Keratinocytes drive the epithelial hyperplasia key to sea lice resistance in coho salmon.

BACKGROUND: Salmonid species have followed markedly divergent evolutionary trajectories in their interactions with sea lice. While sea lice parasitism poses significant economic, environmental, and animal welfare challenges for Atlantic salmon (Salmo salar) aquaculture, coho salmon (Oncorhynchus kisutch) exhibit near-complete resistance to sea lice, achieved through a potent epithelial hyperplasia response leading to rapid louse detachment. The molecular mechanisms underlying these divergent responses to sea lice are unknown. RESULTS: We characterized the cellular and molecular responses of Atlantic salmon and coho salmon to sea lice using single-nuclei RNA sequencing. Juvenile fish were exposed to copepodid sea lice (Lepeophtheirus salmonis), and lice-attached pelvic fin and skin samples were collected 12 h, 24 h, 36 h, 48 h, and 60 h after exposure, along with control samples. Comparative analysis of control and treatment samples revealed an immune and wound-healing response that was common to both species, but attenuated in Atlantic salmon, potentially reflecting greater sea louse immunomodulation. Our results revealed unique but complementary roles of three layers of keratinocytes in the epithelial hyperplasia response leading to rapid sea lice rejection in coho salmon. Our results suggest that basal keratinocytes direct the expansion and mobility of intermediate and, especially, superficial keratinocytes, which eventually encapsulate the parasite. CONCLUSIONS: Our results highlight the key role of keratinocytes in coho salmon's sea lice resistance and the diverged biological response of the two salmonid host species when interacting with this parasite. This study has identified key pathways and candidate genes that could be manipulated using various biotechnological solutions to improve Atlantic salmon sea lice resistance.

Single versus multiple arterial grafting in diabetic patients at 10 years: the Arterial Revascularization Trial.

AIMS: To evaluate the impact of multiple arterial grafting (MAG) vs. single arterial grafting (SAG) in a post hoc analysis of 10-year outcomes in patients with diabetes mellitus (DM) from the Arterial Revascularization Trial (ART). METHODS AND RESULTS: The primary endpoint was all-cause mortality and the secondary endpoint was a composite of major adverse cardiac events (MACE) at 10-year follow-up. Patients were stratified by diabetes status (non-DM and DM) and grafting strategy (MAG vs. SAG). A total of 3020 patients were included in the analysis; 716 (23.7%) had DM. Overall, 55.8% non-DM patients received MAG and 44.2% received SAG, while 56.6% DM patients received MAG and 43.4% received SAG. The use of MAG compared with SAG was associated with lower 10-year mortality for both non-DM [17.7 vs. 21.0%, adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.72-1.06] and DM patients (21.5 vs. 29.9%, adjusted HR 0.65, 95% CI 0.48-0.89; P for interaction = 0.12). For both groups, the rate of 10-year MACE was also lower for MAG vs. SAG. Overall, deep sternal wound infections (DSWIs) were uncommon but more frequent in the MAG vs. SAG group in both non-DM (3.3 vs. 2.1%) and DM patients (7.9 vs. 4.8%). The highest rates of DSWI were in insulin-treated patients receiving MAG (9.6 vs. 6.3%, when compared with SAG). CONCLUSION: In this post hoc analysis of the ART, MAG was associated with substantially lower mortality rates at 10 years after coronary artery bypass grafting in patients with DM. Patients with DM receiving MAG had a higher incidence of DSWI, especially if insulin dependent.

Posterior left pericardiotomy for the prevention of atrial fibrillation after cardiac surgery: an adaptive, single-centre, single-blind, randomised, controlled trial.

