Parents\u27 Goals: An Analysis of Therapist Reasoning

Purpose: Illustrate the use of DDDM to develop parent-identified goals for occupational therapy and to identify underlying sensory integration factors hypothesized to be impacting participation

Adrenergic and mesenchymal signatures are identifiable in cell-free DNA and correlate with metastatic disease burden in children with neuroblastoma

Background: Cell-free DNA (cfDNA) profiles of 5-hydroxymethylcytosine (5-hmC), an epigenetic marker of open chromatin and active gene expression, are correlated with metastatic disease burden in patients with neuroblastoma. Neuroblastoma tumors are comprised of adrenergic (ADRN) and mesenchymal (MES) cells, and the relative abundance of each in tumor biopsies has prognostic implications. We hypothesized that ADRN and MES-specific signatures could be quantified in cfDNA 5-hmC profiles and would augment the detection of metastatic burden in patients with neuroblastoma. Methods: We previously performed an integrative analysis to identify ADRN and MES-specific genes (n = 373 and n = 159, respectively). Purified DNA from cell lines was serial diluted with healthy donor cfDNA. Using Gene Set Variation Analysis (GSVA), ADRN and MES signatures were optimized. We then quantified signature scores, and our prior neuroblastoma signature, in cfDNA from 84 samples from 46 high-risk patients including 21 patients with serial samples. Results: Samples from patients with higher metastatic burden had increased GSVA scores for both ADRN and MES gene signatures (p Conclusions: While it is feasible to identify ADRN and MES signatures using 5-hmC profiles of cfDNA from neuroblastoma patients and correlate these signatures to metastatic burden, additional data are needed to determine the optimal strategies for clinical implementation. Prospective evaluation in larger cohorts is ongoing.</p

Samaki Salama - Promoting healthy child growth and sustainable fisheries in coastal Kenya: A study protocol

Background: One in five young children globally suffer the consequences of stunted growth and development and millions experience deficiencies in zinc, iron, iodine, vitamins A and B12, nutrients found bioavailable in fish foods. Small-scale fisheries have the potential to generate income and augment fish consumption while being environmentally sustainable if appropriately managed. However, those engaged in small-scale fisheries are often marginalized, poor, and malnourished. The Samaki Salama project seeks to better understand and address these challenges through a three-arm, longitudinal matched cluster study which evaluates the impact of an integrated nutrition social marketing and modified fishing trap intervention. Methods: here will be 400 small-scale fisher households enrolled from Kilifi County, Kenya and residing in communities matched on location (rural), livelihoods, and child nutritional status. The sample will include mothers and other caregivers, children 6–60 months, and fishers in the family. Applying a cluster design, the matched communities will be divided into three groups: (1) control (n = 200); (2) multi-component nutrition social marketing intervention to fishers, mothers, and health workers (n = 100); and (3) multi-component nutrition social marketing intervention plus modified fishing traps and training (n = 100). Primary outcomes include child growth, fish food intakes, and fisheries yield of mature fish. Secondary outcomes are diet diversity, child diarrheal morbidity, and fisheries revenue. A process evaluation will be used to monitor and ensure fidelity of intervention delivery. Discussion: This study builds on a growing body of literature illustrating the effectiveness of nutrition focused social marketing campaigns to promote active engagement of participants, high compliance to the intervention, and sustained behavior change. The second intervention element of modified fishing traps that allow immature fish to escape enables participants to act on the messaging they receive and promotes sustainable fishing through increased harvest efficiency and reduced catch of immature fish. The integrated approach of the Samaki Salama intervention provides an example of how to leverage multiple disciplines to address key challenges to human and environmental health and illustrates a pathway for scaling study innovations to other small-scale fisheries systems

