Theoretical determination of the geometric and electronic structures of oligorylenes and poli(peri‐naphthalene)

We present a theoretical investigation of the electronic structure of oligorylenes (from perylene to heptarylene, including also the naphthalene molecule) and their corresponding polymer poly(peri‐naphthalene) (PPN) using the nonempirical valence effective (VEH) method. The geometry of the unit cell used to generate the polymer is extrapolated from the PM3‐optimized molecular geometries of the longest oligorylenes. That geometry shows some bond alternation along the perimeter carbon chains and a bond length of ≊1.46 Å is calculated for the peri bonds connecting the naphthalene units. The VEH one‐electron energy level distributions calculated for oligorylenes are used to interpret the experimental trends reported for the first ionization potentials, redox potentials, and lowest energy optical transitions. An excellent agreement is found between theoretical estimates and experimental values. The VEH band structure calculated for an isolated chain of PPN is interpreted in terms of the molecular orbitals of naphthalene. The ionization potential, electron affinity, and bandwidths obtained for PPN suggest a large capacity to form conducting p‐ or n‐type materials. The small band gap of 0.56 eV predicted for PPN from VEH band structure calculations is in good agreement with theoretical and experimental estimates calculated by extrapolating the data reported for the [email protected] ; [email protected] ; [email protected]

Role of pre-operative frailty status in relation to outcome after carotid endarterectomy:a systematic review

Carotid endarterectomy (CEA) is a surgical treatment option to prevent ischemic cerebrovascular accidents. Patients that present with pre-operative frailty might have an elevated risk for unfavorable outcomes after the CEA. A systematic search, using Medline, Embase, Web of Science and Cochrane Database, was performed for relevant literature on frailty in patients undergoing CEA. The study protocol was registered with PROSPERO (CRD42020190345). Eight articles were included. The pooled prevalence for pre-operative frailty was 23.9% (95% CI: 12.98-34.82). A difference in the incidence of complications between frail and non-frail patients (6.4% vs. 5.2%, respectively) and a difference in hospital length of stay [2 (IQR: 2-3) days vs. 1 (IQR: 1-2) day, respectively] were described. The 30-day mortality after CEA was 0.6% for non-frail patients, 2.6% for frail patients, and 4.9% for very frail patients (P 0.001). For 3-year mortality, a 1.5-fold increased risk was found for frail patients (OR 1.7, 95% CI: 1.4-2.0) and a &gt;2.5-fold increased risk for very frail patients (OR 2.6, 95% CI: 2.2-3.1). In conclusion, this review shows the impact of frailty on outcome after CEA. Pre-operative frailty assessment with a validated, multi-domain tool should be implemented in the clinical setting as it will provide information on post-operative surgical outcomes and mortality risk but also frailty trajectory and cognitive decline.</p

Carotid calcium burden derived from computed tomography angiography as a predictor of all-cause mortality after carotid endarterectomy

OBJECTIVE: Carotid endarterectomy (CEA) aims to reduce the risk of stroke in patients with atherosclerotic carotid disease. Preoperative risk assessments that predict complications are needed to optimize the care in this patient group. The current approach, namely relying solely on symptomatology and degree of stenosis, is outdated and calls for innovation. The Agatston calcium score was applied in several vascular specialties to assess cardiovascular risk profile but has been little studied in carotid surgery. It is hypothesized that a higher calcium burden at initial presentation equates to a worse prognosis attributable to an increased cerebrovascular and cardiovascular risk profile. The aim was to investigate the association between preoperative ipsilateral calcium score and postoperative all-cause mortality in patients undergoing CEA.METHODS: This single-center retrospective cohort study included 89 patients who underwent CEA at a tertiary referral center between 2010 and 2018. Preoperative calcium scores were measured on contrast-enhanced computed tomography images with patient-specific Hounsfield thresholds at the level of the carotid bifurcation. The association between these calcium scores and all-cause mortality was analyzed using multivariable adjusted Cox proportional hazard analysis.RESULTS: Cox proportional hazard analysis demonstrated a significant association between preoperative ipsilateral carotid calcium score and all-cause mortality (hazard ratio, 1.10; 95% confidence interval, 1.03-1.16; P = .003). After adjusting for age, preoperative estimated glomerular filtration rate, and diabetes mellitus, a significant association remained (hazard ratio, 1.07; 95% confidence interval, 1.00-1.15; P = .05).CONCLUSIONS: A higher calcium burden was predictive of worse outcome, which might be explained by an overall poorer health status. These results highlight the potential of calcium measurements in combination with other traditional risk factors, for preoperative risk assessment and thus for improved patient education and care.</p

