The complex polyploid genome architecture of sugarcane.

Sugarcane, the world's most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype ('monoploid') representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.

Structure-Property Optimization of a Series of Imidazopyridines for Visceral Leishmaniasis.

Leishmaniasis is a collection of diseases caused by more than 20 Leishmania parasite species that manifest as either visceral, cutaneous, or mucocutaneous leishmaniasis. Despite the significant mortality and morbidity associated with leishmaniasis, it remains a neglected tropical disease. Existing treatments have variable efficacy, significant toxicity, rising resistance, and limited oral bioavailability, which necessitates the development of novel and affordable therapeutics. Here, we report on the continued optimization of a series of imidazopyridines for visceral leishmaniasis and a scaffold hop to a series of substituted 2-(pyridin-2-yl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoles with improved absorption, distribution, metabolism, and elimination properties.

Localized myxedema histologically mimicking spindle cell lipoma.

In this report, a 55-year-old woman with Graves disease and exophthalmos had a recurrent nodule on the foot. Her initial biopsy and excision specimens were believed to be consistent with spindle cell lipoma, which aligned with her early tumor-like clinical morphology. Her tumor recurred after excision, which is not consistent with spindle cell lipoma. As her condition progressed, her clinical morphology became more consistent with localized myxedema and her biopsies were congruent, securing clinicopathologic correlation. With standard treatment for localized myxedema, she improved significantly. This case emphasizes how clinicians need to have high suspicion for localized myxedema in patients with history of Graves disease and exophthalmos. It also emphasizes how localized myxedema should be included in the histologic differential diagnosis for spindle cell lipoma with prominent myxoid stroma, particularly in those not responding to treatment as anticipated.

Adjustment of publication bias using a cumulative meta-analytic framework.

OBJECTIVES: Publication bias has the potential to adversely impact clinical decision making and patient health if alternative decisions would have been made had there been complete publication of evidence. METHODS: The objective of our analysis was to determine if earlier publication of the complete evidence on rosiglitazone's risk of myocardial infarction (MI) would have changed clinical decision making at an earlier point in time. We tested several methods for adjustment of publication bias to assess the impact of potential time delays to identifying the MI effect. We then performed a cumulative meta-analysis (CMA) for both published studies (published-only data set) and all studies performed (comprehensive data set). We then created an adjusted data set using existing methods of adjustment for publication bias (Harbord regression, Peter's regression, and the nonparametric trim and fill method) applied to the limited data set. Finally, we compared the time to the decision threshold for each data set using CMA. RESULTS: Although published-only and comprehensive data sets did not provide notably different final summary estimates [OR = 1.4 (95 percent confidence interval [CI]: .95-2.05) and 1.42 (95 percent CI: 1.03-1.97)], the comprehensive data set reached the decision threshold 36 months earlier than the published-only data set. All three adjustment methods tested did not show a differential time to decision threshold versus the published-only data set. CONCLUSIONS: Complete access to studies capturing MI risk for rosiglitazone would have led to the evidence reaching a clinically meaningful decision threshold 3 years earlier.

Time to first recurrence, pattern of recurrence, and survival after recurrence in endometrial cancer according to the molecular classification.

OBJECTIVE: Despite its generally favorable prognosis at primary diagnosis, recurrence of endometrial cancer remains an important clinical challenge. The aim of this study was to analyze the value of molecular classification in recurrent endometrial cancer. METHODS: This study included patients with recurrent endometrial cancer who underwent primary surgical treatment between 2004 and 2015 at the Karolinska University Hospital, Sweden and the Bern University Hospital, Switzerland (KImBer cohort) with molecular classification of the primary tumor. RESULTS: Out of 594 molecularly classified endometrial cancer patients, 101 patients experienced recurrence, consisting of 2 POLEmut, 33 MMRd, 30 p53abn, and 36 NSMP tumors. Mean age at recurrence was 71 years and mean follow-up was 54 months. Overall, median time to first recurrence was 16 months (95% CI 12-20); with the shortest median time in MMRd patients, with 13 months (95% CI 5-21). The pattern of recurrence was distinct among molecular subgroups: MMRd tumors experienced more locoregional, while p53abn cases showed more abdominal recurrences (P = .042). Median survival after recurrence was best for MMRd cases (43 months, 95% CI 11-76), compared to 39 months (95% CI 21-57) and 10 months (95% CI 7-13) for the NSMP and p53abn cases respectively (log-rank, P = .001). CONCLUSION: Molecular classification is a significant indicator of survival after recurrence in endometrial cancer patients, and patterns of recurrence differ by molecular subgroups. While MMRd endometrial cancer show more locoregional recurrence and the best survival rates after recurrence, p53abn patients experience abdominal recurrence more often and had the worst prognosis of all recurrent patients.

