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BACKGROUND: In 2022, the US Department of Health and Human Services released the first National Strategy to Support Family Caregivers, identifying actions for both government and the private sector. One of the major goals is to expand data, research, and evidence-based practices to support family caregivers. While IT tools are widely deployed in health care settings, they are rarely available at scale in community agencies. In 2019, the state of California recognized the importance of a statewide database and a platform to serve caregivers remotely by enhancing existing service supports and investing in a web-based platform, CareNav. Implementation commenced in early 2020 across all 11 California Caregiver Resource Centers. OBJECTIVE: This paper describes the implementation strategies and outcomes of the statewide implementation of CareNav, a web-based platform to support family caregivers. METHODS: The Consolidated Framework for Implementation Research (CFIR), including a recent addendum, guided this mixed methods evaluation. Two major approaches were used to evaluate the implementation process: in-depth qualitative interviews with key informants (n=82) and surveys of staff members (n=112) and caregivers (n=2229). We analyzed the interview transcripts using qualitative descriptive methods; subsequently, we identified subthemes and relationships among the ideas, mapping the findings to the CFIR addendum. For the surveys, we used descriptive statistics. RESULTS: We present our findings about implementation strategies, implementation outcomes (ie, adoption, fidelity, and sustainment), and the impact on population health (organizational effectiveness and equity, as well as caregiver satisfaction, health, and well-being). The platform was fully adopted within 18 months, and the system is advancing toward sustainment through statewide collaboration. The deployment has augmented organizational effectiveness and quality, enhanced equity, and improved caregiver health and well-being. CONCLUSIONS: This study provides a use case for technological implementation across a multisite system with diverse community-based agencies. Future research can expand the understanding of the barriers and facilitators to achieving relevant outcomes and population impact.

We hypothesized that the inferior disease-free survival (DFS) seen in older patients who underwent αβ-T-cell/CD19-depleted (AB-TCD) haploidentical hematopoietic cell transplantation (HCT) for hematologic malignancies is caused by excessive exposure to rabbit antithymocyte globulin (rATG; Thymoglobulin). Between 2015 and 2023, 163 patients with a median age of 13 years (range, 0.4-27.4) underwent AB-TCD haploidentical HCT for the treatment of acute lymphoblastic leukemia (n = 98), acute myeloid leukemia/myelodysplastic syndrome (n = 49), or other malignancies (n = 16) at 9 centers in 2 prospective trials. Exposures to rATG before and after HCT were predicted using a validated pharmacokinetic model. Receiver operating characteristic curves were used to identify the optimal target windows for rATG exposure in terms of outcomes. We identified 4 quadrants of rATG exposure, namely quadrant 1 (n = 52) with a high pre-HCT area under curve (AUC; ≥50 arbitrary units [AU] per day per milliliter) and a low post-HCT AUC (

Cyanobacteria frequently constitute integral components of microbial communities known as phototrophic biofilms, which are widespread in various environments. Moreover, assemblages of these organisms, which serve as an expression platform, simplify harvesting the biomass, thereby holding significant industrial relevance. Previous studies of the model cyanobacterium Synechococcus elongatus PCC 7942 revealed that its planktonic growth habit results from a biofilm-suppression mechanism that depends on an extracellular inhibitor, an observation that opens the door to investigating cyanobacterial intercellular communication. Here, we demonstrate that the RNA polymerase sigma factor SigF1, is required for this biofilm-suppression mechanism whereas the S. elongatus paralog SigF2 is not involved in biofilm regulation. Comprehensive transcriptome analyses identified distinct regulons under the control of each of these sigma factors. sigF1 inactivation substantially lowers transcription of genes that code for the primary pilus subunit and consequently prevents pilus assembly. Moreover, additional data demonstrate absence of the biofilm inhibitor from conditioned medium of the sigF1 mutant, further validating involvement of the pilus assembly complex in secretion of the biofilm inhibitor. Consequently, expression is significantly upregulated for the ebfG-operon that encodes matrix components and the genes that encode the corresponding secretion system, which are repressed by the biofilm inhibitor in the wild type. Thus, this study uncovers a basic regulatory component of cyanobacterial intercellular communication, a field that is in its infancy. Elevated expression of biofilm-promoting genes in a sigF1 mutant supports an additional layer of regulation by SigF1 that operates via an intracellular mechanism.

