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Purpose: Self-reported listening-related fatigue in adolescents with hearing loss (HL) was investigated. Specifically, the extent to which listening-related fatigue is associated with school accommodations, audiologic characteristics, and listening breaks was examined. Method: Participants were 144 adolescents with HL ages 12-19 years. Data were collected online via Qualtrics. The Vanderbilt Fatigue Scale-Child was used to measure listening-related fatigue. Participants also reported on their use of listening breaks and school accommodations, including an Individualized Education Program (IEP) or 504 plan, remote microphone systems, closed captioning, preferential seating, sign language interpreters, live transcriptions, and notetakers. Results: After controlling for age, HL laterality, and self-perceived listening difficulty, adolescents with an IEP or a 504 plan reported lower listening-related fatigue compared to adolescents without an IEP or a 504 plan. Adolescents who more frequently used remote microphone systems or notetakers reported higher listening-related fatigue compared to adolescents who used these accommodations less frequently, whereas increased use of a sign language interpreter was associated with decreased listening-related fatigue. Among adolescents with unilateral HL, higher age was associated with lower listening-related fatigue; no effect of age was found among adolescents with bilateral HL. Listening-related fatigue did not differ based on hearing device configuration. Conclusions: Adolescents with HL should be considered at risk for listening-related fatigue regardless of the type of hearing devices used or the degree of HL. The individualized support provided by an IEP or 504 plan may help alleviate listening-related fatigue, especially by empowering adolescents with HL to be self-advocates in terms of their listening needs and accommodations in school. Additional research is needed to better understand the role of specific school accommodations and listening breaks in addressing listening-related fatigue.

Ecosystem engineers can modify habitat, creating structural microhabitats. This structural complexity can affect species richness. Marine ecosystem engineers are able to produce local effects in combination with environmental variables (e.g. to create more humid habitat during low tides). We tested the hypotheses that if there is a relationship between mussel morphology and environmental factors, mussels would be larger at warmer than at cooler locations, and in areas where 2 species of mussels overlap, size and biomass will decrease and density will increase. At a smaller scale, we predicted that there is a relationship between the assemblage structure and hardness of the substratum and sediment content of a mussel bed. Using a nested design, we measured density, biomass and size of 2 species of mussels, Brachidontes rodriguezii and Perumytilus (Brachidontes) purpuratus, and diversity of species associated with mussel beds at 2 rocky intertidal sites at each of 4 shores along the northern Argentinean coast. These variables were correlated with oceanographic conditions and local characteristics. Significant correlations were found between intertidal assemblages and local factors. The largest specimens of B. rodriguezii and P. purpuratus were found at the warmer shores. In areas where they overlapped, size, biomass and density of P. purpuratus were lower, although B. rodriguezii did not change. The mean abundance of invertebrates associated with a mussel bed showed significant differences among shores. These 2 species of mytilids coexist over a small area, and although these species are very similar in their biological and ecological function, the fauna associated with their matrices are very different.

Black pericarp sorghum has notable value due to the biosynthesis of 3-deoxyanthocyanidins (3-DOAs), a rare class of bioactive polyphenols valued as antioxidant food additives and as bioactive compounds with cytotoxicity to human cancer cells. A metabolic and transcriptomic study was conducted to ascertain the cellular events leading to the activation of 3-DOA biosynthesis in black sorghum pericarp. Prolonged exposure of pericarp during grain maturation to high-fluence ultraviolet (UV) light resulted in elevated levels of reactive oxygen species (ROS) and the activation of 3-DOA biosynthesis in pericarp tissues. In conjunction with 3-DOA biosynthesis was the transcriptional activation of specific family members of early and late flavonoid biosynthesis pathway genes as well as the downstream activation of defense-related pathways. Promoter analysis of genes highly correlated with 3-DOA biosynthesis in black pericarp were enriched in MYB and HHO5/ARR-B motifs. Light microscopy studies of black pericarp tissues suggest that 3-DOAs are predominantly localized in the epicarp and are associated with the cell wall. A working model of UV-induced 3-DOA biosynthesis in black pericarp is proposed that shares features of plant immunity associated with pathogen attack or mechanical wounding. The present model depicts ROS accumulation, the transcriptional activation of receptor kinases and transcription factors (TFs) including NAC, WRKY, bHLH, AP2, and C2H2 Zinc finger domain. This study identified key biosynthetic and regulatory genes of 3-DOA accumulation in black pericarp and provided a deeper understanding of the gene networks and cellular events controlling this tissue-and genotype-specific trait.

IntroductionPrickles are often deemed undesirable traits in many crops, including roses (Rosa sp.), and there is demand for rose cultivars with no or very few prickles. This study aims to identify new and/or validate reported quantitative trait loci (QTLs) associated with stem and leaf rachis prickle density, characterize the effects of functional haplotypes for major QTLs, and identify the sources of QTL-alleles associated with increased/decreased prickle density in roses.MethodsQTL mapping using pedigree-based analysis (PBA), and haplotype analysis were conducted on two multi-parental diploid rose populations (TX2WOB and TX2WSE).Results and discussionTwelve QTLs were identified on linkage groups (LGs) 2, 3, 4, and 6. The major QTLs for the stem prickle density were located between 42.25 and 45.66 Mbp on chromosome 3 of the Rosa chinensis genome assembly, with individual QTLs explaining 18 to 49% of phenotypic variance (PVE). The remaining mapped QTLs were minor. As for the rachis prickle density, several QTLs were detected on LG3, 4, and 6 with PVE 8 to 17%. Also, this study identified that ancestors R. wichurana ‘Basye’s Thornless’, ‘Old Blush’, and the pollen parent of M4-4 were common sources of favorable alleles (q) associated with decreased prickle density, whereas ’Little Chief’ and ‘Srche Europy’ were the source of unfavorable alleles (Q) in the TX2WOB and TX2WSE populations, respectively. The outcomes of this work complement other studies to locate factors that affect prickle density. These results can also be utilized to develop high-throughput DNA tests and apply parental selection to develop prickle-free rose cultivars.