BACKGROUND: Atrial fibrillation is the most common complication after cardiac surgery and is associated with extended in-hospital stay and increased adverse outcomes, including death and stroke. Pericardial effusion is common after cardiac surgery and can trigger atrial fibrillation. We tested the hypothesis that posterior left pericardiotomy, a surgical manoeuvre that drains the pericardial space into the left pleural cavity, might reduce the incidence of atrial fibrillation after cardiac surgery. METHODS: In this adaptive, randomised, controlled trial, we recruited adult patients (aged ≥18 years) undergoing elective interventions on the coronary arteries, aortic valve, or ascending aorta, or a combination of these, performed by members of the Department of Cardiothoracic Surgery from Weill Cornell Medicine at the New York Presbyterian Hospital in New York, NY, USA. Patients were eligible if they had no history of atrial fibrillation or other arrhythmias or contraindications to the experimental intervention. Eligible patients were randomly assigned (1:1), stratified by CHA2DS2-VASc score and using a mixed-block randomisation approach (block sizes of 4, 6, and 8), to posterior left pericardiotomy or no intervention. Patients and assessors were blinded to treatment assignment. Patients were followed up until 30 days after hospital discharge. The primary outcome was the incidence of atrial fibrillation during postoperative in-hospital stay, which was assessed in the intention-to-treat (ITT) population. Safety was assessed in the as-treated population. This study is registered with ClinicalTrials.gov, NCT02875405, and is now complete. FINDINGS: Between Sept 18, 2017, and Aug 2, 2021, 3601 patients were screened and 420 were included and randomly assigned to the posterior left pericardiotomy group (n=212) or the no intervention group (n=208; ITT population). The median age was 61·0 years (IQR 53·0-70·0), 102 (24%) patients were female, and 318 (76%) were male, with a median CHA2DS2-VASc score of 2·0 (IQR 1·0-3·0). The two groups were balanced with respect to clinical and surgical characteristics. No patients were lost to follow-up and data completeness was 100%. Three patients in the posterior left pericardiotomy group did not receive the intervention. In the ITT population, the incidence of postoperative atrial fibrillation was significantly lower in the posterior left pericardiotomy group than in the no intervention group (37 [17%] of 212 vs 66 [32%] of 208 [p=0·0007]; odds ratio adjusted for the stratification variable 0·44 [95% CI 0·27-0·70; p=0·0005]). Two (1%) of 209 patients in the posterior left pericardiotomy group and one (<1%) of 211 in the no intervention group died within 30 days after hospital discharge. The incidence of postoperative pericardial effusion was lower in the posterior left pericardiotomy group than in the no intervention group (26 [12%] of 209 vs 45 [21%] of 211; relative risk 0·58 [95% CI 0·37-0·91]). Postoperative major adverse events occurred in six (3%) patients in the posterior left pericardiotomy group and in four (2%) in the no intervention group. No posterior left pericardiotomy related complications were seen. INTERPRETATION: Posterior left pericardiotomy is highly effective in reducing the incidence of atrial fibrillation after surgery on the coronary arteries, aortic valve, or ascending aorta, or a combination of these without additional risk of postoperative complications. FUNDING: None.

Representation of racial minorities in cardiac surgery randomized clinical trials.

BACKGROUND: Racial minorities account for 39.9% of the population in the United States, but are often underrepresented in clinical research. Results from studies predominantly enrolling White patients may not apply to racial minorities. The aim of this analysis is to assess the representation of racial minorities in cardiac surgery randomized clinical trials (RCTs). METHODS: A systematic search of the literature was performed. All RCTs published from 2000 to 2020 including at least 100 patients and comparing two or more adult cardiac surgery procedures were included. Meta-analytic estimates were calculated. RESULTS: Among 51 cardiac surgery RCTs published between 2000 and 2020, only 9 (17.6%) reported the race of patients and were included in the final analysis. All of them were multicentric, with a mean of 33 centers included. Six RCTs enrolled patients undergoing coronary artery bypass grafting (66.7%), while the remaining three were on valve surgery (33.3%). Overall, 9193 patients were included; of them, 8034 (87.4%) were White and 1026 (11.2%) nonWhite (386 [4.2%] Black, 191 [2.1%] Hispanic, 274 [3.0%] from other races, and 175 [1.9%] nonWhite patients of unspecified race). The proportion of nonWhite patients did not change over time. CONCLUSIONS: Only 9 (17.6%) of the 51 cardiac surgery RCTs published between 2000 and 2020 reported the race of the patients enrolled and only 11.2% of them were nonWhite patients. Given the association between race and clinical outcomes, future RCTs should either guarantee a balanced inclusion of racial minorities or be designed to specifically enroll them.

