Search

IntroductionIncreasingly, pharmacogenetic testing helps providers with medication selection based upon patient-specific DNA results. While several government-funded organizations work towards consensus and standardization for testing and interpretation, compliance to these best practices remains inconsistent. Pharmacogenetic testing companies often develop proprietary practices for interpreting and reporting, which can lead to incongruency of reported results among companies and potential discrepancies in interpretation.MethodsTo identify the differences of commercial pharmacogenetic testing vendors’ interpretation of genotype-to-phenotype translations and medication recommendations from the Clinical Pharmacogenetic Implementation Consortium (CPIC) guidelines, a retrospective manual chart review was completed in a large rural healthcare system that utilizes two institution-approved pharmacogenetic vendors. One hundred patients were evaluated: 50 who completed testing through Company A and 50 who completed testing through Company B. Genes of interest for genotype-to-phenotype translation included CYP2B6, CYP2C19, and CYP2D6. Comparison of medication recommendations for drug-gene pairs sertraline (CYP2B6 and/or CYP2C19), escitalopram (CYP2C19), and paroxetine (CYP2D6) were compared with recommendations from CPIC, with consideration of the CPIC Serotonin Reuptake Inhibitor Antidepressants (SSRI) guideline 2023 update. This was accomplished via a novel binning process to enable comparison of company-provided binned medication recommendations with CPIC guideline recommendations. Briefly, the binning system included three categorizations based upon the relevant CPIC guideline recommendations–no action needed (green), recommend monitoring (yellow) and therapeutic intervention or alternative recommended (red).ResultsThere were 32/250 (12.8%) genotype-to-phenotype translation discrepancies from CPIC guidelines, all from Company A. Of 266 evaluated binned medication recommendations, there were 114 (42.9%) discrepancies between the pharmacogenetic testing companies (Company A: 93 discrepancies, Company B: 21 discrepancies) and CPIC’s guideline based upon comparison with the novel binning system.DiscussionSignificant differences were observed between testing companies’ interpretations and recommendations, which is concerning as these discrepancies could lead to providers making medication decisions that are not supported by CPIC’s clinical practice guidelines. This may result in suboptimal outcomes for patients, leading to patient and provider dissatisfaction and erosion of trust with pharmacogenetic testing. A proposed resolution for the discrepancies in company-to-company interpretation is adherence to the CPIC guidelines and transparency in interpretation practices.

Sensorimotor reflex circuits engage distinct neuronal subtypes, defined by precise connectivity, to transform sensation into compensatory behavior. Whether and how motor neuron populations specify the subtype fate and/or sensory connectivity of their pre-motor partners remains controversial. Here, we discovered that motor neurons are dispensable for proper connectivity in the vestibular reflex circuit that stabilizes gaze. We first measured activity following vestibular sensation in pre-motor projection neurons after constitutive loss of their extraocular motor neuron partners. We observed normal responses and topography indicative of unchanged functional connectivity between sensory neurons and projection neurons. Next, we show that projection neurons remain anatomically and molecularly poised to connect appropriately with their downstream partners. Lastly, we show that the transcriptional signatures that typify projection neurons develop independently of motor partners. Our findings comprehensively overturn a long-standing model: that connectivity in the circuit for gaze stabilization is retrogradely determined by motor partner-derived signals. By defining the contribution of motor neurons to specification of an archetypal sensorimotor circuit, our work speaks to comparable processes in the spinal cord and advances our understanding of principles of neural development.

Introduction/Objectives: To understand the impact of introducing Additional Roles Reimbursement Scheme (ARRS) on the General Practice Nurse (GPN) workforce. A workforce/people impact assessment designed as a cross-sectional survey of a stratified sample of 900 GPN on the Queen’s Nursing Institute mailing list. Method: A workforce/people impact assessment was designed based on the UKCS 2014 piloted and distributed as a cross-sectional survey via a survey platform. This included questions on level of impact, kind of impact and perception of prior engagement. Data were analyzed using descriptive statistics and content analysis. Results: The survey consisted of 21 questions (531 responses, response rate of 60%). ARRS deployment appears to have impacted the GPN workforce in several ways. There was positive impact on workloads from ARRS roles working in original scope, for example pharmacists medicine reviews. However, any benefit was offset by the increased workloads created by those new to general practice and/or working outside of traditional scope. This ranged from a lack of resources to provide the support those new to primary care require to practice safely, the expectations of others-that GPN will fill the gap in support and teaching to GPN directly safety netting the work of others. There was a lack of consultation regarding a major workforce change, leading to feelings of devaluation. There are some significant equity issues highlighted particularly around pay and opportunity. Conclusion: The introduction of ARRS has had some positive but mostly negative impact on the workload and introduced pay inequity issues on GPN.

