Relation of Gender to Atherosclerotic Plaque Characteristics by Differing Angiographic Stenosis Severity.

It is unknown whether gender influences the atherosclerotic plaque characteristics (APCs) of lesions of varying angiographic stenosis severity. This study evaluated the imaging data of 303 symptomatic patients from the derivation arm of the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial, all of whom underwent coronary computed tomographic angiography and clinically indicated nonemergent invasive coronary angiography upon study enrollment. Index tests were interpreted by 2 blinded core laboratories, one of which performed quantitative coronary computed tomographic angiography using an artificial intelligence application to characterize and quantify APCs, including percent atheroma volume (PAV), low-density noncalcified plaque (LD-NCP), noncalcified plaque (NCP), calcified plaque (CP), lesion length, positive arterial remodeling, and high-risk plaque (a combination of LD-NCP and positive remodeling ≥1.10); the other classified lesions as obstructive (≥50% diameter stenosis) or nonobstructive (<50% diameter stenosis) based on quantitative invasive coronary angiography. The relation between APCs and angiographic stenosis was further examined by gender. The mean age of the study cohort was 64.4 ± 10.2 years (29.0% female). In patients with obstructive disease, men had more LD-NCP PAV (0.5 ± 0.4 vs 0.3 ± 0.8, p = 0.03) and women had more CP PAV (11.7 ± 1.6 vs 8.0 ± 0.8, p = 0.04). Obstructive lesions had more NCP PAV compared with their nonobstructive lesions in both genders, however, obstructive lesions in women also demonstrated greater LD-NCP PAV (0.4 ± 0.5 vs 1.0 ± 1.8, p = 0.03), and CP PAV (17.4 ± 16.5 vs 25.9 ± 18.7, p = 0.03) than nonobstructive lesions. Comparing the composition of obstructive lesions by gender, women had more CP PAV (26.3 ± 3.4 vs 15.8 ± 1.5, p = 0.005) whereas men had more NCP PAV (33.0 ± 1.6 vs 26.7 ± 2.5, p = 0.04). Men had more LD-NCP PAV in nonobstructive lesions compared with women (1.2 ± 0.2 vs 0.6 ± 0.2, p = 0.02). In conclusion, there are gender-specific differences in plaque composition based on stenosis severity.

Combining morphological and mitochondrial DNA data to describe a new species of Austroniscus Vanhöffen, 1914 (Isopoda, Janiroidea, Nannoniscidae) linking abyssal and hadal depths of the Puerto Rico Trench.

Hadal trenches are perceived as a unique deep-sea ecosystem with fundamentally different communities compared to the nearby abyss. So far, however, scarce information exists about how populations are genetically linked within a trench and about mechanisms for species divergence. The present study presents the morphological and molecular-genetic characterization and description of a new nannoniscid species within the genus Austroniscus Vanhöffen, 1914 obtained from abyssal and hadal depths of the Puerto Rico Trench, NW Atlantic. Samples were collected as part of the Vema-TRANSIT expedition onboard RV Sonne in January 2015. Because of the large depth differences between sampling locations (4,552-8,338 m), we expected to find different species within the genus inhabiting abyssal and hadal sites. Initial morphological examination using traditional light microscopy and Confocal Laser Scanning Microscopy was paired with subsequent molecular analysis based on mtDNA (COI and 16S). Contrary to our assumptions, combined morphological and molecular species delimitation analyses (sGMYC, mPTP, ABGD) revealed the presence of only one species spanning the abyssal and hadal seafloor of the Puerto Rico Trench. In addition, comparison with type material could show that this species belongs to a new species, Austroniscus brandtae n. sp., which is described herein. Incongruence between some species delimitation methods suggesting the presence of multiple species is interpreted as strong genetic population structuring within the trench, which is also supported by the analysis of the haplotype networks. The geographic and bathymetric distribution of Austroniscus species is discussed. The species described herein represents the first in the genus Austroniscus from the Atlantic Ocean and the deepest record of the genus to date, and hence significantly expanding previously known limits of its geographic and bathymetric range.