Abstract Background Virtual reality (VR) is one of the most cutting-edge digital technologies currently used to extend and adapt mental health interventions. When designing therapeutic VR-applications, bias related to representational and behavioral features can be introduced. Specific bias, that could result from ethnic stereotyping, should be averted. However, structured debates and clear guidelines on how to deal with such bias are lacking. Objective In the current paper we describe our iterative, co-design process to develop an augmented version of a 360-degree VR-video that is used in the Street Temptations intervention. In this intervention, aimed at adolescents with disruptive behavior problems, the VR-video provides adolescents with an emotionally engaging situation and forms the basis of Street Temptations’ perspective-taking exercises. By presenting a detailed example of our VR developmental process, specifically focusing on ethnic representation in this virtual environment and related ethical aspects, we aim to positively contribute to the creation of ethically sound therapeutic VR-applications. Method We adopted an experience-based co-design approach. The process started by assembling professionals’ experiences with the original VR-video. Following, we conducted four co-design groups with adolescents, young adults, and professionals within the forensic youth care system, as experiential experts, to collaboratively develop an enhanced VR-scenario for the Street Temptations intervention. In total, ten adolescents, four young adults and four professionals participated. The co-design groups were alternated with sessions with a screenwriter, to reflect on the results of the co-design groups. In this way, we enabled continuous feedback on and design of the ameliorated scenario and let development and data collection reinforce each other. Results The most important adjustments that were brought forward included explicit incorporation of diversity, establishing a clear storyline for the scenario, keeping the content close to reality, casting actors in a way to avoid obvious stigmatization, and using only names for the characters that are commonly used across different cultural and ethnic backgrounds. Discussion By presenting our developmental process, we give a detailed example of how to reflectively develop ethically sound therapeutic VR-content within a forensic youth care setting. We demonstrated that including stakeholders can help in preventing socially irresponsible and conceivably hurtful stereotypes. By describing the process in detail, we hope to contribute to the responsible use of technology within mental health care.

Abstract A key objective of the Perseverance rover mission is to acquire samples of Martian rocks for future return to Earth. Eventual laboratory analyses of these samples would address key questions about the evolution of the Martian climate, interior, and habitability. Many such investigations would benefit greatly from samples of Martian bedrock that are oriented in absolute Martian geographic coordinates. However, the Mars 2020 mission was designed without a requirement for orienting the samples. Here we describe a methodology that we developed for orienting rover drill cores in the Martian geographic frame and its application to Perseverance's first 20 rock samples. To orient the cores, three angles were measured: the azimuth and hade of the core pointing vector (i.e., vector oriented along the core axis) and the core roll (i.e., the solid body angle of rotation around the pointing vector). We estimated the core pointing vector from the attitude of the rover's Coring Drill during drilling. To orient the core roll, we used oriented images of asymmetric markings on the bedrock surface acquired with the rover's Wide Angle Topographic Sensor for Operations and eNgineering (WATSON) camera. For most samples, these markings were in the form of natural features on the outcrop, while for four samples they were artificial ablation pits produced by the rover's SuperCam laser. These cores are the first geographically‐oriented (

Abstract Pharmacogenomics has the potential to inform drug dosing and selection, reduce adverse events, and improve medication efficacy; however, provider knowledge of pharmacogenomic testing varies across provider types and specialties. Given that many actionable pharmacogenomic genes are implicated in cardiovascular medication response variability, this study aimed to evaluate cardiology providers' knowledge and attitudes on implementing clinical pharmacogenomic testing. Sixty‐one providers responded to an online survey, including pharmacists (46%), physicians (31%), genetic counselors (15%), and nurses (8%). Most respondents (94%) reported previous genetics education; however, only 52% felt their genetics education prepared them to order a clinical pharmacogenomic test. In addition, most respondents (66%) were familiar with pharmacogenomics, with genetic counselors being most likely to be familiar (p

Abstract Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1+, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.

Antarctica's ice shelves resist the flow of grounded ice towards the ocean through “buttressing” arising from their contact with ice rises, rumples, and lateral margins. Ice shelf thinning and retreat reduce buttressing, leading to increased delivery of mass to the ocean that adds to global sea level. Ice shelf response to large annual cycles in atmospheric and oceanic processes provides opportunities to study the dynamics of both ice shelves and the buttressed grounded ice. Here, we explore whether seasonal variability of sea surface height (SSH) can explain observed seasonal variability of ice velocity. We investigate this hypothesis using several time series of ice velocity from the Ross Ice Shelf (RIS), satellite-based estimates of SSH seaward of the RIS front, ocean models of SSH under and near RIS, and a viscous ice sheet model. The observed annual changes in RIS velocity are of the order of 1–10 m a−1 (roughly 1 % of mean flow). The ice sheet model, forced by the observed and modelled range of SSH of about 10 cm, reproduces the observed velocity changes when sufficiently large basal drag changes near the grounding line are parameterised. The model response is dominated by grounding line migration but with a significant contribution from SSH-induced tilt of the ice shelf. We expect that climate-driven changes in the seasonal cycles of winds and upper-ocean summer warming will modify the seasonal response of ice shelves to SSH and that nonlinear responses of the ice sheet will affect the longer trend in ice sheet response and its potential sea-level rise contribution.