Relationship between atrial fibrillatory rate based on analysis of a modified base-apex surface electrocardiogram analysis and the results of transvenous electrical cardioversion in horses with spontaneous atrial fibrillation.

OBJECTIVES: To compare the atrial fibrillatory rate (AFR) derived from a local right atrial intracardiac recording (RA-FR) and from a single-lead surface electrocardiogram (ECG) during atrial fibrillation (AF) and to evaluate the correlation with transvenous electrical cardioversion (TVEC) threshold (in Joules), number of shocks and cardioversion success rate in horses. ANIMALS: ECGs and clinical records of horses with AF treated by TVEC. Horses were included if a simultaneous recording of the right atrial intracardiac electrogram and a modified base-apex ECG were available. MATERIALS AND METHODS: Clinical records of horses with AF treated by TVEC were reviewed. Three-minute long episodes of simultaneous electrograms and surface ECG during AF were selected for analysis and compared using Bland-Altman analysis. The mean RA-FR was measured from the deflections on the intracardiac electrogram, while the AFR was extracted from the surface ECG using spatiotemporal QRS and T-wave cancellation. RESULTS: Seventy-three horses satisfied the inclusion criteria. The mean difference between RA-FR and AFR was -13 fibrillations per minute (fpm), the 95% limits of agreement were between -66 and 40 fpm, and there was a moderate (ρ = 0.65) correlation between RA-FR and AFR (p < 0.001). Neither RA-FR nor AFR appeared to influence the TVEC cardioversion threshold or the number of TVEC shocks applied. CONCLUSIONS: The AFR may allow non-invasive long-term monitoring of AF dynamics. Neither RA-FR nor AFR could be used to predict the minimal defibrillation threshold for TVEC.

Combination of Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) with sonographic and demographic characteristics in preoperative prediction of recurrence or progression of endometrial cancer.