Sex differences in outcomes after coronary artery bypass grafting: a pooled analysis of individual patient data.

AIMS: Data suggest that women have worse outcomes than men after coronary artery bypass grafting (CABG), but results have been inconsistent across studies. Due to the large differences in baseline characteristics between sexes, suboptimal risk adjustment due to low-quality data may be the reason for the observed differences. To overcome this limitation, we undertook a systematic review and pooled analysis of high-quality individual patient data from large CABG trials to compare the adjusted outcomes of women and men. METHODS AND RESULTS: The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and repeat revascularization (major adverse cardiac and cerebrovascular events, MACCE). The secondary outcome was all-cause mortality. Multivariable mixed-effect Cox regression was used. Four trials involving 13 193 patients (10 479 males; 2714 females) were included. Over 5 years of follow-up, women had a significantly higher risk of MACCE [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.21; P = 0.004] but similar mortality (adjusted HR 1.03, 95% CI 0.94-1.14; P = 0.51) compared to men. Women had higher incidence of MI (adjusted HR 1.30, 95% CI 1.11-1.52) and repeat revascularization (adjusted HR 1.22, 95% CI 1.04-1.43) but not stroke (adjusted HR 1.17, 95% CI 0.90-1.52). The difference in MACCE between sexes was not significant in patients 75 years and older. The use of off-pump surgery and multiple arterial grafting did not modify the difference between sexes. CONCLUSIONS: Women have worse outcomes than men in the first 5 years after CABG. This difference is not significant in patients aged over 75 years and is not affected by the surgical technique.

Screening two biodegradable polymers in enhanced efficiency fertiliser formulations reveals the need to prioritise performance goals.

Enhanced efficiency fertilisers (EEF) may reduce nitrogen (N) losses and improve uptake efficiency through synchronising N release with in-season plant requirements. We hypothesised that EEF formed via matrix encapsulation in biodegradable polymers will improve N use efficiency when compared to conventional urea fertiliser. This hypothesis was investigated for two biodegradable polymer matrices: polyhydroxyalkanoate (PHA), containing 11.6% urea (by mass), and polybutylene-adipate-co-terephthalate (PBAT), containing either 19.4 or 32.7% urea; and two contrasting soil types: sand and clay. Nitrogen availability and form was investigated under leaching conditions (water) with a growth accelerator pot experiment involving a horticultural crop and novel non-destructive three-dimensional scanning to measure in-season biomass development. The PBAT 32.7% formulation enabled greater above ground biomass production at both 50 and 100 kg N ha-1 equivalent application rates compared to conventional urea. For the sandy soil, plant scanning indicated that improved uptake performance with PBAT 32.7% was probably the result of greater N availability after 25 days than for conventional urea. Two of the encapsulated formulations (PHA and PBAT 19.4%) tended to decrease nitrogen leaching losses relative to urea (P < 0.05 for the red clay soil). However, decreased N leaching loss was accompanied by poorer N uptake performance, indicative of N being less available in these biopolymer formulations. A snapshot of nitrous oxide emissions collected during peak nitrate concentration (prior to planting and leaching) suggested that the biopolymers promoted N loss via gaseous emission relative to urea in the sandy soil (P < 0.05), and carbon dioxide emissions data suggested that biopolymer-carbon increased microbial activity (P < 0.1). Controlled testing of N release in water was a poor predictor of biomass production and leaching losses. The diverse behaviours of the tested formulations present the potential to optimise biopolymers and their N loadings by taking into account soil and environmental factors that influence the efficient delivery of N to target crops. The greater N uptake efficiency demonstrated for the PBAT 32.7% formulation confirms our hypothesis that matrix encapsulation can enable better synchronisation of N release with crop requirements and decrease leaching losses.