Maintaining or introducing genetic diversity into plant breeding programs is necessary for continual genetic gain; however, diversity at the cost of reduced performance is not something sought by breeders. To this end, backcross-nested association mapping (BC-NAM) populations, in which the recurrent parent is an elite line, can be employed as a strategy to introgress diversity from unadapted accessions while maintaining agronomic performance. This study evaluates (i) the hybrid performance of sorghum lines from 18 BC1-NAM families and (ii) the potential of genomic prediction to screen lines from BC1-NAM families for hybrid performance prior to phenotypic evaluation. Despite the diverse geographical origins and agronomic performance of the unadapted parents for BC1-NAM families, many BC1-derived lines performed significantly better in the hybrid trials than the elite recurrent parent, R.Tx436. The genomic prediction accuracies for grain yield, plant height, and days to mid-anthesis were acceptable, but the prediction accuracies for plant height were lower than expected. While the prediction accuracies increased when including more individuals in the training set, improvements tended to plateau between two and five lines per family, with larger training sets being required for more complex traits such as grain yield. Therefore, genomic prediction models can be optimized in a large BC1-NAM population with a relatively low fraction of individuals needing to be evaluated. These results suggest that genomic prediction is an effective method of pre-screening lines within BC1-NAM families prior to evaluation in extensive hybrid field trials.

PurposePeople with developmental disabilities and mental health service experiences have a right to be included in healthcare decisions, including the evaluation of their mental health services and providers. However, few self-report measures address this need. This study aimed to fill this gap by developing and evaluating the content validity, including comprehension, relevance, and comprehensiveness, of the Person Experiences Interview Survey (PEIS) with people with developmental disabilities and mental health experiences.MethodsThe research team established a measurement framework based on the Family Experiences Interview Survey (FEIS), resulting in 21 PEIS items that were written in collaboration with young adults with developmental disabilities and mental health service experiences. Comprehension, relevance, and comprehensiveness were evaluated through cognitive interviews with people with developmental disabilities and mental health service experiences (respondents; n = 9) ages 23–49 years. Comprehensiveness and relevance were also evaluated in focus groups with family caregivers (n = 9) and mental health providers (n = 10) who serve this population. Two researchers independently coded open-ended responses to the PEIS for comprehension. A content validity index (CVI), indicating relevance, was calculated for each participant group for each item, and comprehensiveness was rated for item sets.ResultsFifteen of the 21 items met the criteria of ≥80% comprehension, with 89–100% of responses containing all or some intended information. All items met the CVI ≥80% criterion in at least two of the three groups. In all item sets, between 1 and 4 family members or providers felt one question was missing. Respondents used the response scale in a manner that corresponded with their open-ended descriptions, and family caregivers and providers had positive feedback about the response scale’s visual cues and number of choices. Using these findings, four items were removed and six items were revised, resulting in a 17-item measure.ConclusionThis study presents a novel and promising measure, the Person Experiences Interview Survey (PEIS). It also demonstrates that the employment of accessible methods allows people with developmental disabilities to meaningfully evaluate mental health services and providers. The PEIS shows great promise for application in the field by engaging those directly involved in the evaluation of mental health services and providers.

BackgroundWe developed Street Temptations (ST) as an add-on intervention to increase the treatment responsivity of adolescents with disruptive behavior problems. ST’s primary aim is to improve adolescents’ mentalizing abilities in order to help them engage in and benefit from psychotherapy. Additionally, virtual reality (VR) is used to work in a more visual, less verbal, fashion. ObjectiveBy recapping the lessons learned while developing ST so far, we aim to design the following study on ST. Furthermore, we aim to enhance the development and study of new health care interventions in clinical practice, together with adolescents as their end users. MethodsWe followed an iterative co-creation process to develop a prototype of ST, in collaboration with adolescents and professionals from a secured residential facility in Amsterdam, the Netherlands. The prototype was tested during a pilot phase, involving 2 test runs, in which 4 adolescents and 4 professionals participated. Qualitative data were collected through interviews with the adolescents and by conducting a group interview with the professionals, in order to gain first insights into ST’s usability, feasibility, and its added value to clinical practice. In between the first and second test runs, the prototype was enhanced. On the basis of the complete pilot phase, we reflected on the future development and implementation of ST to design a subsequent study. ResultsOver the course of 6 months, ST’s first prototype was developed during multiple creative sessions. Included was the development of a short 360° VR video, to serve as a base for the mentalization exercises. The final version of ST consisted of 7 individual therapy sessions, incorporating both the VR video and a VR StreetView app. On the basis of the qualitative data collected during the pilot phase, we found preliminary signs of ST’s potential to support adolescents’ perspective-taking abilities specifically. Additionally, using VR to focus on real-life situations that adolescents encounter in their daily lives possibly helps to facilitate communication. However, several challenges and requests concerning the VR hardware and software and the implementation of ST emerged, pointing toward further development of ST as an add-on intervention. These challenges currently limit large-scale implementation, resulting in specific requirements regarding a subsequent study. ConclusionsIn order to gather more extensive information to shape further development and study treatment effects, a small-scale and individually oriented research design seems currently more suitable than a more standard between-subjects design. Using the reflection on the lessons learned described in this report, a research protocol for a forthcoming study on ST has been developed. By presenting our co-creation journey thus far, we hope to be of inspiration for a more co-creative mindset and in that way contribute to the mutual reinforcement of science and clinical practice.