We report on a large-scale, log-based study of the associations between persistence and success in an online game-based learning environment for elementary school mathematics. While working with applets, learners can rerun a task after completing it or can halt before completing and rerun it again; both of these mechanisms may improve the score. We analyzed about 3.1 million applet runs by N=44,323 1st-6th-grade students to have a nuanced understanding of persistence patterns, by identifying sequences of consecutive single applet runs (SoCSARs). Overall, we analyzed 2,249,647 SoCSARs and identified six patterns, based on halting and rerunning tasks, and their completion: 1) Single Complete, 2) Single Incomplete, 3) Some Incomplete and Single Complete, 4) Multiple Incomplete and No Complete, 5) Multiple Complete and No Incomplete, and 6) Multiple Complete and Some Incomplete. Expectedly, we found a positive correlation between SoCSAR length and success. Some patterns demonstrate low to medium positive associations with success, while others demonstrate low to medium negative associations. Furthermore, the associations between the type of persistence and success vary by grade level. We discuss these complex relationships and suggest metacognitive and motivational factors that may explain why some patterns are productive and others are not.

Abstract: Global change is impacting biodiversity across all habitats on earth. New selection pressures from changing climatic conditions and other anthropogenic activities are creating heterogeneous ecological and evolutionary responses across many species' geographic ranges. Yet we currently lack standardised and reproducible tools to effectively predict the resulting patterns in species vulnerability to declines or range changes. We developed an informatic toolbox that integrates ecological, environmental and genomic data and analyses (environmental dissimilarity, species distribution models, landscape connectivity, neutral and adaptive genetic diversity, genotype‐environment associations and genomic offset) to estimate population vulnerability. In our toolbox, functions and data structures are coded in a standardised way so that it is applicable to any species or geographic region where appropriate data are available, for example individual or population sampling and genomic datasets (e.g. RAD‐seq, ddRAD‐seq, whole genome sequencing data) representing environmental variation across the species geographic range. To demonstrate multi‐species applicability, we apply our toolbox to three georeferenced genomic datasets for co‐occurring East African spiny reed frogs (Afrixalus fornasini, A. delicatus and A. sylvaticus) to predict their population vulnerability, as well as demonstrating that range loss projections based on adaptive variation can be accurately reproduced from a previous study using data for two European bat species (Myotis escalerai and M. crypticus). Our framework sets the stage for large scale, multi‐species genomic datasets to be leveraged in a novel climate change vulnerability framework to quantify intraspecific differences in genetic diversity, local adaptation, range shifts and population vulnerability based on exposure, sensitivity and landscape barriers.

In the wake of recent interventions to better connect the subfields of international migration and race and ethnicity through a sociology of racialized immigration, we push this further by arguing for the necessity of a global Blackness perspective on global migration. Such a focus does not just reflect the role of race in the dynamics of migration, and vice versa, but more importantly shifts assumptions about this relationship. So, it is not enough to say that race matters in migration but rather that blackness and Black lives matter in how migration unfolds. Using global blackness as a starting point in our analyses of migration reveals a clearer and closer entanglement of race, racism, colonialism, and migration. We argue that global Blackness structures notions of who migrates and under what conditions, as well as our ideas regarding migrants and their descendants and use the examples of New York City, Paris, and France as paradigmatic sites for understanding this relationship.

