Using drone-retrieved multispectral data for phenomic selection in potato breeding.

Predictive breeding approaches, like phenomic or genomic selection, have the potential to increase the selection gain for potato breeding programs which are characterized by very large numbers of entries in early stages and the availability of very few tubers per entry in these stages. The objectives of this study were to (i) explore the capabilities of phenomic prediction based on drone-derived multispectral reflectance data in potato breeding by testing different prediction scenarios on a diverse panel of tetraploid potato material from all market segments and considering a broad range of traits, (ii) compare the performance of phenomic and genomic predictions, and (iii) assess the predictive power of mixed relationship matrices utilizing weighted SNP array and multispectral reflectance data. Predictive abilities of phenomic prediction scenarios varied greatly within a range of - 0.15 and 0.88 and were strongly dependent on the environment, predicted trait, and considered prediction scenario. We observed high predictive abilities with phenomic prediction for yield (0.45), maturity (0.88), foliage development (0.73), and emergence (0.73), while all other traits achieved higher predictive ability with genomic compared to phenomic prediction. When a mixed relationship matrix was used for prediction, higher predictive abilities were observed for 20 out of 22 traits, showcasing that phenomic and genomic data contained complementary information. We see the main application of phenomic selection in potato breeding programs to allow for the use of the principle of predictive breeding in the pot seedling or single hill stage where genotyping is not recommended due to high costs.

Fine mapping a QTL for BYDV-PAV resistance in maize.

Barley yellow dwarf (BYD) is one of the economically most important virus diseases of cereals worldwide, causing yield losses up to 80%. The means to control BYD are limited, and the use of genetically resistant cultivars is the most economical and environmentally friendly approach. The objectives of this study were i) to identify the causative gene for BYD virus (BYDV)-PAV resistance in maize, ii) to identify single nucleotide polymorphisms and/or structural variations in the gene sequences, which may cause differing susceptibilities to BYDV-PAV of maize inbreds, and iii) to characterize the effect of BYDV-PAV infection on gene expression of susceptible, tolerant, and resistant maize inbreds. Using two biparental mapping populations, we could reduce a previously published quantitative trait locus for BYDV-PAV resistance in maize to ~ 0.3 Mbp, comprising nine genes. Association mapping and gene expression analysis further reduced the number of candidate genes for BYDV-PAV resistance in maize to two: Zm00001eb428010 and Zm00001eb428020. The predicted functions of these genes suggest that they confer BYDV-PAV resistance either via interfering with virus replication or by inducing reactive oxygen species signaling. The gene sequence of Zm00001eb428010 is affected by a 54 bp deletion in the 5`-UTR and a protein altering variant in BYDV-PAV-resistant maize inbreds but not in BYDV-PAV-susceptible and -tolerant inbreds. This finding suggests that altered abundance and/or properties of the proteins encoded by Zm00001eb428010 may lead to BYDV-PAV resistance.

Modelling the potential increase in eligible participants in clinical trials with inclusion of community intensive care unit patients in Alberta, Canada: a decision tree analysis.

PURPOSE: Critical care research in Canada is conducted primarily in academically affiliated intensive care units (ICUs) with established research infrastructure. Efforts are made to engage community hospital ICUs in research, although the impacts of their inclusion in clinical research have never been explicitly quantified. We therefore sought to determine the number of additional eligible patients that could be recruited into critical care trials and the change in time to study completion if community ICUs were included in clinical research. METHODS: We conducted a decision tree analysis using 2018 Alberta Health Services data. Patient demographics and clinical characteristics for all ICU patients were compared against eligibility criteria from ten landmark, randomized, multicentre critical care trials. Individual patients from academic and community ICUs were assessed for eligibility in each of the ten studies, and decision tree analysis models were built based on prior inclusion and exclusion criteria from those trials. RESULTS: The number of potentially eligible patients for the ten trials ranged from 2,082 to 10,157. Potentially eligible participants from community ICUs accounted for 40.0% of total potentially eligible participants. The recruitment of community ICU patients in trials would have increased potential enrolment by an average of 64.0%. The inclusion of community ICU patients was predicted to decrease time to trial completion by a mean of 14 months (43% reduction). CONCLUSION: Inclusion of community ICU patients in critical care research trials has the potential to substantially increase enrolment and decrease time to trial completion.

