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Pharmacogenomic (PGx) testing identifies individual genetic variation that may inform medication treatment. Sentiment and barriers may limit PGx testing. Here we compare confidence in utilizing PGx testing and barriers to implementation by type of provider and treatment condition as identified in a survey.
Methods
Healthcare providers in the primary care setting were targeted between November 2022 and February 2023 via the Medscape Members paid market research program. The survey included 5 demographic, 5 multiple-choice, and 4 multi-component five-point Likert scale questions to assess PGx sentiments, use, and education in mental health (e.g., depression) and primary care (e.g., cardiovascular disease) conditions. Responses were descriptively compared.
Results
Of 305 U.S. provider respondents [40% nurse practitioners (NPs), 33% frontline MDs/DOs, 3% physician assistants (PAs), 24% other], 32% of NPs/PAs and 29% of MDs/DOs had used PGx testing for mental health conditions. The major barriers to adopt PGx testing were similar for mental health and primary care conditions yet differed by provider type. NPs/PAs (72-77%) were more concerned with patient cost than MDs/DOs (46-55%), whereas MDs/DOs were more concerned with evidence of clinical utility (54-59%) than NPs/PAs (40-42%). In respondents who use PGx testing, MDs/DOs reported slightly more confidence utilizing PGx than NPs/PAs. For both groups, confidence in using PGx for mental health conditions was somewhat greater than for non-mental health conditions.
Conclusions
These data illuminate the implementation barriers and confidence levels of clinicians utilizing PGx testing. Increasing awareness around patient cost and evidence of clinical utility for PGx testing may improve utilization.
Pharmacogenomic (PGx) testing identifies individual genetic variation that may inform medication treatment. Lack of awareness and education may be barriers to implementing routine PGx testing. To characterize current PGx testing utilization and educational needs we conducted a survey of various provider types.
Methods
Healthcare providers in the primary care setting were targeted between November 2022 and February 2023 via the Medscape Members paid market research program. The survey included 5 demographic, 5 multiple-choice, and 4 multi-component five-point Likert scale questions to assess PGx sentiments, use, and education in mental health (e.g., depression) and primary care (e.g., cardiovascular disease) conditions. Responses were descriptively compared.
Results
Of 305 U.S. provider respondents [40% nurse practitioners (NPs), 33% frontline MDs/DOs, 3% physician assistants (PAs), 24% other], most indicated that they “don’t use” (44-49%) or “have never heard of” (19-20%) PGx testing for mental health conditions. The most helpful sources to learn about PGx testing were accredited CE/CME activities (55-61%) and peer-reviewed publications (57-59%). Most NPs/PAs preferred webinars (62%) or online learning portal (57%) formats. MDs/DOs had no preference for webinars or learning portals over conferences, written materials, or academic presentations (45-47%). NPs/PAs were more interested in learning about PGx testing than MDs/DOs (4.29/5 vs. 3.96/5 average score).
Conclusions
These data reveal awareness level and desired learning opportunities for PGx testing between types of healthcare providers. Education should be tailored to meet providers’ preferred learning formats and information sources, such as offering CE/CME through an online learning portal.
