bluuebunny/crossref_metadata_2025 huggingface dataset:
P463 LEFT ATRIAL APPENDAGE CLOSURE VERSUS TRIPLE ANTITHROMBOTIC THERAPY IN PATIENTS WITH LONG TIME INDICATION TO DUAL ANTIPLATELET THERAPY
Authors: Vella C , Festorazzi C , Ancona M , Bellini B , Ferri L , Russo F , Ghizzoni G , Gentile D , Montorfano M
Published: May 2023

Introduction

Recent guidelines suggest a limited duration of triple antithrombotic therapy (TAT) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) at elevated bleeding risk. Indeed, in patients who are also at elevated thrombotic risk and with indication to prolonged dual antiplatelet therapy, percutaneous left atrial appendage closure (LAAC) could be a possible safe and effective option to prevent both bleeding and thrombotic events.

Methods

retrospective single–center study enrolling all consecutive patients between September 2012 and February 2020, comparing patients deemed at increased thrombotic and bleeding risk who received LAA percutaneous closure to avoid TAT before or after PCI with patients who received TAT after PCI. The aim of the study was to establish the safety and efficacy of LAAC in comparison to TAT.

Results

A total of 168 patients were included in the study: 56 underwent percutaneous LAAC while 112 were discharged in TAT. Median age was 75 (69–79). TAT patients had a CHA2DS2–VASc score of 4 (3–5) and a mean HAS–BLED score of 3 (2–3), whereas in LAAC patients the mean CHA2DS2–VASc was 4.9 (±1.5) and the mean HAS–BLED was 3.9 (±0.9); the difference in Score Points was statistically significant (p=0.001). The population who underwent LAAC was characterized by a remarkable procedural PCI complexity with a mean DAPT score of 1.4 (±1.3), with respect to the population discharged in TAT which was 0 (0–2). At follow–up (mean follow–up period in days: 727 [489–1000]), four bleeding episodes were recorded in LAAC population in comparison to 16 bleeding episodes observed in TAT population (12.6% vs. 15.4%; p–value=0.142): two bleeding episodes were major in LAAC group and five in TAT group (3.6% vs. 4.8%; p–value=1). One case of stroke (1.8%) occurred in LAAC population and two cases (1.8%) in TAT population (p=1.000).

Conclusions

In a single–centre retrospective study no significant difference was observed in terms of bleeding between TAT and LAAC, in patients at high ischemic and thrombotic risk with indication to prolonged dual antiplatelet therapy after PCI and anticoagulation for AF. Nevertheless, the non statistical trend to reduction of bleeding events in LAAC group might be explored in a larger study population.
P468 CLINICAL CHARACTERISTICS OF PATIENTS AFFECTED BY HEART FAILURE PATIENTS WITH REDUCED EJECTION FRACTION AND UNDERGOING SGLT2I THERAPY
Authors: Alcidi G , Pugliese R , Ioannoni S , Romano M , Granatiero M , Diomede D , Benvenuto M , Correale M , Brunetti N , Gronda E , Iacoviello M
Published: May 2023

Background

The type–2 sodium–glucose cotransporters inhibitors (SGLT2i) are a new relevant therapeutic option for patients affected by chronic heart failure with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the clinical characteristics and therapy of HFrEF patients undergoing SGLT2i therapy.

Methods

We evaluated the consecutive patients affected by HFrEF in whom the SGLT2i therapy was prescribed since December 2021. At baseline clinical visit, ECG, echocardiography, assessment of sodium, potassium, fasting glucose, hemoglobin, hematocrit, glomerular filtration rate (GFR) by creatinine were assessed.

Results

Ninety patients were enrolled. In the Table clinical characteristics and therapy are reported. Interestingly, most of patients were already trated with the classes of drugs currently recommended fo HFrEF treatment.

Conclusions

In this “real world” study, SGLT2i were prescribed in HFrEF patients most of all already in therapy with the other classes of drugs currently recommended for their treatment. These data further support the use of this therapeutic approach in routine clinical practice.
P470 BERBERINE ASSOCIATED TO DAPAGLIFLOZIN EXERTS SYNERGISTIC CARDIOPROTECTIVE EFFECTS IN CARDIAC CELLS EXPOSED TO THE HER2–BLOKING AGENT TRASTUZUMAB THROUGH PAMPK ACTIVATION AND REDUCTION IN INTERLEUKIN–6 LEVELS
Authors: Quagliariello V , Scherillo M , Maurea F , Iovine M , Paccone A , Maurea N
Published: May 2023

Background

Trastuzumab has improved the prognosis in patients with HER2–positive breast cancer, but it can induce left ventricular dysfunction with reduced ejection fraction or HF during treatment. Dapagliflozin is a SGLT2i with cardio–renal benefits. In the DAPA–HF (Dapagliflozin And Prevention of Adverse–outcomes in Heart Failure) trial, the sodium–glucose cotransporter 2 inhibitor dapagliflozin decreased the risk of worsening HF events and cardiovascular death in patients with HF and reduced ejection fraction. Berberine is a nutraceutical compound characterized by multiple metabolic effects in patients with/without cardiovascular diseases. Purpose: To investigate on the potential cardioprotective properties of Berberine associated to SGLT2i Dapagliflozin against HER–2 blocking agent–induced cardiotoxicity

Methods

Human fetal cardiomyocytes (HFC cell line) were exposed to subclinical concentration of trastuzumab (200 nM) alone or co–incubated with Berberine (200 mM) or Dapagliflozin (50 nM) or both in combination for 48 h. After the incubation period, we performed the following tests: cell viability, apoptosis, expression of NLRP3 inflammasome, methylglyoxal and leukotrienes–B4. Expression of pAMPK was analyzed through western blot. Moreover, quantification of IL–6 was performed through ELISA method.