Accuracy of Leg Length and Offset Measurements During Total Hip Arthroplasty Using an Imageless Navigation System.

Introduction Leg length and offset are important considerations in total hip arthroplasty (THA). Navigation systems are capable of providing intra-operative measurements of leg length and offset, and high accuracy has been shown in experimental studies. This study assesses the accuracy of an imageless navigation system with a pinless femoral array (Hip 5.1, BrainLAB, Feldkirchen, Germany) in measuring leg length and offset changes in vivo. Methods A prospective, consecutive series of 37 patients undergoing navigated THA were included in the study. Intra-operative measurements of leg length and offset were recorded using the navigation system. For each patient, pre- and post-operative digital radiographs were scaled and analyzed to provide radiographic measurements for comparison. Results Measurements of leg length change made by the navigation system showed a strong correlation with the size of change measured radiographically (R = 0.71; p<0.0001). The mean difference between the radiographic and navigational measurement was 2.6mm ± 3.0mm (0.0-16.0mm) (mean, SD, range). The navigation system was accurate to within 1mm of the radiographic measurement in 49% of cases, within 2mm in 66% of cases, and within 5mm in 89% of cases. Measurements of offset change by the navigation system also showed a correlation with radiographic measurements, albeit less pronounced (R = 0.35; p=0.035). The mean difference between navigational and radiographic measurements was 5.5mm ± 4.7mm (0.0-16.0mm) (mean, SD, range). The navigation system was accurate within 1mm of the radiographic measurement in 22% of cases, within 2mm in 35% of cases, and within 5mm in 57% of cases. Conclusions This research demonstrates in vivo that an imageless, non-invasive navigation system is a reliable tool for intra-operative leg length (accurate within 2mm) and to a lesser extent offset measurement (accurate within 5mm) when compared to standard practice of plain film radiographs.

Diabetes, Atherosclerosis, and Stenosis by AI.

OBJECTIVE: This study evaluates the relationship between atherosclerotic plaque characteristics (APCs) and angiographic stenosis severity in patients with and without diabetes. Whether APCs differ based on lesion severity and diabetes status is unknown. RESEARCH DESIGN AND METHODS: We retrospectively evaluated 303 subjects from the Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia (CREDENCE) trial referred for invasive coronary angiography with coronary computed tomographic angiography (CCTA) and classified lesions as obstructive (≥50% stenosed) or nonobstructive using blinded core laboratory analysis of quantitative coronary angiography. CCTA quantified APCs, including plaque volume (PV), calcified plaque (CP), noncalcified plaque (NCP), low-density NCP (LD-NCP), lesion length, positive remodeling (PR), high-risk plaque (HRP), and percentage of atheroma volume (PAV; PV normalized for vessel volume). The relationship between APCs, stenosis severity, and diabetes status was assessed. RESULTS: Among the 303 patients, 95 (31.4%) had diabetes. There were 117 lesions in the cohort with diabetes, 58.1% of which were obstructive. Patients with diabetes had greater plaque burden (P = 0.004). Patients with diabetes and nonobstructive disease had greater PV (P = 0.02), PAV (P = 0.02), NCP (P = 0.03), PAV NCP (P = 0.02), diseased vessels (P = 0.03), and maximum stenosis (P = 0.02) than patients without diabetes with nonobstructive disease. APCs were similar between patients with diabetes with nonobstructive disease and patients without diabetes with obstructive disease. Diabetes status did not affect HRP or PR. Patients with diabetes had similar APCs in obstructive and nonobstructive lesions. CONCLUSIONS: Patients with diabetes and nonobstructive stenosis had an association to similar APCs as patients without diabetes who had obstructive stenosis. Among patients with nonobstructive disease, patients with diabetes had more total PV and NCP.

Serial analysis of coronary artery disease progression by artificial intelligence assisted coronary computed tomography angiography: early clinical experience.