A captive sand tiger shark (Carcharias taurus) presented with progressive, hard, raised, miliary skin lesions localized to the lateral trunk and peduncle. Histopathologic evaluation of biopsy samples revealed dysplastic proliferation of odontogenic epithelium with the production of collagenous material. Inclusion bodies and viral particles were not observed with light or transmission electron microscopy, respectively. However, using next generation sequencing with Illumina MiSeq and PCR followed by Sanger sequencing, the complete genome of a novel adomavirus, tentatively named sand tiger shark adomavirus (STAdoV), was obtained from the affected tissue. The genome was circular and 18.5 kilobases with bidirectionally transcribed genes, namely EO1, EO2 & 4, EO3, LO4, LO5, LO6, LO7, LO8, and SET. In situ hybridization using RNAscope® technology and a STAdoV specific probe localized viral DNA to the nuclei of proliferating epithelial cells. Adomaviruses are an emerging viral group with structural and replicative genes sharing a complex evolutionary history with adenoviruses and small circular DNA tumor viruses including papillomaviruses and polyomaviruses. Adomaviruses are described in a number of fish species in association with both necrotizing and proliferative diseases. BLAST analysis of the viral genome revealed greatest nucleotide identity (71.29%) to guitarfish adomavirus (GAdoV), another elasmobranch virus associated with proliferative (epidermal) skin lesions. Lesions in the index animal persisted for approximately 1 year during which time four conspecifics developed similar proliferations. Ultimately, lesions in all sharks regressed spontaneously without recurrence for 2 years.

In this publication, we present an overview of stakeholder concerns regarding hydrilla management, synthesizing insights gathered from the largest state-wide survey of Florida residents about invasive aquatic plant management in the state’s public waters. Our objective is to equip decision-makers, including agencies like FWC, with valuable insights. By understanding stakeholder concerns, decision-makers can formulate policies for the effective management of aquatic invasive species that garner public support.

IntroductionIn the setting of pediatric and adolescent young adult cancer, increased access to genomic profiling has enhanced the detection of genetic variation associated with cancer predisposition, including germline syndromic conditions. Noonan syndrome (NS) is associated with the germline RAS pathway activating alterations and increased risk of cancer. Herein, we describe our comprehensive molecular profiling approach, the association of NS with glioma and glioneuronal tumors, and the clinical and histopathologic characteristics associated with the disease.MethodsWithin an institutional pediatric cancer cohort (n = 314), molecular profiling comprised of paired somatic disease–germline comparator exome analysis, RNA sequencing, and tumor classification by DNA methylation analysis was performed.ResultsThrough the implementation of paired analysis, this study identified 4 of 314 (1.3%) individuals who harbored a germline PTPN11 variant associated with NS, of which 3 individuals were diagnosed with a glioma or glioneuronal tumor. Furthermore, we extend this study through collaboration with a peer institution to identify two additional individuals with NS and a glioma or glioneuronal tumor. Notably, in three of five (60%) individuals, paired genomic profiling led to a previously unrecognized diagnosis of Noonan syndrome despite an average age of cancer diagnosis of 16.8 years. The study of the disease-involved tissue identified signaling pathway dysregulation through somatic alteration of genes involved in cellular proliferation, survival, and differentiation.DiscussionComparative pathologic findings are presented to enable an in-depth examination of disease characteristics. This comprehensive analysis highlights the association of gliomas and glioneuronal tumors with RASopathies and the potential therapeutic challenges and importantly demonstrates the utility of genomic profiling for the identification of germline cancer predisposition.