Group elastic symmetries common to continuum and discrete defective crystals

The Lie group structure of crystals which have uniform continuous distributions of dislocations allows one to construct associated discrete structures—these are discrete subgroups of the corresponding Lie group, just as the perfect lattices of crystallography are discrete subgroups of R 3 , with addition as group operation. We consider whether or not the symmetries of these discrete subgroups extend to symmetries of (particular) ambient Lie groups. It turns out that those symmetries which correspond to automorphisms of the discrete structures do extend to (continuous) symmetries of the ambient Lie group (just as the symmetries of a perfect lattice may be embedded in ‘homogeneous elastic’ deformations). Other types of symmetry must be regarded as ‘inelastic’. We show, following Kamber and Tondeur, that the corresponding continuous automorphisms preserve the Cartan torsion, and we characterize the discrete automorphisms by a commutativity condition, (6.14), that relates (via the matrix exponential) to the dislocation density tensor. This shows that periodicity properties of corresponding energy densities are determined by the dislocation density

Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.

Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies

A classification of the symmetries of uniform discrete defective crystals

Crystals which have a uniform distribution of defects are endowed with a Lie group description which allows one to construct an associated discrete structure. These structures are in fact the discrete subgroups of the ambient Lie group. The geometrical symmetries of these structures can be computed in terms of the changes of generators of the discrete subgroup which preserve the discrete set of points. Here a classification of the symmetries for the discrete subgroups of a particular class of three-dimensional solvable Lie group is presented. It is a fact that there are only three mathematically distinct types of Lie groups which model uniform defective crystals, and the calculations given here complete the discussion of the symmetries of the corresponding discrete structures. We show that those symmetries corresponding to automorphisms of the discrete subgroups extend uniquely to symmetries of the ambient Lie group and we regard these symmetries as (restrictions of) elastic deformations of the continuous defective crystal. Other symmetries of the discrete structures are classified as ‘inelastic’ symmetries

Resilient Pedagogy: Practical Teaching Strategies to Overcome Distance, Disruption, and Distraction

Resilient Pedagogy offers a comprehensive collection on the topics and issues surrounding resilient pedagogy framed in the context of the COVID-19 pandemic and the social justice movements that have swept the globe. As a collection, Resilient Pedagogy is a multi-disciplinary and multi-perspective response to actions taken in different classrooms, across different institution types, and from individuals in different institutional roles with the purpose of allowing readers to explore the topics to improve their own teaching practice and support their own students through distance, disruption, and distraction

Preclinical Models for Neuroblastoma: Establishing a Baseline for Treatment

Preclinical models of pediatric cancers are essential for testing new chemotherapeutic combinations for clinical trials. The most widely used genetic model for preclinical testing of neuroblastoma is the TH-MYCN mouse. This neuroblastoma-prone mouse recapitulates many of the features of human neuroblastoma. Limitations of this model include the low frequency of bone marrow metastasis, the lack of information on whether the gene expression patterns in this system parallels human neuroblastomas, the relatively slow rate of tumor formation and variability in tumor penetrance on different genetic backgrounds. As an alternative, preclinical studies are frequently performed using human cell lines xenografted into immunocompromised mice, either as flank implant or orthtotopically. Drawbacks of this system include the use of cell lines that have been in culture for years, the inappropriate microenvironment of the flank or difficult, time consuming surgery for orthotopic transplants and the absence of an intact immune system.Here we characterize and optimize both systems to increase their utility for preclinical studies. We show that TH-MYCN mice develop tumors in the paraspinal ganglia, but not in the adrenal, with cellular and gene expression patterns similar to human NB. In addition, we present a new ultrasound guided, minimally invasive orthotopic xenograft method. This injection technique is rapid, provides accurate targeting of the injected cells and leads to efficient engraftment. We also demonstrate that tumors can be detected, monitored and quantified prior to visualization using ultrasound, MRI and bioluminescence. Finally we develop and test a "standard of care" chemotherapy regimen. This protocol, which is based on current treatments for neuroblastoma, provides a baseline for comparison of new therapeutic agents.The studies suggest that use of both the TH-NMYC model of neuroblastoma and the orthotopic xenograft model provide the optimal combination for testing new chemotherapies for this devastating childhood cancer