RéSUMé: OBJECTIF: La recherche en soins intensifs au Canada est principalement réalisée dans des unités de soins intensifs affiliées à des centres universitaires jouissant d'infrastructures de recherche bien établies. Des efforts ont été déployés pour engager les unités de soins intensifs des hôpitaux communautaires en recherche, mais les impacts de leur participation à la recherche clinique n'ont jamais été explicitement quantifiés. Nous avons conséquemment cherché à déterminer le nombre de patient·es additionnel·les pouvant être recruté·es dans des études de soins critiques ainsi que la variation du temps nécessaire pour compléter les études si la patientèle issue d'unités de soins intensifs d'hôpitaux communautaires participait à la recherche clinique. MéTHODE: Une analyse par arbre de décision a été réalisée à partir de données provenant des Alberta Health Services pour l'année 2018. Les données démographiques et les caractéristiques cliniques de tou·tes les patient·es admis·es aux soins intensifs ont été comparées avec les critères d'éligibilité de dix importantes études multicentriques, randomisées, contrôlées en soins intensifs. Les patient·es des unités de soins intensifs universitaires et communautaires ont tou·tes été évalué·es pour leur éligibilité à chacune des dix études, et des modèles d'arbres décisionnels ont été construits en se basant sur les critères originaux d'inclusion et d'exclusion. RéSULTATS: Le nombre de personnes potentiellement éligibles pour les dix études s'est situé entre 2082 et 10 157. Les patient·es potentiellement admissibles en provenance d'unités de soins intensifs communautaires ont représenté 40,0 % de toutes les personnes potentiellement admissibles. Le recrutement de patient·es en provenance d'unités de soins intensifs communautaires aurait permis une hausse moyenne du recrutement potentiel de 64,0 %. L'inclusion de patient·es des unités de soins intensifs communautaires pourrait également réduire le temps nécessaire à la complétion des études de 14 mois en moyenne (réduction de 43 %). CONCLUSION: L'inclusion de patient·es en provenance d'unités de soins intensifs d'hôpitaux communautaires dans la recherche clinique en soins critiques a le potentiel d'augmenter substantiellement le recrutement et de diminuer le temps nécessaire à la complétion des études.

Nonsteroidal anti-inflammatory drugs for analgesia in intensive care units: a survey of Canadian critical care physicians.

PURPOSE: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs). METHODS: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing. RESULTS: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care. CONCLUSIONS: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients.

RéSUMé: OBJECTIF: Les opioïdes restent le pilier de l'analgésie pour les patient·es gravement malades, mais l'exposition à ces agents est associée à des effets négatifs, notamment à leur utilisation persistante après le congé de l'hôpital. Les anti-inflammatoires non stéroïdiens (AINS) pourraient constituer une alternative efficace aux opioïdes avec moins d'effets indésirables. Nous avons cherché à décrire les croyances et les attitudes à l'égard de l'utilisation des AINS dans les unités de soins intensifs (USI) pour adultes. MéTHODE: Notre sondage auprès des médecins intensivistes au Canada a été mené à l'aide d'une plateforme Web et distribué aux personnes sur la liste de distribution électronique de la Société canadienne de soins intensifs (SCSI). Nous avons utilisé une méthodologie d'élaboration d'enquêtes décrite précédemment, y compris la génération et la réduction de questions, les tests préalables, la sensibilité clinique et les tests pilotes. RéSULTATS: Nous avons reçu 115 sondages remplis par 321 membres de la SCSI (36 %). L'utilisation d'anti-inflammatoires non stéroïdiens a été décrite comme « rare ¼ (59 répondant·es, 51 %), la principale préoccupation étant les événements indésirables (insuffisance rénale aiguë [108 répondant·es, 94 %] et saignements gastro-intestinaux [92 répondant·es, 80 %]). Le principal analgésique préféré était l'acétaminophène (75 répondant·es, 65 %), suivi des opioïdes (40 répondant·es, 35 %). La plupart des répondant·es (91 répondant·es, 80 %) seraient prêt·es à participer à une étude randomisée contrôlée examinant l'utilisation des AINS en soins intensifs. CONCLUSION: Dans notre sondage, les médecins intensivistes au Canada n'ont pas mentionné l'utilisation courante d'AINS, principalement en raison de préoccupations concernant leurs effets indésirables. Néanmoins, les répondant·es étaient intéressé·es à étudier plus avant le kétorolac, un AINS couramment utilisé en dehors des soins intensifs, chez les patient·es gravement malades.

Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Needs Assessment Survey Identifying Research Processes Which may be Improved by Automation or Artificial Intelligence: ICU Community Modeling and Artificial Intelligence to Improve Efficiency (ICU-Comma).

BACKGROUND: Critical care research in Canada is conducted primarily in academically-affiliated intensive care units with established research infrastructure, including research coordinators (RCs). Recently, efforts have been made to engage community hospital ICUs in research albeit with barriers. Automation or artificial intelligence (AI) could aid the performance of routine research tasks. It is unclear which research study processes might be improved through AI automation. METHODS: We conducted a cross-sectional survey of Canadian ICU research personnel. The survey contained items characterizing opinions regarding research processes that may be amenable to AI automation. We distributed the questionnaire via email distribution lists of 3 Canadian research societies. Open-ended questions were analyzed using a thematic content analysis approach. RESULTS: A total of 49 survey responses were received (response rate: 8%). Tasks that respondents felt were time-consuming/tedious/tiresome included: screening for potentially eligible patients (74%), inputting data into case report forms (65%), and preparing internal tracking logs (53%). Tasks that respondents felt could be performed by AI automation included: screening for eligible patients (59%), inputting data into case report forms (55%), preparing internal tracking logs (51%), and randomizing patients into studies (45%). Open-ended questions identified enthusiasm for AI automation to improve information accuracy and efficiency while freeing up RCs to perform tasks that require human interaction. This enthusiasm was tempered by the need for proper AI education and oversight. CONCLUSIONS: There were balanced supportive (increased efficiency and re-allocation of tasks) and challenges (informational accuracy and oversight) with regards to AI automation in ICU research.

Association between frailty and short- and long-term outcomes among critically ill patients: a multicentre prospective cohort study.

BACKGROUND: Frailty is a multidimensional syndrome characterized by loss of physiologic and cognitive reserves that confers vulnerability to adverse outcomes. We determined the prevalence, correlates and outcomes associated with frailty among adults admitted to intensive care. METHODS: We prospectively enrolled 421 critically ill adults aged 50 or more at 6 hospitals across the province of Alberta. The primary exposure was frailty, defined by a score greater than 4 on the Clinical Frailty Scale. The primary outcome measure was in-hospital mortality. Secondary outcome measures included adverse events, 1-year mortality and quality of life. RESULTS: The prevalence of frailty was 32.8% (95% confidence interval [CI] 28.3%-37.5%). Frail patients were older, were more likely to be female, and had more comorbidities and greater functional dependence than those who were not frail. In-hospital mortality was higher among frail patients than among non-frail patients (32% v. 16%; adjusted odds ratio [OR] 1.81, 95% CI 1.09-3.01) and remained higher at 1 year (48% v. 25%; adjusted hazard ratio 1.82, 95% CI 1.28-2.60). Major adverse events were more common among frail patients (39% v. 29%; OR 1.54, 95% CI 1.01-2.37). Compared with nonfrail survivors, frail survivors were more likely to become functionally dependent (71% v. 52%; OR 2.25, 95% CI 1.03-4.89), had significantly lower quality of life and were more often readmitted to hospital (56% v. 39%; OR 1.98, 95% CI 1.22-3.23) in the 12 months following enrolment. INTERPRETATION: Frailty was common among critically ill adults aged 50 and older and identified a population at increased risk of adverse events, morbidity and mortality. Diagnosis of frailty could improve prognostication and identify a vulnerable population that might benefit from follow-up and intervention.