BackgroundCancer patients are at risk of pulmonary embolism (PE). Catheter-based therapies (CBT) are novel reperfusion options for PE though data in patients with cancer is lacking.Study design and methodsPatients with intermediate- or high-risk PE were identified using the National Readmission Database (NRD) from 2017 to 2020. Primary outcome were in-hospital death and 90-day readmission. Secondary outcomes were in-hospital bleeding, 90-day readmission for venous thromboembolism (VTE)-related or right heart failure-related reasons and bleeding. Propensity scores were estimated using logistic regression and inverse-probability treatment weighting (IPTW) was utilized to compare outcomes between CBT and no CBT as well as CBT versus systemic thrombolysis.ResultsA total of 7785 patients were included (2511 with high-risk PE) of whom 1045 (13.4%) were managed with CBT. After IPTW, CBT was associated with lower rates of index hospitalization death (OR 0.89, 95% CI 0.83-0.96) and 90-day readmission (HR 0.75, 95% CI 0.69-0.81) but higher rates of in-hospital bleeding (OR 1.11, 95% CI 1.03-1.20) which was predominantly post-procedural bleeding. CBT was associated with lower risk of major bleeding (20.8% vs 24.8%; OR 0.80, 95% CI 0.68-0.94) compared with systemic thrombolysis.InterpretationAmong patients with cancer with intermediate or high-risk PE, CBT was associated with lower in-hospital death and 90-day readmission. CBT was also associated with decreased risk of index hospitalization major bleeding compared with systemic thrombolysis. Prospective, randomized trials with inclusion of patients with cancer are needed to confirm these findings.

Substantial global attention is focused on how to reduce the risk of future pandemics. Reducing this risk requires investment in prevention, preparedness, and response. Although preparedness and response have received significant focus, prevention, especially the prevention of zoonotic spillover, remains largely absent from global conversations. This oversight is due in part to the lack of a clear definition of prevention and lack of guidance on how to achieve it. To address this gap, we elucidate the mechanisms linking environmental change and zoonotic spillover using spillover of viruses from bats as a case study. We identify ecological interventions that can disrupt these spillover mechanisms and propose policy frameworks for their implementation. Recognizing that pandemics originate in ecological systems, we advocate for integrating ecological approaches alongside biomedical approaches in a comprehensive and balanced pandemic prevention strategy.

We present results from a 3.25 kg-day target exposure of two silicon charge-coupled devices (CCDs), each with 24 megapixels and skipper readout, deployed in the DAMIC setup at SNOLAB. With a reduction in pixel readout noise of a factor of 10 relative to the previous detector, we investigate the excess population of low-energy events in the CCD bulk previously observed above expected backgrounds. We address the dominant systematic uncertainty of the previous analysis through a depth fiducialization designed to reject surface backgrounds on the CCDs. The measured bulk ionization spectrum confirms the presence of an excess population of low-energy events in the CCD target with characteristic rate of ∼7 events per kg-day and electron-equivalent energies of ∼80 eV, whose origin remains unknown.

Abstract Alpha-synuclein (αS) aggregation is a widely regarded hallmark of Parkinson’s disease (PD) and can be detected through synuclein amplification assays (SAA). This study investigated the association between cerebrospinal fluid (CSF) radiological measures in 41 PD patients (14 iPD, 14 GBA1-PD, 13 LRRK2-PD) and 14 age-and-sex-matched healthy controls. Quantitative measures including striatal binding ratios (SBR), whole-brain and deep gray matter volumes, neuromelanin-MRI (NM-MRI), functional connectivity (FC), and white matter (WM) diffusion-tensor imaging (DTI) were calculated. Nine LRRK2-PD patients were SAA-negative (PD-SAA−). PD-SAA+ patients showed lower whole-brain gray matter, putamenal, brainstem, and substantia nigra volumes, reduced FC in the left caudate, and lower fractional anisotropy in the left fronto-occipital fasciculus compared to PD-SAA−. Taken together, αS aggregation was observed in iPD, GBA1-PD, and 38% of LRRK2-PD patients, and this was associated with reduced regional brain volumes, altered caudal FC, and SBRs. These changes were less pronounced in PD-SAA−, possibly suggesting a milder neurodegenerative process.