Results

Berberine and Dapagliflozin increased significantly the cell viability of cardiomyocytes exposed to Trastuzumab. When combined, Berberine and Dapagliflozin increased synergistically cell viability of cardiac cells (p<0.001 vs Trastuzumab). Cell apoptosis was reduced of 32.5, 41.8 and 72.7% for berberine, dapagliflozin and both combined (vs trastuzumab group). Methylglyoxal,a marker of AGEs, was strongly reduced compared to untreated cells. Western blot analysis clearly demonstrate that pAMPK was induced by berberine and Dapagliflozin, improving mitochondrial metabolism. No significant changes in Leukotriene B4 expression were seen. Intracellular levels of IL–6 were reduced of 46.3, 62.7 and 86.3% for berberine, dapagliflozin and both combined (vs trastuzumab group).

Conclusion

Berberine and Dapagliflozin exerts significant cardioprotective effects in cardiac cells exposed to the HER2–bloking agent Trastuzumab. Berberine and Dapagliflozin in combination induces an anti–inflammatory phenotype to myocardial cells through the reduction of biomarkers involved in heart failure and apoptosis.
P472 SACUBITRIL/VALSARTAN IMPROVES EXERCISE PERFORMANCE IN PATIENTS WITH HEART FAILURE: A DOSE–DEPENDENT EFFECT
Authors: Mapelli M , Mattavelli I , Salvioni E , Paolillo S , Basile C , De Martino F , Vignati C , Magrì D , Mantegazza V , Tamborini G , Agostoni P
Published: May 2023

Background

Sacubitril/Valsartan therapy has become a cornerstone of heart failure with reduced ejection fraction (HFrEF) pharmacological therapy due to its positive prognostic impact. However, conflicting results have emerged on the effects of sacubitril/valsartan on exercise performance assessed by cardiopulmonary exercise test (CPET). Aim of the study: The aim of this study was to prospectively evaluate the effects of sacubitril/valsartan on prognostically significant CPET parameters in a larger population of HFrEF patients at different drug doses.

Methods

We prospectively enrolled HFrEF outpatients eligible to start sacubitril/valsartan according to 2016 ESC Guidelines in 3 Heart Failure Units. Patients underwent CPET at baseline (before sacubitril/valsartan treatment), after 1, 2, 3 months (respectively after a month taking the 24/26 – 49/51 – 97/103mg doses), and 6 months after the maximum tolerated dose was reached (end–study). The subjective impression of disease–related limitation was assessed using the 12–item Kansas City Cardiomyopathy Questionnaire (KCCQ).

Results

113 patients were enrolled (age 64.5±9.7, 81% males). Peak oxygen intake (peakVO2) improved at each step from 15.0±4.5 mL/min/kg at baseline to 16.5±4.9 mL/min/kg at end study visit, corresponding to 61.5±16.0 and 67.9±17.4 % of predicted, respectively (p<0.05). Minute ventilation/carbon dioxide production relationship (VE/VCO2 slope) reduced from 39.6±5.5 to 35.9±7.1 (p = 0.005) in the 39 patients (42%) with pathological VE/VCO2≥34 at baseline. KCCQ improved significantly since the first visit with an overall summary score increase from 47.9±11.1 to 52.6±9.8 (p<0.001).

Conclusions

These findings suggest that sacubitril/valsartan benefits on exercise capacity are immediately evident at the lowest dose and progressively improve as the dose increases.
P480 SUBMITRAL LEFT VENTRICULAR ANEURYSM AND STROKE IN A YOUNG CAUCASIAN WOMAN
Authors: Ferrari V , Mazzanti C
Published: May 2023

Submitral aneurysms are infrequent and they are generally described in populations from Subsaharian Africa. The aetiology is still unclear: it has been proposed that they could be caused by congenital alterations of ventricular wall, infectious events, chest trauma, cardiac surgery or Myocardial Infarction. Submitral aneurysms can induce arrhythmias, stroke, heart failure secondary to mitral insufficiency, and can facilitate infections. We report the case of a 39–year–old Caucasian woman who was hospitalized in our Institution after relapsing fever episodes, presenting with altered state of consciousness. The ECG showed sinus rhythm and normal morphology. When she was hospitalized, laboratory test findings included normocytic anaemia (Hb 9,8 g/dl), thrombocytopenia (94x103 platelets), neutrophilia (81% neutrophils), ESR 32 mm/h, CRP 8,84, low electolyte level, procalcitonin 11,54 ng/ml. Blood culture was positive for Candida Albicans. A transthoracic echocardiogram showed normal left ventricle dimensions and wall thickness, without abnormalities of global or segmental wall motion, thickening of mitral valve leaflets, which appeared slightly hyperechogen. It was found an aneurysmatic area in correspondence of subvalvular apparatus of mitral valve, between mitral annulus and posterior papillary muscle. Mitral annulus was shifted toward the atrial roof. These findings were confirmed by a thransesophageal echocardiogram. The aneurysm measured 33x22 mm in correspondence to the atrio–ventricular junction. A cardiac MRI confirmed these morphologic alterations without evidence of infarction areas, supposing the presence of an infectious lesion. A brain MRI showed multiple and diffuse areas of altered signal referred to stroke. The patient was referred to the Heart Surgery of our Institution. Intraoperatively, a large aneurysm arose from submitral area; moreover, the posterior leaflet of the mitral valve was characterized by some fissures. The aneurysm was excluded by a direct suturing and the mitral valve was replaced with a biological valve. In our patient, mitral annulus dislocation was evident, supporting the hypothesis of a congenital malformation that can have promoted a mycotic infection and the formation of thrombi responsible for the cerebral disease. In patients with cardiac arrhythmias or embolic events, without other motivating factors, it’s necessary to pay attention and to make a differential diagnosis with these types of aneurysms.
P481 PREDICTIVE FACTORS OF CLINICAL OUTCOME IN PATIENTS WITH AORTIC STENOSIS: DATA FROM THE VENETO REGISTER
Authors: Pagliani L , Buso R , Nicolosi E , Di Naro A , Denas G , Antonini–canterin F , Simmini S , Rattazzi M
Published: May 2023

