Local adaptation drives the diversification of effectors in the fungal wheat pathogen Parastagonospora nodorum in the United States

Filamentous fungi rapidly evolve in response to environmental selection pressures in part due to their genomic plasticity. Parastagonospora nodorum, a fungal pathogen of wheat and causal agent of septoria nodorum blotch, responds to selection pressure exerted by its host, influencing the gain, loss, or functional diversification of virulence determinants, known as effector genes. Whole genome resequencing of 197 P. nodorum isolates collected from spring, durum, and winter wheat production regions of the United States enabled the examination of effector diversity and genomic regions under selection specific to geographically discrete populations. 1,026,859 SNPs/InDels were used to identify novel loci, as well as SnToxA and SnTox3 as factors in disease. Genes displaying presence/absence variation, predicted effector genes, and genes localized on an accessory chromosome had significantly higher pN/pS ratios, indicating a higher rate of sequence evolution. Population structure analyses indicated two P. nodorum populations corresponding to the Upper Midwest (Population 1) and Southern/Eastern United States (Population 2). Prevalence of SnToxA varied greatly between the two populations which correlated with presence of the host sensitivity gene Tsn1 in the most prevalent cultivars in the corresponding regions. Additionally, 12 and 5 candidate effector genes were observed to be under diversifying selection among isolates from Population 1 and 2, respectively, but under purifying selection or neutrally evolving in the opposite population. Selective sweep analysis revealed 10 and 19 regions that had recently undergone positive selection in Population 1 and 2, respectively, involving 92 genes in total. When comparing genes with and without presence/absence variation, those genes exhibiting this variation were significantly closer to transposable elements. Taken together, these results indicate that P. nodorum is rapidly adapting to distinct selection pressures unique to spring and winter wheat production regions by rapid adaptive evolution and various routes of genomic diversification, potentially facilitated through transposable element activity