Abstract Use of trifluoromethanesulfonamide (TFMSA), a male gametocide, increases the opportunities to identify promising B‐lines because large quantities of F1 seed can be generated prior to the laborious task of B‐line sterilization. Combining TFMSA technology with genomic selection could efficiently evaluate sorghum B‐lines in hybrid combination to maximize the rates of genetic gain of the crop. This study used two recombinant inbred B‐line populations, consisting of 217 lines, which were testcrossed to two R‐lines to produce 434 hybrids. Each population of testcross hybrids were evaluated across five environments. Population‐based genomic prediction models were assessed across environments using three different cross‐validation (CV) schemes, each with 70% training and 30% validation sets. The validation schemes were as follows: CV1—hybrids chosen randomly for validation; CV2—B‐lines were randomly chosen, and each chosen B‐line had one of the two corresponding testcross hybrids randomly chosen for the validation; and CV3—B‐lines were randomly chosen, and each chosen B‐line had both corresponding testcross hybrids chosen for the validation. CV1 and CV2 presented the highest prediction accuracies; nonetheless, the prediction accuracies of the CV schemes were not statistically different in many environments. We determined that combining the B‐line populations could improve prediction accuracies, and the genomic prediction models were able to effectively rank the poorest 70% of hybrids even when genomic prediction accuracies themselves were low. Results indicate that combining genomic prediction models and TFMSA technology can effectively aid breeders in predicting B‐line hybrid performance in early generations prior to the laborious task of generating A/B‐line pairs.

Abstract Treatment with oncolytic measles vaccines (MV) elicits activation of immune cells, including natural killer (NK) cells. However, we found that MV-activated NK cells show only modest direct cytotoxic activity against tumor cells. To specifically direct NK cells towards tumor cells, we developed oncolytic measles vaccines encoding bispecific killer engagers (MV-BiKE) targeting CD16A on NK cells and carcinoembryonic antigen (CEA) as a model tumor antigen. MV-BiKE are only slightly attenuated compared to parental MV and mediate secretion of functional BiKE from infected tumor cells. We tested MV-BiKE activity in cocultures of colorectal or pancreatic cancer cells with primary human NK cells. MV-BiKE mediate expression of effector cytokines, degranulation and specific anti-tumor cytotoxicity by NK cells. Experiments with patient-derived pancreatic cancer cultures indicate that efficacy of MV-BiKE may vary between individual tumors with differential virus permissiveness. Remarkably, we confirmed MV-BiKE activity in primaryhuman colorectal carcinoma specimens with autochthonous tumor and NK cells.This study provides proof-of-concept for MV-BiKE as a novel immunovirotherapy to harness virus-activated NK cells as anti-tumor effectors.

Abstract Background Pharmacogenomics (PGx) aims to utilize a patient’s genetic data to enable safer and more effective prescribing of medications. The Clinical Pharmacogenetics Implementation Consortium (CPIC) provides guidelines with strong evidence for 24 genes that affect 72 medications. Despite strong evidence linking PGx alleles to drug response, there is a large gap in the implementation and return of actionable pharmacogenetic findings to patients in standard clinical practice. In this study, we evaluated opportunities for genetically guided medication prescribing in a diverse health system and determined the frequencies of actionable PGx alleles in an ancestrally diverse biobank population. Methods A retrospective analysis of the Penn Medicine electronic health records (EHRs), which includes ~ 3.3 million patients between 2012 and 2020, provides a snapshot of the trends in prescriptions for drugs with genotype-based prescribing guidelines (‘CPIC level A or B’) in the Penn Medicine health system. The Penn Medicine BioBank (PMBB) consists of a diverse group of 43,359 participants whose EHRs are linked to genome-wide SNP array and whole exome sequencing (WES) data. We used the Pharmacogenomics Clinical Annotation Tool (PharmCAT), to annotate PGx alleles from PMBB variant call format (VCF) files and identify samples with actionable PGx alleles. Results We identified ~ 316.000 unique patients that were prescribed at least 2 drugs with CPIC Level A or B guidelines. Genetic analysis in PMBB identified that 98.9% of participants carry one or more PGx actionable alleles where treatment modification would be recommended. After linking the genetic data with prescription data from the EHR, 14.2% of participants (n = 6157) were prescribed medications that could be impacted by their genotype (as indicated by their PharmCAT report). For example, 856 participants received clopidogrel who carried CYP2C19 reduced function alleles, placing them at increased risk for major adverse cardiovascular events. When we stratified by genetic ancestry, we found disparities in PGx allele frequencies and clinical burden. Clopidogrel users of Asian ancestry in PMBB had significantly higher rates of CYP2C19 actionable alleles than European ancestry users of clopidrogrel (p