Background

Aortic valve stenosis represents the most relevant valve disease in the Western world, with a mortality rate exceeding 50%. Calcific aortic valve stenosis was once considered a passive process of the valve deposition of calcium salts, but is now considered a cell–mediated disease. The aim of the present study is to search for predictors of mortality, cardiovascular events and valve replacement in patients with aortic stenosis. Materials and

Methods

A subgroup of 140 patients affected by moderate–severe aortic valve stenosis from the Cardiology departments of the Treviso Hospital and the High Specialization Hospital of Motta di Livenza included in the Veneto Register. For each patient, information relating to deaths, cardiovascular events and valve staging was therefore collected over time.

Results

The deceased were 36% of which 22.9% without having replaced the valve. The mean follow–up was 24.99±21.72 months. In the follow–up, the deceased were characterized by an older age, a greater frequency of ischemic heart disease, atrial fibrillation and chronic kidney disease (CKD), a worse eGFR, a higher phosphate level. Among the Cox regression biohumoral data, serum phosphate was significantly associated with mortality in the univariate survey, and eGFR values were also always independently significantly associated with mortality. Kaplan Meyer curves also showed significant differences in the risk of CV events over time between groups with eGFR values greater than equal and less than 60 mL/min.

Conclusions

The results of the study suggest that the pathology appears to be linked to senescence processes and shares a common basis with atherosclerotic pathology, but also appears to be influenced in its evolution by further determinants such as CKD and blood phosphorus values. These considerations prompt us to reflect on the need for studies aimed at understanding the pathogenetic mechanisms of the proven relationship between cardiovascular MACE and phosphorus values, and that between worse renal function and cardiovascular mortality/morbidity. On the other hand, it seems urgent to be able to propose in the near future an internationally shared prognostic score that considers these predictive variables and can help us to better stratify the clinical evolution of aortic stenosis and influencing the surgical timing.
P484 IMPACT OF VISCERAL FAT ON MORTALITY IN PATIENTS TREATED BY TAVI
Authors: Somaschini A , Casirati A , Olivotti L , Cornara S , Giachello V , Astuti M , Ghione M , Botta M , Buscemi M , Caccialanza R , Bellone P , Cordone S
Published: May 2023

Introduction

Sarcopenia, evaluated by body composition analysis through CT scan at the third lumbar vertebra level (L3–CT), is a promising prognostic stratification parameter in patients undergoing Transcatheter Aortic Valve Implantation (TAVI). Conversely, only a few data are available on the impact of visceral fat, a metabolic active tissue associated with unfavorable cardiovascular outcome. AIMS. We investigated the correlation between baseline visceral fat and 30–days mortality in patients undergoing TAVI.

Methods

We prospectively collected anamnestic and clinical data of 81 patients (42.5% males) who underwent TAVI in 2010–2020. Trough retrospective analysis of 55 available CT–L3 images (Fig 1), we measured visceral adipose tissue index (VATi), expressed as cm2/m2. The sample was classified according to the median VATi value (>50percentile VS <50p). The two groups were compared by Mann–Whitney test for continuous variables (expressed as median value 25p–75p) and cross tables with Chi–square test for categorical variables (expressed as %).

Results

VATi median value was 57.4 cm2/m2. Patients with VATi>50p were younger (83.3 [76.5–87] vs. 86 [83–88] years, p=0.020) and showed more often pre–operative NYHA class >2 (78% vs. 40%, p=0.021) as compared with patients with VATi<50p. No differences were found in the incidence of atrial fibrillation, diabetes, COPD, advanced CKD, previous stroke / MI / surgical or percutaneous revascularization. STS mortality score and Euroscore II did not differ significantly. Thirty–days and 1–year mortality were respectively 3.6% and 12.7%. As showed in Fig 2, VATi>50p group presented a higher 1–year mortality (21.4% vs. 3.7%, HR=7.01, p=0.05), whereas no differences were found in 30–days mortality (3.6% vs. 3.7%, p=0.745).