Carotid calcium burden derived from computed tomography angiography as a predictor of all-cause mortality after carotid endarterectomy

OBJECTIVE: Carotid endarterectomy (CEA) aims to reduce the risk of stroke in patients with atherosclerotic carotid disease. Preoperative risk assessments that predict complications are needed to optimize the care in this patient group. The current approach, namely relying solely on symptomatology and degree of stenosis, is outdated and calls for innovation. The Agatston calcium score was applied in several vascular specialties to assess cardiovascular risk profile but has been little studied in carotid surgery. It is hypothesized that a higher calcium burden at initial presentation equates to a worse prognosis attributable to an increased cerebrovascular and cardiovascular risk profile. The aim was to investigate the association between preoperative ipsilateral calcium score and postoperative all-cause mortality in patients undergoing CEA.METHODS: This single-center retrospective cohort study included 89 patients who underwent CEA at a tertiary referral center between 2010 and 2018. Preoperative calcium scores were measured on contrast-enhanced computed tomography images with patient-specific Hounsfield thresholds at the level of the carotid bifurcation. The association between these calcium scores and all-cause mortality was analyzed using multivariable adjusted Cox proportional hazard analysis.RESULTS: Cox proportional hazard analysis demonstrated a significant association between preoperative ipsilateral carotid calcium score and all-cause mortality (hazard ratio, 1.10; 95% confidence interval, 1.03-1.16; P = .003). After adjusting for age, preoperative estimated glomerular filtration rate, and diabetes mellitus, a significant association remained (hazard ratio, 1.07; 95% confidence interval, 1.00-1.15; P = .05).CONCLUSIONS: A higher calcium burden was predictive of worse outcome, which might be explained by an overall poorer health status. These results highlight the potential of calcium measurements in combination with other traditional risk factors, for preoperative risk assessment and thus for improved patient education and care.</p

Carotid calcium burden derived from computed tomography angiography as a predictor of all-cause mortality after carotid endarterectomy

OBJECTIVE: Carotid endarterectomy (CEA) aims to reduce the risk of stroke in patients with atherosclerotic carotid disease. Preoperative risk assessments that predict complications are needed to optimize the care in this patient group. The current approach, namely relying solely on symptomatology and degree of stenosis, is outdated and calls for innovation. The Agatston calcium score was applied in several vascular specialties to assess cardiovascular risk profile but has been little studied in carotid surgery. It is hypothesized that a higher calcium burden at initial presentation equates to a worse prognosis attributable to an increased cerebrovascular and cardiovascular risk profile. The aim was to investigate the association between preoperative ipsilateral calcium score and postoperative all-cause mortality in patients undergoing CEA.METHODS: This single-center retrospective cohort study included 89 patients who underwent CEA at a tertiary referral center between 2010 and 2018. Preoperative calcium scores were measured on contrast-enhanced computed tomography images with patient-specific Hounsfield thresholds at the level of the carotid bifurcation. The association between these calcium scores and all-cause mortality was analyzed using multivariable adjusted Cox proportional hazard analysis.RESULTS: Cox proportional hazard analysis demonstrated a significant association between preoperative ipsilateral carotid calcium score and all-cause mortality (hazard ratio, 1.10; 95% confidence interval, 1.03-1.16; P = .003). After adjusting for age, preoperative estimated glomerular filtration rate, and diabetes mellitus, a significant association remained (hazard ratio, 1.07; 95% confidence interval, 1.00-1.15; P = .05).CONCLUSIONS: A higher calcium burden was predictive of worse outcome, which might be explained by an overall poorer health status. These results highlight the potential of calcium measurements in combination with other traditional risk factors, for preoperative risk assessment and thus for improved patient education and care.</p

Carotid calcium burden derived from computed tomography angiography as a predictor of all-cause mortality after carotid endarterectomy