Trifludimoxazin is a PPO-inhibiting herbicide currently under development for preplant burndown and soil residual weed control in soybean [Glycine max (L.) Merr.] and other crops. Greenhouse dose response experiments with foliar applications of trifludimoxazin, fomesafen, and saflufenacil were conducted on susceptible and PPO-inhibitor resistant (PPO-R) waterhemp [Amaranthus tuberculatus (Moq.) Sauer] and Palmer amaranth (Amaranthus palmeri S. Watson) biotypes. These PPO-R biotypes contained the PPO2 target site (TS) mutations ΔG210 (A. tuberculatus and A. palmeri), R128G (A. tuberculatus), and V361A (A. palmeri). The R/S ratios for fomesafen and saflufenacil ranged from 2.0 to 9.2 across all PPO-R biotypes. In contrast, the response of known PPO inhibitor-susceptible and -resistant biotypes to trifludimoxazin did not differ within each Amaranthus species. In 2017 and 2018 experiments at the Meigs and Davis Purdue Agriculture Centers were conducted in fields with native A. tuberculatus populations comprised of 3% and 30% PPO-R plants (ΔG210 mutation), respectively. At Meigs in 2018, A. tuberculatus control following foliar applications of fomesafen, lactofen, saflufenacil, and trifludimoxazin was greater than 95%. When averaged across the other three site-years, applications of 25 g ai ha-1 trifludimoxazin resulted in 95% control of A. tuberculatus 28 DAA, while applications of fomesafen (343 g ai ha-1), lactofen (219 g ai ha-1), or saflufenacil (25.0 or 50 g ai ha-1), resulted in 80 to 88% control. Thus, at these relative application rates, the foliar efficacy of trifludimoxazin was comparable or greater on A. tuberculatus, when compared to other commercial PPO inhibitors, even in populations where low frequencies of PPO inhibitor-resistant plants exist. The lack of cross resistance for common PPO2 TS mutations to trifludimoxazin, and the level of foliar field efficacy observed on populations containing PPO-R individuals suggests that trifludimoxazin may be a valuable herbicide in an integrated approach for managing herbicide-resistant Amaranthus weeds.
Ion cyclotron resonance heating is a versatile heating method that has been demonstrated to be able to efficiently couple power directly to the ions via the fast magnetosonic wave. However, at temperatures relevant for reactor grade devices such as DEMO, electron damping becomes increasingly important. To reduce electron damping, it is possible to use an antenna with a power spectrum dominated by low parallel wavenumbers. Moreover, using an antenna with a unidirectional spectrum, such as a travelling wave array antenna, the parallel wavenumber can be downshifted by mounting the antenna in an elevated position relative to the equatorial plane. This downshift can potentially enhance ion heating as well as fast wave current drive efficiency. Thus, such a system could benefit ion heating during the ramp-up phase and be used for current drive during flat-top operation. To test this principle, both ion heating and current drive have been simulated in a DEMO-like plasma for a few different mounting positions of the antenna using the FEMIC code. We find that moving the antenna off the equatorial plane makes ion heating more efficient for all considered plasma temperatures at the expense of on-axis heating. Moreover, although current drive efficiency is enhanced, electron damping is reduced for lower mode numbers, thus reducing the driven current in this part of the spectrum.
In this paper I present a class of discrete choice models for ordinal response variables based on a generalization of the stereotype model. The stereotype model can be derived and generalized as a random utility model for ordered alternatives. Random utility models can be specified to account for heteroscedastic and correlated utilities. In the case of the generalized stereotype model this includes category-specific random effects due to individual differences in response style. But unlike standard random utility models the generalized stereotype model is better suited for ordinal response variables and can be interpreted as a kind of unidimensional unfolding model. This paper discusses the specification, interpretation, identification, and estimation of generalized stereotype models. Two applications are provided for illustration.
This paper proposes a general approach to accounting for individual differences in the extreme response style in statistical models for ordered response categories. This approach uses a hierarchical ordinal regression modeling framework with heterogeneous thresholds structures to account for individual differences in the response style. Markov chain Monte Carlo algorithms for Bayesian inference for models with heterogeneous thresholds structures are discussed in detail. A simulation and two examples based on ordinal probit models are given to illustrate the proposed methodology. The simulation and examples also demonstrate that failing to account for individual differences in the extreme response style can have adverse consequences for statistical inferences.