Conclusions

Visceral fat is associated with a higher 1–year all cause mortality in patients treated by TAVI. Further studies on wider populations are needed to confirm this finding. Adding the evaluation of visceral fat to the clinical practice could help to optimize pre–operative mid–term mortality risk stratification in this setting.
P487 THE NEW PCSK9–INHIBITOR INCLISIRAN: AN EXCEPTIONAL REDUCTION IN LDL CHOLESTEROL FROM THE FIRST PATIENTS OF THE NIGUARDA HOSPITAL
Authors: Merlo A , Maloberti A , Ossola P , Caccia A , Busti A , Garofani I , Fabbri S , Senni M , Giannattasio C
Published: May 2023

Background

Dyslipidemia is one of the most prominent risk factors in coronary artery disease. With the new strict target of Low Density Lipoprotein (LDL) cholesterol in secondary prevention in some patients oral medication may not be sufficient. Inclisiran is a small interfiring RNA that inhibits the hepatic PCSK–9 synthesis inducing a reduction in low–density lipoprotein levels up to 50%. Conveniently, it only requires one administration every six months. Case description: a 53–year–old man, with no previous cardiologic history, presented to our emergency department reporting acute chest pain and left arm paresthesia developed after an emotional stress. Electrocardiogram was normal with a slightly and stable increased of high sensitivity troponin T levels (18 ng/l). The patient had the following cardiovascular risk factors: type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea syndrome, obesity (body mass index 30), sedentary lifestyle. Taking into consideration his clinical presentation and his cardiovascular risk, a coronary computer tomography was performed showing severe stenosis in Left Anterior Descending (LAD) and right coronary arteries. The subsequent coronary angiography confirms the severe stenosis in the proxymal LAD and the mild stenosis (30%) in the right coronary artery. The LAD was treated with a drug eluting stent. At the time of the event the patient was already on therapy with rosuvastatina/ezetimibe 10/10 mg that we increased to a dosage of 20/10 mg. At the first medical examination after the hospitalization, his blood tests showed uncontrolled LDL cholesterol (70 mg/dl). We therefore decided to try lowering his cholesterol levels with addition of inclisiran. After 3 months of inclisiran therapy, his blood test showed a surprisingly decrease in cholesterol levels (total cholesterol 78 mg/dl and LDL 11 mg/dl) reaching the desirable target.

Conclusion

Inclisiran is a valid therapeutic strategy for reaching the desiderable cholesterol target in patient at high cardiovascular risk. In our first patients inclisiran, added to statin and ezetimibe therapy, successfully lowered LDL to the desirable target. Surprinsigly, it lowered LDL up to 85%, much more than expected. Further studies will be needed to identify which patients may be super responders to Inclisiran.
P491 YOUNG AND MIDDLE–AGED PATIENTS PRESENTING WITH ACUTE CORONARY SYNDROME: THE ROLE OF LIPOPROTEIN(A)
Authors: Meringolo F , Panattoni G , Proietti G , Jacomelli I , Lanzillo C , Calò L
Published: May 2023

Background

Lipoprotein(a) [Lp(a)] is a liver–derived lipoprotein with genetically determined concentrations. High level of lipoprotein(a) is a common risk factor for cardiovascular disease and stroke. Higher plasma Lp(a) concentrations are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), through mechanisms associated with increased atherogenesis, inflammation, and thrombosis.

Methods

The study enrolled patients ≤ 55 years of age referred to Cardiology Department of Policlinico Casilino with acute coronary syndrome (ACS). In order to identify patients with high cardiovascular risk, we measured, according to current guidelines, Lp(a) value.

Results

A total of 73 patients (84% males, mean age 47±7 years old) were enrolled from July 2020 to March 2022. Mean Lp(a) level was 50.9± 46.7 mg/dL. High Lp(a) > 50 mg/dL was documented in 31.5 % of patients, while the interim grey zone of elevated Lp (a) (30–50 mg/dL) in 27.4%.

Conclusion

In our experience, elevated levels of Lp(a) was documented in more than half of patients, presenting with ACS at a relatively young age. This support recent guidelines recommendation to measure Lp (a) at least once in adults, preferably in the first lipid profile, to identify patients with high cardiovascular risk of recurrence. This result focus on the potential use in clinical practice of efficacious Lp(a)–lowering drugs.
Immune Modulation of HIV-1 Reservoir Size in Early-Treated Neonates
Authors: Hartana Ciputra Adijaya , Broncano Pilar Garcia , Maswabi Kenneth , Ajibola Gbolahan , Moyo Sikhulile , Mohammed Terence , Maphorisa Comfort , Makhema Joseph , Powis Kathleen M , Lockman Shahin , Burbelo Peter D , Gao Ce , Yu Xu G , Kuritzkes Daniel R , Shapiro Roger , Lichterfeld Mathias
Published: May 2023

Immune mechanisms that modulate human immunodeficiency virus-1 (HIV-1) reservoir size in neonates are poorly understood. Using samples from neonates who initiated antiretroviral therapy shortly after birth, we demonstrate that interleukin-8–secreting CD4 T cells, which are selectively expanded in early infancy, are more resistant to HIV-1 infection and inversely correlated with the frequency of intact proviruses at birth. Moreover, newborns with HIV-1 infection displayed a distinct B-cell profile at birth, with reduction of memory B cells and expansion of plasmablasts and transitional B cells; however, B-cell immune perturbations were unrelated to HIV-1 reservoir size and normalized after initiation of antiretroviral therapy.