Coronary artery bypass grafting in low ejection fraction: state of the art.

PURPOSE OF REVIEW: As the number of patients with reduced ejection fraction secondary to ischemic cardiomyopathy (ICM) increases, coronary artery bypass grafting is being used with increasing frequency. In this review, we summarize the different operative considerations in this vulnerable patient population. RECENT FINDINGS: Preoperative optimization with mechanical circulatory support devices, especially in the setting of hemodynamic instability, can reduce perioperative morbidity and mortality. The advantage of advanced techniques, such as off-pump CABG and multiple arterial grafting remains unclear. Concomitant procedures, such as ablation for atrial fibrillation remain important considerations that should be tailored to the individual patients risk profile. SUMMARY: Despite improvements in perioperative care of patients undergoing CABG, patients with a reduced ejection fraction remain at elevated risk of major morbidity and mortality. Preoperative optimization and careful selection of intraoperative techniques can lead to improved outcomes.

Surgical repair of a giant coronary artery aneurysm.

We present a rare case of a giant coronary aneurysm of the circumflex artery measuring 4.8 × 4.2 × 7.2 cm in a 67-year-old man, recently diagnosed with type B aortic dissection. Surgical management was successfully performed by proximal end ligation and bypass of the dual-ostium distal end with a reverse saphenous vein graft.

Decision analysis and personalized clinical tool for cerebrospinal fluid drains in thoracoabdominal aortic aneurysms repair.

BACKGROUND AND AIM: The routine use of cerebrospinal fluid (CSF) drainage in patients undergoing operative repair of thoracoabdominal aneurysms (TAAA) has been associated with decreased rates of spinal cord ischemia. The use of CSF drains is not without consequence, however with complications including subarachnoid hemorrhage, epidural hematoma, meningitis, and, in 1% of cases, death. To date, a decision analysis tool to help clinicians decide when to use and not to use a CSF drain does not exist. In this analysis, we set out to develop a decision analysis tool for CSF drain placement in patients undergoing operative repair of TAAA. METHODS: A Markov state-transition cohort model that compared TAAA repair with adjunctive CSF drain insertion to TAAA repair without drain insertion for the outcome of life expectancy was developed in TreeAge 2020. The cycle length was 1 month and the time horizon was 60 months. RESULTS: The use of a CSF drain was associated with improved 5-year life expectancy (3.21 ± 0.10 vs. 3.09 ± 0.11 life-years gained). In the sensitivity analysis that varied the effectiveness of a CSF drain (odds ratio closer to 1 = less effective), the use of a CSF drain resulted in higher life expectancy in almost all scenarios. CONCLUSIONS: The routine use of a CSF drain in patients undergoing TAAA repair is safe and effective, with few exceptions. This decision analysis tool can be used by clinicians to develop a personalized approach.

Results of surgical ventricular reconstruction in a specialized center and in comparison to the STICH trial: Rationale and study protocol for a patient-level pooled analysis.

INTRODUCTION: Post-infarction left ventricular remodeling is associated with increased mortality in patients with ischemic heart disease. Surgical ventricular reconstruction (SVR) in addition to coronary artery bypass grafting (CABG) has been proposed to reduce left ventricular volume and improve clinical outcomes. The Surgical Treatment for Ischemic Heart Failure (STICH) trial found that the addition of SVR to CABG did not reduce the rates of death or rehospitalization in the 5 years after surgery compared to CABG alone. Like all randomized trials, STICH has limitations and it has been hypothesized that it may have underestimated the treatment effect of SVR. The aim of this study is to evaluate the results of SVR in one of the largest contemporary single-center series and to compare the results with those of the STICH trial using individual patient's data. METHODS AND ANALYSIS: Individual data of patients who underwent SVR with or without CABG will be obtained from San Donato University Hospital in Milan. Using multivariable Cox regression analysis, significant prognostic indicators in this cohort will be identified. We will then compare the San Donato cohort to individual patient's data from the SVR arm of Hypothesis 2 of the STICH trial and from both arms of the STICH Extended Study (STICHES). To reduce confounders, propensity score adjustment will be used for this comparison. The primary endpoint will be all-cause mortality. Data will be merged and analyzed independently at Weill Cornell Medicine in New York.

