Time to Pivot: A Guide to Holistic Admissions.

ABSTRACT: As an ever-increasing number of physician assistant (PA) programs moves toward holistic admissions, a better understanding of how to achieve their stated admission goals becomes more important. With the June 2023 US Supreme Court decision effectively ending affirmative action in higher education, navigating holistic admissions is now an even greater challenge. In this article, the PA Education Association's Presidents Commission offers a guide for programs to use in implementing holistic admissions at their institutions and key considerations. Is the process mission-driven? Does it follow principles of quality improvement and incorporate ongoing assessment of that process? Using data can be a constructive and insightful way to inform the process. The authors hope that tools, resources, and recommendations offered in this article will serve as valuable resources for any program attempting to institute or improve its holistic admissions process.

Two haplotype-resolved genomes reveal important flower traits in bigleaf hydrangea (Hydrangea macrophylla) and insights into Asterid evolution.

The Hydrangea genus belongs to the Hydrangeaceae family, in the Cornales order of flowering plants, which early diverged among the Asterids, and includes several species that are commonly used ornamental plants. Of them, Hydrangea macrophylla is one of the most valuable species in the nursery trade, yet few genomic resources are available for this crop or closely related Asterid species. Two high-quality haplotype-resolved reference genomes of hydrangea cultivars 'Veitchii' and 'Endless Summer' [highest quality at 2.22 gigabase pairs (Gb), 396 contigs, N50 22.8 megabase pairs (Mb)] were assembled and scaffolded into the expected 18 pseudochromosomes. Utilizing the newly developed high-quality reference genomes along with high-quality genomes of other related flowering plants, nuclear data were found to support a single divergence point in the Asterids clade where both the Cornales and Ericales diverged from the euasterids. Genetic mapping with an F1 hybrid population demonstrated the power of linkage mapping combined with the new genomic resources to identify the gene for inflorescence shape, CYP78A5 located on chromosome 4, and a novel gene, BAM3 located on chromosome 17, for causing double flower. Resources developed in this study will not only help to accelerate hydrangea genetic improvement but also contribute to understanding the largest group of flowering plants, the Asterids.

Enhanced multi-year predictability after El Niño and La Niña events.

Several aspects of regional climate including near-surface temperature and precipitation are predictable on interannual to decadal time scales. Despite indications that some climate states may provide higher predictability than others, previous studies analysing decadal predictions typically sample a variety of initial conditions. Here we assess multi-year predictability conditional on the phase of the El Niño-Southern Oscillation (ENSO) at the time of prediction initialisation. We find that predictions starting with El Niño or La Niña conditions exhibit higher skill in predicting near-surface air temperature and precipitation multiple years in advance, compared to predictions initialised from neutral ENSO conditions. This holds true in idealised prediction experiments with the Community Climate System Model Version 4 and to a lesser extent also real-world predictions using the Community Earth System Model and a multi-model ensemble of hindcasts contributed to the Coupled Model Intercomparison Project Phase 6 Decadal Climate Prediction Project. This enhanced predictability following ENSO events is related to phase transitions as part of the ENSO cycle, and related global teleconnections. Our results indicate that certain initial states provide increased predictability, revealing windows of opportunity for more skillful multi-year predictions.

Evaluation of Hydrangea Cultivars for Tolerance Against Root Rot Caused by Fusarium oxysporum.

Root rot caused by Fusarium oxysporum Schltdl. is a newly identified disease in oakleaf hydrangea. Some cultivars such as Pee Wee and Queen of Hearts grown in pot-in-pot container systems showed root rot symptoms after late spring frost in May 2018 with 40 and 60% incidence in the infected nursery, respectively. This experiment was carried out to evaluate the tolerance among different hydrangea cultivars against root rot caused by F. oxysporum. Fifteen hydrangea cultivars from four different species were selected, and rooted cuttings were prepared from new spring flushes. Twelve plants from each cultivar were transplanted in a 1-gallon pot. Half of transplanted plants (six single plants) were inoculated by drenching 150 ml of F. oxysporum conidial suspension to maintain the concentration of 1 × 106 conidia/ml. Half of the plants remain noninoculated (control) and were drenched with sterile water. After 4 months, root rot was assessed using a scale of 0 to 100% root area affected, and recovery of F. oxysporum was recorded by plating 1-cm root sections in Fusarium selective medium. Fusaric acid (FA) and mannitol were extracted from the roots of inoculated and noninoculated plants to see the effect and role on pathogenesis. Further, mannitol concentration was analyzed using absorption wavelength in a spectrophotometer, and FA was analyzed using high-performance liquid chromatography (HPLC). Results indicated that no cultivars were resistant to F. oxysporum. Cultivars from Hydrangea arborescens, H. macrophylla, and H. paniculata were more tolerant to F. oxysporum compared to cultivars from H. quercifolia. Among H. quercifolia, cultivars Snowflake, John Wayne, and Alice were more tolerant to F. oxysporum.