Clinical Trials Registration. NCT02369406.
Extracellular vesicles in systemic juvenile idiopathic arthritis
Authors: Maller Justine , Morgan Terry , Morita Mayu , McCarthy Frank , Jung Yunshin , Svensson Katrin J , Elias Joshua E , Macaubas Claudia , Mellins Elizabeth
Published: May 2023

Systemic juvenile idiopathic arthritis is a chronic pediatric inflammatory disease of unknown etiology, characterized by fever, rash, hepatosplenomegaly, serositis, and arthritis. We hypothesized that intercellular communication, mediated by extracellular vesicles, contributes to systemic juvenile idiopathic arthritis pathogenesis and that the number and cellular sources of extracellular vesicles would differ between inactive and active states of systemic juvenile idiopathic arthritis and healthy controls. We evaluated plasma from healthy pediatric controls and patients with systemic juvenile idiopathic arthritis with active systemic flare or inactive disease. We isolated extracellular vesicles by size exclusion chromatography and determined total extracellular vesicle abundance and size distribution using microfluidic resistive pulse sensing. Cell-specific extracellular vesicle subpopulations were measured by nanoscale flow cytometry. Isolated extracellular vesicles were validated using a variety of ways, including nanotracking and cryo-electron microscopy. Extracellular vesicle protein content was analyzed in pooled samples using mass spectrometry. Total extracellular vesicle concentration did not significantly differ between controls and patients with systemic juvenile idiopathic arthritis. Extracellular vesicles with diameters <200 nm were the most abundant, including the majority of cell-specific extracellular vesicle subpopulations. Patients with systemic juvenile idiopathic arthritis had significantly higher levels of extracellular vesicles from activated platelets, intermediate monocytes, and chronically activated endothelial cells, with the latter significantly more elevated in active systemic juvenile idiopathic arthritis relative to inactive disease and controls. Protein analysis of isolated extracellular vesicles from active patients showed a proinflammatory profile, uniquely expressing heat shock protein 47, a stress-inducible protein. Our findings indicate that multiple cell types contribute to altered extracellular vesicle profiles in systemic juvenile idiopathic arthritis. The extracellular vesicle differences between systemic juvenile idiopathic arthritis disease states and healthy controls implicate extracellular vesicle–mediated cellular crosstalk as a potential driver of systemic juvenile idiopathic arthritis disease activity.
XTE J1906+090: a persistent low-luminosity Be X-ray binary
Authors: Sguera V , Sidoli L , Bird A J , La Palombara N
Published: May 2023

We present new results from INTEGRAL and Swift observations of the hitherto poorly studied and unidentified X-ray source XTE J1906+090. A bright hard X-ray outburst (luminosity of ∼1036 erg s−1 above 20 keV) has been discovered with INTEGRAL observations in 2010, this being the fourth outburst ever detected from the source. Such events are sporadic, the source duty cycle is in the range (0.8–1.6) per cent as inferred from extensive INTEGRAL and Swift monitoring in a similar hard X-ray band. Using five archival unpublished Swift/X-Ray Telescope (XRT) observations, we found that XTE J1906+090 has been consistently detected at a persistent low X-ray luminosity value of ∼1034 erg s−1, with limited variability (a factor as high as 4). Based on our findings, we propose that XTE J1906+090 belongs to the small and rare group of persistent low-luminosity Be X-ray binaries.
Characterizing abundance–age relations of GALAH stars using oxygen-enhanced stellar models
Authors: Sun Tiancheng , Chen Xunzhou , Bi Shaolan , Ge Zhishuai , Xiang Maosheng , Wu Yaqian
Published: May 2023

Main-sequence turn-off (MSTO) stars and subgiant stars are good tracers of Galactic populations. We present a study of 41 034 MSTO and subgiant stars from the GALAH survey. Using a grid of stellar models that accounts for the variation of O abundances, we determine their ages with a median age uncertainty of ∼9.4 per cent. Our analysis reveals that the ages of high-O stars based on O-enhanced models are smaller than those determined with α-enhanced models, resulting in a mean fractional age difference of −5.3 per cent at [O/α] = 0.2 and −11.0 per cent at [O/α] = 0.4. This age difference significantly impacts the age distribution of thick disc and halo stars, leading to a steeper downward trend in the [Fe/H]–age plane from 8 to 14 Gyr, indicating a shorter formation time-scale and a faster chemical-enhanced history for these populations. We confirm the V-shape of the normalized age-metallicity distribution p(τ∣[Fe/H]) of thin disc stars, which is presumably a consequence of the second gas infall. Additionally, we find that the halo stars in our sample can be divided into two sequences, a metal-rich sequence (Splash stars) and a metal-poor sequence (accreted stars), with the Splash stars predominantly older than 9 Gyr and the accreted halo stars older than 10 Gyr. Finally, we observe two distinct sequences in the relations between various chemical abundances and ages for disc stars, namely a young sequence with ages < ∼8 Gyr and an old sequence with ages > ∼8 Gyr.
Extending the theory of propagating fluctuations: the first fully relativistic treatment and analytical Fourier–Green’s functions
Authors: Mummery Andrew
Published: May 2023