The global population and status of Snowy Owls Bubo scandiacus are particularly challenging to assess because individuals are irruptive and nomadic, and the breeding range is restricted to the remote circumpolar Arctic tundra. The International Union for Conservation of Nature (IUCN) uplisted the Snowy Owl to “Vulnerable” in 2017 because the suggested population estimates appeared considerably lower than historical estimates, and it recommended actions to clarify the population size, structure, and trends. Here we present a broad review and status assessment, an effort led by the International Snowy Owl Working Group (ISOWG) and researchers from around the world, to estimate population trends and the current global status of the Snowy Owl. We use long-term breeding data, genetic studies, satellite-GPS tracking, and survival estimates to assess current population trends at several monitoring sites in the Arctic and we review the ecology and threats throughout the Snowy Owl range. An assessment of the available data suggests that current estimates of a worldwide population of 14,000–28,000 breeding adults are plausible. Our assessment of population trends at five long-term monitoring sites suggests that breeding populations of Snowy Owls in the Arctic have decreased by more than 30% over the past three generations and the species should continue to be categorised as Vulnerable under the IUCN Red List Criterion A2. We offer research recommendations to improve our understanding of Snowy Owl biology and future population assessments in a changing world.
Trifludimoxazin is a novel protoporphyrinogen oxidase (PPO)-inhibiting herbicide currently under development for foliar and residual control of several problematic weeds in preplant applications for soybean production. Field experiments were conducted in 2017 and 2018 to evaluate the foliar efficacy of trifludimoxazin applied alone and in combination with other herbicides on waterhemp, giant ragweed, and horseweed. Foliar applications of trifludimoxazin alone at 12.5 or 25.0 g ai ha−1 were highly efficacious on glyphosate-resistant waterhemp (94% to 99% control) and moderately effective on giant ragweed (78% to 79% control) and resulted in minor efficacy on horseweed (≤20% control). Combinations of trifludimoxazin with glufosinate, glyphosate, paraquat, or saflufenacil remained highly effective (≥91% control) on waterhemp and giant ragweed. All herbicide mixtures with trifludimoxazin applied to horseweed were classified as additive interactions. Greenhouse experiments and Isobole analysis indicated that trifludimoxazin mixtures with glyphosate and glufosinate on waterhemp and giant ragweed were additive. Mixtures of trifludimoxazin + paraquat were slightly antagonistic under greenhouse conditions when applied to either waterhemp or giant ragweed, whereas trifludimoxazin + saflufenacil was synergistic when applied to giant ragweed. Overall, trifludimoxazin applied alone at 12.5 or 25.0 g ha−1 is effective for managing waterhemp and, to an extent, giant ragweed, but not horseweed, in preplant burndown applications. Furthermore, the addition of glufosinate, glyphosate, paraquat, or saflufenacil to applications of trifludimoxazin does not appreciably reduce weed control for these mixtures. As such, applications of trifludimoxazin alone and in combination with these herbicides may be utilized for effective preplant management of several problematic weeds in soybean.
Educational attainment (EduA) is correlated with life outcomes, and EduA itself is influenced by both cognitive and non-cognitive factors. A recent study performed a ‘genome-wide association study (GWAS) by subtraction,’ subtracting genetic effects for cognitive performance from an educational attainment GWAS to create orthogonal ‘cognitive’ and ‘non-cognitive’ factors. These cognitive and non-cognitive factors showed associations with behavioral health outcomes in adults; however, whether these correlations are present during childhood is unclear.
Methods
Using data from up to 5517 youth (ages 9–11) of European ancestry from the ongoing Adolescent Brain Cognitive DevelopmentSM Study, we examined associations between polygenic scores (PGS) for cognitive and non-cognitive factors and cognition, risk tolerance, decision-making & personality, substance initiation, psychopathology, and brain structure (e.g. volume, fractional anisotropy [FA]). Within-sibling analyses estimated whether observed genetic associations may be consistent with direct genetic effects.
Results
Both PGSs were associated with greater cognition and lower impulsivity, drive, and severity of psychotic-like experiences. The cognitive PGS was also associated with greater risk tolerance, increased odds of choosing delayed reward, and decreased likelihood of ADHD and bipolar disorder; the non-cognitive PGS was associated with lack of perseverance and reward responsiveness. Cognitive PGS were more strongly associated with larger regional cortical volumes; non-cognitive PGS were more strongly associated with higher FA. All associations were characterized by small effects.