Editorial: Advances in breeding for wheat disease resistance

Wheat is the most widely planted crop on the planet and contributes up to 20% of total calorie intake for humankind. Maintaining wheat yields is crucial to feeding the world’s people, especially as climate models suggest that rising global temperatures will negatively affect wheat production (Asseng et al., 2015). Diseases of wheat take an important toll, annually robbing humanity of 20% or more of the crop on a global basis (Savary et al., 2019; Savary and Willocquet, 2021). Changes in weather patterns may accelerate pathogen life cycles and escalate shifts in pathogen populations and virulence, posing significant challenges to disease resistance breeding. As well, global trade may increase the chances for a pathogen to spread rapidly and adapt to novel environments and even hosts, leading to emerging diseases. The release and use of wheat cultivars with effective and durable disease resistance is more important now than ever. This is so for multiple reasons. First, disease resistance stabilizes yields and reduces economic losses, saving money for producers who are already facing major challenges due to rising temperatures, more frequent and unpredictable natural disasters, and high and rising costs of inputs such as pesticides (FAO, 2021; Lüttringhaus et al., 2021; Miedaner and Juroszek, 2021). Second, greater reliance on disease resistance can slow pathogen spread and multiplication, prolonging the useful life of available pesticide chemistries so they will be effective when needed to manage severe epidemics (Brent et al., 2007). Third, the growing use of conservation tillage, which is vital for soil health and stabilization, has elevated the importance of diseases such as Fusarium head blight that cannot be completely managed with fungicides (Aboukhaddour et al., 2020). Breeding for disease resistance in wheat has made major technological advances, but still faces important challenges. Prominent among those challenges is the need to develop cultivars for a tremendous diversity of agro-ecological environments, production practices, and discrete market classes (Cowger, 2021). Another challenge is that major genes such as those traditionally deployed to manage wheat rust diseases are often rapidly overcome. This requires a focus on quantitative and race non-specific resistance that may be harder to introgress, select for, and retain in a multi-trait context (Cowger and Brown, 2019; van Esse et al., 2020). The more genes are identified and their mechanisms of action elucidated, the more tools will be available to researchers and breeders to assemble genetically novel germplasm with improved and more durable resistance. The authors who have contributed to this Research Topic tackle those challenges by providing new resources and tools to aid wheat breeders across the globe. The 18 original articles cover a good sample of the world’s most important wheat diseases and the state-of-the-art techniques applied by researchers to identify and evaluate the relevant disease resistance traits. For example, wheat blast is an emergent and damaging disease that has jumped continents from Latin America to Asia, as explained in a comprehensive review by Singh et al., 2021. A team of blast researchers has compared marker-assisted and genomic selection using precision phenotyping of blast resistance conferred by the 2NS translocation (Juliana et al., 2022), which is partial and sometimes background-dependent. Another major threat to global wheat production is Fusarium head blight. Three articles in this Research Topic offer important new resources for breeding cultivars with effective FHB resistance. The Brazilian spring cultivar Surpresa provides a new source of resistance not currently used (Poudel et al. 2022). Three resistance loci (Fhb1, Fhb4, and Fhb5) were introgressed as a pyramid into desirable Chinese white and red semi-winter wheat lines (Zhang et al., 2021). And a novel technique could speed up the development of FHB-resistant winter wheat germplasm, increasing breeding generations from two to three per year (Zakieh et al. 2021). Researchers used various approaches to identify new sources of resistance to the three wheat rusts (stem, stripe, and leaf). A new stem rust resistance gene was mapped in the durum wheat variety Kronos and introgressed into common wheat using co-segregating DNA markers (Li et al., 2021). The effects of combinations of leaf rust resistance genes were investigated in a Canadian wheat double-haploid population (McCallum and Hiebert, 2022) and in a durably resistant Canadian wheat cultivar (Bokore et al., 2022). A multi-parent advanced generation intercross (MAGIC) wheat population was used to map adult-plant and seedling resistance to stripe rust in Germany (Rollar et al., 2021). A genome-wide association study was used to identify stripe rust resistance loci in a panel of Chinese wheat landraces (Yao et al., 2021). And QTL mapping led to identification of stripe and leaf rust loci in an Afghan landrace (Zhang et al., 2022), a Chinese landrace (Wang et al., 2022), and the CIMMYT wheat line “Mucuy” (Lan et al., 2022; so far this is an abstract, need the URL to the full article when it’s available). Breeding wheat cultivars with resistance to powdery mildew requires a constant stream of new resistance sources, thanks to the pathogen’s ability to rapidly overcome host resistance through adaptation. The efficacy of a set of new resistance genes introgressed from Middle Eastern wild wheat relatives was measured using powdery mildew populations from various wheat growing regions affected by the disease (Kloppe et al., 2022). A more unusual wild relative of wheat, Psathyrostachys huashanica, which is found only in the Huashan Mountains of China, also furnished novel resistance to wheat powdery mildew (Liu et al., 2021). A previously unidentified source of resistance to Hessian fly was identified in spring wheat cultivars of the U.S. Pacific Northwest (Prather et al., 2022). And in a twist, a locus conferring not resistance but susceptibility, in this case to tan spot, was identified in U.S. bi-parental spring wheat mapping populations and narrowed to a region encompassing seven candidate genes (Running et al., 2022). Last but not least, an interesting look under the ground revealed that rhizosphere microbiomes differed among wheat genotypes and had an impact on pathogenicity of Rhizoctonia solani, suggesting the potential to manage Rhizoctonia root rot with wheat genotypes that recruit microbiomes associated with improved plant fitness and suppression of the fungal pathogen (Dilla-Ermita et al., 2021). For this Research Topic, we have collected articles that demonstrate how cutting-edge approaches to breeding are being brought to bear on some of the chief diseases threatening the world’s wheat production systems. The authors’ contributions are of the highest quality, and illustrate the strong international interest in this topic. These reports help breeders everywhere assess and employ novel and potentially durable resistance to wheat diseases. They will make a practical difference in helping safeguard global wheat yields in the challenging years to come

Power, Pathological Worldviews, and the Strengths Perspective in Social Work

This article takes up Blundo’s (2001) assertion in this journal that in order to practice from the strengths perspective, social workers need to alter their “frames.” Expanding on this assertion, we specify a particular frame that requires change: a pathological worldview. Examining the strengths perspective with regard to a Foucauldian analysis of power, we argue that to thoroughly implement the strengths perspective, we need to consider the dividing practices that allow us to maintain power and that reflect a pathological worldview. This article provides considerations for social work practice that will be of interest to practicing social workers and social work educators interested in continuing to develop their strengths-based practice