Rose (Rosa spp.) is one of the most economically important ornamental species worldwide. Flower diameter, flower weight, and the number of petals and petaloids are key flower-size parameters and attractive targets for DNA-informed breeding. Pedigree-based analysis (PBA) using FlexQTL software was conducted using two sets of multi-parental diploid rose populations. Phenotypic data for flower diameter (Diam), flower weight (fresh (FWT)/dry (DWT)), number of petals (NP), and number of petaloids (PD) were collected over six environments (seasons) at two locations in Texas. The objectives of this study were to 1) identify new and/or validate previously reported QTL(s); 2) identify SNP haplotypes associated with QTL alleles (Q-/q-) of a trait and their sources; and 3) determine QTL genotypes for important rose breeding parents. Several new and previously reported QTLs for NP and Diam traits were identified. In addition, QTLs associated with flower weight and PD were identified for the first time. Two major QTLs with large effects were mapped for all traits. The first QTL was at the distal end of LG1 (60.44–60.95 Mbp) and was associated with Diam and DWT in the TX2WOB populations. The second QTL was consistently mapped in the middle region on LG3 (30.15–39.34 Mbp) and associated with NP, PD, and flower weight across two multi-parent populations (TX2WOB and TX2WSE). Haplotype results revealed a series of QTL alleles with differing effects at important loci for most traits. This work is distinct from previous studies by conducting co-factor analysis to account for the DOUBLE FLOWER locus while mapping QTL for NP. Sources of high-value (Q) alleles were identified, namely, ‘Old Blush’ and Rosa wichuraiana from J14-3 for Diam, while ‘Violette’ and PP-J14-3 were sources for other traits. In addition, the source of the low-value (q) alleles for Diam was ‘Little Chief’, and Rosa wichuraiana through J14-3 was the source for the remaining traits. Hence, our results can potentially inform parental/seedling selections as means to improve ornamental quality in roses and a step towards implementing DNA-informed techniques for use in rose breeding programs.

Background: This study aimed to assess the preferred operative treatment for patients over the age of 60 with end-stage ankle arthritis and perspectives on total ankle replacement (TAR) among American Orthopaedic Foot & Ankle Society (AOFAS) members. Associated factors were analyzed for potential contraindications among members with different levels of experience. Method: A questionnaire containing 6 questions was designed and sent to 2056 members of the AOFAS. Responses were received from 467 orthopaedic surgeons practicing in the United States (76%), Canada (5%), and 26 other countries (20%). Participants were grouped for response comparisons according to country as well as experience level. Differences in contraindications were compared using χ 2 tests or exact tests. Results: Respondents practicing in the United States and surgeons who perform 11 or more TARs per year tended to recommend operative treatments favoring TAR and displayed recognition of its increasing role (P < .05). Overall, respondents felt that 41% of typical patients over 60 years old with end-stage arthritis would be best treated with TAR. Talus avascular necrosis, morbid obesity (body mass index >40 kg/m 2 ), and poorly controlled diabetes with neuropathy were most recognized as the absolute contraindications to TAR. Surgeon’s experience affected the consideration of these clinical factors as contraindications. Conclusions: Total ankle replacement has a substantial and increasing role in the treatment of end-stage ankle arthritis in patients over the age of 60. Absolute and potential contraindications of the procedures were indicated from a cross-sectional survey of AOFAS members. Surgeons more experienced with total ankle replacement felt more comfortable employing it in a wider range of clinical settings. Level of Evidence: Level III, therapeutic.

Garden roses are an economically important horticultural crop worldwide, and two major fungal pathogens, black spot (Diplocarpon rosae F.A. Wolf) and cercospora leaf spot of rose (Rosisphaerella rosicola Pass.), affect both the health and ornamental value of the plant. Most studies on black spot disease resistance have focused on diploid germplasm, and little work has been performed on cercospora leaf spot resistance. With the use of newly developed software tools for autopolyploid genetics, two interconnected tetraploid garden rose F1 populations (phenotyped over the course of 3 years) were used for quantitative trait locus (QTL) analysis of black spot and cercospora leaf spot resistance as well as plant defoliation. QTLs for black spot resistance were mapped to linkage groups (LGs) 1–6. QTLs for cercospora resistance and susceptibility were found in LGs 1, 4, and 5 and for defoliation in LGs 1, 3, and 5. The major locus on LG 5 for black spot resistance coincides with the previously discovered Rdr4 locus inherited from Rosa L. ‘Radbrite’ (Brite Eyes™), the common parent used in these mapping populations. This work is the first report of any QTL for cercospora resistance/susceptibility in tetraploid rose germplasm and the first report of defoliation QTL in roses. A major QTL for cercospora susceptibility coincides with the black spot resistance QTL on LG 5 (Rdr4). A major cercospora resistance QTL was found on LG 1. These populations provide a genetic resource that will further the knowledge base of rose genetics as more traits are studied. Studying more traits from these populations will allow for the stacking of various QTLs for desirable traits.

Arithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and non-neocortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far. Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n = 73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct gray-to-gray matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit. Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.

Background: Ankle fractures are among the most common injuries treated by orthopaedic surgeons, yet little guidance exists in postoperative protocols for ankle fractures concerning time of immobilization. Here, we aim to investigate the association between early mobilization and patient-reported outcomes. Our null hypothesis was that no difference in Patient-Reported Outcomes Measurement Information System (PROMIS) scores would be identified in patients when comparing the effect of time of immobilization. Methods: A retrospective review identified ankle fractures that underwent surgical fixation between 2015 and 2020 at a level 1 trauma center and its associated facilities. One hundred nineteen patients from 9 providers met inclusion criteria for our final analysis. Forty-seven patients were immobilized for .05). Furthermore, we found no differences in complications associated with fracture fixation ( P > .05). Across our cohort, lower physical function scores were associated with higher BMI, increasing age, and longer time to return to work/play ( P