OBJECTIVE: To evaluate the ability of demographic and sonographic variables and the Proactive Molecular Risk Classifier for Endometrial cancer (ProMisE) classification to predict preoperatively tumor recurrence or progression in women with endometrial cancer. METHODS: The study included 339 women with histologically confirmed endometrial cancer who underwent expert transvaginal ultrasound in a single center before surgery as part of the prospective International Endometrial Tumor Analysis 4 study or who were evaluated using the same protocol. The tumors were classified according to histotype, FIGO (International Federation of Gynecology and Obstetrics) grade and FIGO stage. In addition, molecular analysis was performed for classification into the four ProMisE subtypes: polymerase-ϵ exonuclease domain mutations (POLE EDM), mismatch repair proteins deficiency (MMR-D), protein 53 wild type (p53 wt) and protein 53 abnormal (p53 abn). Demographic and preoperative sonographic characteristics, tumor recurrence or progression and survival were compared between the ProMisE subgroups. Cox regression analysis was used to identify prognostic factors associated with recurrence or progression, using univariable models to study crude associations and multivariable models to study adjusted associations. Logistic regression and receiver-operating-characteristics (ROC)-curve analysis were used to assess the predictive ability of the preoperative prognostic factors regarding recurrence or progression of cancer within 3 years after surgery, and to compare their predictive ability to that of the European Society for Medical Oncology (ESMO) preoperative (based on depth of myometrial invasion, histotype and grade) and postoperative (based on histotype, grade, surgical stage and lymphovascular space invasion) risk classifications. In a separate subanalysis, cases were stratified according to ProMisE p53 abn status (present vs absent) and sonographic tumor size (anteroposterior (AP) diameter < 2 cm vs ≥ 2 cm). RESULTS: Median follow-up time from surgery was 58 months (interquartile range, 48-71 months; range, 0-102 months). Recurrence or progression of cancer occurred in 51/339 (15%) women, comprising 14% of those with MMR-D, 8% of those with POLE EDM, 9% of those with p53 wt and 45% of those with p53 abn ProMisE subtype. On multivariable analysis, age, waist circumference, ProMisE subtype and tumor extension and AP diameter on ultrasound were associated with tumor recurrence or progression. A multivariable model comprising ProMisE subtype, age, waist circumference and sonographic tumor extension and size (area under the ROC curve (AUC), 0.89 (95% CI, 0.85-0.93)) had comparable ability to predict tumor recurrence/progression to that of a multivariable model comprising histotype, grade, age, waist circumference and sonographic tumor extension and size (AUC, 0.88 (95% CI, 0.83-0.92)), and better predictive ability than both the preoperative (AUC, 0.74 (95% CI, 0.67-0.82); P < 0.01) and postoperative (AUC, 0.79 (95% CI, 0.72-0.86); P < 0.01) ESMO risk classifications. Women with a combination of non-p53 abn subtype and tumor size < 2 cm (164/339 (48%)) had a very low risk (1.8%) of tumor recurrence or progression. CONCLUSIONS: The combination of demographic characteristics, sonographic findings and ProMisE subtype had better preoperative predictive ability for tumor recurrence or progression than did the ESMO classification, supporting their use in the preoperative risk stratification of women with endometrial cancer. The combination of p53 status with ultrasound tumor size has the potential to identify preoperatively a large group of women with a very low risk of recurrence or progression. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. - Legal Statement: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Clustering of Four-Component Unitary Fermions.

Ab initio nuclear physics tackles the problem of strongly interacting four-component fermions. The same setting could foreseeably be probed experimentally in ultracold atomic systems, where two- and three-component experiments have led to major breakthroughs in recent years. Both due to the problem's inherent interest and as a pathway to nuclear physics, in this Letter we study four-component fermions at unitarity via the use of quantum Monte Carlo methods. We explore novel forms of the trial wave function and find one which leads to a ground state of the eight-particle system whose energy is almost equal to that of two four-particle systems. We investigate the clustering properties involved and also extrapolate to the zero-range limit. In addition to being experimentally testable, our results impact the prospects of developing nuclear physics as a perturbation around the unitary limit.

Decoding collective communications using information theory tools.

Organisms have evolved sensory mechanisms to extract pertinent information from their environment, enabling them to assess their situation and act accordingly. For social organisms travelling in groups, like the fish in a school or the birds in a flock, sharing information can further improve their situational awareness and reaction times. Data on the benefits and costs of social coordination, however, have largely allowed our understanding of why collective behaviours have evolved to outpace our mechanistic knowledge of how they arise. Recent studies have begun to correct this imbalance through fine-scale analyses of group movement data. One approach that has received renewed attention is the use of information theoretic (IT) tools like mutual information, transfer entropy and causation entropy, which can help identify causal interactions in the type of complex, dynamical patterns often on display when organisms act collectively. Yet, there is a communications gap between studies focused on the ecological constraints and solutions of collective action with those demonstrating the promise of IT tools in this arena. We attempt to bridge this divide through a series of ecologically motivated examples designed to illustrate the benefits and challenges of using IT tools to extract deeper insights into the interaction patterns governing group-level dynamics. We summarize some of the approaches taken thus far to circumvent existing challenges in this area and we conclude with an optimistic, yet cautionary perspective.

SERINE-910 Phosphorylated Focal Adhesion Kinase Expression Predicts Better Overall and Disease-free Survival in Melanoma.

