Of 284 participants, 13% reported current prednisone use and 20% reported 90‐day use. Sensitivity, specificity, PPV and NPV were 0.70, 0.98, 0.84, and 0.96 for current use, and 0.71, 0.92, 0.72, and 0.92 for 90‐day use. Cohen's kappa was 0.68 for current use and 0.63 for 90‐day use. Among participants reporting ≤5mg/day, agreement for dose was high (weighted kappa 0.67). One in 4 participants reported a stockpile, and 1 in 4 reported receiving prednisone from a non‐VA provider. Conclusions Algorithms derived from VA claims detecting prednisone prescriptions have high validity compared to patient self‐report. The modest sensitivity of these algorithms may reflect stockpiling and non‐VA prescriptions. These findings form a basis for contextualizing real‐world studies of glucocorticoid use in RA and improve clinical estimation of glucocorticoid use not captured in claims.

Importance Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population. Objective To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method. Design, Setting, and Participants Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection. Exposures Participants were required to complete a screening colonoscopy after blood collection. Main Outcomes and Measures The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions. Results The median age of participants in the evaluable cohort (n = 27 010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion. Conclusions and Relevance In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity. Trial Registration ClinicalTrials.gov Identifier: NCT04369053

Multicenter studies describing electrocardiogram (ECG) patterns in children presenting with anomalous left coronary artery from the pulmonary artery (ALCAPA), to our knowledge, have not been published. This study aimed to describe the ECG findings at presentation and over time in a multicenter cohort of children with ALCAPA and assess their association with clinical outcomes. We performed a retrospective ECG analysis of 188 patients with ALCAPA who presented between 1/2009 and 3/2018 at 21 centers affiliated with Collaborative Research for the Pediatric Cardiac Intensive Care Society. ECGs were categorized apriori as Classic (pathologic Q waves in anterolateral leads), non-classic (abnormal but without pathologic Q waves), and normal. The primary outcome was major adverse cardiac events (MACE) following ALCAPA repair, defined as extracorporeal support, cardiopulmonary resuscitation, heart transplantation, or death. Classic, non-classic, and normal ECG findings were seen at presentation in 124 (66%), 49 (26%), and 15 (8%) patients, respectively. There was no association between ECG category and MACE. Patients with non-classic or normal ECG findings were significantly more likely to present with normal or mildly diminished left ventricular systolic function and had significantly shorter duration of ventilation and hospital stay. Among 70 patients with ECGs at ~ 3 years following surgery, classic, non-classic, and normal ECG patterns were seen in 6 (8%), 29 (41%), and 35 (50%) patients, respectively. In conclusion, one-third of patients with ALCAPA presented with non-Classic or normal ECG patterns, and these patients were more likely to have preserved cardiac function and recover more quickly following surgical repair.

The scarcity of transplantable organs has led to the development of normothermic regional perfusion (NRP) to enhance organ viability and supply. While NRP offers promise to increase the quality and quantity of transplantable organs, its implementation raises significant ethical concerns regarding the Dead Donor Rule (DDR), consent/authorization, and physician participation. These concerns are further magnified in pediatric organ donation given such patients' increased vulnerability and lack of decision‐making authority. While arguments continue to play out in the literature, several OPOs in the US perform NRP and are requesting institutions to implement this practice. As pediatric ethicists, our aim is to create guidelines for the ethical implementation of NRP in pediatric donors. We highlight the challenges regarding the DDR, discuss requirements for informed consent, outline a thoughtful approach for engaging with families during crises, and address conscientious objections for clinicians who are morally apprehensive about participating in NRP. We recommend collaboration with hospital/organizational leadership, transplant programs, organ procurement organizations, and clinical ethicists to collaboratively plan to address these ethical controversies at the institutional level. Use of a pre‐NRP checklist may help ensure that all potential donor families and patients are treated with respect and fully informed about the process and that there is sufficient education of and support for clinicians who participate in NRP. If institutions and OPOs collaborate to implement these guidelines, they will ensure that they honor donors and their families without negatively impacting public trust in organ donation, increase organ supply and viability, and ultimately improve outcomes for transplant recipients.