The aperiodic variability ubiquitously observed from accreting black hole X-ray binary systems is generally analysed within the framework of the so-called ‘theory of propagating fluctuations’. In this paper we derive the Fourier transforms of the Green’s function solutions of the thin disc equations. These solutions suffice to describe all possible solutions through standard convolution techniques. Solutions are found for both Newtonian discs and general relativistic solutions with a vanishing ISCO stress. We use this new relativistic theory to highlight the Kerr black hole spin dependence of a number of observable variability properties of black hole discs. The phase lags, coherence, and power density spectra of Kerr discs are shown to be strong functions of black hole spin. Observations of the aperiodic variability of black hole accretion sources may now, at least in principle, offer a new avenue to directly constrain black hole spins.
Writing the Approach and Methods Section
Authors: Robinson Marin S. , Stoller Fredricka L
Published: May 2023

This chapter illustrates the process of writing the Approach and Methods section of the research proposal, in which authors tell readers how they will conduct the proposed work. It is typically the longest section of the proposal. Unlike the experimental section of a journal article, where authors describe work completed in the past, here they describe what they propose to do in the future (if funded). Reviewers, after reading this section, should be convinced that the work is plausible and that the investigator has the background and expertise necessary to carry out the proposed work. The chapter then distinguishes between prior accomplishments and preliminary findings. It also looks at how to describe the proposed methods, develop project aims, identify obstacles, and suggest possible contingency plans.
Language Tips
Authors: Robinson Marin S. , Stoller Fredricka L
Published: May 2023

This chapter provides details about many of the language features and chemistry writing conventions highlighted throughout the book. Each Language Tip includes helpful hints for communicating effectively in writing. Tips for writing concisely, one of the hallmarks of writing in chemistry, are presented. Writing in chemistry requires that authors use vocabulary that is more formal and academic than they would use in speaking, thus word choice is addressed. Unlike chemistry-specific writing conventions, however, English grammar rules apply across the disciplines. The chapter covers parallelism, plural and singular scientific words, split infinitives, and subject–verb agreement. Correct punctuation also contributes substantially to writing clarity. The chapter also considers word usage, looking at 12 word pairs that are commonly confused by writers.
The Overlap Between Patent and Design Protection
Authors: Musker David
Published: May 2023

This chapter looks into the overlap between patent and design protection and its respective laws. It starts with the patent of the Circular Beach Towel and its subsequent grounds that invalidate the design. Intellectual property practitioners are accustomed to multiple coexisting patents or copyrights in the same work, but the objection to overlap often refers to stretch, election, post expiry right to use, mismatched defences, circumventing, and undermining. The chapter explains how avoiding the overlap leads to creating gaps, so utility models were originally a gap-fill between patents and designs. It also elaborates on how the Paris Convention provides cross-priority claims between a utility model and a design.
The Relationship Between Trademark Rights and Unfair Competition Law
Authors: Nordemann Axel , Aaron-Stelluto Tara
Published: May 2023

This chapter expounds on the relationship between trademark rights and unfair competition law. Laws against unfair competition ensure the proper execution of the competition between market participants and the observation of the rules of fairness. Moreover, the federal law of trademarks and unfair competition primarily exists for the benefit of consumers while also offering market players advantages like nationwide protection and the ability to bring cases in federal court. The chapter looks into scenarios wherein trademark infringements and unfair competitive practices coincide, while simultaneously referencing German law, American laws, and European laws. It also cites that national laws and jurisdiction are influenced by the Court of Justice of the European Union (CJEU) jurisdiction.
Dreyfus Time
Authors: Wood Michael
Published: May 2023

The Dreyfus Affair in many ways defined history for Proust, and we could say that both the Affair and his writing are symptoms of the problematic late days of the nineteenth century. This chapter explores Proust’s portraits of this period and concentrates especially on what happens when too many parties and people have special interests and when prejudice becomes a major form of social education. Proust learns to see politics as a kind of epistemology, a matter of how we know what we think we know. The perspective may seem familiar to many of us, living as we do in a world of fake facts, a world where real facts, although not non-existent, can seem desperately scarce.
Constitutional Courts and Politics in the European Legal Space
Authors: Huber Peter M
Published: May 2023

Due to the particular role constitutional courts play—on a national level but also specifically within the multi-level cooperation of the European legal space—their relationship to politics is complex and multifaceted. The contribution reflects on various aspects and factors determining the relations between constitutional courts and politics from a comparative perspective, including notably the recruitment, status and professional ethics of justices, institutionalized and informal contacts between the actors on both sides, the public’s influence, and the political dimension of constitutional jurisprudence. Its objective in doing so is to map the specific role of the constitutional courts in the European legal space and to identify common challenges. Despite considerable differences between different national States, constitutional courts generally act as a sort of ‘structural opposition’ against the (national) legislature and government because they enforce the protection of minority rights against the democratic majority. Within the process of European integration, constitutional courts additionally fulfil a specific task, namely, to safeguard—where necessary—the conditions and limits of their state’s integration into the European Union. Overall, the idea of constitutional adjudication has expanded throughout the European legal space, and Europeanization has contributed to a noticeable enlargement of the powers of the third branch. Constitutional courts have in that course partially emancipated themselves from politics. However, their success has given rise to backlash and—partly exaggerated—criticism, which pose new challenges in the relationship between constitutional courts and politics.
Innovative Policies and Technologies to Achieve Water Security and Green Growth
Authors: Brears Robert C.
Published: May 2023