Conclusions
While the small sizes of these associations suggest that they are not effective for prediction within individuals, cognitive and non-cognitive PGS show unique associations with phenotypes in childhood at the population level.
Clinical research is critical for healthcare advancement, but participant recruitment remains challenging. Clinical research professionals (CRPs; e.g., clinical research coordinator, research assistant) perform eligibility prescreening, ensuring adherence to study criteria while upholding scientific and ethical standards. This study investigates the key information CRP prioritizes during eligibility prescreening, providing insights to optimize data standardization, and recruitment approaches.
Methods:
We conducted a freelisting survey targeting 150 CRPs from diverse domains (i.e., neurological disorders, rare diseases, and other diseases) where they listed essential information they look for from medical records, participant/caregiver inquiries, and discussions with principal investigators to determine a potential participant’s research eligibility. We calculated the salience scores of listed items using Anthropac, followed by a two-level analytic procedure to classify and thematically categorize the data.
Results:
The majority of participants were female (81%), identified as White (44%) and as non-Hispanic (64.5%). The first-level analysis universally emphasized age, medication list, and medical history across all domains. The second-level analysis illuminated domain-specific approaches in information retrieval: for instance, history of present illness was notably significant in neurological disorders during participant and principal investigator inquiries, while research participation was distinctly salient in potential participant inquiries within the rare disease domain.
Conclusion:
This study unveils the intricacies of eligibility prescreening, with both universal and domain-specific methods observed. Variations in data use across domains suggest the need for tailored prescreening in clinical research. Incorporating these insights into CRP training and refining prescreening tools, combined with an ethical, participant-focused approach, can advance eligibility prescreening practices.
Given the dramatic growth in the financial burden of cancer care over the past decades, individuals with cancer are increasingly susceptible to developing social needs (e.g., housing instability and food insecurity) and experiencing an adverse impact of these needs on care management and health outcomes. However, resources required to connect individuals with needed social and community services typically exceed the available staffing within clinical teams. Using input from focus groups, key informant interviews, user experience/user interface testing, and a multidisciplinary community advisory board, we developed a new technology solution, ConnectedNest, which connects individuals in need to community based organizations (CBOs) that provide services through direct and/or oncology team referrals, with interfaces to support all three groups (patients, CBOs, and oncology care teams). After prototype development, we conducted usability testing, with participants noting the importance of the technology for filling a current gap in screening and connecting individuals with cancer with needed social and community services. We employ a patient-empowered approach that engages the support of an individual’s healthcare team and community organizations. Future work will examine the integration and implementation of ConnectedNest for oncology patients, oncology care teams, and cancer-focused CBOs to build capacity for effectively addressing distress in this population.
Metabolite supplementation during in vitro embryo development improves blastocyst quality, however, our understanding of the incorporation of metabolites during in vitro maturation (IVM) is limited. Two important metabolites, follistatin and choline, have beneficial impacts during in vitro culture; however, effects of supplementation during IVM are unknown. The objective of this study was to investigate combining choline and follistatin during IVM on bovine oocytes and subsequent early embryonic development. We hypothesized that supplementation of choline with follistatin would synergistically improve oocyte quality and subsequent early embryonic development. Small follicles were aspirated from slaughterhouse ovaries to obtain cumulus oocyte complexes for IVM with choline (0, 1.3 or 1.8 mM) and follistatin (0 or 10 ng/mL) supplementation in a 3 × 2 design. A subset of oocytes underwent transcriptomic analysis, the remaining oocytes were used for IVF and in vitro culture (IVC). Transcript abundance of CEPT1 tended to be reduced in oocytes supplemented with 1.8 mM choline and follistatin compared to control oocytes (P = 0.07). Combination of follistatin with 1.8 mM choline supplementation during maturation, tended (P = 0.08) to reduce CPEB4 in oocytes. In the blastocysts, HDCA8, NANOG, SAV1 and SOX2 were increased with choline 1.8 mM supplementation without follistatin (P < 0.05), while HDCA8 and SOX2 were increased when follistatin was incorporated (P < 0.05). The combination of choline and follistatin during oocyte maturation may provide a beneficial impact on early embryonic development. Further research is warranted to investigate the interaction between these two metabolites during early embryonic development and long-term influence on fetal development.