A Perspective from New York of COVID 19: Effect and impact on cardiac surgery.

BACKGROUND AND AIM: First reported in December of 2019, the COVID-19 pandemic caused by SARS-CoV-2 has had a profound impact on the implementation of care. Here, we describe our institutional experience with a rapid influx of patients at the epicenter of the pandemic. METHODS: We retrospectively review our experience with the departments of cardiology, cardiothoracic surgery, anesthesia, and critical care medicine and summarize protocols developed in the midst of the pandemic. RESULTS: The rapid influx of patients requiring an intensive level of care required a complete restructuring of units, including the establishment of a new COVID-19 negative unit for the care of patients requiring urgent or emergent non-COVID-19 related care including open-heart surgery. This unique unit allowed for the delivery of safe and effective care in the epicenter of the pandemic. CONCLUSIONS: Here, we demonstrate the response of a large tertiary academic medical center to the COVID-19 pandemic. Specifically, we demonstrate how rapid structural changes can allow for the continued delivery of cardiac surgical care with similar outcomes as those reported before the pandemic.

Impact of aortic valve disease on outcomes of aortic root replacement.

BACKGROUND AND AIM OF THE STUDY: Aortic stenosis (AS) has been associated with higher mortality in patients undergoing aortic root replacement (ARR). In this analysis, we compare the outcomes among patients with moderate to severe AS or aortic insufficiency (AI) undergoing ARR in a tertiary aortic center. METHODS: A total of 889 patients underwent ARR from 1997 to 2020, of whom 798 had AI and 91 had AS. We excluded valve-sparing procedures. The primary endpoint consisted of major adverse events (MAEs), including operative mortality, myocardial infarction, tracheostomy, new dialysis, and cerebrovascular accidents. All patients had either a mechanical or biologic composite valve-graft implanted using button and exclusion techniques. Propensity score matching (PSM) was used to compare outcomes. Long-term survival was estimated using the Kaplan-Meier method. RESULTS: Patients with AI had a higher incidence of connective tissue disorder (8.0% vs. 0.0%; p = .01) and were more likely to be classified as having an urgent or emergent procedure (22.4% vs. 8.8%; p = .004). PSM achieved a good balance between the groups. There was no difference in MAE rates, postoperatively (AI vs. AS, 1.6% vs. 1.6%; p = .85). Long-term survival was similar at 5 years in the matched cohorts (AI vs. AS, 75.9% vs. 95.5%; p = .36). CONCLUSION: In patients undergoing ARR, the presence of moderate to severe AI or AS does not impact operative outcomes. ARR can be carried out with excellent outcomes and low operative mortality when performed in specialized centers.

Comparison of the effects of hemodialysis and hemodiafiltration on left ventricular hypertrophy in end-stage renal disease patients: A systematic review and meta-analysis.

Whether hemodiafiltration (HDF) is better than conventional hemodialysis (HD) in improving left ventricular hypertrophy (LVH), defined as reduction of the left ventricular mass index (LVMi) and increasing the ejection fraction (EF), is unclear. A systematic literature search was performed. Primary outcome was the mean difference between pre- and post-procedural LVMi. Secondary outcome was the mean difference in EF. Seven studies with a total of 845 patients were included. The pooled mean difference between pre-and post-procedural LVMi was -8.0 g/m2 (95% confidence interval [CI] -13.1, -2.8). On subgroup analysis, the mean differences between pre- and post-procedural LVMi for HD and HDF were -6.7 g/m2 (95% CI -14.5, 1.1) and -9.3 g/m2 (95% CI -16.3, -2.3), respectively (P for subgroups = .62). Pooled mean difference between pre- and post-procedural EF was 2.4% (95% CI -1.8, 6.5). On subgroup analysis, the mean differences between pre- and post-procedural EF for HD and HDF were 3.6% (95% CI -2.7, 9.8) and 2.0% (95% CI 2.9, 6.8), respectively (P for subgroups = .68). On meta-regression, age (Beta -0.35 ± 0.05, P < .001) and longer dialysis duration (Beta -0.12 ± 0.02, P < .001) were associated with lower mean difference between pre-and post-procedural EF. No significant effects on changes in LVMi and EF were observed with HDF compared with conventional HD.