Novel and Engineered Type II CRISPR Systems from Uncultivated Microbes with Broad Genome Editing Capability.

Type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 nucleases have been extensively used in biotechnology and therapeutics. However, many applications are not possible owing to the size, targetability, and potential off-target effects associated with currently known systems. In this study, we identified thousands of CRISPR type II effectors by mining an extensive, genome-resolved metagenomics database encompassing hundreds of thousands of microbial genomes. We developed a high-throughput pipeline that enabled us to predict tracrRNA sequences, to design single guide RNAs, and to demonstrate nuclease activity in vitro for 41 newly described subgroups. Active systems represent an extensive diversity of protein sequences and guide RNA structures and require diverse protospacer adjacent motifs (PAMs) that collectively expand the known targeting capability of current systems. Several nucleases showed activity levels comparable to or significantly higher than SpCas9, despite being smaller in size. In addition, top systems exhibited low levels of off-target editing in mammalian cells, and PAM-interacting domain engineered chimeras further expanded their targetability. These newly discovered nucleases are attractive enzymes for translation into many applications, including therapeutics.

Meeting the Accreditation Standard for Diversity.

ABSTRACT: While increasing diversity has been an ongoing concern in physician assistant (PA) education, there is now a concentrated focus on diversity, equity, inclusion, and social justice, elevating these to top priorities. To achieve the goal of diversifying the PA workforce, PA programs, with their institution's support, must systematically inculcate strategies for overcoming and dismantling barriers against students of color and students underrepresented in medicine (URiM). These strategies should disrupt the status quo and expand structural processes that ensure successful diversification of students, especially URiM students, LGBTQ students, students from medically underserved areas, and first-generation college students.

Consensus on a netball video analysis framework of descriptors and definitions by the netball video analysis consensus group.

Using an expert consensus-based approach, a netball video analysis consensus (NVAC) group of researchers and practitioners was formed to develop a video analysis framework of descriptors and definitions of physical, technical and contextual aspects for netball research. The framework aims to improve the consistency of language used within netball investigations. It also aims to guide injury mechanism reporting and identification of injury risk factors. The development of the framework involved a systematic review of the literature and a Delphi process. In conjunction with commercially used descriptors and definitions, 19 studies were used to create the initial framework of key descriptors and definitions in netball. In a two round Delphi method consensus, each expert rated their level of agreement with each of the descriptors and associated definition on a 5-point Likert scale (1-strongly disagree; 2-somewhat disagree; 3-neither agree nor disagree; 4-somewhat agree; 5-strongly agree). The median (IQR) rating of agreement was 5.0 (0.0), 5.0 (0.0) and 5.0 (0.0) for physical, technical and contextual aspects, respectively. The NVAC group recommends usage of the framework when conducting video analysis research in netball. The use of descriptors and definitions will be determined by the nature of the work and can be combined to incorporate further movements and actions used in netball. The framework can be linked with additional data, such as injury surveillance and microtechnology data.

PAs in the Republic of Ireland.

ABSTRACT: The physician associate/assistant (PA) profession was introduced into the Republic of Ireland following a 2-year pilot project with the Irish Department of Health between 2015 and 2017. Four PAs from North America were recruited into four designated surgical services at a large teaching hospital in Dublin. To date, the PA numbers are small in Ireland, with one university, in Dublin, running the program and 61 graduates working mostly in the hospital setting, with a small number in primary care. The cautious introduction of PAs partly is due to a delay in follow-up from the Department of Health after the pilot project and in the university's decision to increase the student intake slowly to ensure all graduates secure employment.

A survey exploring factors affecting employment of physician associates in Ireland.