Modons, or dipolar vortices, are common and long-lived features of the upper ocean, consisting of a pair of counter-rotating monopolar vortices moving through self-advection. Such structures remain stable over long times and may be important for fluid transport over large distances. Here, we present a semi-analytical method for finding fully nonlinear modon solutions in a multi-layer quasi-geostrophic model with arbitrarily many layers. Our approach is to reduce the problem to a multi-parameter linear eigenvalue problem which can be solved using numerical techniques from linear algebra. The method is shown to replicate previous results for one- and two-layer models and is applied to a three-layer model to find a solution describing a mid-depth propagating, topographic vortex.
Structure-switching aptamers have become ubiquitous in several applications, notably in analytical devices such as biosensors, due to their ease of supporting strong signaling. Aside from their ability to bind specifically with their respective target, this class of aptamers also undergoes a conformational rearrangement upon target recognition. While several well-studied and early-developed aptamers (e.g., cocaine, ATP, and thrombin) have been found to have this structure-switching property, the vast majority do not. As a result, it is common to try to engineer aptamers into switches. This proves challenging in part because of the difficulty in obtaining structural and functional information about aptamers. In response, we review various readily available biophysical characterization tools that are capable of assessing structure switching of aptamers. In doing so, we delve into the fundamentals of these different techniques and detail how they have been utilized in characterizing structure-switching aptamers. While each of these biophysical techniques alone has utility, their real power to demonstrate the occurrence of structural change with ligand binding is when multiple techniques are used. We hope that through a deeper understanding of these techniques, researchers will be better able to acquire biophysical information about their aptamer–ligand systems and accelerate the translation of aptamers into biosensors.
Autistic people have a high likelihood of developing mental health difficulties but a low chance of receiving effective mental healthcare. Therefore, there is a need to identify and examine strategies to improve mental healthcare for autistic people.
Aims
To identify strategies that have been implemented to improve access, experiences of care and mental health outcomes for autistic adults, and to examine evidence on their acceptability, feasibility and effectiveness.
Method
A co-produced systematic review was conducted. MEDLINE, PsycINFO, CINHAL, medRxiv and PsyArXiv were searched. We included all study designs reporting acceptability or feasibility outcomes and empirical quantitative study designs reporting effectiveness outcomes. Data were synthesised using a narrative approach.
Results
A total of 30 articles were identified. These included 16 studies of adapted mental health interventions, eight studies of service improvements and six studies of bespoke mental health interventions developed for autistic people. There was no conclusive evidence on effectiveness. However, most bespoke and adapted approaches appeared to be feasible and acceptable. Identified adaptations appeared to be acceptable and feasible, including increasing knowledge and detection of autism, providing environmental adjustments and communication accommodations, accommodating individual differences and modifying the structure and content of interventions.
Conclusion
Many identified strategies are feasible and acceptable, and can be readily implemented in services with the potential to make mental healthcare more suitable for autistic people, but important research gaps remain. Future research should address these and investigate a co-produced package of service improvement measures.
The authors consider the legal and ethical considerations of offering a time-limited trial of a potentially non-beneficial intervention in the setting of patient or surrogate requests to pursue aggressive treatment. The likelihood of an intervention’s success is rarely a zero-sum game, and an intervention’s risk-to-benefit ratio may be indiscernible without further information (often, a matter of time).