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that mediates multiple cellular functions such as survival, invasion, and migration. FAK has been found to be over-expressed in various human cancers, including melanoma. FAK molecule has several tyrosine, serine, and threonine phosphorylation sites which have an important regulatory role. Tyrosine phosphorylation of FAK has been extensively studied, however little is known about the role of serine phosphorylation. We sought to examine the frequency and extent of serine-910 phosphorylated FAK (P-FAKSer910) expression in a spectrum of melanocytic proliferations as well as it's correlation with other histopathologic predictors and its effect on patient's survival. Clinicopathologic features and immunohistochemical expression of P-FAKSer910 were evaluated in 147 melanocytic proliferations: 73 primary melanoma (PM), 19 metastatic melanoma (MetM), 2 melanoma in situ, and 53 melanocytic nevi (MN). Higher cytoplasmic intensity predicted better overall survival (OS) in PM (χ=5.69; P=0.034) and was associated with 48% decrease in death risk (HR, 0.52; 95% CI, 0.28-0.95; P=0.036). In contrast, increased nuclear intensity was significantly associated with better disease-free survival (DFS) when stratified by tumor stage Log-rank test, trend of survival (χ=5.83, P=0.015) and independently on multivariate analysis when subcategorized into 3-tier categories (HR, 0.43; 95% CI, 0.18-0.98; P=0.045). Also, Clark's level and tumor-infiltrating lymphocytes (TILS) were independent predictors of DFS. Cytoplasmic intensity correlated inversely with American Joint Commission on Cancer stage in primary melanoma cases as well with vascularity in both primary and metastatic melanoma. Nuclear intensity independently correlated negatively with angioinvasion and TILS when subcategorized to 3 tier system. We found American Joint Commission on Cancer tumor stage, Clark's level, depth, ulceration, TILS, mitosis, angioinvasion, and tumor vascularity predictors of both DFS and OS. There was no significant difference in cytoplasmic or nuclear expression among the major categories of melanocytic proliferation. In this pilot immunohistochemistry-based study, we found P-FAKSer910 expression in melanoma by cytoplasmic intensity to correlate with better OS while nuclear intensity correlated with better DFS.

Validation of ultrasound strategies to assess tumor extension and to predict high-risk endometrial cancer in women from the prospective IETA (International Endometrial Tumor Analysis)-4 cohort.

OBJECTIVES: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). METHODS: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The 'subjective prediction model' included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the 'objective prediction model' included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. RESULTS: In 1275 patients with measurable lesions, the sensitivity and specificity of SA for detecting deep MI was 70% and 80%, respectively, in patients with a Grade-1 or -2 endometrioid or mucinous tumor vs 76% and 64% in patients with a Grade-3 endometrioid or mucinous or a non-endometrioid tumor. The corresponding values for the detection of CSI were 51% and 94% vs 50% and 91%. Tumor AP diameter and tumor/uterine AP diameter ratio showed the best performance for predicting deep MI (area under the receiver-operating characteristics curve (AUC) of 0.76 and 0.77, respectively), and Dist-OCO had the best performance for predicting CSI (AUC, 0.72). The proportion of patients classified correctly as having high-risk cancer was 80% when simply combining SA with biopsy grade vs 80% and 74% when using the subjective and objective two-step strategies, respectively. The subjective and objective models had an AUC of 0.76 and 0.75, respectively, when applied to Grade-1 and -2 endometrioid tumors. CONCLUSIONS: In the hands of experienced ultrasound examiners, SA was superior to ultrasound measurements for the prediction of deep MI and CSI of endometrial cancer, especially in patients with a Grade-1 or -2 tumor. The mathematical models for the prediction of high-risk cancer performed as expected. The best strategies for predicting high-risk endometrial cancer were combining SA with biopsy grade and the subjective two-step strategy, both having an accuracy of 80%. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Pilot GWAS of caries in African-Americans shows genetic heterogeneity.