With challenges to the water sector increasing over the course of the century, there is an expectation that demand for innovative water management solutions will increase—in particular, solutions that enable the more efficient use of available water resources, enhance the quality of water for humans and nature, improve water resource planning to balance rising demand with limited, and often variable, supplies of water, enhance resilience to extreme weather events, and mitigate carbon emissions. This chapter will first define the concept of innovative water management before discussing the various innovative policies and technologies available to achieve water security and green growth, including demand management, smart digital water management, alternative water supplies, nature-based solutions, renewable energy, and resource recovery.
Exploring characteristics and outcomes of UN military protection operations
Authors: Kjeksrud Stian
Published: May 2023

This chapter provides descriptive statistics of the key characteristics of military operations from 1999 to 2017 where Blue Helmets used force to protect and it estimates the outcomes of operations across time and missions in Africa. The basic statistics are valuable to better understand the phenomenon at the center of this book—the application of force by Blue Helmets—and point to where we should look to learn more about successes and failures. The outcome estimations are a first attempt at analyzing the effectiveness of UN troops’ military efforts to protect civilians from violence across time and place. It finds that UN troops succeed about as often as they fail when they use force to protect, indicating that there is reason for optimism in their ability to provide physical protection to threatened populations, under the right conditions.
Discovering causal pathways to successful protection outcomes
Authors: Kjeksrud Stian
Published: May 2023

This chapter explores combinations of conditions—so-called “causal recipes”—that may systematically explain variations in outcomes of UN military protection operations across time and UN missions, applying fuzzy set Qualitative Comparative Analysis (fsQCA) to 126 cases from the UNPOCO dataset. The cases are studied along four conditions frequently identified as causally relevant in existing literature: deterrent presence, willingness to accept risk, pre-emption, and matching. It finds that matching and pre-emption unite in the most promising recipe to explain positive outcomes across cases. Still, many cases remain unexplained, demanding other methods to search for other possible causal conditions, which is performed in later chapters.
Protecting Civilians from the M23
Authors: Kjeksrud Stian
Published: May 2023

This chapter studies a typical case where Blue Helmets matched the perpetrators’ use of violence against civilians, the 2013 joint operations conducted by the Forces armées de la république démocratique du Congo (FARDC) and the UN’s Force Intervention Brigade (FIB) against the armed insurgent group Mouvement du 23 Mars (M23) in the eastern parts of the Democratic Republic of the Congo. Under an exceptionally strong mandate—where the UN Security council expected the Force Intervention Brigade to use of force to protect civilians—Blue Helmets and Congolese armed forces deterred, coerced, and destroyed the armed group’s ability to conduct operations, ceasing its threats and attacks against civilians. While the case underscores the need for tailored and timely operations to protect, other factors emerge to explain successful outcomes.
The Long Beginning
Authors: Cunliffe Barry
Published: May 2023

The chapter focuses on the hunter-gatherer communities who spread to all parts of Northern Africa from the time of the early hominids up to about 6000 bc. Climate change played a vital role. Cyclic changes in climate conditioned the spread of Homo sapiens throughout the continent. During warm, humid periods hunter-gatherers could move fairly freely crossing the Sahara and could flourish in the more congenial regions but with the onset of hot, dryer periods the desert became a barrier to movement, separating the communities of the south from those of the North African zone which experienced an inflow of population from the Levant. The last of the Humid periods, when the Sahara region became habitable, c. 10000–6000 bc, - a period known as the greening of the Sahara – saw hunter-gatherers colonizing many parts of what had been desert, adapting to the different micro-environments, hunting wild animals, fishing in the lakes and rivers and gathering plant food. For some life became more sedentary.
Emerging States
Authors: Cunliffe Barry
Published: May 2023

The ethnic mix in North Africa was now complex. An influx of Arabs and Persians introduced new value systems and new knowledge but the greater part of the population clung to its Berber heritage. The political unity, introduce after the Arab invasion, soon fragmented in the face of Berber revolts breaking out in 740, and tribal confederacies took over ruled by the Idrisids, Rustamids, Aghlabids and Tulumids, and later the Fatimids. The Fatimids, controlling Egypt, encouraged trade with the East Coast of Africa. In the western parts of the Sahara, Berber tribes, the Zanta and Sanhaja, were instrumental in organizing trade between the North African states and the western Sahel, which was now dominated by the empire of Ghana. Salt from the desert was exchanged for gold from the southern goldfields. The empire of Ghana, benefitting from the increased volume of trade which passed through its territory, became large and powerful. In the woodlands and forests to the south of the Sahel, local elites, commanding resource, were also able to engage in the trading systems, some growing rich on the proceeds. The disparate Berber tribes in the western were unified by charismatic religious leaders into a powerful state, the Almoravids, who established their authority over a vast tract from the river Senegal to the river Ebro in the second half of the twelfth century.
“Stronger”
Authors: Stocking Charles H.
Published: May 2023

Chapter 1 builds on the work of Émile Benveniste, Pierre Bourdieu, and Richard Martin on authoritative speech in Homer in order to further explore the relationship between force and speech in the Iliad. This chapter focuses specifically on the role of the comparative term “stronger”—pherteros/karteros—in speeches pertaining to the genealogy of Achilles. Based on the speeches of Nestor (1.247–84), Apollo (20.104–9), Aeneas (Iliad 20.200–58), and Achilles himself (Iliad 21.184–91), one may observe how the seemingly “natural” force that comes with genealogy is often invoked as though it were a function of external, objectively determined conditions of inheritance. Yet the larger narrative contexts of the speeches demonstrate that the supposedly inherited force of genealogy is itself forged through performative speech.
Conclusion
Authors: Stocking Charles H.
Published: May 2023

