Functional variants of DOG1 control seed chilling responses and variation in seasonal life-history strategies in Arabidopsis thaliana.

The seasonal timing of seed germination determines a plant's realized environmental niche, and is important for adaptation to climate. The timing of seasonal germination depends on patterns of seed dormancy release or induction by cold and interacts with flowering-time variation to construct different seasonal life histories. To characterize the genetic basis and climatic associations of natural variation in seed chilling responses and associated life-history syndromes, we selected 559 fully sequenced accessions of the model annual species Arabidopsis thaliana from across a wide climate range and scored each for seed germination across a range of 13 cold stratification treatments, as well as the timing of flowering and senescence. Germination strategies varied continuously along 2 major axes: 1) Overall germination fraction and 2) induction vs. release of dormancy by cold. Natural variation in seed responses to chilling was correlated with flowering time and senescence to create a range of seasonal life-history syndromes. Genome-wide association identified several loci associated with natural variation in seed chilling responses, including a known functional polymorphism in the self-binding domain of the candidate gene DOG1. A phylogeny of DOG1 haplotypes revealed ancient divergence of these functional variants associated with periods of Pleistocene climate change, and Gradient Forest analysis showed that allele turnover of candidate SNPs was significantly associated with climate gradients. These results provide evidence that A. thaliana's germination niche and correlated life-history syndromes are shaped by past climate cycles, as well as local adaptation to contemporary climate.

Risk Factors Associated With Postoperative Mortality Among COVID-19 Positive Patients: Results of 3027 Operations and Procedures.

OBJECTIVE: To investigate the predictors of postoperative mortality in coronavirus disease 2019 (COVID-19)-positive patients. BACKGROUND: COVID-19-positive patients have more postoperative complications. Studies investigating the risk factors for postoperative mortality in COVID-19-positive patients are limited. METHODS: COVID-19-positive patients who underwent surgeries/procedures in Cleveland Clinic between January 2020 and March 2021 were identified retrospectively. The primary outcome was postoperative/procedural 30-day mortality. Secondary outcomes were length of stay, intensive care unit admission, and 30-day readmission. RESULTS: A total of 2543 patients who underwent 3027 surgeries/procedures were included. Total 48.5% of the patients were male. The mean age was 57.8 (18.3) years. A total of 71.2% had at least 1 comorbidity. Total 78.7% of the cases were elective. The median operative time was 94 (47.0-162) minutes and mean length of stay was 6.43 (13.4) days. Postoperative/procedural mortality rate was 4.01%. Increased age [odds ratio (OR): 1.66, 95% CI, 1.4-1.98; P <0.001], being a current smoker [2.76, (1.3-5.82); P =0.008], presence of comorbidity [3.22, (1.03-10.03); P =0.043], emergency [6.35, (3.39-11.89); P <0.001] and urgent versus [1.78, (1.12-2.84); P =0.015] elective surgery, admission through the emergency department [15.97, (2.00-127.31); P =0.009], or inpatient service [32.28, (7.75-134.46); P <0.001] versus outpatients were associated with mortality in the multivariable analysis. Among all specialties, thoracic surgery [3.76, (1.66-8.53); P =0.002] had the highest association with mortality. Total 17.5% of the patients required intensive care unit admission with increased body mass index being a predictor [1.03, (1.01-1.05); P =0.005]. CONCLUSIONS: COVID-19-positive patients have higher risk of postintervention mortality. Risk factors should be carefully evaluated before intervention. Further studies are needed to understand the impact of pandemic on long-term surgical/procedural outcomes.

Adaptive significance of flowering time variation across natural seasonal environments in Arabidopsis thaliana.

The relevance of flowering time variation and plasticity to climate adaptation requires a comprehensive empirical assessment. We investigated natural selection and the genetic architecture of flowering time in Arabidopsis through field experiments in Europe across multiple sites and seasons. We estimated selection for flowering time, plasticity and canalization. Loci associated with flowering time, plasticity and canalization by genome-wide association studies were tested for a geographic signature of climate adaptation. Selection favored early flowering and increased canalization, except at the northernmost site, but was rarely detected for plasticity. Genome-wide association studies revealed significant associations with flowering traits and supported a substantial polygenic inheritance. Alleles associated with late flowering, including functional FRIGIDA variants, were more common in regions experiencing high annual temperature variation. Flowering time plasticity to fall vs spring and summer environments was associated with GIGANTEA SUPPRESSOR 5, which promotes early flowering under decreasing day length and temperature. The finding that late flowering genotypes and alleles are associated with climate is evidence for past adaptation. Real-time phenotypic selection analysis, however, reveals pervasive contemporary selection for rapid flowering in agricultural settings across most of the species range. The response to this selection may involve genetic shifts in environmental cuing compared to the ancestral state.