BACKGROUND: Dental caries is the most common chronic disease in the US and disproportionately affects racial/ethnic minorities. Caries is heritable, and though genetic heterogeneity exists between ancestries for a substantial portion of loci associated with complex disease, a genome-wide association study (GWAS) of caries specifically in African Americans has not been performed previously. METHODS: We performed exploratory GWAS of dental caries in 109 African American adults (age > 18) and 96 children (age 3-12) from the Center for Oral Health Research in Appalachia (COHRA1 cohort). Caries phenotypes (DMFS, DMFT, dft, and dfs indices) assessed by dental exams were tested for association with 5 million genotyped or imputed single nucleotide polymorphisms (SNPs), separately in the two age groups. The GWAS was performed using linear regression with adjustment for age, sex, and two principal components of ancestry. A maximum of 1 million adaptive permutations were run to determine empirical significance. RESULTS: No loci met the threshold for genome-wide significance, though some of the strongest signals were near genes previously implicated in caries such as antimicrobial peptide DEFB1 (rs2515501; p = 4.54 × 10- 6) and TUFT1 (rs11805632; p = 5.15 × 10- 6). Effect estimates of lead SNPs at suggestive loci were compared between African Americans and Caucasians (adults N = 918; children N = 983). Significant (p < 5 × 10- 8) genetic heterogeneity for caries risk was found between racial groups for 50% of the suggestive loci in children, and 12-18% of the suggestive loci in adults. CONCLUSIONS: The genetic heterogeneity results suggest that there may be differences in the contributions of genetic variants to caries across racial groups, and highlight the critical need for the inclusion of minorities in subsequent and larger genetic studies of caries in order to meet the goals of precision medicine and to reduce oral health disparities.

Aortocavitary fistula secondary to vegetative endocarditis in a rabbit.

A 4-year-old intact male mini lop rabbit (Oryctolagus cuniculus) was presented with a 2-week history of severe progressive lethargy. A right parasternal continuous heart murmur and an irregular rhythm were detected on physical examination. Echocardiography identified vegetative aortic and tricuspid valve (TV) endocarditis. There was an aortocavitary fistula between the right sinus of Valsalva into the right ventricle, creating a left-to-right intracardiac shunt. Based on the echocardiographic findings, it was suspected that the infection originated in the aortic valve, eroded through the periannular tissue, and secondarily infected the TV. Pleural and peritoneal effusion secondary to right-sided congestive heart failure was also found during the echocardiogram. Atrial fibrillation, conducted with a left bundle branch block morphology, was identified using electrocardiography. Necropsy findings directly correlated with the echocardiographic diagnosis; marked periodontal disease was also identified. Aerobic culture of the aortic and tricuspid vegetations resulted in significant growth of Haemophilus parainfluenzae. Haemophilus spp. belong to a group of similar gram-negative coccobacillus bacteria (HACEK group), which can act as an uncommon cause of endocarditis in humans. HACEK endocarditis is most commonly associated with oral infection and/or dental procedures in people. This is the first case report of a rabbit with periannular complications of infective endocarditis. It remains unknown whether dental disease resulted in endocarditis in this patient.

Interatrial block in prediction of all-cause mortality after first-ever ischemic stroke.

BACKGROUND: Interatrial block (IAB) is an ECG indicator of atrial fibrosis related to atrial remodeling and thrombus formation thus leading to embolic stroke and increasing mortality. We aimed to assess weather IAB predicted all-cause mortality during 10 years after ischemic stroke. METHODS: The study sample comprised 235 patients (median age 74 (interquartile range 25-75% 65-81) years, 95 female) included in the Lund Stroke Register in 2001-2002, who had sinus rhythm ECGs at stroke admission. IAB was defined as a P-wave duration ≥120 ms without = partial IAB (n = 56) or with = advanced IAB (n = 41) biphasic morphology (±) in the inferior ECG leads. All-cause mortality was assessed via linkage with the Swedish Causes of Death Register. RESULTS: During follow-up 126 patients died (54%). Advanced IAB, but not partial, was associated with all-cause mortality in univariate Cox regression analysis (hazard ratio (HR) 1.98, 95% CI 1.27-3.09, p = 0.003). After adjustment for age, gender, severity of stroke measured by NIHSS scale and smoking status in patients without additional comorbidities advanced IAB independently predicted all-cause mortality (HR 7.89, 95% CI 2.01-30.98, p = 0.003), while in patients with comorbidities it did not (HR 1.01 95% CI 0.59-1.72, p = 0.966). CONCLUSION: Advanced IAB predicted all-cause mortality after ischemic stroke, but mostly in patients without additional cardiovascular comorbidities.