BACKGROUND: Studies have shown that quantitative evaluation of coronary artery plaque on Coronary Computed Tomography Angiography (CCTA) can identify patients at risk of cardiac events. Recent demonstration of artificial intelligence (AI) assisted CCTA shows that it allows for evaluation of CAD and plaque characteristics. Based on publications to date, we are the first group to perform AI augmented CCTA serial analysis of changes in coronary plaque characteristics over 13 years. We evaluated whether AI assisted CCTA can accurately assess changes in coronary plaque progression, which has potential clinical prognostic value in CAD management. CASE PRESENTATION: 51-year-old male with hypertension, hyperlipidemia and family history of myocardial infarction, underwent CCTA exams for anginal symptom evaluation and CAD assessment. 5 CCTAs were performed between 2008 and 2021. Quantitative atherosclerosis plaque characterization (APC) using an AI platform (Cleerly), was performed to assess CAD burden. Total plaque volume (TPV) change-over-time demonstrated decreasing low-density non-calcified plaque (LD-NCP) with increasing overall NCP and calcified-plaque (CP). Examination of individual segments revealed a proximal-LAD lesion with decreasing NCP over-time and increasing CP. In contrast, although the D2/D1/ramus lesions showed increasing stenosis, CP, and total plaque, there were no significant differences in NCP over-time, with stable NCP and increased CP. Remarkably, we also consistently visualized small plaques, which typically readers may interpret as false positives due to artifacts. But in this case, they reappeared each study in the same locations, generally progressing in size and demonstrating expected plaque transformation over-time. CONCLUSIONS: We performed the first AI augmented CCTA based serial analysis of changes in coronary plaque characteristics over 13 years. We were able to consistently assess progression of plaque volumes, stenosis, and APCs with this novel methodology. We found a significant increase in TPV composed of decreasing LD-NCP, and increasing NCP and CP, with variations in the evolution of APCs between vessels. Although the significance of evolving APCs needs to be investigated, this case demonstrates AI-based CCTA analysis can serve as valuable clinical tool to accurately define unique CAD characteristics over time. Prospective trails are needed to assess whether quantification of APCs provides prognostic capabilities to improve clinical care.

Interobserver variability among expert readers quantifying plaque volume and plaque characteristics on coronary CT angiography: a CLARIFY trial sub-study.

BACKGROUND: The difference between expert level (L3) reader and artificial intelligence (AI) performance for quantifying coronary plaque and plaque components is unknown. OBJECTIVE: This study evaluates the interobserver variability among expert readers for quantifying the volume of coronary plaque and plaque components on coronary computed tomographic angiography (CCTA) using an artificial intelligence enabled quantitative CCTA analysis software as a reference (AI-QCT). METHODS: This study uses CCTA imaging obtained from 232 patients enrolled in the CLARIFY (CT EvaLuation by ARtificial Intelligence For Atherosclerosis, Stenosis and Vascular MorphologY) study. Readers quantified overall plaque volume and the % breakdown of noncalcified plaque (NCP) and calcified plaque (CP) on a per vessel basis. Readers categorized high risk plaque (HRP) based on the presence of low-attenuation-noncalcified plaque (LA-NCP) and positive remodeling (PR; ≥1.10). All CCTAs were analyzed by an FDA-cleared software service that performs AI-driven plaque characterization and quantification (AI-QCT) for comparison to L3 readers. Reader generated analyses were compared among readers and to AI-QCT generated analyses. RESULTS: When evaluating plaque volume on a per vessel basis, expert readers achieved moderate to high interobserver consistency with an intra-class correlation coefficient of 0.78 for a single reader score and 0.91 for mean scores. There was a moderate trend between readers 1, 2, and 3 and AI with spearman coefficients of 0.70, 0.68 and 0.74, respectively. There was high discordance between readers and AI plaque component analyses. When quantifying %NCP v. %CP, readers 1, 2, and 3 achieved a weighted kappa coefficient of 0.23, 0.34 and 0.24, respectively, compared to AI with a spearman coefficient of 0.38, 0.51, and 0.60, respectively. The intra-class correlation coefficient among readers for plaque composition assessment was 0.68. With respect to HRP, readers 1, 2, and 3 achieved a weighted kappa coefficient of 0.22, 0.26, and 0.17, respectively, and a spearman coefficient of 0.36, 0.35, and 0.44, respectively. CONCLUSION: Expert readers performed moderately well quantifying total plaque volumes with high consistency. However, there was both significant interobserver variability and high discordance with AI-QCT when quantifying plaque composition.