Abstract Background Conducted in May 2024, this study examines the well-being of Israeli evacuees and non-evacuees from conflict zones. We assess health-related quality of life (HRQoL), meaning in life (MIL), coping strategies, psychological symptoms, and self-mastery. Aims include exploring effects of trauma and socio-demographics on HRQoL and MIL, analyzing mediating roles of psychological symptoms and coping, and evaluating if evacuation status moderates these relationships during ongoing conflict. Methods In May 2024, seven months post–October 7th attacks, we conducted a cross-sectional study with 366 participants (221 evacuated, 145 non-evacuated) via a survey company. We assessed HRQoL (SF-12), MIL (MLQ), psychological symptoms (PHQ-4), self-related and other-related coping strategies (Brief COPE), and self-mastery (Self-Mastery Scale) through self-reported measures. Path and moderated mediation analyses evaluated relationships among socio-demographics, psychological symptoms, coping variables, HRQoL, and MIL. Results Except for self-mastery, northern and southern evacuees showed no significant differences and were combined into one group. Path analysis revealed significant associations between traumatic life events, HRQoL, and MIL. Traumatic events were negatively associated with the physical component summary (PCS) of HRQoL and positively with anxiety, depression, and coping (self and others- problem-solving). Depression negatively related to PCS, mental component summary (MCS), and MIL, while coping (self and others) was positively associated with MIL. Moderated mediation analysis showed evacuated participants had higher dysfunctional coping, whereas non-evacuated participants demonstrated a stronger positive relationship between anxiety and the search for meaning. Conclusion Despite regional differences, evacuees exhibited similar psychological responses, likely due to the shared experience of displacement. Traumatic events negatively impacted their HRQoL and MIL. Adaptive coping strategies—self-related and problem-focused coping through helping others—played significant roles in mitigating these effects. The theoretical frameworks of Conservation of Resources (COR) theory, Taylor’s “tend and befriend” model, and Frankl’s existential framework provided a basis for explaining these findings.

The number of Black suburbs has expanded since the 1960s, however, research on gender and how Black women contribute to their formation is understudied. Grounded in an intersectional framework, this article places women at the center of the analysis of Black suburban life. Using a multisite ethnography conducted during the Great Recession, I make a case for a Black diasporic suburb model and analyze the labor and household practices Black women use to sustain their families' suburban lives. This article generates new insights into the heterogeneity of and Black suburbs in general, and the dynamic culture and economies of Black suburban women, in particular. Thus it contributes to new thought in Black feminist geography and the sociology of suburbs.

Service-learning models serve as noteworthy curriculum paradigms that can help students engage with their communities while continuously learning. This article recounts the implementation of a service-learning model within a student initiative aimed to help combat vaccine hesitancy and promote the uptake of vaccinations within the Rhode Island community. Through a collaborative effort between students, faculty, and the university, the student initiative was able to construct a credit-bearing course to help assess and alleviate vaccine hesitancy within Rhode Island. This article highlights the journey the organization took to develop a service-learning model within the course, the project details, and the impact of their project on the community. A detailed analysis of the service-learning model's impact on students as well as key takeaways of the project are also highlighted below.

This article presents a study of a full-day, university-organized, online hackathon that aimed at designing solutions to problems raised in remote learning and teaching. The event, with about 80 participants, was carried out during the COVID-19 pandemic when many schools were closed and shifted to emergency remote teaching. The hackathon participants were challenged to design innovative solutions to authentic problems that have been raised during this situation. Using an online questionnaire, to which 28 of the hackathon participants responded, we quantitatively and qualitatively examined how the event had affected them. Findings suggest that participating in the hackathon mostly contributed to the participants' recognition of the importance of collaboration, and their thinking about academy-society relations. These contributions were driven by the way the hackathon was designed and handled, and the fact that it was held online enabled some of its unique contributions. We also show that online, shorter-than-usual hackathon still has a meaningful, multi-faceted contribution to their participants, and conclude with recommendations for planning such events.