The concluding chapter revisits the problem of force and the Homeric subject initiated by Weil and Snell within the context of the major findings of the previous chapters. The chapter interprets the language of Homeric force in light of a posthumanist subjectivity distinct from the idea of the individual inherent in Weil’s Judeo-Christian model and Snell’s Hegelian model. Relying on the work of Donna Haraway and anthropological precedents such as that of Louis Dumont and Marylin Strathern, this chapter suggests that the Homeric subject be considered not merely as a negated or failed individual, but as an intersubjective dividual, one who is defined by a human-divine symbiosis. Furthermore, this chapter shows that the symbiotic relationship between human and divine remains a point of contention and frustration for humans throughout the poem, and especially for Achilles, from Athena’s prevention of Achilles’ murder of Agamemnon in Iliad 1 to Achilles’ vain attempts at mutilating the corpse of Hector in Iliad 24.
Evolution and historical biogeography
Authors: Buskirk Steven W.
Published: May 2023

The origin and phylogeny of the Carnivora is inferred from fossils, their geological contexts, and genetic data. Modern estimates of divergence times of lineages employ both kinds of evidence. While the earliest eutherians pre-date the Cretaceous–Paleogene boundary, the major eutherian radiation followed the bolide impact on the coast of Yucatan around 66 million years ago. The immediate fossil ancestor of the earliest carnivoran is now uncertain; the most closely related lineage to the Carnivora is Pholidota, the pangolins. Carnivorans arose in North America, and all family-level diversification occurred in North America and Eurasia. Suborder Caniformia underwent its earliest radiations in North America; Feliformia did so in Eurasia. The Paleocene–Eocene Thermal Maximum may have been the impetus for the radiations of Carnivorans and other mammalian lineages. Subsequent dispersals of carnivorans between continents depended on episodic land bridges resulting from continent drift and sea level fluctuations. The bridge between North and South America caused highly asymmetrical exchanges of carnivorous eutherian lineages; lineages from South America made few and brief colonizations in Central America, whereas North American lineages colonized southward very successfully, displacing the dominant carnivorous forms. The morphological disparity of carnivorans varies strongly across families. Considering only the skull, the lowest disparity is found in the Felidae, and the highest in the Eupleridae. Post-cranial morphology varies strongly across the Mustelidae, but only little across the Canidae. Competition was a strong structuring force in paleocommunities of Carnivorans as it is in modern ones.
Community ecology
Authors: Buskirk Steven W.
Published: May 2023

Carnivorans interact in diverse ways with other community members, in addition to eating them. All heterotrophs cycle nutrients; carnivorans cycle animal bodies and deposit carrion and waste in patterns that structure vegetation communities. The best-documented case of transporting nutrients across ecological boundaries involves bears moving carcasses of spawning salmon from stream beds to adjacent forest along the North Pacific Rim. Salmon carcasses increase soil concentrations of nitrogen and phosphorous, stimulating woody plant growth. Badgers affect soils directly by mixing soil layers and providing aeration. Predaceous species play important roles in pathogen life cycles, affecting the incidence and virulence of diseases in prey and non-prey hosts. That carnivorans occur at lower densities and are mostly asocial does not result in lower prevalence or parasite loads; in fact, the opposite pattern has been reported. The potential for carnivorans to decrease disease prevalence via predation on symptomatic animals depends on disease characteristics. Carnivorans facilitate access to carrion; access is strongly structured by body size. Pollination of flowering plants is suggested by some carnivoran behaviors, but seed dispersal is much more common and is better documented. This function is enhanced by large carnivoran home ranges and movement rates and their lack of grinding dentition, which tends to reduce germination of medium-sized seeds.
Interactions with non-prey animals
Authors: Buskirk Steven W.
Published: May 2023

Carnivorans interact with community members via channels other than killing them. They hunt cooperatively with other carnivorans and some predaceous birds and share burrows and vigilance duties with some rodents. There is evidence of exploitation competition between carnivoran species, but interference competition is more common. In the latter, one species harasses or threatens another species, in the most extreme cases killing it. Interspecific killing is common between carnivoran species and can have important demographic effects on the victim species. Attacks tend to be carried out by species 2.5–8 times the size of the victim species, with a factor of 4 leading to the highest likelihood of killing. Secondary effects of benefitting still smaller species have been reported. Conflict between sympatric carnivoran species is influenced by the number of large carnivorans in the community, morphological and dietary similarity of potential competitors, the robustness of the canine teeth, adaptations to climbing trees or burrowing underground, habitat heterogeneity, and the spatial and temporal scale of the analysis. Abiotic factors can mediate competitive interactions, as when snow attributes affect species differently. Humans strongly mediate competition–coexistence interactions, favoring some species over others. Domestic dogs likewise participate in and mediate these relationships.
Refugee Protection and Duties among States
Authors: Milazzo Eleonora
Published: May 2023

This chapter addresses the question of what general reciprocal duties states have towards each other in relation to refugee protection. Firstly, the chapter defines who should count as refugees and why states owe anything to them. It then turns to the grounds of states’ collective responsibility for discharging these obligations. The third part of the chapter deals with how individual states are assigned perfect duties to discharge their collective responsibility for asylum, and the associated moral and practical challenges. In the concluding part, the author brings together the results of the previous steps and proposes a reasoned set of duties that states have towards each other in relation to the protection of refugees.