What If the Destination Is Transplant? Outcomes of Destination Therapy Patients Who Were Transplanted

We sought to characterize patients who underwent heart transplant (HTx) following destination therapy (DT) implant in the combined ENDURANCE/ENDURANCE Supplemental Trials (DT/DT2). A post hoc analysis of the DT/DT2 trials was performed. Baseline characteristics and adverse events between the HTx and no-HTx cohorts were analyzed. Reasons for transplant were examined. Time to HTx was compared with contemporaneous HVAD BTT trial patients. Of the 604 DT/DT2 HVAD patients, 80 (13%) underwent HTx. The HTx cohort was younger (53.6 ± 11.1 vs. 65.2 ± 10.8, P \u3c 0.0001) with fewer Caucasians (60.0% vs. 76.5%, P = 0.002), less ischemic cardiomyopathy (42.5% vs. 58.8%, P = 0.01), and atrial fibrillation (38.8% vs. 54.4%, P = 0.01). The HTx cohort had longer 6-minute walk distances (183.6 vs. 38.0 m, P = 0.02). Most HTx in DT/DT2 were categorized as elective (n = 63, 79%) and, of these, 70% were due to modification of behavioral issues and weight loss. Adverse events were the main indication for urgent HTx (n = 17, 21%). Median times to HTx were longer in DT/DT2 (550.0 days) versus BTT/lateral (285.2 days). In this post hoc analysis of the DT/DT2 trials, over 1 in 10 underwent heart transplantation within 3 years of HVAD support. In DT therapy patients, consideration for transplant following DT VAD implant may be feasible

Hemodynamic and Echocardiographic Assessment of Left Ventricle Recovery with Left Ventricular Assist Devices: Do We Explant?

Introduction: Explantation of left ventricular assist devices (LVAD) after left ventricular (LV) recovery is estimated to occur in 1-2% of cases. Herein, we present a case of hemodynamic and echocardiographic assessment of LV recovery during outflow graft balloon occlusion leading to LVAD explantation. Case Report: A 56-year-old female with medical history of systolic heart failure due to non-ischemic cardiomyopathy with LVEF 25%. She underwent an urgent HeartMate 3 LVAD implant after an admission for cardiogenic shock. Post LVAD course was complicated by driveline infection. History was notable for admissions due to low-flow alarms in the setting of dehydration. On echocardiogram, progressive LVEF improvement was noted although with suboptimal images. CT angiography did not demonstrate any occlusion of the cannulas. Right heart catheterization showed stable cardiac index despite minimal flow on LVAD. Cardiopulmonary testing was favorable. After multi-disciplinary discussion, patient underwent LVAD wean study in the cath lab under hemodynamic and transesophageal echo (TEE) guidance with therapeutic anticoagulation. LVAD was turned off for 10 minutes with outflow graft occluded by Armada 14 mm x 20 cm peripheral balloon. Wiring of the outflow graft from aorta and balloon occlusion were visualized by TEE (Figure). The left and right ventricular function were similar to baseline with no change in mitral regurgitation. Cardiac index was normal (Figure). Patient subsequently underwent successful LVAD explant. She is doing well with NYHA class I symptoms and LVEF 45-50% noted upon 3-months follow-up LVAD explantation is a feasible option in LV recovery after appropriate hemodynamic and echocardiographic assessment. TEE is an essential tool, especially in patients with suboptimal windows. Outflow graft balloon occlusion can be used if there is concern about falsely poor results related to backflow or ongoing LVAD support at low speed leading to falsely improved results

Concomitant Valvular Procedures During LVAD Implantation and Outcomes: An Analysis of the MOMENTUM 3 Trial Portfolio