Quantitative plaque analysis with A.I.-augmented CCTA in end-stage renal disease and complex CAD.

BACKGROUND: Adverse cardiovascular events are a significant cause of mortality in end-stage renal disease (ESRD) patients. High-risk plaque anatomy may be a significant contributor. However, their atherosclerotic phenotypes have not been described. We sought to define atherosclerotic plaque characteristics (APC) in dialysis patients using artificial-intelligence augmented CCTA. METHODS: We retrospectively analyzed ESRD patients referred for CCTA using an FDA approved artificial-intelligence augmented-CCTA program (Cleerly). Coronary lesions were evaluated for APCs by CCTA. APCs included percent atheroma volume(PAV), low-density non-calcified-plaque (LD-NCP), non-calcified-plaque (NCP), calcified-plaque (CP), length, and high-risk-plaque (HRP), defined by LD-NCP and positive arterial remodeling >1.10 (PR). RESULTS: 79 ESRD patients were enrolled, mean age 65.3 years, 32.9% female. Disease distribution was non-obstructive (65.8%), 1-vessel disease (21.5%), 2-vessel disease (7.6%), and 3-vessel disease (5.1%). Mean total plaque volume (TPV) was 810.0 mm3, LD-NCP 16.8 mm3, NCP 403.1 mm3, and CP 390.1 mm3. HRP was present in 81.0% patients. Patients with at least one >50% stenosis, or obstructive lesions, had significantly higher TPV, LD-NCP, NCP, and CP. Patients >65 years had more CP and higher PAV. CONCLUSION: Our study provides novel insight into ESRD plaque phenotypes and demonstrates that artificial-intelligence augmented CCTA analysis is feasible for CAD characterization despite severe calcification. We demonstrate elevated plaque burden and stenosis caused by predominantly non-calcified-plaque. Furthermore, the quantity of calcified-plaques increased with age, with men exhibiting increased number of 2-feature plaques and higher plaque volumes. Artificial-intelligence augmented CCTA analysis of APCs may be a promising metric for cardiac risk stratification and warrants further prospective investigation.

The effect of scan and patient parameters on the diagnostic performance of AI for detecting coronary stenosis on coronary CT angiography.