Large-effect flowering time mutations reveal conditionally adaptive paths through fitness landscapes in Arabidopsis thaliana.

Contrary to previous assumptions that most mutations are deleterious, there is increasing evidence for persistence of large-effect mutations in natural populations. A possible explanation for these observations is that mutant phenotypes and fitness may depend upon the specific environmental conditions to which a mutant is exposed. Here, we tested this hypothesis by growing large-effect flowering time mutants of Arabidopsis thaliana in multiple field sites and seasons to quantify their fitness effects in realistic natural conditions. By constructing environment-specific fitness landscapes based on flowering time and branching architecture, we observed that a subset of mutations increased fitness, but only in specific environments. These mutations increased fitness via different paths: through shifting flowering time, branching, or both. Branching was under stronger selection, but flowering time was more genetically variable, pointing to the importance of indirect selection on mutations through their pleiotropic effects on multiple phenotypes. Finally, mutations in hub genes with greater connectedness in their regulatory networks had greater effects on both phenotypes and fitness. Together, these findings indicate that large-effect mutations may persist in populations because they influence traits that are adaptive only under specific environmental conditions. Understanding their evolutionary dynamics therefore requires measuring their effects in multiple natural environments.

TERMINAL FLOWER-1/CENTRORADIALIS inhibits tuberisation via protein interaction with the tuberigen activation complex.

Potato tuber formation is a secondary developmental programme by which cells in the subapical stolon region divide and radially expand to further differentiate into starch-accumulating parenchyma. Although some details of the molecular pathway that signals tuberisation are known, important gaps in our knowledge persist. Here, the role of a member of the TERMINAL FLOWER 1/CENTRORADIALIS gene family (termed StCEN) in the negative control of tuberisation is demonstrated for what is thought to be the first time. It is shown that reduced expression of StCEN accelerates tuber formation whereas transgenic lines overexpressing this gene display delayed tuberisation and reduced tuber yield. Protein-protein interaction studies (yeast two-hybrid and bimolecular fluorescence complementation) demonstrate that StCEN binds components of the recently described tuberigen activation complex. Using transient transactivation assays, we show that the StSP6A tuberisation signal is an activation target of the tuberigen activation complex, and that co-expression of StCEN blocks activation of the StSP6A gene by StFD-Like-1. Transcriptomic analysis of transgenic lines misexpressing StCEN identifies early transcriptional events in tuber formation. These results demonstrate that StCEN suppresses tuberisation by directly antagonising the function of StSP6A in stolons, identifying StCEN as a breeding marker to improve tuber initiation and yield through the selection of genotypes with reduced StCEN expression.

Combining conventional QTL analysis and whole-exome capture-based bulk-segregant analysis provides new genetic insights into tuber sprout elongation and dormancy release in a diploid potato population.

Tuber dormancy and sprouting are commercially important potato traits as long-term tuber storage is necessary to ensure year-round availability. Premature dormancy release and sprout growth in tubers during storage can result in a significant deterioration in product quality. In addition, the main chemical sprout suppressant chlorpropham has been withdrawn in Europe, necessitating alternative approaches for controlling sprouting. Breeding potato cultivars with longer dormancy and slower sprout growth is a desirable goal, although this must be tempered by the needs of the seed potato industry, where dormancy break and sprout vigour are required for rapid emergence. We have performed a detailed genetic analysis of tuber sprout growth using a diploid potato population derived from two highly heterozygous parents. A dual approach employing conventional QTL analysis allied to a combined bulk-segregant analysis (BSA) using a novel potato whole-exome capture (WEC) platform was evaluated. Tubers were assessed for sprout growth in storage at six time-points over two consecutive growing seasons. Genetic analysis revealed the presence of main QTL on five chromosomes, several of which were consistent across two growing seasons. In addition, phenotypic bulks displaying extreme sprout growth phenotypes were subjected to WEC sequencing for performing BSA. The combined BSA and WEC approach corroborated QTL locations and served to narrow the associated genomic regions, while also identifying new QTL for further investigation. Overall, our findings reveal a very complex genetic architecture for tuber sprouting and sprout growth, which has implications both for potato and other root, bulb and tuber crops where long-term storage is essential.

The Adult Cardiac Anesthesiology Section of STS Adult Cardiac Surgery Database: 2020 Update on Quality and Outcomes.