BACKGROUND: In the Republic of Ireland, the employment of physician associates (PAs) is growing. Following a pilot project in a hospital setting, PAs are now employed across primary and secondary care in public and private sectors. Most of the Irish PA graduates are working in hospital settings. AIMS: The aim of the study was to explore factors which supported or inhibited the employment of PAs in Irish hospital settings and the perceived supports or challenges for potential employers in recruiting PAs. METHODS: An online survey gathered data via human resources departments of public and private hospitals, with a 25% response rate. RESULTS: Similar to previous studies, the barriers included the lack of recognition and regulation of the role and the small number of PAs to fill available posts. Enablers, which influenced the employment of PAs, included improving workflow, continuity of care and helping to address junior doctors' working hours. CONCLUSIONS: Our data suggests that there is a keen interest and willingness to employ PAs and there is great potential to expand the role in Irish healthcare. However, there are some key issues around funding and recognition to be addressed at government level for this profession to highlight its worth.

A Multimodal Intervention for Reducing Unnecessary Repeat Glycated Hemoglobin Testing.

OBJECTIVES: Reducing unnecessary tests that do not enhance quality can promote health-care value. Glycated hemoglobin (A1C) is often ordered at a frequency exceeding the recommendation of once every 3 months. We conducted a quality improvement (QI) initiative aimed to reduce unnecessary repeat testing by 75% at a tertiary care academic hospital. METHODS: A retrospective baseline analysis was conducted on laboratory data from 2019 that enumerated unnecessary A1C tests, defined as repeat tests ordered within 60 days. A multifaceted change intervention with iterative plan-do-study-act cycles was introduced in March 2019 to educate providers and to automatically cancel A1C tests requested within 60 days. Monthly totals of A1C testing processed were plotted on statistical process control charts. RESULTS: In 2019, 11% of all A1C tests ordered were unnecessary. Between March 2020 and January 2021, 11% of the tests (N=14,247 tests) were unnecessary, of which 84% were cancelled with our intervention. Providers in cardiology and nephrology accounted for over half (55%) of the unnecessary tests ordered. CONCLUSIONS: A 2-pronged approach informed by root-cause analysis, and comprised of gatekeeping and provider education, can effectively promote resource stewardship for reducing unnecessary A1C testing.

Compact Cas9d and HEARO enzymes for genome editing discovered from uncultivated microbes.

Programmable, RNA-guided nucleases are diverse enzymes that have been repurposed for biotechnological applications. However, to further expand the therapeutic application of these tools there is a need for targetable systems that are small enough to be delivered efficiently. Here, we mined an extensive genome-resolved metagenomics database and identified families of uncharacterized RNA-guided, compact nucleases (between 450 and 1,050 aa). We report that Cas9d, a new CRISPR type II subtype, contains Zinc-finger motifs and high arginine content, features that we also found in nucleases related to HEARO effectors. These enzymes exhibit diverse biochemical characteristics and are broadly targetable. We show that natural Cas9d enzymes are capable of genome editing in mammalian cells with >90% efficiency, and further engineered nickase variants into the smallest base editors active in E. coli and human cells. Their small size, broad targeting potential, and translatability suggest that Cas9d and HEARO systems will enable a variety of genome editing applications.

Pipeline to the Physician Assistant Profession: A Look to the Future.

ABSTRACT: The current pipeline of physician assistant (PA) school applicants reflects the future workforce of the profession, which is why the admissions process with all its components and variables is so important. Many studies have shown that a workforce that represents the patients it cares for leads to improved health outcomes, especially among underrepresented minority populations. Yet, PA programs have made little progress over the past 2 decades in increasing the diversity of matriculants and graduates. As a profession, it is our collective responsibility to intentionally advance diversity, equity, and inclusion, and examining the admissions process would be the most logical place to start.

Management of Phytophthora cinnamomi Using Fungicides and Host Plant Defense Inducers Under Drought Conditions: A Case Study of Flowering Dogwood.