OBJECTIVES: To determine whether coronary computed tomography angiography (CCTA) scanning, scan preparation, contrast, and patient based parameters influence the diagnostic performance of an artificial intelligence (AI) based analysis software for identifying coronary lesions with ≥50% stenosis. BACKGROUND: CCTA is a noninvasive imaging modality that provides diagnostic and prognostic benefit to patients with coronary artery disease (CAD). The use of AI enabled quantitative CCTA (AI-QCT) analysis software enhances our diagnostic and prognostic ability, however, it is currently unclear whether software performance is influenced by CCTA scanning parameters. METHODS: CCTA and quantitative coronary CT (QCT) data from 303 stable patients (64 ± 10 years, 71% male) from the derivation arm of the CREDENCE Trial were retrospectively analyzed using an FDA-cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination. The algorithm's diagnostic performance measures (sensitivity, specificity, and accuracy) for detecting coronary lesions of ≥50% stenosis were determined based on concordance with QCA measurements and subsequently compared across scanning parameters (including scanner vendor, model, single vs dual source, tube voltage, dose length product, gating technique, timing method), scan preparation technique (use of beta blocker, use and dose of nitroglycerin), contrast administration parameters (contrast type, infusion rate, iodine concentration, contrast volume) and patient parameters (heart rate and BMI). RESULTS: Within the patient cohort, 13% demonstrated ≥50% stenosis in 3 vessel territories, 21% in 2 vessel territories, 35% in 1 vessel territory while 32% had <50% stenosis in all vessel territories evaluated by QCA. Average AI analysis time was 10.3 ± 2.7 min. On a per vessel basis, there were significant differences only in sensitivity for ≥50% stenosis based on contrast type (iso-osmolar 70.0% vs non isoosmolar 92.1% p = 0.0345) and iodine concentration (<350 mg/ml 70.0%, 350-369 mg/ml 90.0%, 370-400 mg/ml 90.0%, >400 mg/ml 95.2%; p = 0.0287) in the context of low injection flow rates. On a per patient basis there were no significant differences in AI diagnostic performance measures across all measured scanner, scan technique, patient preparation, contrast, and individual patient parameters. CONCLUSION: The diagnostic performance of AI-QCT analysis software for detecting moderate to high grade stenosis are unaffected by commonly used CCTA scanning parameters and across a range of common scanning, scanner, contrast and patient variables. CONDENSED ABSTRACT: An AI-enabled quantitative CCTA (AI-QCT) analysis software has been validated as an effective tool for the identification, quantification and characterization of coronary plaque and stenosis through comparison to blinded expert readers and quantitative coronary angiography. However, it is unclear whether CCTA screening parameters related to scanner parameters, scan technique, contrast volume and rate, radiation dose, or a patient's BMI or heart rate at time of scan affect the software's diagnostic measures for detection of moderate to high grade stenosis. AI performance measures were unaffected across a broad range of commonly encountered scanner, patient preparation, scan technique, intravenous contrast and patient parameters.

Relationship of age, atherosclerosis and angiographic stenosis using artificial intelligence.

OBJECTIVE: The study evaluates the relationship of coronary stenosis, atherosclerotic plaque characteristics (APCs) and age using artificial intelligence enabled quantitative coronary computed tomographic angiography (AI-QCT). METHODS: This is a post-hoc analysis of data from 303 subjects enrolled in the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial who were referred for invasive coronary angiography and subsequently underwent coronary computed tomographic angiography (CCTA). In this study, a blinded core laboratory analysing quantitative coronary angiography images classified lesions as obstructive (≥50%) or non-obstructive (<50%) while AI software quantified APCs including plaque volume (PV), low-density non-calcified plaque (LD-NCP), non-calcified plaque (NCP), calcified plaque (CP), lesion length on a per-patient and per-lesion basis based on CCTA imaging. Plaque measurements were normalised for vessel volume and reported as % percent atheroma volume (%PAV) for all relevant plaque components. Data were subsequently stratified by age <65 and ≥65 years. RESULTS: The cohort was 64.4±10.2 years and 29% women. Overall, patients >65 had more PV and CP than patients <65. On a lesion level, patients >65 had more CP than younger patients in both obstructive (29.2 mm3 vs 48.2 mm3; p<0.04) and non-obstructive lesions (22.1 mm3 vs 49.4 mm3; p<0.004) while younger patients had more %PAV (LD-NCP) (1.5% vs 0.7%; p<0.038). Younger patients had more PV, LD-NCP, NCP and lesion lengths in obstructive compared with non-obstructive lesions. There were no differences observed between lesion types in older patients. CONCLUSION: AI-QCT identifies a unique APC signature that differs by age and degree of stenosis and provides a foundation for AI-guided age-based approaches to atherosclerosis identification, prevention and treatment.

Evolution and phylogeny of the deep-sea isopod families Desmosomatidae Sars, 1897 and Nannoniscidae Hansen, 1916 (Isopoda: Asellota).