Background Sleep is an important determinant of health and well-being. Poor sleep among nurses is associated with medical errors, poor decision-making, and decreased patient safety. National research priorities have underscored the need to understand the impact of nursing job characteristics on sleep health and mitigation strategies. Objective We aimed to test whether sleep hygiene behaviors moderated the association between job characteristics and sleep health among nurses. Methods A cross-sectional analysis was conducted on data from the Nurses’ Health Study 3 ( N = 1272). Logistic regression analysis tested the modifying effect of sleep hygiene behaviors when examining the association between job characteristics and sleep health among nurses practicing in various care settings and specialties. Results Sleep hygiene behaviors were associated with increased odds of healthy sleep on workdays and work-free days; however, sleep hygiene did not moderate associations between job characteristics and sleep health. Working 12-hour or longer shifts was not associated with decreased odds of healthy sleep compared with working <12-hour shifts on workdays or work-free days. Working in schools and critical care was associated with 50% or higher odds of unhealthy sleep compared with working in the operating room and oncology on work-free days. Discussion Findings suggest sleep hygiene behaviors cannot fully mitigate the effect of job characteristics on sleep health. Study results indicate sleep health may vary by nursing care setting and specialties. Future research should consider factors that may impact sleep health such as short staffing, commuting during work, and time off between shifts.

We present an overview of visible self-emission and laser imaging diagnostics for the Z Machine at Sandia National Laboratories. First, we review the Self-Emission Gated Optical Imager (SEGOI) diagnostic. SEGOI utilizes the Z Line Velocity Interferometer System for Any Reflector (Z Line VISAR) imaging relay system and detectors with a modified in-chamber optical configuration that is more flexible and significantly lower in cost. Detectors include eight intensified CCD (ICCD) cameras (540–600 nm) and two streak cameras (532 nm). The choice of in-chamber lens is flexible and determines the field-of-view (6.8–14 mm) and spatial resolution (∼32–74 μm edge widths). Next, we review the Laser Imaging on Z (LIONZ) diagnostic. LIONZ injects an open-beam 532 nm laser into the Z chamber via the Z Line VISAR beam transport system. This beam is redirected to the back of the target and then collected utilizing SEGOI. An additional 4-frame ICCD camera collects laser shadowgraphs, and one or both of the SEGOI streak cameras may be configured for streaked shadowgraphy, while the eight ICCD cameras for SEGOI may be simultaneously fielded for self-emission imaging. Currently, two open beam lasers with adjustable trigger times and a full-width-half-maximum of 20 ns are injected. Together, SEGOI and LIONZ offer valuable insight into the dynamics of low density plasmas on Z.

Hydropower is a critical electricity resource in the United States which, in addition to low-cost electricity generation, provides valuable ancillary grid services, and supports the integration of nondispatchable weather-dependent resources (e.g., wind and solar). Despite its value to the grid, there are very few comprehensive datasets available from which to study both historical and future impacts of climate, weather driven energy droughts, and integration of other weather driven generation. In this paper, we present a hydropower generation dataset covering 1,452 hydroelectric plants in the contiguous U.S. The dataset contains monthly and weekly hydropower generation estimates for both historical (1982–2019) and future (2020–2099) periods which includes 4 future climate scenarios. In addition, this dataset provides weekly and monthly constraints such as minimum and maximum power which are particularly useful in power system models which are used to study grid reliability, transmission planning and capacity expansion.

This cohort study evaluates the association between patient age and first seizure length in electroconvulsive therapy.

Ecologists seek to understand the ways that human activities are altering the structures and processes that support biodiversity and nature's contributions to people. Food web research at the interface of community and ecosystem ecology is promising in this regard. An industry of studies has utilized stable isotopes in recent decades to rapidly characterize energy and material transfer among organisms in freshwater food webs. Nevertheless, these efforts have been somewhat siloed and mainly locally-based, and lack of a centralized database has limited efforts to tackle questions about food web change using isotopes at a global scale. Here we present IsoFresh, a freshwater food web database that contains species-level carbon (δ¹³C) and nitrogen (δ¹⁵N) stable isotope values for 15343 organisms, representing 1001 food webs and including > 1600 fish species and associated potential prey, from 65 countries around the globe. Our hope is that IsoFresh is used to explore fundamental and applied food web questions, contributing new knowledge about global environmental change so that human societies can better conserve and manage freshwater ecosystems along desirable future trajectories.

Brake the Outbreak (BTO) is a free, online simulation of infectious outbreaks designed for educational use. A student using the simulation chooses a disease, vaccination percentage, social distancing rates, and other inputs. BTO then visually displays the resulting outbreak as it proceeds, including summary data, such as incidence and prevalence. BTO also shows emergent results like reproductive rate (R), which can be used to determine and test the herd immunity threshold (HIT) of the outbreak. BTO has been tested in the undergraduate microbiology classroom, where results suggest its use can enhance the learning of epidemiological content.