Phytophthora cinnamomi is considered one of the most destructive pathogens of ornamental crops. Different fungicides and host plant defense inducers were tested for their efficacy in managing Phytophthora root rot in drought conditions. In this study, the drought conditions were maintained by evaluating the moisture-holding capacity of the pine bark in a 10.2-cm nursery container. Four controls and nine different treatments were used in two trials for this greenhouse study. All treatments were drench-applied as a preventative or curative treatment. Seedlings were artificially inoculated with P. cinnamomi. Regular irrigation was carried out using overhead irrigation for 1 month after inoculation. Irrigation was regulated by drip irrigation after the first month. A moisture level of 15% to 18% of total moisture-holding capacity was maintained using the gravimetric method throughout the drought period. Physiological parameters of the seedlings were recorded a week after seedlings were drought stressed. In both trials of preventative and curative treatments, all treatments were able to suppress the disease significantly except Orkestra Intrinsic. Orkestra Intrinsic had a disease severity statistically similar to the inoculated and stressed control in trial 1 of the curative treatment. Net photosynthesis, stomatal conductance, and leaf moisture potential were significantly greater in seedlings treated with Subdue MAXX, Signature Xtra, and Empress Intrinsic in both trials of preventative and curative treatments. Effective quantum yield of Photosystem II was significantly lower in the inoculated stressed control in both trials of preventative and curative treatments. Net chlorophyll content through the SPAD meter showed higher values for Subdue MAXX treated seedlings compared with the noninoculated nonstressed controls in trial 1 as both a curative and preventative application. In trial 2, Subdue MAXX and Signature Xtra were the best curative treatments, whereas Empress Intrinsic, Interface, and Subdue MAXX were the best preventative treatments for higher chlorophyll content. This case study will help growers perform successful management of Phytophthora root rot in woody ornamental crops during drought or water deficit conditions.

Reflections on a Physician Assistant Entrance Exam: Does the Profession Need One?

ABSTRACT: Standardized entrance exams are used in many health professions as one way to objectively measure knowledge and facilitate comparisons across student groups. The physician assistant (PA) profession has historically not employed a profession-specific entrance exam, and the idea was never seriously explored until the Physician Assistant College Admissions Test was developed recently by a commercial assessment publisher, with field testing in some volunteer programs in 2018 and the exam's first administration in May of 2020. The 2020 Physician Assistant Education Association Presidents Commission chose to investigate the issues raised by a consensus-derived, PA-specific entrance exam to stimulate more informed discussion on the efficacy of such an exam. While it may have the potential to enhance efficiency in PA admissions and reduce variability in admissions requirements, a PA entrance exam would also likely introduce new challenges, including increased costs, impact on the diversity of the applicant pool, and incongruence with an increasingly holistic admissions process. The biggest barrier would likely be the lack of current consensus on the knowledge, skills, and attributes that matriculants need to be successful in the program and in clinical practice. Development of a consensus-derived PA entrance exam would be a complex, expensive, and time-consuming endeavor, requiring considerable attention to technical issues of psychometric quality, process transparency, and legal defensibility. Changes being made to health professions admissions practices due to the COVID-19 pandemic, including the dropping of test scores as a requirement by some institutions, may make some of the issues raised in this paper more timely than ever.

Novel Type V-A CRISPR Effectors Are Active Nucleases with Expanded Targeting Capabilities.

Cas12a enzymes are quickly being adopted for use in a variety of genome-editing applications. These programmable nucleases are part of adaptive microbial immune systems, the natural diversity of which has been largely unexplored. Here, we identified novel families of Type V-A CRISPR nucleases through a large-scale analysis of metagenomes collected from a variety of complex environments, and developed representatives of these systems into gene-editing platforms. The nucleases display extensive protein variation and can be programmed by a single-guide RNA with specific motifs. The majority of these enzymes are part of systems recovered from uncultivated organisms, some of which also encode a divergent Type V effector. Biochemical analysis uncovered unexpected protospacer adjacent motif diversity, indicating that these systems will facilitate a variety of genome-engineering applications. The simplicity of guide sequences and activity in human cell lines suggest utility in gene and cell therapies.

Drivers and impacts of the most extreme marine heatwaves events.