PRDM16 is a dynamic transcriptional regulator of various stem cell niches, including adipocytic, hematopoietic, cardiac progenitors, and neural stem cells. PRDM16 has been suggested to contribute to 1p36 deletion syndrome, one of the most prevalent subtelomeric microdeletion syndromes. We report a patient with a de novo nonsense mutation in the PRDM16 coding sequence, accompanied by lissencephaly and microcephaly features. Human stem cells were genetically modified to mimic this mutation, generating cortical organoids that exhibited altered cell cycle dynamics. RNA sequencing of cortical organoids at day 32 unveiled changes in cell adhesion and WNT-signaling pathways. ChIP-seq of PRDM16 identified binding sites in postmortem human fetal cortex, indicating the conservation of PRDM16 binding to developmental genes in mice and humans, potentially at enhancer sites. A shared motif between PRDM16 and LHX2 was identified and further examined through comparison with LHX2 ChIP-seq data from mice. These results suggested a collaborative partnership between PRDM16 and LHX2 in regulating a common set of genes and pathways in cortical radial glia cells, possibly via their synergistic involvement in cortical development.

Abstract Global change is impacting biodiversity across all habitats on earth. New selection pressures from changing climatic conditions and other anthropogenic activities are creating heterogeneous ecological and evolutionary responses across many species' geographic ranges. Yet we currently lack standardised and reproducible tools to effectively predict the resulting patterns in species vulnerability to declines or range changes. We developed an informatic toolbox that integrates ecological, environmental and genomic data and analyses (environmental dissimilarity, species distribution models, landscape connectivity, neutral and adaptive genetic diversity, genotype‐environment associations and genomic offset) to estimate population vulnerability. In our toolbox, functions and data structures are coded in a standardised way so that it is applicable to any species or geographic region where appropriate data are available, for example individual or population sampling and genomic datasets (e.g. RAD‐seq, ddRAD‐seq, whole genome sequencing data) representing environmental variation across the species geographic range. To demonstrate multi‐species applicability, we apply our toolbox to three georeferenced genomic datasets for co‐occurring East African spiny reed frogs (Afrixalus fornasini, A. delicatus and A. sylvaticus) to predict their population vulnerability, as well as demonstrating that range loss projections based on adaptive variation can be accurately reproduced from a previous study using data for two European bat species (Myotis escalerai and M. crypticus). Our framework sets the stage for large scale, multi‐species genomic datasets to be leveraged in a novel climate change vulnerability framework to quantify intraspecific differences in genetic diversity, local adaptation, range shifts and population vulnerability based on exposure, sensitivity and landscape barriers.

Abstract Background Cannabis sativa L. is a versatile medicinal plant known for its therapeutic properties, derived from its diverse array of secondary metabolites synthesized primarily in female flower organs. Breeding cannabis is challenging due to its dioecious nature, strict regulatory requirements, and the need for photoperiod control to trigger flowering, coupled with highly dispersible pollen that can easily contaminate nearby female flowers. This study aimed to develop a protocol for in vitro flowering in cannabis, investigate factors affecting in vitro flower production, and generate viable in vitro seeds, potentially offering a method for producing sterile cannabinoids or advancing breeding techniques. Results We show that the life cycle of cannabis can be fully completed in tissue culture; plantlets readily produce inflorescences and viable seeds in vitro. Our findings highlight the superior performance of DKW medium with 2% sucrose in a filtered vessel and emphasize the need for low light intensity during flower induction to optimize production. The improved performance in filtered vessels suggests that plants conduct photosynthesis in vitro, highlighting the need for future investigations into the effects of forced ventilation to refine this system. All tested lines readily developed inflorescences upon induction, with a 100% occurrence rate, including male flowering. We revealed the non-dehiscent trait of in vitro anthers, which is advantageous as it allows for multiple crosses to be conducted in vitro without concerns about cross-contamination. Conclusion The current work developed and optimized an effective protocol for in vitro flowering and seed production in cannabis, potentially providing a platform for sterile cannabinoid production and an efficient tool for breeding programs. This system allows for the full and consistent control of plant growth conditions year-round, potentially offering the reliable production of sterile molecules suitable for pharmacological use. As a breeding strategy, this method overcomes the complex challenges of breeding cannabis, such as the need for large facilities, by enabling the production of hundreds of lines in a small facility. By offering precise control over factors such as plant growth regulators, light intensity, photoperiod, and temperature, this system also serves as a valuable tool for studying flowering aspects in cannabis.