Pediatric brain tumors are the leading cause of cancer-related death in children in the United States and contribute a disproportionate number of potential years of life lost compared to adult cancers. Moreover, survivors frequently suffer long-term side effects, including secondary cancers. The Children's Brain Tumor Network (CBTN) is a multi-institutional international clinical research consortium created to advance therapeutic development through the collection and rapid distribution of biospecimens and data via open-science research platforms for real-time access and use by the global research community. The CBTN's 32 member institutions utilize a shared regulatory governance architecture at the Children's Hospital of Philadelphia to accelerate and maximize the use of biospecimens and data. As of August 2022, CBTN has enrolled over 4700 subjects, over 1500 parents, and collected over 65,000 biospecimen aliquots for research. Additionally, over 80 preclinical models have been developed from collected tumors. Multi-omic data for over 1000 tumors and germline material are currently available with data generation for > 5000 samples underway. To our knowledge, CBTN provides the largest open-access pediatric brain tumor multi-omic dataset annotated with longitudinal clinical and outcome data, imaging, associated biospecimens, child-parent genomic pedigrees, and in vivo and in vitro preclinical models. Empowered by NIH-supported platforms such as the Kids First Data Resource and the Childhood Cancer Data Initiative, the CBTN continues to expand the resources needed for scientists to accelerate translational impact for improved outcomes and quality of life for children with brain and spinal cord tumors.

As the number of students pursuing opportunities in higher education from communities that are underrepresented and marginalized has increased over the last decade or so (National Center for Education Statistics 2022; Wilson et al. 2022), the student population of the University of Arizona Global Campus (UAGC) has exemplified this trend with 48% identifying as members of the Black or African American and Hispanic or Latinx communities (UAGC 2022). This diverse classroom means it is increasingly important that higher education institutions (HEIs) carefully reflect on their curriculum as it relates to diversity, equity, and inclusion. These are the questions that confront HEIs: (1) is the learning environment one where all students feel valued, welcomed, and heard?; (2) is the current curriculum preparing students for a more diverse workplace?; and (3) how does the HEI contribute to either maintaining or deconstructing the status quo? Answering these questions is never an easy task, as self-reflection can come with difficult realizations about an institution's contributions to and perpetuation of inequitable social systems. The Diversity, Equity, and Inclusion (DEI) Course Audit Rubric at UAGC is one tool used to guide conversations around creating more diverse, equitable, and inclusive curriculum in the online classroom.

The chief goal of the Blood Profiling Atlas in Cancer (BloodPAC) consortium is to promote collaborative efforts that support the development and implementation of liquid biopsy tests. Here, we report the results of a pilot study conducted by three BloodPAC members that aimed to demonstrate a multisite liquid biopsy testing framework using longitudinal blood specimens from 38 patients with metastatic breast cancer. Three laboratories receiving identical samples from two clinical sites each applied a different targeted sequencing platform to analyze mutations in cell-free DNA (cfDNA). The resulting mutational profiles reflected common breast cancer alterations, including clinically actionable mutations for 40% of hormone- receptor-positive patients. In 12 genes with shared target regions across sequencing panels, perfect inter-assay concordance was also observed for mutations detected above the lowest common assay limit of detection. Whole-genome copy number profiling of cfDNA and circulating tumor cells (CTCs) further revealed marked heterogeneity in copy number alterations and cfDNA tumor fractions across patients. Additionally, comparison of tumor fraction and CTC abundance demonstrated the complementary nature of cfDNA and CTC analyses. Overall, the framework described in this study may serve as a resource for future trials aiming to identify multimodal liquid biopsy biomarkers to guide clinical care.