Resistance of Wheat Genotypes to Root-Lesion Nematode (Pratylenchus thornei) Can be Used to Predict Final Nematode Population Densities, Crop Greenness, and Grain Yield in the Field.

The root-lesion nematode Pratylenchus thornei is a major pathogen of wheat (Triticum aestivum) in many regions globally. Resistance of wheat genotypes to P. thornei can be determined from final nematode population densities in glasshouse experiments but combining results across multiple experiments presents challenges. Here, we use a factor analytic method for multiexperiment analysis of final population densities of P. thornei for 1,096 unique wheat genotypes in 22 glasshouse experiments. The resistance to P. thornei of the genotypes was effectively represented by a two-factor model with rotation of the axes to a principal components solution. Principal axes 1 and 2 (PA1 and PA2) accounted for 79 and 11% of the genetic variance, respectively, over all experiments. Final population densities of P. thornei as empirical best linear unbiased predictors (PA[1+2]-eBLUPs) from the combined glasshouse experiments were highly predictive (P < 0.001) of final nematode population densities in the soil profile, crop canopy greenness (normalized difference vegetation index), and grain yield of wheat genotypes in P. thornei-infested fields in the Australian subtropical grain region. Nine categories of resistance ratings for wheat genotypes from resistant to very susceptible were based on subdivision of the range of PA(1+2)-eBLUPs for use in growers' sowing guides. Nine genotypes were nominated as references for future resistance experiments. Most (62%) Australian wheat genotypes were in the most susceptible three categories (susceptible, susceptible to very susceptible, and very susceptible). However, resistant germplasm characterized in this study could be used in plant breeding to considerably improve the overall resistance of Australian wheat crops.

Shunting away from transradial arterial access?

Due to its increased safety and decrease in significant vascular complications and bleeding events, the use of the radial artery for percutaneous coronary intervention (PCI) is increasing. Transradial access (TRA), however, is not without consequence. TRA arteries when used for coronary artery bypass grafting (CABG) are associated with decreased graft patency rates. Here we comment on a case report in which a patient developed a clinically significant arteriovenous fistula following TRA treated with surgical ligation. We offer insights on the increased use of the radial artery in both PCI and CABG.

Is endoscopic radial artery harvesting open for business?

With the resurgence of the radial artery in coronary artery bypass grafting, the debate on the optimal harvesting technique continues. Here, we comment on a randomized series in which the authors conclude that endoscopic harvesting techniques offer the benefit of improved cosmetic outcomes and decreased neurological complications with comparable graft-related outcomes when compared with open harvesting. We conclude that although this study is well designed and conducted, there are several areas of concern including surgical technique and statistical power.

Publication of cardiac surgery research papers in top cardiovascular journals.

BACKGROUND AND AIM: To evaluate the publication rate of articles related to cardiac surgery in the four main cardiovascular journals over the last 5 years. METHODS: A bibliometric review of all full-length articles published between January 2014 and March 2020 in the top four cardiovascular journals (Circulation, European Heart Journal (EHJ), Journal of the American College of Cardiology (JACC), and JAMA Cardiology) was conducted. For each eligible article in the four journals, the journal of publication, study design, area of interest, country of origin, and type of intervention tested (for cardiac surgery and interventional cardiology studies) were extracted. The affiliations of all editorial board members were identified from journal websites or from online searches and recorded as from cardiac surgery, cardiology, or another discipline. Correlations between variables were evaluated. RESULTS: A total of 4835 articles were reviewed. Cardiac surgery studies amounted to 6.2% (104) of total research publications in JACC, 4.4% (74) in Circulation, 3.6% (13) in JAMA Cardiology, and 2.0% (22) in EHJ (P < .001). The percentage of cardiac surgery publications was significantly less than interventional cardiology publications (P < .001). CONCLUSIONS: Cardiac surgery studies represent only a small minority of the articles published in the top cardiovascular journals over the last 5 years, with significant differences between individual journals. Cardiac surgery studies were more often observational and this may constitute one important reason for their under-representation.