OBJECTIVE: Carotid endarterectomy (CEA) aims to reduce the risk of stroke in patients with atherosclerotic carotid disease. Preoperative risk assessments that predict complications are needed to optimize the care in this patient group. The current approach, namely relying solely on symptomatology and degree of stenosis, is outdated and calls for innovation. The Agatston calcium score was applied in several vascular specialties to assess cardiovascular risk profile but has been little studied in carotid surgery. It is hypothesized that a higher calcium burden at initial presentation equates to a worse prognosis attributable to an increased cerebrovascular and cardiovascular risk profile. The aim was to investigate the association between preoperative ipsilateral calcium score and postoperative all-cause mortality in patients undergoing CEA.METHODS: This single-center retrospective cohort study included 89 patients who underwent CEA at a tertiary referral center between 2010 and 2018. Preoperative calcium scores were measured on contrast-enhanced computed tomography images with patient-specific Hounsfield thresholds at the level of the carotid bifurcation. The association between these calcium scores and all-cause mortality was analyzed using multivariable adjusted Cox proportional hazard analysis.RESULTS: Cox proportional hazard analysis demonstrated a significant association between preoperative ipsilateral carotid calcium score and all-cause mortality (hazard ratio, 1.10; 95% confidence interval, 1.03-1.16; P = .003). After adjusting for age, preoperative estimated glomerular filtration rate, and diabetes mellitus, a significant association remained (hazard ratio, 1.07; 95% confidence interval, 1.00-1.15; P = .05).CONCLUSIONS: A higher calcium burden was predictive of worse outcome, which might be explained by an overall poorer health status. These results highlight the potential of calcium measurements in combination with other traditional risk factors, for preoperative risk assessment and thus for improved patient education and care.</p

Carotid calcium burden derived from computed tomography angiography as a predictor of all-cause mortality after carotid endarterectomy

OBJECTIVE: Carotid endarterectomy (CEA) aims to reduce the risk of stroke in patients with atherosclerotic carotid disease. Preoperative risk assessments that predict complications are needed to optimize the care in this patient group. The current approach, namely relying solely on symptomatology and degree of stenosis, is outdated and calls for innovation. The Agatston calcium score was applied in several vascular specialties to assess cardiovascular risk profile but has been little studied in carotid surgery. It is hypothesized that a higher calcium burden at initial presentation equates to a worse prognosis attributable to an increased cerebrovascular and cardiovascular risk profile. The aim was to investigate the association between preoperative ipsilateral calcium score and postoperative all-cause mortality in patients undergoing CEA.METHODS: This single-center retrospective cohort study included 89 patients who underwent CEA at a tertiary referral center between 2010 and 2018. Preoperative calcium scores were measured on contrast-enhanced computed tomography images with patient-specific Hounsfield thresholds at the level of the carotid bifurcation. The association between these calcium scores and all-cause mortality was analyzed using multivariable adjusted Cox proportional hazard analysis.RESULTS: Cox proportional hazard analysis demonstrated a significant association between preoperative ipsilateral carotid calcium score and all-cause mortality (hazard ratio, 1.10; 95% confidence interval, 1.03-1.16; P = .003). After adjusting for age, preoperative estimated glomerular filtration rate, and diabetes mellitus, a significant association remained (hazard ratio, 1.07; 95% confidence interval, 1.00-1.15; P = .05).CONCLUSIONS: A higher calcium burden was predictive of worse outcome, which might be explained by an overall poorer health status. These results highlight the potential of calcium measurements in combination with other traditional risk factors, for preoperative risk assessment and thus for improved patient education and care.</p

Carotid calcium burden derived from computed tomography angiography as a predictor of all-cause mortality after carotid endarterectomy