Prolonged high-temperature extreme events in the ocean, marine heatwaves, can have severe and long-lasting impacts on marine ecosystems, fisheries and associated services. This study applies a marine heatwave framework to analyse a global sea surface temperature product and identify the most extreme events, based on their intensity, duration and spatial extent. Many of these events have yet to be described in terms of their physical attributes, generation mechanisms, or ecological impacts. Our synthesis identifies commonalities between marine heatwave characteristics and seasonality, links to the El Niño-Southern Oscillation, triggering processes and impacts on ocean productivity. The most intense events preferentially occur in summer, when climatological oceanic mixed layers are shallow and winds are weak, but at a time preceding climatological maximum sea surface temperatures. Most subtropical extreme marine heatwaves were triggered by persistent atmospheric high-pressure systems and anomalously weak wind speeds, associated with increased insolation, and reduced ocean heat losses. Furthermore, the most extreme events tended to coincide with reduced chlorophyll-a concentration at low and mid-latitudes. Understanding the importance of the oceanic background state, local and remote drivers and the ocean productivity response from past events are critical steps toward improving predictions of future marine heatwaves and their impacts.

Reimagining Physician Assistant Education.

The physician assistant (PA) profession has successfully flourished for over 50 years, demand for graduates remains strong, and there is a wealth of research on the quality of care that PA graduates provide. Nevertheless, health care and education are constantly changing, and we must change with them. We must continually scan the horizon and consider how best to adapt to current issues like the clinical sites crisis, as well as evolutions in technology, pedagogy, and in our students themselves. The Physician Assistant Education Association Presidents Commission, a group of past presidents, sought to stimulate a conversation on "reimagining PA education" through the lens of advances in our knowledge of the neuroscience of learning and changes in technology, including simulation, and a broader focus on innovation and "thinking outside the box." Through interviews with PA faculty and leaders, we provide some examples of areas of innovation in education, especially on the possibilities presented by a more flexible approach to innovation from the accreditation body than many PA faculty might perceive. One initial conclusion is that PA educators should focus more on helping students to "think like clinicians" from the start of their education. This paper is primarily intended to stimulate dialog, and we encourage all PA educators to form-and more importantly, share-their own thoughts and questions, through the PAEA professional learning communities and Digital Learning Hub (PAEAlearning.org/learn/digital-learning-hub/).

Single-Molecule Studies of Protein Folding with Optical Tweezers.

Manipulation of individual molecules with optical tweezers provides a powerful means of interrogating the structure and folding of proteins. Mechanical force is not only a relevant quantity in cellular protein folding and function, but also a convenient parameter for biophysical folding studies. Optical tweezers offer precise control in the force range relevant for protein folding and unfolding, from which single-molecule kinetic and thermodynamic information about these processes can be extracted. In this review, we describe both physical principles and practical aspects of optical tweezers measurements and discuss recent advances in the use of this technique for the study of protein folding. In particular, we describe the characterization of folding energy landscapes at high resolution, studies of structurally complex multidomain proteins, folding in the presence of chaperones, and the ability to investigate real-time cotranslational folding of a polypeptide.

Ploidy Level Influences Pollen Tube Growth and Seed Viability in Interploidy Crosses of Hydrangea macrophylla.

All Hydrangea macrophylla cultivars tested to date are diploid or triploid and triploid H. macrophylla have thicker stems, larger flowers, and larger stoma compared to related diploids. It is unknown whether interploidy crosses between diploid and triploid hydrangeas can be used to develop triploid varieties. The objective of this study was to compare pollen tube development, fruit formation, and seed viability among intra- and interploidy pollinations of H. macrophylla and evaluate the genome size and pollen viability of resultant progeny. By 24 h post-pollination, pollen tubes had reached the ovaries of diploid flowers in 48.7% of samples while pollen tubes reached the ovaries in only 8.7% of triploid flowers (χ 2 = 30.6, p < 0.001). By 48 h post-pollination pollen tubes reached the ovaries of diploid and triploid flowers in 72.5% and 53.8% of samples, respectively (χ 2 = 26.5, p = 0.001). There was no difference in percentage of flowers with pollen tubes reaching the ovaries in diploid and triploid flowers at 72 h after pollination (χ 2 = 7.5, p = 0.60). Analysis of covariance showed that pollen tube length at 24 and 48 h post-pollination was significantly influenced by ploidy and flower length of the female parent. Progeny of interploidy crosses was diploid and aneuploid; no triploid progeny were recovered from crosses using triploid parents. Mean genome sizes of offspring from each cross type ranged from 4.56 pg for 2x × 2x offspring to 5.17 pg for 3x × 3x offspring. Estimated ploidy of offspring ranged from 2x for 2x × 2x crosses to 2.4x for 3x × 3x crosses. Pollen stainability rates of flowering offspring using a modified Alexander's stain ranged from 69.6% to 76.4%.