The Society of Cardiovascular Anesthesiologists, in partnership with The Society of Thoracic Surgeons, has developed the Adult Cardiac Anesthesiology Section of the Adult Cardiac Surgery Database. The goal of this landmark collaboration is to advance clinical care, quality, and knowledge, and to demonstrate the value of cardiac anesthesiology in the perioperative care of cardiac surgical patients. Participation in the Adult Cardiac Anesthesiology Section has been optional since its inception in 2014 but has progressively increased. Opportunities for further growth and improvement remain. In this first update report on quality and outcomes of the Adult Cardiac Anesthesiology Section, we present an overview of the clinically significant anesthesia and surgical variables submitted between 2015 and 2018. Our review provides a summary of quality measures and outcomes related to the current practice of cardiothoracic anesthesiology. We also emphasize the potential for addressing high-impact research questions as data accumulate, with the overall goal of elucidating the influence of cardiac anesthesiology contributions to patient outcomes within the framework of the cardiac surgical team.

Interest in Improving Access to Pediatric Trauma Care Through Telemedicine.

Despite improved outcomes at pediatric trauma centers (PTC), 90% of injured children are not treated at PTCs. Telemedicine may play a role in ensuring patients are transferred to the appropriate level of care. We aimed to determine the level of interest in trauma telemedicine with our PTC among referring facilities. A survey was conducted with the trauma program directors of 45 hospitals in Utah, which consisted of four multiple choice questions designed to determine interest in pediatric trauma telemedicine support, projected frequency of use, anticipated uses of telemedicine, and perceived barriers to implementation. Forty-one directors (91%) responded. 88% of directors were interested in developing a pediatric trauma telemedicine network. 20% estimated their center would use telemedicine more than once a week, 17% once a week, 24% once a month, and 37% a few times a year. The most frequently cited uses of a telemedicine program were triage/transfer decisions and provider support. Inadequate volume and insufficient funding were the most common perceived barriers. These data show there is a strong interest amongst hospitals in our state in pediatric trauma telemedicine. Inadequate volume to warrant a program and insufficient facility funding remain concerns for development of a program.

Natural allelic variation of GVS1 confers diversity in the regulation of leaf senescence in Arabidopsis.

Leaf senescence affects plant fitness. Plants that evolve in different environments are expected to acquire distinct regulations of leaf senescence. However, the adaptive and evolutionary roles of leaf senescence are largely unknown. We investigated leaf senescence in 259 natural accessions of Arabidopsis by quantitatively assaying dark-induced senescence responses using a high-throughput chlorophyll fluorescence imaging system. A meta-analysis of our data with phenotypic and climatic information demonstrated biological and environmental links with leaf senescence. We further performed genome-wide association mapping to identify the genetic loci underlying the diversity of leaf senescence responses. We uncovered a new locus, Genetic Variants in leaf Senescence (GVS1), with high similarity to reductase, where a single nonsynonymous nucleotide substitution at GVS1 mediates the diversity of the senescence trait. Loss-of-function mutations of GVS1 in Columbia-0 delayed leaf senescence and increased sensitivity to oxidative stress, suggesting that this GVS1 variant promotes optimal responses to developmental and environmental signals. Intriguingly, gvs1 loss-of-function mutants display allele- and accession-dependent phenotypes, revealing the functional diversity of GVS1 alleles not only in leaf senescence, but also oxidative stress. Our discovery of GVS1 as the genetic basis of natural variation in senescence programs reinforces its adaptive potential in modulating life histories across diverse environments.

Exploring Surgeon Variability in Recommendations for Contralateral Prophylactic Mastectomy: What Matters Most?

BACKGROUND: American Society of Breast Surgeons (ASBrS) guidelines state that it is the responsibility of the surgeon to discuss the risks/benefits of and give a recommendation regarding contralateral prophylactic mastectomy (CPM). We conducted a survey of ASBrS members to evaluate the factors that affect this recommendation, confidence in this recommendation, and awareness/adoption of the guidelines. METHODS: A survey was sent to the ASBrS membership. Vignettes with the following variables about breast cancer patient were randomly included: age, disease stage, receptor status, family history (FH) of breast cancer, and patient preference for CPM. Respondents were asked to estimate the patient's chance of developing contralateral cancer, whether they would recommend CPM, and their confidence in this recommendation, and about their familiarity with and use of the guidelines. RESULTS: 536 members (21.9%) responded. The odds of recommending CPM and confidence in recommendation were higher in a younger patient, higher-stage disease, triple-negative and human epidermal growth factor receptor (HER)2+ relative to estrogen receptor (ER)+, and in women with FH. Of surgeons, 51% were familiar or very familiar with the guidelines and 38% used the guidelines most or all of the time. Surgeons who used the guidelines were not less likely to recommend CPM. CONCLUSIONS: While surgeons generally agree on the factors that are important in making a recommendation on CPM, there is variability in how strongly the different factors influence the recommendation and their confidence in that recommendation. In addition, while most surgeons were at least a little familiar with the ASBrS guidelines, the vast majority do not routinely use them.