Background Disparities in implantable cardioverter‐defibrillator (ICD) implant rates and survival to hospital discharge exist, negatively impacting Black individuals, women, or people with lower socioeconomic status. This study examined if social determinants of health (SDOH) were associated with ICD shocks, all‐cause hospitalization, death, or patient‐reported outcomes during the first year following an initial ICD. Methods This secondary analysis used data from a comparative effectiveness randomized controlled trial of a post‐ICD patient intervention. Participants were followed for 1 year, and outcomes included ICD shocks, hospitalizations, death, physical function, psychological adjustment, and self‐efficacy. SDOH indicators included age, biological sex, race and ethnicity, education level, employment status, household income, and rural/urban residence. Descriptive statistics, Pearson's χ ² , and multivariate logistic regression were used to examine differences in outcomes by SDOH across the first year after ICD implant. Results Participants (N=301) were aged 64±12 years; 1% Asian/Pacific Islander, 4% Black, 2% Latinx, 2% Native American/Alaskan, and 91% White; 74% men; 87% urban residents; 65% retired/disabled/unemployed; 45% household income <$50 000/year; and 48$50 000 ( P <0.001), while White participants ( P =0.03) and rural residents ( P =0.01) showed a greater reduction in ICD concerns. Conclusions SDOH were not associated with the incidence of ICD shocks, hospitalization, or death in the first year after receipt of an initial ICD. There were limited differences in the change in patient‐reported outcomes over time by SDOH.

Teachers often face barriers, including time constraints and a lack of resources, to accessing professional development ( PD ) for implementing evidence-based practices in schools. One strategy which affords the flexibility to meet teacher needs while increasing the likelihood of strong implementation is providing PD remotely. The current study is a replication of a pilot study that examined the acceptability, feasibility, and effectiveness of providing remote PD for interventionists to implement a kindergarten mathematics intervention ( ROOTS ) for students with mathematics difficulties. Findings from the current study provide support for the pilot study and indicate that (a) a remote approach for ROOTS PD was acceptable for teachers; (b) the intervention was implemented as intended; and (c) students who received the ROOTS intervention outperformed their control group peers on mathematics outcome measures. Taken together, these results suggest that remote PD for ROOTS is a viable alternative to traditional face-to-face PD and warrants additional investigation. The Impact Sheet to this article is available online at 10.6084/m9.figshare.28723274.

Teaching topics like racism, diversity, and social justice have complex effects on counselor education faculty, including personal discomfort, exposure to student microaggressions, and negative student evaluations. We conducted an autoethnography-style inquiry into the collective experiences of three counselor educators who teach multicultural courses. We found areas of convergence in the identified burdens associated with teaching multicultural courses, as well as areas of divergence in experiences among Faculty of Color compared to White faculty. We also noted subthemes of psychoemotional impacts, teaching trap, and professional costs. We consider implications for future research and application within counselor education.

This study interpreted and translated a home visiting parenting program, Promoting First Relationships® (PFR), from English into Spanish and assessed if participants’ preferred language for PFR (Spanish, English) moderated its effect. This was a randomized controlled trial (PFR v. control) among 252 Spanish- and English-speaking mother-infant dyads (infant aged 6–12 weeks at enrollment) with low income who had previously received a mental health referral during their pregnancy. Outcomes were assessed at baseline, immediately post-intervention, and 6 months post-intervention. Outcomes included parenting sensitivity, dyadic synchrony, caregiver understanding of infant/toddler social-emotional needs (“caregiver understanding,” for brevity), maternal confidence, infant difficulty, and infant social-emotional development. Results showed that differences in outcomes by condition were similar across the preferred language groups, with the exception of caregiver understanding measured at 6 months post-intervention (b = 1.52, SE = 0.52). On this outcome, PFR demonstrated a greater effect among mothers who preferred Spanish (d = 0.69) than English (d = 0.40). Follow-up analyses of self-identified ethnicity (Hispanic or non-Hispanic) and nativity (non-US-born or US-born) as moderators showed similar results. There was no evidence that PFR worked differently across language, self-identified ethnicity, and nativity groups, with the exception of stronger PFR-related gains on caregiver understanding among mothers who preferred Spanish, self-identified as Hispanic, and were born outside the US. Trial registration: ClinicalTrials.gov, NCT02724774, registered 3/31/2016