Purpose: Correction of valvular pathology is often undertaken in patients undergoing LVAD implantation but impact on outcomes is uncertain. We compared clinical outcomes with HeartMate 3 (HM3) LVAD implantation in those with concurrent valve procedures (VP) to those with an isolated LVAD implant within the MOMENTUM3 trial portfolio, including the Pivotal Trial (n=515, NCT02224755) and Continued Access Protocol/ CAP (n=1685, NCT02892955). Methods: The study included 2200 HM3 implanted patients. Among 820 concurrent procedures (including VP, CABG, RVAD, LAA closure), 466 (21.8%) were VPs (HM3+VP), including 81 aortic, 61 mitral, 163 tricuspid, and 85 patients with multiple VPs. Short and Long-term outcomes including peri-operative complications and healthcare resource use, major adverse events and survival were analyzed. Results: Patients undergoing HM3+VP were older (63[54-70] vs. 62[52-68] yrs), with a sicker INTERMACS profile (1-2:41% vs.31%) and higher central venous pressure (11[8-16] vs. 9[6-14] mmHg) compared to HM3 alone (all p\u3c0.05). The cardiopulmonary bypass time (124[97-158] vs.76[59-96] mins); ICU (8.5 [5-16] vs. 7 [5-13]) and hospital length of stay (20 [15-30] vs. 18 [14-24] days) were longer in HM3+VP (all p\u3c0.0001). A significantly higher incidence of stroke (4.9% vs. 2.4%), bleeding (33.9% vs. 23.8%) and right heart failure (41.5% vs. 29.6%) was noted in HM3+VP for 0-30 days post-implant (all p\u3c0.01), but 30-day survival was similar between groups (96.7% vs. 96.1%). There was no difference in 2-year survival in HM3+VP vs HM3 alone patients (HR[95%CI]:0.93 [0.71-1.21];p=0.60). Analysis of individual VPs showed no significant differences in survival compared to HM3 alone (Figure). Conclusion: Concurrent VPs are commonly performed during LVAD implantation, are associated with increased morbidity during the index hospitalization, but short and long-term survival are not impacted adversely when compared with those that undergo an isolated LVAD procedure

Primary results of long-term outcomes in the MOMENTUM 3 pivotal trial and continued access protocol study phase: a study of 2200 HeartMate 3 left ventricular assist device implants

AIM: The MOMENTUM 3 pivotal trial established superiority of the HeartMate 3 (HM3) left ventricular assist device (LVAD), a fully magnetically levitated centrifugal-flow pump, over the HeartMate II axial-flow pump. We now evaluate HM3 LVAD outcomes in a single-arm prospective continuous access protocol (CAP) post-pivotal trial study. METHODS AND RESULTS: We enrolled 2200 HM3 implanted patients (515 pivotal trial and 1685 CAP patients) and compared outcomes including survival free of disabling stroke or reoperation to replace or remove a malfunctioning device (primary composite endpoint), overall survival and major adverse events at 2 years. The 2-year primary endpoint [76.7% vs. 74.8%; adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.71-1.08, P = 0.21] and overall survival (81.2% vs. 79.0%) were similar among CAP and pivotal cohorts despite sicker patients (more intra-aortic balloon pump use and INTERMACS profile 1) in CAP who were more often intended for destination therapy. Survival was similar between the CAP and pivotal trial in transplant ineligible patients (79.1% vs. 76.7%; adjusted HR 0.89, 95% CI 0.68-1.16, P = 0.38). In a pooled analysis, the 2-year primary endpoint was similar between INTERMACS profiles 1-2 (\u27unstable\u27 advanced heart failure), profile 3 (\u27stable\u27 on inotropic therapy), and profiles 4-7 (\u27stable\u27 ambulatory advanced heart failure) (75.7% vs. 77.6% vs. 72.9%, respectively). The net burden of adverse events was lower in CAP (adjusted rate ratio 0.93, 95% CI 0.88-0.98, P = 0.006), with consequent decrease in hospitalization. CONCLUSIONS: The primary results of accumulating HM3 LVAD experience suggest a lower adverse event burden and similar survival compared to the pivotal MOMENTUM 3 trial

Clinical outcomes and healthcare expenditures in the real world with left ventricular assist devices - The CLEAR-LVAD study