Background: We sought to understand the innovativeness of nurses engaging in innovative behaviors and quantify the associated characteristics that make nurses more able to innovate in practice. We first compared the innovativeness scores of our population; then we examined those who self-identified as an innovator versus those who did not to explore differences associated with innovativeness between these groups. Methods: A cross-sectional survey study of nurses in the US engaging in innovative behaviors was performed. We performed an exploratory factor analysis (EFA) to determine the correlates of innovative behavior. Results: Three-hundred and twenty-nine respondents completed the survey. Respondents who viewed themselves as innovators had greater exposure to HCD/DT workshops in the past year (55.8% vs. 36.6%, p = 0.02). The mean innovativeness score of our sample was 120.3 ± 11.2 out of a score of 140. The mean innovativeness score was higher for those who self-identified as an innovator compared with those who did not (121.3 ± 10.2 vs. 112.9 ± 14.8, p =< 0.001). The EFA created four factor groups: Factor 1 (risk aversion), Factor 2 (willingness to try new things), Factor 3 (creativity and originality) and Factor 4 (being challenged). Conclusion: Nurses who view themselves as innovators have higher innovativeness scores compared with those who do not. Multiple individual and organizational characteristics are associated with the innovativeness of nurses.

The provision of undergraduate statistics teaching varies across UK dental schools, but some challenges are faced in all schools. These include the need to (i) demonstrate the relevance of statistics to dentistry, (ii) address the phenomenon of statistical anxiety likely to be experienced, and (iii) deliver the teaching with a limited number of statistically trained staff. Our objective was to design a research methods course that combined epidemiology and statistics teaching for undergraduates at Bristol Dental School (University of Bristol) that was clinically relevant, focused on concepts and interpretation rather than calculation, and was sustainable, using new technology to enhance learning. The research methods course was introduced in 2008, extensively developed over the next two years based on student and tutor feedback, and has run with only minor updates ever since. The aim of the course is to introduce year 2 dental students to the skills needed to practice evidence-based dentistry, i.e. understand and critically appraise published research. Basic epidemiological concepts, different types of study design, summarising and interpreting data, and choosing appropriate statistical analyses are covered. The course is introduced by a face-to-face lecture. This emphasises the relevance to future careers, and pre-empts the feelings of statistical anxiety by presenting evidence that exam results for this course are not associated with having achieved an A-level in mathematics. The rest of the course is delivered using the flipped classroom approach. Didactic teaching is in the form of nine e-lectures, each lasting 20-25 minutes. These are split into chapters to allow easy navigation, and include pop-up questions. Small group (up to 10 students) structured tutorials (one per e-lecture) are used to reinforce the material covered in the e-lectures, drawing on real clinical examples from research publications. They are interactive, and also include e-voting quizzes to allow the tutors and students to gauge the level of understanding that is being achieved. At the end of the course there is a revision session and written assessment, which must be passed before students can progress to year 3 of the dental degree. Approximately 70 students take the course each year, split into eight groups, and tutorials are based on pre-prepared materials. Tutoring on this course provides an attractive opportunity to gain teaching experience, with only a modest investment in time. Therefore, it has always been possible to recruit enough statisticians or epidemiologists in the Faculty of Health Sciences, University of Bristol to act as tutors. At least 89% of the students have passed the exam on first sitting each year, and all students have passed their re-sit exam. Marks ranged from 50-86% in 2019, and similar ranges were seen in previous years. Student feedback is consistently high, with virtually all students rating all components of the course at least satisfactory, and high percentages rating them good or excellent (e-lectures and tutorials were rated to be good or excellent by 72% and 95% of the students respectively in 2019). External examiners have been very complimentary, and only ever requested minor changes. Hence it has been possible to run a sustainable research methods course that engages students' interest and produces excellent learning outcomes.

The growth of online learning has created a need for instructors who can competently teach online. This literature review explores the research questions, program recommendations, and future research suggestions related to professional development for online instructors. Articles were selected and coded based on date of publication and the context of the professional development. Results indicate that most research questions focused on (a) professional development programs, (b) instructors, and (c) instructors' online courses. Most program recommendations focused on (a) professional development programs, (b) context of professional development, and (c) instructors' activity during professional development. Future recommendations for research topics focused on professional development programs and instructors, while future recommendations for research methods focused on research design and institutional settings. The findings suggest that while professional development for online instructors is important, consistency in both design and delivery is lacking. Future research is needed to provide guidance to programs, instructors, and institutions leading to satisfaction and success for more online students.