Prolonged Tpeak-Tend interval is associated with ventricular fibrillation during reperfusion in ST-elevation myocardial infarction.

AIM: Ventricular fibrillation (VF) during reperfusion in ST-elevation myocardial infarction (STEMI) is associated with increased in-hospital mortality. Dispersion of ventricular repolarization contributes to ventricular vulnerability during ischemia. Tpeak-Tend interval was proposed as a ventricular repolarization dispersion marker, however its value for prediction of reperfusion VF remains uncertain. We aimed to assess whether Tpeak-Tend before PCI in STEMI is associated with reperfusion VF. METHODS: STEMI patients admitted for primary PCI were retrospectively assessed for VF during reperfusion. Pre-PCI ECGs recorded in 40 patients with reperfusion VF (rVF group; age 65 ±â€¯13 years, 80% male) were compared with 374 consecutive patients without reperfusion arrhythmias (No-rVF group; age 67 ±â€¯12 years; 68% male). Digital ECGs were automatically processed and Tpeak-Tend interval computed on a per-lead basis. The global Tpeak-Tend was calculated between the earliest Tpeak and the latest Tend in any lead, and tested for association with reperfusion VF using logistic regression analysis. RESULTS: The leftward shift of Tpeak toward QRS complex in ischemic leads resulted in Tpeak-Tend prolongation. Global Tpeak-Tend in rVF group was higher than in No-rVF group (142 ±â€¯24 vs 130 ±â€¯27 ms; p = 0.007). Global Tpeak-Tend ≥ 131 ms predicted reperfusion VF (OR = 3.41; 95% CI 1.66-7.04; p = 0.001) and remained a significant predictor of reperfusion VF in multivariable analysis. CONCLUSION: Tpeak-Tend interval before PCI in STEMI was an independent predictor of reperfusion VF. Our findings warrants further research aimed at prospective validation of Tpeak-Tend as a marker of periprocedural arrhythmic risk.

Properties of Nuclei up to A=16 using Local Chiral Interactions.

We report accurate quantum Monte Carlo calculations of nuclei up to A=16 based on local chiral two- and three-nucleon interactions up to next-to-next-to-leading order. We examine the theoretical uncertainties associated with the chiral expansion and the cutoff in the theory, as well as the associated operator choices in the three-nucleon interactions. While in light nuclei the cutoff variation and systematic uncertainties are rather small, in ^{16}O these can be significant for large coordinate-space cutoffs. Overall, we show that chiral interactions constructed to reproduce properties of very light systems and nucleon-nucleon scattering give an excellent description of binding energies, charge radii, and form factors for all these nuclei, including open-shell systems in A=6 and 12.

CKS1 expression in melanocytic nevi and melanoma.

Cyclin-dependent kinase subunit 1 (Cks1) regulates the degradation of p27, an important G1-S inhibitor, which is up regulated by MAPK pathway activation. In this study, we sought to determine whether Cks1 expression is increased in melanocytic tumors and correlates with outcome and/or other clinicopathologic prognostic markers. Cks1 expression was assessed by immunohistochemistry in 298 melanocytic lesions. The frequency and intensity of cytoplasmic and nuclear expression was scored as a labeling index and correlated with clinico-pathological data. Nuclear Cks1 protein was found in 63% of melanocytic nevi, 89% primary and 90% metastatic melanomas with mean labeling index of 7 ± 16, 19 ± 20, and 30 ± 29, respectively. While cytoplasmic Cks1 was found in 41% of melanocytic nevi, 84% primary and 95% metastatic melanomas with mean labeling index of 18 ± 34, 35 ± 34, and 52 ± 34, accordingly. Histologic stepwise model of tumor progression, defined as progression from benign nevi to primary melanomas, to melanoma metastases, revealed a significant increase in nuclear and cytoplasmic Cks1 expression with tumor progression. Nuclear and cytoplasmic Cks1 expression correlated with the presence of ulceration, increased mitotic rate, Breslow depth, Clark level, tumor infiltrating lymphocytes and gender. However, other well-known prognostic factors (age, anatomic site, and regression) did not correlate with any type of Cks1 expression. Similarly, increasing nuclear expression of Cks1 significantly correlated with worse overall survival. Thus, Cks1 expression appears to play a role in the progression of melanoma, where high levels of expression are associated with poor outcome. Cytoplasmic expression of Cks1 might represent high turnover of protein via the ubiquination/proteosome pathway.