BACKGROUND: Several distinctly engineered left ventricular assist devices (LVADs) are in clinical use. However, contemporaneous real world comparisons have not been conducted, and clinical trials were not powered to evaluate differential survival outcomes across devices. OBJECTIVES: Determine real world survival outcomes and healthcare expenditures for commercially available durable LVADs. METHODS: Using a retrospective observational cohort design, Medicare claims files were linked to manufacturer device registration data to identify de-novo, durable LVAD implants performed between January 2014 and December 2018, with follow-up through December 2019. Survival outcomes were compared using a Cox proportional hazards model stratified by LVAD type and validated using propensity score matching. Healthcare resource utilization was analyzed across device types by using nonparametric bootstrap analysis methodology. Primary outcome was survival at 1-year and total Part A Medicare payments. RESULTS: A total of 4,195 de-novo LVAD implants were identified in fee-for-service Medicare beneficiaries (821 HeartMate 3; 1,840 HeartMate II; and 1,534 Other-VADs). The adjusted hazard ratio for mortality at 1-year (confirmed in a propensity score matched analysis) for the HeartMate 3 vs HeartMate II was 0.64 (95% CI; 0.52-0.79, p\u3c 0.001) and for the HeartMate 3 vs Other-VADs was 0.51 (95% CI; 0.42-0.63, p \u3c 0.001). The HeartMate 3 cohort experienced fewer hospitalizations per patient-year vs Other-VADs (respectively, 2.8 vs 3.2 EPPY hospitalizations, p \u3c 0.01) and 6.1 fewer hospital days on average (respectively, 25.2 vs 31.3 days, p \u3c 0.01). The difference in Medicare expenditures, conditional on survival, for HeartMate 3 vs HeartMate II was -$10,722, p \u3c 0.001 (17.4$17,947, p \u3c 0.001 (26.1% reduction). CONCLUSIONS: In this analysis of a large, real world, United States. administrative dataset of durable LVADs, we observed that the HeartMate 3 had superior survival, reduced healthcare resource use, and lower healthcare expenditure compared to other contemporary commercially available LVADs

Variability Across Implanting Centers in Short and Long-Term Mortality and Adverse Events in Patients on HeartMate 3 Support: A Momentum 3 Secondary Analysis

Purpose: We aimed to characterize center-specific variability in HeartMate 3 (HM3) patient survival within the MOMENTUM 3 studies and to examine the correlation between implanting center survival and major adverse events (AEs). Methods: Center HM3 implant volume during the MOMENTUM 3 pivotal (n=515) and continued access protocol (n=1685) trials were tallied. Centers implanting ≤16 HM3 patients (25th percentile) were excluded. De-identified center variability in mortality was assessed at 90 days and 2 years using direct adjusted survival while accounting for key baseline risk factors. The 90-day frequency and 2-year rates of stroke, bleeding, and infection were compared across centers and correlations between survival and event rate variability were assessed. Results: Among 48 centers, 1957 HM3 patients were included in this analysis with site implants ranging between 17 to 103 patients. Patient cohorts differed across the sites by age (average 52-68 years), sex (60-95% male), destination therapy intent (25-100%), and %INTERMACS profile 1-2 (2-81%). At 90 days, center adjusted median mortality was 6.5%, nadiring at ≤3.2% (25th percentile) and peaking at ≥10.5% (75th percentile). Median 2-year center adjusted mortality was 18.6%, nadiring at ≤14.0% and peaking at ≥25.2% (figure A). AEs were also highly variable across centers; centers with low mortality tended to have lower AE rates at 2 years (figure B). Conclusion: Patient characteristics and outcomes were highly variable across MOMENTUM 3 centers despite trial preoperative inclusion/exclusion criteria. Many centers had exemplary risk-adjusted HM3 patient outcomes. Studies are needed to improve our understanding of top performing centers’ best practices as they relate to HM3 care in the pre, interoperative, and chronic support stages in an effort to further improve HM3 LVAD-associated clinical outcomes

The Efficacy of Simulation as a Pedagogy in Facilitating Pre-Service Teachers’ Learning About Emotional Self-Regulation and its Relevance to the Teaching Profession

This study was undertaken in response to the imperative of teacher education courses incorporating National Professional Standards for Teachers, in particular Standard 7, which deals with the professional engagement of teachers (AITSL, 2011). It aimed to evaluate the efficacy of simulation and active recall as a learner-centred pedagogy in facilitating pre-service teachers’ learning about their capacity to self-regulate emotionally and its relevance to the profession. A simulated ‘critical incident’ was used in a lecture to guide students (n=106) to analyse and understand their emotional responses to an altercation between the lecturer and a colleague. The evaluation involved both quantitative and qualitative data collection. The study generated six useful insights associated with the efficacy of simulation pedagogy and revealed convincingly that this pedagogy can engage students actively in learning about the importance of emotional self-regulation in relation to their professional role as a teacher