Cercospora leaf spot (CLS) (Cercospora rosicola) is a major fungal disease of roses (Rosa sp.) in the southeastern U.S. Developing CLS-resistant cultivars offers a potential solution to reduce pesticide use. Yet, no work has been performed on CLS resistance. This study aimed to identify QTLs and to characterize alleles for resistance to CLS. The study used pedigree-based QTL analysis to dissect the genetic basis of CLS resistance using two multi-parental diploid rose populations (TX2WOB and TX2WSE) evaluated across five years in two Texas locations. A total 38 QTLs were identified across both populations and distributed over all linkage groups. Three QTLs on LG3, LG4, and LG6 were consistently mapped over multiple environments. The LG3 QTL was mapped in a region between 18.9 and 27.8 Mbp on the Rosa chinensis genome assembly. This QTL explained 13 to 25% of phenotypic variance. The LG4 QTL detected in the TX2WOB population spanned a 35.2 to 39.7 Mbp region with phenotypic variance explained (PVE) up to 48%. The LG6 QTL detected in the TX2WSE population was localized to 17.9 to 33.6 Mbp interval with PVE up to 36%. Also, this study found multiple degrees of favorable allele effects (q-allele) associated with decreasing CLS at major loci. Ancestors ‘OB’, ‘Violette’, and PP-M4-4 were sources of resistance q-alleles. These results will aid breeders in parental selection to develop CLS-resistant rose cultivars. Ultimately, high throughput DNA tests that target major loci for CLS could be developed for routine use in a DNA-informed breeding program.

Rose rosette disease (RRD), caused by the Rose rosette emaravirus (RRV), is a major threat to the garden rose industry in the United States. There has been limited work on the genetics of host plant resistance to RRV. Two interconnected tetraploid garden rose F1 biparental mapping populations were created to develop high-quality tetraploid rose linkage maps that allowed the discovery of RRD resistance quantitative trait loci (QTLs) on linkage groups (LGs) 5, 6, and 7. These QTLs individually accounted for around 18–40% of the phenotypic variance. The locus with the greatest effect on partial resistance was found in LG 5. Most individuals with the LG 5 QTL were in the simplex configuration; however, two individuals were duplex (likely due to double reduction). Identification of resistant individuals and regions of interest can help the development of diagnostic markers for marker-assisted selection in a breeding program.

Oxinium implants are composed of a zirconium alloy with a hard ceramic surface formed by oxidization of the outer layer. This material has been shown to be an effective bearing surface for total joint arthroplasty and an alternative material for use in patients with metal hypersensitivity. Reports exist of metallosis due to unintended wear of Oxinium components from multiple mechanisms including polyethylene liner dissociation and joint instability. This metallosis creates a distinct appearance on radiographic imaging similar to that of an arthrogram. We report 2 cases of metallosis and describe the characteristic radiographic appearance of failed oxidized zirconium implants.

Total hip arthroplasty is one of the most successful operations in all of medicine. Femoral deformities from malunion, prior osteotomy, and retained surgical implants all present unique challenges. Corrective osteotomy and hardware removal add significant morbidity to an operation that typically has a fast recovery. Short stems can be used in these cases to spare patients' increased morbidity. We present a case-based illustration and surgical technique for the use of short stems in complex primary total hip arthroplasty with femoral deformity and retained hardware. We discuss how these implants can spare significant morbidity, show radiographic examples of their use, and present short-term outcomes.

Background: As America’s third highest opioid prescribers, orthopedic surgeons have contributed to the opioid abuse crisis. This study evaluated opioid use after primary total joint replacement. We hypothesized that patients who underwent total hip arthroplasty (THA) use fewer opioids than patients who underwent total knee arthroplasty (TKA) and that both groups use fewer opioids than prescribed. Methods: A prospective study of 110 patients undergoing primary THA or TKA by surgeons at an academic center during 2018 was performed. All were prescribed oxycodone 5 mg, 84 tablets, without refills. Demographics, medical history, and operative details were collected. Pain medication consumption and patient-reported outcomes were collected at 2 and 6 weeks postoperatively. Analysis of variance was performed on patient and surgical variables. Results: Sixty-one patients scheduled for THA and 49 for TKA were included. THA patients consumed significantly fewer opioids than TKA patients at 2 weeks (28.1 tablets vs 48.4, P = .0003) and 6 weeks (33.1 vs 59.3, P = .0004). Linear regression showed opioid use decreased with age at both time points (P = .0002). A preoperative mental health disorder was associated with higher usage at 2 weeks (58.3 vs 31.4, P < .0001) and 6 weeks (64.7 vs 39.2, P = .006). Higher consumption at 2 weeks was correlated with worse outcome scores at all time points. Conclusions: TKA patients required more pain medication than THA patients, and both groups received more opioids than necessary. In addition, younger patients and those with a preexisting mental health disorder required more pain medication. These data provide guidance on prescribing pain medication to help limit excess opioid distribution.

Ageing of historical documents often results in changes in the optical properties of the constituent materials. Imaging spectroscopy (IS) can be a valuable tool for monitoring of such changes, if the method fulfils two important conditions. Firstly, compared to natural ageing, the accumulated light dose from repeated measurements of the monitored document must not induce any significant degradation. Secondly, the monitoring instrumentation and procedures should be sensitive enough to detect changes in the materials before they become visible. We present experimental methods to evaluate the suitability of IS instrumentation for monitoring purposes. In the first set of experiments, the impact of repeated monitoring measurements was determined using a set of Blue Wool Standard materials. In the second set of experiments, the capability of the instrument to detect spectral changes was tested using ISO standard materials and several documents representative of European archive collections. It is concluded that the tested hyperspectral instrument is suitable for monitoring of the colour change of documents during display. The described experimental approach can be recommended to test the suitability of other imaging spectroscopy instruments for monitoring applications.