Identification of TIMING OF CAB EXPRESSION 1 as a temperature-sensitive negative regulator of tuberization in potato.

For many potato cultivars, tuber yield is optimal at average daytime temperatures in the range 14-22 °C. Above this range, tuber yield is reduced for most cultivars. We previously reported that moderately elevated temperature increases steady-state expression of the core circadian clock gene TIMING OF CAB EXPRESSION 1 (StTOC1) in developing tubers, whereas expression of the StSP6A tuberization signal is reduced, along with tuber yield. In this study we provide evidence that StTOC1 links environmental signalling with potato tuberization by suppressing StSP6A autoactivation in the stolons. We show that transgenic lines silenced in StTOC1 expression exhibit enhanced StSP6A transcript levels and changes in gene expression in developing tubers that are indicative of an elevated sink strength. Nodal cuttings of StTOC1 antisense lines displayed increased tuber yields at moderately elevated temperatures, whereas tuber yield and StSP6A expression were reduced in StTOC1 overexpressor lines. Here we identify a number of StTOC1 binding partners and demonstrate that suppression of StSP6A expression is independent of StTOC1 complex formation with the potato homolog StPIF3. Down-regulation of StTOC1 thus provides a strategy to mitigate the effects of elevated temperature on tuber yield.

A member of the TERMINAL FLOWER 1/CENTRORADIALIS gene family controls sprout growth in potato tubers.

Potato tuber bud dormancy break followed by premature sprouting is a major commercial problem which results in quality losses and decreased tuber marketability. An approach to controlling premature tuber sprouting is to develop potato cultivars with a longer dormancy period and/or reduced rate of sprout growth. Our recent studies using a potato diploid population have identified several quantitative trait loci (QTLs) that are associated with tuber sprout growth. In the current study, we aim to characterize a candidate gene associated with one of the largest effect QTLs for rapid tuber sprout growth on potato chromosome 3. Underlying this QTL is a gene encoding a TERMINAL FLOWER 1/CENTRORADIALIS homologue (PGSC0003DMG400014322). Here, we use a transgenic approach to manipulate the expression level of the CEN family member in a potato tetraploid genotype (cv. Désirée). We demonstrate a clear effect of manipulation of StCEN expression, with decreased expression levels associated with an increased rate of sprout growth, and overexpressing lines showing a lower rate of sprout growth than controls. Associated with different levels of StCEN expression were different levels of abscisic acid and cytokinins, implying a role in controlling the levels of plant growth regulators in the apical meristem.

Use of a modified Delphi approach to develop research priorities in HPB surgery across the United Kingdom.

BACKGROUND: Research prioritisation can help identify clinically relevant questions and encourage high-quality, patient-centred research. Delphi methodology aims to develop consensus opinion within a group of experts, with recent Delphi projects helping to define the research agenda and funding within several medical and surgical specialties. METHODS: All members of the Association of Upper Gastrointestinal Surgeons (AUGIS) were asked to submit clinical research questions using an online survey (Phase 1). Two consecutive rounds of Delphi prioritisation by multidisciplinary HPB healthcare professionals (Phase 2) were undertaken to establish a final list of the most highly prioritised research questions. A multidisciplinary steering committee analysed the results of each phase. RESULTS: Ninety-three HPB-focussed questions were identified in Phase 1, with thirty-seven questions of sufficient priority to enter a further prioritisation round. A final group of 11 questions considered highest priority were identified. The most highly ranked research questions related to treatment pathways, operative strategies and the impact of HPB procedures on quality of life, particularly for malignant disease. CONCLUSION: Expert consensus has identified research priorities within the UK HPB surgical community over the coming years. Funding applications, to establish well-designed, high quality collaborative research are now required to address these questions.

Engineering heat tolerance in potato by temperature-dependent expression of a specific allele of HEAT-SHOCK COGNATE 70.