Simplifying sampling for African swine fever surveillance: Assessment of antibody and pathogen detection from blood swabs.

African swine fever (ASF) is a notifiable disease with serious socio-economic consequences that has been present in wild boar in the Baltic States and Poland since 2014. An introduction of ASF is usually accompanied by increased mortality, making fallen wild boar and hunted animals with signs of disease the main target for early warning and passive surveillance. It is difficult, however, to encourage hunters and foresters to report and take samples from these cases. A pragmatic and easy sampling approach with quick-drying swabs could facilitate this. In this study, we further evaluated the use of dry blood swabs for the detection of ASFV antibody and genome with samples from animal trials and diagnostic submissions (blood, bone and organs) from Estonia. Compared to serum samples, dried blood swabs yielded 93.1% (95% confidence interval: [83.3, 98.1]) sensitivity and 100% [95.9, 100.0] specificity in a commercial ASFV antibody ELISA. Similarly, the swabs gave a sensitivity of 98.9% [93.4, 100.0] and a specificity of 98.1% [90.1, 100.0] for genome detection by a standard ASFV p72 qPCR when compared to EDTA blood. The same swabs were tested in a VP72-antibody lateral flow device, with a sensitivity of 94.7% [85.4, 98.9] and specificity of 96.1% [89.0, 99.2] compared to the serum ELISA. When GenoTube samples tested in ELISA and LFD were compared, the sensitivity was 96.3% [87.3, 99.5] and the specificity was 93.8% [86.0, 97.9]. This study demonstrates reliable detection of ASFV antibody and genome from swabs. A field test of the swabs with decomposed wild boar carcasses in an endemic area in Estonia also gave promising results. Thus, this technique is a practical approach for surveillance of ASF in both free and endemic areas.

Ultrasound characteristics of endometrial cancer as defined by International Endometrial Tumor Analysis (IETA) consensus nomenclature: prospective multicenter study.

OBJECTIVE: To describe the sonographic features of endometrial cancer in relation to tumor stage, grade and histological type, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective multicenter study of 1714 women with biopsy-confirmed endometrial cancer undergoing standardized transvaginal grayscale and Doppler ultrasound examination according to the IETA study protocol, by experienced ultrasound examiners using high-end ultrasound equipment. Clinical and sonographic data were entered into a web-based database. We assessed how strongly sonographic characteristics, according to IETA, were associated with outcome at hysterectomy, i.e. tumor stage, grade and histological type, using univariable logistic regression and the c-statistic. RESULTS: In total, 1538 women were included in the final analysis. Median age was 65 (range, 27-98) years, median body mass index was 28.4 (range 16-67) kg/m2 , 1377 (89.5%) women were postmenopausal and 1296 (84.3%) reported abnormal vaginal bleeding. Grayscale and color Doppler features varied according to grade and stage of tumor. High-risk tumors, compared with low-risk tumors, were less likely to have regular endometrial-myometrial junction (difference of -23%; 95% CI, -27 to -18%), were larger (mean endometrial thickness; difference of +9%; 95% CI, +8 to +11%), and were more likely to have non-uniform echogenicity (difference of +7%; 95% CI, +1 to +13%), a multiple, multifocal vessel pattern (difference of +21%; 95% CI, +16 to +26%) and a moderate or high color score (difference of +22%; 95% CI, +18 to +27%). CONCLUSION: Grayscale and color Doppler sonographic features are associated with grade and stage of tumor, and differ between high- and low-risk endometrial cancer. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.