In the deep sea, the phylogeny and biogeography of only a few taxa have been well studied. Although more than 200 species in 32 genera have been described for the asellote isopod families Desmosomatidae Sars, 1897 and Nannoniscidae Hansen, 1916 from all ocean basins, their phylogenetic relationships are not completely understood. There is little doubt about the close relationship of these families, but the taxonomic position of a number of genera is so far unknown. Based on a combined morphological phylogeny using the Hennigian method with a dataset of 107 described species and a molecular phylogeny based on three markers (COI, 16S, and 18S) with 75 species (most new to science), we could separate Desmosomatidae and Nannoniscidae as separate families. However, we could not support the concept of the subfamilies Eugerdellatinae Hessler, 1970 and Desmosomatinae Hessler, 1970. Most genera of both families were well supported, but several genera appear as para- or even polyphyletic. Within both families, convergent evolution and analogies caused difficulty in defining apomorphies for phylogenetic reconstructions and this is reflected in the results of the concatenated molecular tree. There is no biogeographic pattern in the distribution as the genera occur over the entire Atlantic and Pacific Ocean, showing no specific phylogeographical pattern. Poor resolution at deep desmosomatid nodes may reflect the long evolutionary history of the family and rapid evolutionary radiations. Supplementary Information: The online version contains supplementary material available at 10.1007/s13127-021-00509-9.

Integrative systematics and ecology of a new deep-sea family of tanaidacean crustaceans.

A new family of paratanaoidean Tanaidacea - Paranarthrurellidae fam. nov. - is erected to accommodate two genera without family classification (Paratanaoidea incertae sedis), namely Armatognathia Kudinova-Pasternak, 1987 and Paranarthrurella Lang, 1971. Seven new species of Paranarthrurella and two of Armatognathia are described from material taken in different deep-sea areas of the Atlantic and Pacific oceans. The type species of Paranarthrurella - P. caudata (Kudinova-Pasternak, 1965) - is redescribed based on the paratype. The genus Cheliasetosatanais Larsen and Araújo-Silva, 2014 originally classified within Colletteidae is synonymised with Paranarthrurella, and Arthrura shiinoi Kudinova-Pasternak, 1973 is transferred to Armatognathia. Amended diagnoses of Armatognathia and Paranarthrurella genera are given. Choosing characters for distinguishing and defining both genera was supported by Principal Component Analysis. Designation of the new family is supported by molecular phylogenetic analysis of COI and 18S datasets. The distribution of all species currently included in the new family was visualised and their bathymetric distribution analysed.

The therapeutic role of ivabradine in heart failure.

Heart failure represents a major global cause of morbidity and mortality. Ivabradine is a selective funny current (If) inhibitor, which acts on the sinoatrial node, resulting in a reduction in heart rate. Ivabradine is currently licensed for use in patients with symptomatic heart failure with reduced ejection fraction and a heart rate persistently at least 70 beats per minute in spite of otherwise optimal prognostic heart failure pharmacotherapy. In this review article, we examine the mechanism of action of ivabradine, evaluate the clinical trials underpinning its application in heart failure and discuss its current recommended clinical use in this capacity.

Ischemic QRS prolongation as a predictor of ventricular fibrillation in a canine model.

OBJECTIVES: An acute coronary occlusion and its possible subsequent complications is one of the most common causes of death. One such complication is ventricular fibrillation (VF) due to myocardial ischemia. The severity of ischemia is related to the amount of coronary arterial collateral flow. In dog studies collateral flow has also been shown to be associated with QRS prolongation. The aim of this study was to investigate whether ischemic QRS prolongation (IQP) is associated with impending VF in an experimental acute ischemia dog model. METHODS: Degree of IQP and occurrence of VF were measured in dogs (n = 21) during coronary occlusion for 15 min and also during subsequent reperfusion (experiments conducted in 1984). RESULTS: There was a significant difference in absolute IQP between dogs which developed VF during reperfusion (47 ± 29 ms, mean ± SD) and those which did not (12 ± 10 ms; p = .001). CONCLUSIONS: IQP during acute coronary occlusion is associated with reperfusion VF in an experimental dog model and might therefore be a potential predictor of malignant arrhythmias in patients with acute coronary syndrome.