OBJECTIVE: Carotid endarterectomy (CEA) aims to reduce the risk of stroke in patients with atherosclerotic carotid disease. Preoperative risk assessments that predict complications are needed to optimize the care in this patient group. The current approach, namely relying solely on symptomatology and degree of stenosis, is outdated and calls for innovation. The Agatston calcium score was applied in several vascular specialties to assess cardiovascular risk profile but has been little studied in carotid surgery. It is hypothesized that a higher calcium burden at initial presentation equates to a worse prognosis attributable to an increased cerebrovascular and cardiovascular risk profile. The aim was to investigate the association between preoperative ipsilateral calcium score and postoperative all-cause mortality in patients undergoing CEA.METHODS: This single-center retrospective cohort study included 89 patients who underwent CEA at a tertiary referral center between 2010 and 2018. Preoperative calcium scores were measured on contrast-enhanced computed tomography images with patient-specific Hounsfield thresholds at the level of the carotid bifurcation. The association between these calcium scores and all-cause mortality was analyzed using multivariable adjusted Cox proportional hazard analysis.RESULTS: Cox proportional hazard analysis demonstrated a significant association between preoperative ipsilateral carotid calcium score and all-cause mortality (hazard ratio, 1.10; 95% confidence interval, 1.03-1.16; P = .003). After adjusting for age, preoperative estimated glomerular filtration rate, and diabetes mellitus, a significant association remained (hazard ratio, 1.07; 95% confidence interval, 1.00-1.15; P = .05).CONCLUSIONS: A higher calcium burden was predictive of worse outcome, which might be explained by an overall poorer health status. These results highlight the potential of calcium measurements in combination with other traditional risk factors, for preoperative risk assessment and thus for improved patient education and care.</p

The Disrupt CAD II Study

BACKGROUND: The feasibility of intravascular lithotripsy (IVL) for modification of severe coronary artery calcification (CAC) was demonstrated in the Disrupt CAD I study (Disrupt Coronary Artery Disease). We next sought to confirm the safety and effectiveness of IVL for these lesions. METHODS: The Disrupt CAD II study was a prospective multicenter, single-arm post-approval study conducted at 15 hospitals in 9 countries. Patients with severe CAC with a clinical indication for revascularization underwent vessel preparation for stent implantation with IVL. The primary end point was in-hospital major adverse cardiac events (cardiac death, myocardial infarction, or target vessel revascularization). An optical coherence tomography substudy was performed to evaluate the mechanism of action of IVL, quantifying CAC characteristics and calcium plaque fracture. Independent core laboratories adjudicated angiography and optical coherence tomography, and an independent clinical events committee adjudicated major adverse cardiac events. RESULTS: Between May 2018 and March 2019, 120 patients were enrolled. Severe CAC was present in 94.2% of lesions. Successful delivery and use of the IVL catheter was achieved in all patients. The post-IVL angiographic acute luminal gain was 0.83±0.47 mm, and residual stenosis was 32.7±10.4%, which further decreased to 7.8±7.1% after drug-eluting stent implantation. The primary end point occurred in 5.8% of patients, consisting of 7 non-Q-wave myocardial infarctions. There was no procedural abrupt closure, slow or no reflow, or perforations. In 47 patients with post-percutaneous coronary intervention optical coherence tomography, calcium fracture was identified in 78.7% of lesions with 3.4±2.6 fractures per lesion, measuring 5.5±5.0 mm in length. CONCLUSIONS: In patients with severe CAC who require coronary revascularization, IVL was safely performed with high procedural success and minimal complications and resulted in substantial calcific plaque fracture in most lesions. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03328949

The coordination of cell growth during fission yeast mating requires Ras1-GTP hydrolysis

The spatial and temporal control of polarity is fundamental to the survival of all organisms. Cells define their polarity using highly conserved mechanisms that frequently rely upon the action of small GTPases, such as Ras and Cdc42. Schizosaccharomyces pombe is an ideal system with which to study the control of cell polarity since it grows from defined tips using Cdc42-mediated actin remodeling. Here we have investigated the importance of Ras1-GTPase activity for the coordination of polarized cell growth during fission yeast mating. Following pheromone stimulation, Ras1 regulates both a MAPK cascade and the activity of Cdc42 to enable uni-directional cell growth towards a potential mating partner. Like all GTPases, when bound to GTP, Ras1 adopts an active conformation returning to an inactive state upon GTP-hydrolysis, a process accelerated through interaction with negative regulators such as GAPs. Here we show that, at low levels of pheromone stimulation, loss of negative regulation of Ras1 increases signal transduction via the MAPK cascade. However, at the higher concentrations observed during mating, hyperactive Ras1 mutations promote cell death. We demonstrate that these cells die due to their failure to coordinate active Cdc42 into a single growth zone resulting in disorganized actin deposition and unsustainable elongation from multiple tips. These results provide a striking demonstration that the deactivation stage of Ras signaling is fundamentally important in modulating cell polarity