Data Structures and Algorithms (DS) is a basic computer science course that is a prerequisite for taking advanced information systems (IS) curriculum courses. The course aims to teach students how to analyze a problem, design a solution, and implement it using pseudocode to construct knowledge and develop the necessary skills for algorithmic problem solving and abstract thinking. While the literature acknowledges the difficulty of this course, few references were found that examine the process students undergo while solving DS algorithmic problems. The study's objective is to explore and describe IS students' problem-solving processes and challenges requiring a high level of abstract thinking in a "black box" approach. During the study, 13 students were observed while solving a complex problem, using "think aloud" (TA) techniques. Each observation was recorded, transcribed, and iteratively analyzed using principles of provisional coding in qualitative data analysis. The findings suggest that the quality and correctness of the solutions depend on three main factors: abstract thinking, flexibility applied during the solution process, and an absence of misconceptions related to concepts and the basic understanding of the problem. The students' levels of abstract thinking also influenced the quality of visualization used while trying to solve the problem. This study's findings may raise the awareness of DS course designers and instructors regarding the importance of the role of abstract thinking, possible misconceptions, and strategies used in problem solving as factors influencing students' ability to solve complex problems.

Pulmonary embolism (PE) is a common complication among patients with cancer and is a significant contributor to morbidity and mortality. Catheter-based therapies (CBT), including catheter-directed thrombolysis (CDT) and mechanical thrombectomy, have been developed and are used in patients with intermediate or high-risk PE. However, there is a paucity of data on outcomes in patients with cancer as most clinical studies exclude this group of patients.To characterize outcomes of patients with cancer admitted with intermediate or high-risk PE treated with CBT compared with no CBT.Patients with an admission diagnosis of intermediate or high-risk PE and a history of cancer from October 2015 to December 2018 were identified using the National Inpatient Sample. Outcomes of interest were in-hospital death or cardiac arrest (CA) and major bleeding. Inverse probability treatment weighting (IPTW) was utilized to compare outcomes between patients treated with and without CBT. Variables that remained unbalanced after IPTW were adjusted using multivariable logistic regression.A total of 2084 unweighted admissions (10,420 weighted) for intermediate or high-risk PE and cancer were included, of which 136 (6.5%) were treated with CBT. After IPTW, CBT was associated with lower death or CA (aOR 0.54, 95% CI 0.46-0.64) but higher major bleeding (aOR 1.41, 95% CI 1.21-1.65). After stratifying by PE risk type, patients treated with CBT had lower risk of death or CA in both intermediate (aOR 0.52, 95% CI 0.36-0.75) and high-risk PE (aOR 0.48, 95% CI 0.33-0.53). However, patients with CBT were associated with increased risk of major bleeding in intermediate-risk PE (aOR 2.12, 95% CI 1.67-2.69) but not in those with high-risk PE (aOR 0.84, 95% CI 0.66-1.07).Among patients with cancer hospitalized with intermediate or high-risk PE, treatment with CBT was associated with lower risk of in-hospital death or CA but higher risk of bleeding. Prospective studies and inclusion of patients with cancer in randomized trials are warranted to confirm our findings.