Morbidity and Safety of Iliac Crest Reference Array Pins in Navigated Total Hip Arthroplasty: A Prospective Cohort Study.

BACKGROUND: Navigated total hip arthroplasty (THA) can employ intra-osseous pins through a separate incision to secure reference arrays to the iliac crest. This study is the first to investigate the consequences of pin use in THA in vivo. METHODS: A prospective, consecutive series of 43 patients presenting for navigated THA were included. Two temporary 125 × 4 mm Schanz screws were inserted into the iliac crest for the attachment of a reference array. Telephone follow-up occurred at 6 and 12 weeks post-operatively. Patients were asked about pain, interference with daily activities, how often the wound was noticed, and duration of discomfort. Patient body mass index was recorded. RESULTS: The follow-up rate was 100%. Pin site pain at any time post-operatively was reported by 24 patients (56%). This improved to 30%, 9%, and 2% at 3, 6, and 12 weeks, respectively. On average, pain lasted for 16 days total. The most common complaints after pain were clothing discomfort (23%), pain when wearing a belt (12%), or pain when mobilizing (9%). For the majority (98%) of patients, all symptoms had resolved by 12 weeks. There was no nerve injury, pin site fracture, infection, or screw breakage. Patients with body mass index greater than 30 kg/m2 were up to 3 times more likely to experience pin site pain (P = .05), and had a longer duration of pain (P = .04). CONCLUSION: Surgeons and patients should be aware that using navigational pins for array fixation carries low complication rates but often will cause pain and irritation that resolves in the short term.

Photosystem I, when excited in the chlorophyll Qy absorption band, feeds on negative entropy.

It is often suggested that Life may lay outside the normal laws of Physics and particularly of Thermodynamics, though this point of view is refuted by many. As the Living State may be thought of as an open system, often far from equilibrium, most attempts at placing Life under the umbrella of the laws of Physics have been based, particularly in recent years, on non-equilibrium Thermodynamics and particularly the Maximum Entropy Production Principle. In this view it is the dissipation of entropy (heat) which permits the ever increasing complexity of Living Systems in biological evolution and the maintenance of this complexity. However, these studies usually consider such biological entities as whole cells, organs, whole organisms and even Life itself at the entire terrestrial level. This requires making assumptions concerning the Living State, which are often not soundly based on observation and lack a defined model structure. The present study is based on an entirely different approach, in which a classical thermodynamic analysis of a well-defined biological nanoparticle, plant Photosystem I, is performed. This photosynthetic structure, which absorbs light and performs primary and secondary charge separation, operates with a quantum efficiency close to one. It is demonstrated that when monochromatic light is absorbed by the lowest lying electronic transition, the chlorophyll Qy transition, entropy production in the system bath plus entropy changes internal to the system are numerically less than the entropy decrease of the light field. A Second Law violation is therefore suggested for these experimental conditions. This conclusion, while at first sight is supportive of the famous and much discussed statement of Schroedinger, that "Life feeds on negentropy", is analysed and the conditions in which this statement may be considered valid for a Plant Photosystem are defined and delimited. The remarkably high quantum efficiency, leading to minimal entropy production (energy wastage), seems to suggest that evolution of Photosystem I has gone down the road of maximal energy efficiency as distinct from maximal entropy production. Photosystem I cannot be considered a maximum entropy dissipation structure.

Novel targets and future strategies for acute cardioprotection: Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart.

Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic-however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing. Therefore, in this Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart, we critically analyse the current state of ischaemic conditioning in both the experimental and clinical settings, provide recommendations for improving its translation into the clinical setting, and highlight novel therapeutic targets and new treatment strategies for reducing acute myocardial IRI.