BackgroundSerious disruptive behavior among adolescents is a prevalent and often persistent problem. This highlights the importance of adequate and effective treatment to help adolescents with disruptive behavior problems react less hostile and aggressive. In order to create a treatment environment in which behavioral change can be enhanced, treatment motivation plays an essential role. Regarding treatment itself, a focus on challenging self-serving cognitive distortions in order to achieve behavioral change is important. Street Temptations (ST) is a new training program that was developed to address both treatment motivation and cognitive distortions in adolescents with disruptive behavior problems. One of the innovative aspects of ST is the use of virtual reality (VR) techniques to provide adolescents during treatment with visually presented daily social scenarios to activate emotional engagement and dysfunctional cognitions. By using the VR scenarios as an integral starting point of ST’s sessions and transferring the power of the VR experience into playful and dynamic exercises to practice social perspective–taking, adolescents are encouraged to reflect on both their own behavior and that of others. This focus on reflection is grounded in ST’s main treatment mechanism to influence treatment motivation and cognitive distortions, namely, mentalizing (ie, reflective functioning). ObjectiveThe aim of this study is to describe the research protocol to evaluate the effects of ST on treatment motivation and cognitive distortions. We take a closer look at the use of ST and the methodology used, namely, the repeated single-case experimental design (SCED). MethodsThe effects of ST are studied through a multiple baseline SCED, using both quantitative and qualitative data. In total, 18 adolescents from secure residential youth care facilities and secondary special education schools are randomly assigned to 1 of the 3 different baseline conditions. Throughout the baseline phase (1, 2, or 3 weeks), intervention phase (4 weeks), and follow-up phase (1, 2, or 3 weeks), daily measurements on treatment motivation and cognitive distortions are conducted. Secondary study parameters are assessed before baseline, after intervention, and after follow-up. Qualitative data are collected after intervention, as well as at 3 months and 6 months after the intervention. ResultsData collection for this study started in November 2021 and is planned to be completed by August 2023. The results will be published in peer-reviewed journals and presented at national and international conferences. ConclusionsST aims to improve the disruptive behavior problems of adolescents. This study will be the first to gain insights into the effectiveness of ST. The strengths of this study include its thorough and individually focused design (SCED), the focus on a residential as well as a secondary special education setting, and the ecological validity. The implications for practice are discussed. Trial RegistrationCentral Committee on Research Involving Human Subjects NL75545.029.20. Netherlands Trial Register NL9639; https://www.trialregister.nl/trial/9639 International Registered Report Identifier (IRRID)PRR1-10.2196/33555

PurposeTo investigate if accounting for a cup-to-disc ratio (CDR) genetic risk score (GRS) modified the association between large CDR and cognitive function among women.DesignThis was a retrospective study using data from the Women's Health Initiative.MethodsPatients with glaucoma or ocular hypertension were excluded. Large CDR was defined as ≥ 0.6 in either eye. Cognitive function was measured by the Modified Mini-Mental State Examination (3MSE). We used the combined effects from 13 single nucleotide polymorphisms (SNPs) to formulate the GRS for CDR. We used logistic regression to investigate associations between weighted GRS and large CDR, then a linear regression to assess the association between weighted GRS and 3MSE scores, and between weighted GRS, CDR, and 3MSE scores, adjusted for demographic and clinical characteristics.ResultsFinal analyses included 1,196 White women with mean age of 69.60 ± 3.62 years and 7.27% with large CDR. Mean GRS in women with and without large CDR was 1.51 ± 0.31 vs. 1.41 ± 0.36, respectively (p = 0.004). The odds of large CDR for a one unit increase in GRS was 2.30 (95% CI: (1.22, 4.36), p = 0.011). Adding the CDR GRS in the model with CDR and 3MSE, women with large CDR still had statistically significantly lower 3MSE scores than those without large CDR, yielding a predicted mean difference in 3MSE scores of 0.84 (p = 0.007).ConclusionsIndependent of the CDR GRS, women with large CDR had a lower cognitive function.

To exploit the novel genetic diversity residing in tropical sorghum germplasm, an expansive backcross nested-association mapping (BC-NAM) resource was developed in which novel genetic diversity was introgressed into elite inbreds. A major limitation of exploiting this type of genetic resource in hybrid improvement programs is the required evaluation in hybrid combination of the vast number of BC-NAM populations and lines. To address this, the utility of genomic information was evaluated to predict the hybrid performance of BC-NAM populations. Two agronomically elite BC-NAM populations were chosen for evaluation in which elite inbred RTx436 was the recurrent parent. Each BC1F3 line was evaluated in hybrid combination with an elite tester in two locations with phenotypes of grain yield, plant height, and days to anthesis collected on all test cross hybrids. Lines from both populations were found to outperform their recurrent parent. Efforts to utilize genetic distance based on genotyping-by-sequence (GBS) as a predictive tool for hybrid performance was ineffective. However, utilizing genomic prediction models using additive and dominance GBLUP kernels to screen germplasm appeared to be an effective method to eliminate inferior-performing lines that will not be useful in a hybrid breeding program.

Jejunal vascular ligation is an essential step in performing jejunojejunostomy. Hand sewn ligation is typically used and can increase operative time with long sections of bowel to be removed. Nylon cable ties (NCT) have been used for vascular ligation in horses but are yet to be investigated for application on the mesenteric vasculature of the gastrointestinal tract. Our objective was to evaluate the efficacy and short-term safety of NCT jejunal mesenteric vessel ligation in healthy horses. Eight healthy adult horses underwent midline celiotomy. A segment of jejunal mesentery was identified (≥4 arcades). Briefly, three fenestrations (proximal, middle, distal) were made 5–10 mm apart adjacent to the first and last vascular arcade to be ligated. Two sterilized NCT were passed to encircle the mesentery through the proximal and middle fenestrations, separated by intact mesentery. NCT were closed tightly and the vascular pedicle transected with Mayo scissors through the distal fenestration. Jejunojejunostomy was then performed and the mesentery sutured closed. The number of vascular arcades and time to ligate using NCT were recorded. At 2 weeks, horses underwent repeat celiotomy to assess the healing of the NCT ligation site and an equal number of vascular arcades were hand sewn double ligated using 2-0 Polyglactin 910 as a timed comparison. NCT mesenteric ligation was significantly faster than hand sewn methods (P < 0.01). Effective hemostasis was achieved in all cases. There was no evidence of local infection or adhesions at 14 days post-operatively. Further investigation in the long-term effects in horses as well as horses with strangulating jejunal lesions are needed for clinical application.