LIBERATE: a study protocol for midodrine for the early liberation from vasopressor support in the intensive care unit (LIBERATE): protocol for a randomized controlled trial.

BACKGROUND: Intravenous (IV) vasopressors to support hemodynamics are a primary indication for intensive care unit (ICU) admission. Utilization of oral vasopressor therapy may offer an alternative to IV vasopressor therapy in the ICU, thus decreasing the need for ICU admission. Oral vasopressors, such as midodrine, have been used for hemodynamic support in non-critically ill patients, but their evaluation in critically ill patients to potentially spare IV vasopressor therapy has been limited. METHODS: The LIBERATE study will be a multicenter, parallel-group, blinded, randomized placebo-controlled trial. It will recruit adult (i.e., age ≥ 18 years) critically ill patients receiving stable or decreasing doses of IV vasopressors. Eligible patients will be randomized to receive either midodrine 10 mg administered enterally every 8 h or placebo until 24 h post-discontinuation of IV vasopressors. The primary outcome will be ICU length of stay. Secondary outcomes include all-cause mortality at 90 days, hospital length of stay, length of IV vasopressor support, re-initiation of IV vasopressors, rates of ICU readmission, and occurrence of AEs. Health economic outcomes including ICU, hospital and healthcare costs, and cost-effectiveness will be evaluated. Pre-planned subgroup analyses include age, sex, frailty, severity of illness, etiology of shock, and comorbid conditions. DISCUSSION: LIBERATE will rigorously evaluate the effect of oral midodrine on duration of ICU stay and IV vasopressor support in critically ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05058612 . Registered on September 28, 2021.

Chromosome-scale reference genome assembly of a diploid potato clone derived from an elite variety.

Potato (Solanum tuberosum L.) is one of the most important crops with a worldwide production of 370 million metric tons. The objectives of this study were (1) to create a high-quality consensus sequence across the two haplotypes of a diploid clone derived from a tetraploid elite variety and assess the sequence divergence from the available potato genome assemblies, as well as among the two haplotypes; (2) to evaluate the new assembly's usefulness for various genomic methods; and (3) to assess the performance of phasing in diploid and tetraploid clones, using linked-read sequencing technology. We used PacBio long reads coupled with 10x Genomics reads and proximity ligation scaffolding to create the dAg1_v1.0 reference genome sequence. With a final assembly size of 812 Mb, where 750 Mb are anchored to 12 chromosomes, our assembly is larger than other available potato reference sequences and high proportions of properly paired reads were observed for clones unrelated by pedigree to dAg1. Comparisons of the new dAg1_v1.0 sequence to other potato genome sequences point out the high divergence between the different potato varieties and illustrate the potential of using dAg1_v1.0 sequence in breeding applications.

Clinical significance and comparison of flotillin 1 expression in left and right colon cancer.

Flotillin 1 (FLOT1) is increasingly implicated in various types of cancer, and has been reported to influence tumorigenesis and cancer progression, leading to poor prognosis for survival time; however, its expression in colorectal cancer (CRC) and its influence on various clinicopathological parameters of this disease remain unknown. In the present study, FLOT1 expression and its effect on different clinicopathological parameters were assessed immunohistochemically and histologically in 81 CRC and 81 non-tumorous colon tissue samples. The immunohistochemical staining was scored semi-quantitatively. The association of FLOT1 expression with various parameters and its effect on overall survival time was also assessed. FLOT1 was upregulated in the CRC tissue, with increased expression in the right colon tissue samples compared with those of left colon. Increased FLOT1 expression in CRC tissue samples was associated with tumor volume, differentiation, tumor grade and poor overall survival time. In the right colon tissue samples in particular, there was a notable association with tumor volume and grade, indicating its effect on proliferation and tumor stage at this site. A multivariate Cox regression hazard analysis revealed that only tumor grade and differentiation were the independent predictors of overall survival time in patients with CRC. Together, the results of the present study suggest that FLOT1 serves important functions in the proliferation and progression of CRC, contributes to decreased survival time, and may serve as a novel therapeutic target for the treatment of CRC.