Sex-related differences in outcomes after coronary artery bypass surgery-A patient-level pooled analysis of randomized controlled trials: rationale and study protocol.

INTRODUCTION: The impact of sex on the outcomes after coronary artery bypass grafting (CABG) is controversial. The majority of CABG studies are retrospectively collected clinical or registry data, women comprise only a minority, and the reported findings represent the male predominated cohort. This individual patient meta-analysis is aimed at evaluating sex-related differences in outcomes after CABG using high quality data from randomized controlled trials (RCTs). METHODS AND ANALYSIS: A systematic literature search will be performed to identify all CABG RCTs (minimum follow-up: 5 years). Detailed specification for the minimum deidentified patient records' data requirements will be provided to RCT primary contact to request their deidentified data for pooling. The pooled analysis will follow the prospective register of systematic reviews (PROSPERO) and the preferred reporting items for systematic reviews and meta-analyses for individual patient data systematic reviews (PRISMA-IPD) recommendations and will compare sex-related outcomes after CABG. The main hypothesis is that outcomes after CABG are worse in women than in men. We will also test whether treatment effects for off-pump and the use of multiple arterial grafts are present within each sex, and also, whether there are differential treatment effects between sexes. The primary endpoint will be a composite of all-cause mortality, myocardial infarction, stroke, and repeat revascularization at long-term follow up. ETHICS AND DISSEMINATION: Ethics approval and participant consent for the study will be obtained locally by each study team if needed. Data will be disseminated and submitted to peer-reviewed scientific journals and meetings irrespective of study outcome.

Identification of loci affecting sexually dimorphic patterns for height and recurrent laryngeal neuropathy risk in American Belgian Draft Horses.

Equine recurrent laryngeal neuropathy (RLN) is a bilateral mononeuropathy with an unknown etiology. In Thoroughbreds (TB), we previously demonstrated that the haplotype association for height (LCORL/NCAPG locus on ECA3, which affects body size) and RLN was coincident. In the present study, we performed a genome-wide association scan (GWAS) for RLN in 458 American Belgian Draft Horses, a breed fixed for the LCORL/NCAPG risk alelle. In this breed, RLN risk is associated with sexually dimorphic differences in height, and we identified a novel locus contributing to height in a sex-specific manner: MYPN (ECA1). Yet this specific locus contributes little to RLN risk, suggesting that other growth traits correlated to height may underlie the correlation to this disease. Controlling for height, we identified a locus on ECA15 contributing to RLN risk specifically in males. These results suggest that loci with sex-specific gene expression play an important role in altering growth traits impacting RLN etiology, but not necessarily adult height. These newly identified genes are promising targets for novel preventative and treatment strategies.

Time-resolved stimulated emission depletion and energy transfer dynamics in two-photon excited EGFP.

Time and polarization-resolved stimulated emission depletion (STED) measurements are used to investigate excited state evolution following the two-photon excitation of enhanced green fluorescent protein (EGFP). We employ a new approach for the accurate STED measurement of the hitherto unmeasured degree of hexadecapolar transition dipole moment alignment α40 present at a given excitation-depletion (pump-dump) pulse separation. Time-resolved polarized fluorescence measurements as a function of pump-dump delay reveal the time evolution of α40 to be considerably more rapid than predicted for isotropic rotational diffusion in EGFP. Additional depolarization by homo-Förster resonance energy transfer is investigated for both α20 (quadrupolar) and α40 transition dipole alignments. These results point to the utility of higher order dipole correlation measurements in the investigation of resonance energy transfer processes.