For many commercial potato cultivars, tuber yield is optimal at average daytime temperatures in the range of 14-22 °C. Further rises in ambient temperature can reduce or completely inhibit potato tuber production, with damaging consequences for both producer and consumer. The aim of this study was to use a genetic screen based on a model tuberization assay to identify quantitative trait loci (QTL) associated with enhanced tuber yield. A candidate gene encoding HSc70 was identified within one of the three QTL intervals associated with elevated yield in a Phureja-Tuberosum hybrid diploid potato population (06H1). A particular HSc70 allelic variant was linked to elevated yield in the 06H1 progeny. Expression of this allelic variant was much higher than other alleles, particularly on exposure to moderately elevated temperature. Transient expression of this allele in Nicotiana benthamiana resulted in significantly enhanced tolerance to elevated temperature. An TA repeat element was present in the promoter of this allele, but not in other HSc70 alleles identified in the population. Expression of the HSc70 allelic variant under its native promoter in the potato cultivar Desiree resulted in enhanced HSc70 expression at elevated temperature. This was reflected in greater tolerance to heat stress as determined by improved yield under moderately elevated temperature in a model nodal cutting tuberization system and in plants grown from stem cuttings. Our results identify HSc70 expression level as a significant factor influencing yield stability under moderately elevated temperature and identify specific allelic variants of HSc70 for the induction of thermotolerance via conventional introgression or molecular breeding approaches.

Are the current difficulty scores for laparoscopic liver surgery telling the whole story? An international survey and recommendations for the future.

BACKGROUND: Recent studies have suggested that the difficulty of laparoscopic liver resections are related to both patient and tumour factors, however the available difficulty scoring systems only incorporate tumour factors. The aim of this study was to assess the opinion of laparoscopic liver surgeons regarding the factors that affect the perceived difficulty of laparoscopic liver resections. METHOD: Using a Visual Analogue Scale an international survey of laparoscopic liver surgeons was undertaken to assess the perceived difficulty of 26 factors previously demonstrated to affect the difficulty of a laparoscopic liver resection. RESULTS: 80 surgeons with a combined experience of over 7000 laparoscopic liver resections responded to the survey. The difficulty of laparoscopic liver surgery was suggested to be increased by a BMI > 35 by 89% of respondents; neo-adjuvant chemotherapy by 79%; repeated liver resection by 99% and concurrent procedures by 59% however these factors have not been included in the previous difficulty scoring systems. CONCLUSION: The results suggests that the difficulty of laparoscopic liver surgery is not fully assessed by the available difficulty scoring systems and prompts the development of a new difficulty score that incorporates all factors believed to increase difficulty.

Interacting effects of genetic variation for seed dormancy and flowering time on phenology, life history, and fitness of experimental Arabidopsis thaliana populations over multiple generations in the field.

Major alleles for seed dormancy and flowering time are well studied, and can interact to influence seasonal timing and fitness within generations. However, little is known about how this interaction controls phenology, life history, and population fitness across multiple generations in natural seasonal environments. To examine how seed dormancy and flowering time shape annual plant life cycles over multiple generations, we established naturally dispersing populations of recombinant inbred lines of Arabidopsis thaliana segregating early and late alleles for seed dormancy and flowering time in a field experiment. We recorded seasonal phenology and fitness of each genotype over 2 yr and several generations. Strong seed dormancy suppressed mid-summer germination in both early- and late-flowering genetic backgrounds. Strong dormancy and late-flowering genotypes were both necessary to confer a winter annual life history; other genotypes were rapid-cycling. Strong dormancy increased within-season fecundity in an early-flowering background, but decreased it in a late-flowering background. However, there were no detectable differences among genotypes in population growth rates. Seasonal phenology, life history, and cohort fitness over multiple generations depend strongly upon interacting genetic variation for dormancy and flowering. However, similar population growth rates across generations suggest that different life cycle genotypes can coexist in natural populations.

Day length dependent restructuring of the leaf transcriptome and metabolome in potato genotypes with contrasting tuberization phenotypes.

Recent advances have defined some of the components of photoperiodic signalling that lead to tuberization in potato including orthologues of FLOWERING LOCUS T (StSP6A) and CYCLING DOF FACTOR (StCDF1). The aim of the current study is to investigate the molecular basis of permissive tuber initiation under long days in Solanum tuberosum Neo-Tuberosum by comparative analysis with an obligate short-day S. tuberosum ssp. Andigena accession. We show that the Neo-Tuberosum accession, but not the Andigena, contains alleles that encode StCDF1 proteins modified in the C-terminal region, likely to evade long day inhibition of StSP6A expression. We also identify an allele of StSP6A from the Neo-Tuberosum accession, absent in the Andigena, which is expressed under long days. Other leaf transcripts and metabolites that show different abundances in tuberizing and non-tuberizing samples were identified adding detail to tuberization-associated processes. Overall, the data presented in this study highlight the subtle interplay between components of the clock-CONSTANS-StSP6A axis which collectively may interact to fine-tune the timing of tuberization.