Resistance to rose rosette disease (RRD), a fatal disease of roses (Rosa spp.), is a high priority for rose breeding. As RRD resistance is time-consuming to phenotype, the identification of genetic markers for resistance could expedite breeding efforts. However, little is known about the genetics of RRD resistance. Therefore, we performed a quantitative trait locus (QTL) analysis on a set of inter-related diploid rose populations phenotyped for RRD resistance and identified four QTLs. Two QTLs were found in multiple years. The most consistent QTL is qRRV_TX2WSE_ch5, which explains approximately 20% and 40% of the phenotypic variation in virus quantity and severity of RRD symptoms, respectively. The second, a QTL on chromosome 1, qRRD_TX2WSE_ch1, accounts for approximately 16% of the phenotypic variation for severity. Finally, a third QTL on chromosome 3 was identified only in the multiyear analysis, and a fourth on chromosome 6 was identified in data from one year only. In addition, haplotypes associated with significant changes in virus quantity and severity were identified for qRRV_TX2WSE_ch5 and qRRD_TX2WSE_ch1. This research represents the first report of genetic determinants of resistance to RRD. In addition, marker trait associations discovered here will enable better parental selection when breeding for RRD resistance and pave the way for marker-assisted selection for RRD resistance.

Background: Although a successful operation, almost 20% of patients are dissatisfied with total knee arthroplasty (TKA). The purpose of this retrospective cohort study was to see if a medial congruent (MC) polyethylene would offer satisfactory early outcomes and patient satisfaction after TKA. Methods: We reviewed prospectively collected data on 327 TKAs using multiple bearings within the same implant system. Ninety-six received an MC bearing, 70 received a cruciate-retaining (CR) bearing, and 161 received a posterior-stabilized (PS) bearing. We evaluated the visual analog scale pain scores and range of motion (ROM) at 2 weeks, 6 weeks, 3 months, and 1 year; Patient-Reported Outcomes Measurement Information System (PROMIS-10) score and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 3 months and 1 year; and Forgotten Joint Score (FJS-12) at 1 year. Results: All groups had similar KOOS and PROMIS-10 scores. MC knees had lower visual analog scale scores than PS knees at all time points (P < .05) and a higher ROM than PS at 2 weeks (98.6 vs 93.7, P = .002). MC knees had a significantly higher FJS-12 than CR knees (71.6 vs 58.7, P = .02). More MC knees were “very satisfied” than CR (92.6% vs 81.5%, P = .04). Fewer MC knees were “not at all satisfied” than CR (1.2% vs 9.2%, P = .04). There were similar satisfaction ratings with MC and PS. Conclusions: An MC bearing provided similar or improved early pain, ROM, KOOS, PROMIS-10, FJS-12, and patient satisfaction as compared with standard bearings in TKA.

The label ‘conspiracy theory’, while part of everyday media discourse, is considered by many as problematic. In this research, we posit that there exists diverging social representations associated with this label and that their relative endorsement is a function of preexisting beliefs. To evaluate this possibility, we examine how generic conspiracist beliefs are associated with two forms of rejection of the label: 1) Belief in a meta-conspiracy theory, that is, the belief that the label ‘conspiracy theory’ was purposely created by the elites in order to discredit dissent, and 2) a particularist view of conspiracy theories, that is, the idea that ‘conspiracy theories’ are too diverse to draw any generic conclusions regarding their (ir)rationality and that the label is therefore inadequate. Across two studies ('Ns' = 1297), using principal components (Study 1) and confirmatory factor analyses (Study 2), we found that generic conspiracist beliefs and belief in meta-conspiracy theory were tightly related. Moreover, in Study 2, generic conspiracist beliefs were substantially associated with the endorsement of a particularist view of conspiracy theories. Using lexicometric analyses of open-ended questions about the origin and the perceived validity of the label, we identified four main criticisms addressed to the label: historical (real conspiracies happen), conceptual (the label has no clear definition), normative (the label has a negative connotation), and political (the label is weaponized by powerholders). By contrast, acceptance of the label was justified by arguments referring to common psychological mechanisms, as well as similar narrative and argumentative structures. Theoretical and practical implications are discussed.

Genetics: A DNA map of roses A genetic map of rose DNA could help flower breeders develop ornamental crops that are more resistant to disease or have other desirable traits. Rose breeder, David Byrne and molecular geneticist, Patricia Klein along with their colleagues from Texas A&M University in College Station, USA, bred five different strains of ‘diploid’ rose, each with two full sets of chromosomes, to create 234 offspring plants. Using the full genome from strawberry, a closely related species, as a reference, the researchers then looked for sites in the genome where either single DNA letters differed between individual offspring or where short sequences of DNA repeated themselves to create easily identifiable genetic markers. They created genetic maps of each parental cross, and then formed a consensus map that can now serve as a tool for future genetically guided breeding efforts of horticulturally important traits.