Nonlinear Uncertainty Propagation in Astrodynamics Using Differential Algebra and Graphics Processing Units

In this paper, two numerical methods for nonlinear uncertainty propagation in astrodynamics are presented and thoroughly compared. Both methods are based on the Monte Carlo idea of evaluating multiple samples of an initial statistical distribution around the nominal state. However, whereas the graphics processing unit implementation aims at increasing the performances of the classical Monte Carlo approach exploiting the massively parallel architecture of modern general-purpose computing on graphics processing units, the method based on differential algebra is aimed at the improvement and generalization of standard linear methods for uncertainty propagation. The two proposed numerical methods are applied to test cases considering both simple two-body dynamics and a full n-body dynamics with accurate ephemeris. The results of the propagation are thoroughly compared with particular emphasis on both accuracy and computational performances

Immune Checkpoint Inhibitors in Malignant Pleural Mesothelioma: A Systematic Review and Meta-Analysis

Many clinical trials have investigated the role of ICIs in PM, with contrasting results. We performed a systematic review and meta-analysis of clinical trials testing single-agent anti-Programmed Death -1 (PD-1)/Programmed Death-Ligand 1 (PD-L1), anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) or combined treatment in PM patients, analyzing response and survival rate as well as safety data. We selected 17 studies including 2328 patients. Both OS and PFS rates were significantly higher with combined ICI treatments than with single agent anti-PD-1/PD-L1 (p < 0.001 and p = 0.006, respectively) or anti CTLA-4 (p < 0.001) treatments. ORR and DCR for all ICI treatments were 20% (95% CI 13–27%) and 56% (95% CI 45–67%), respectively, and they did not significantly differ between combined and single agent treatments (p = 0.088 and p = 0.058, respectively). The 12-month OS and 6-month PFS rates did not differ significantly (p = 0.0545 and p = 0.1464, respectively) among pre-treated or untreated patients. Combined ICI treatments had a significantly higher rate of Adverse Events (AEs) (p = 0.01). PD-L1-positive patients had a higher probability of response and survival. In conclusion, combined ICI treatments have higher efficacy than single agents but are limited by higher toxicity. Efficacy was independent of treatment line, so a customized sequential strategy should still be speculated. PD-L1 expression could influence response to ICIs; however, reliable biomarkers are warranted

REGIONAL MAPPING OF MYOCARDIAL HIBERNATION PHENOTYPE IN IDIOPATHIC END-STAGE DILATED CARDIOMYOPATHY

Myocardial hibernation (MH) is a well-known feature of human ischaemic cardiomyopathy (ICM), whereas its presence in human idiopathic dilated cardiomyopathy (DCM) is still controversial. We investigated the histological and molecular features of MH in left ventricle (LV) regions of failing DCM or ICM hearts. We examined failing hearts from DCM (n = 11; 41.9 ± 5.45 years; left ventricle-ejection fraction (LV-EF), 18 ± 3.16%) and ICM patients (n = 12; 58.08 ± 1.7 years; LVEF, 21.5 ± 6.08%) undergoing cardiac transplantation, and normal donor hearts (N, n = 8). LV inter-ventricular septum (IVS) and antero-lateral free wall (FW) were transmurally (i.e. sub-epicardial, mesocardial and sub-endocardial layers) analysed. LV glycogen content was shown to be increased in both DCM and ICM as compared with N hearts (P < 0.001), with a U-shaped transmural distribution (lower values in mesocardium). Capillary density was homogenously reduced in both DCM and ICM as compared with N (P < 0.05 versus N), with a lower decrease independent of the extent of fibrosis in sub-endocardial and sub-epicardial layers of DCM as compared with ICM. HIF1-α and nestin, recognized ischaemic molecular hallmarks, were similarly expressed in DCM-LV and ICM-LV myocardium. The proteomic profile was overlapping by ~50% in DCM and ICM groups. Morphological and molecular features of MH were detected in end-stage ICM as well as in end-stage DCM LV, despite epicardial coronary artery patency and lower fibrosis in DCM hearts. Unravelling the presence of MH in the absence of coronary stenosis may be helpful to design a novel approach in the clinical management of DCM

Shaping Mediterranean landscapes:The cultural impact of anthropogenic fires in Tyrrhenian southern Tuscany during the Iron and Middle Ages (800–450 BC / AD 650–1300)

Charcoal analysis, applied in sediment facies analysis of the Pecora river palaeochannel (Tyrrhenian southern Tuscany, Italy), detected the occurrence of past fire events in two different fluvial landforms at 800–450 BC and again at AD 650–1300. Taking place in a central Mediterranean district adequately studied through palaeoenvironmental and archaeological research, the investigation determined land changes, time phases and socio-economic driving forces involved in dynamic processes of fire. The fire sequences had purely anthropogenic origins and were linked to forest opening and reduction by local communities. Introduced by the Etruscans, fires dated to 800–450 BC involved mainly the forest cover on the hilly slopes, ensuring agricultural exploitation. From AD 650, fires contributed to Medieval upstream reclamation and vegetation clearing of flat swamplands. From AD 850 to 1050, the use of fire spread over a wider area in the river valley, increasing arable lands. Between AD 1150 and 1300, fires belonged to a regional forest clearance phase. Medieval fire episodes had a paramount importance in shaping and determining the character of the Tuscan Mediterranean landscape. From AD 850, Medieval fire clearing influenced regional vegetation history contributing to the decline of the dominant deciduous Quercus woodland. Open habitats became the new form of a clearly detectable agricultural landscape from AD 950. The use of fire clearing and the resulting landscape changes in the Pecora river valley depended on the political strategies adopted by Medieval authorities and marked, in fact, the progression of a cultural landscape still characterizing central Tyrrhenian Italy

Taste Alterations Do Not Affect Change in Food Habits and Body Weight in Breast Cancer Patients

Background/Aim: Chemotherapy-induced taste alterations (TAs) affect approximately 53-84% of breast cancer patients with significant consequences on flavor perception, possibly leading to food aversion and changes in daily dietary habits. The aim of this study was to investigate the relationship between TAs and changes in food habits and body weight among early breast cancer (EBC) patients undergoing adjuvant chemotherapy. Patients and Methods: TAs were prospectively evaluated in 182 EBC patients from April 2014 to June 2018. TAs, dietary habits, and body weight were collected by a trained dietician. TAs were classified into different subtypes according to the following basic taste perception: metallic, sweet, bitter, salty, sour, and umami taste. Results: During adjuvant chemotherapy, a significant reduction in the consumption of bread, breadsticks, red meat, fat salami, snacks, added sugar, milk, and alcoholic beverages was observed, regardless of TAs onset. No correlation between these dietary changes and different TAs subtypes was found. Body weight remained stable in most EBC patients (71.4%) and was not influenced by TAs onset and by different TAs subtypes. Conclusion: EBC patients change their dietary habits during adjuvant chemotherapy, mostly following the World Cancer Research Fund recommendations, irrespective of TAs onset and without affecting body weight

Fat Body Mass and Vertebral Fracture Progression in Women With Breast Cancer

Importance Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date.Objectives To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM.Design, Setting, and Participants For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022.Exposure Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy.Main Outcomes and MeasuresVF progression, defined as either new or worsening of preexisting VFs, between the 2 time points.Results Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression.Conclusions and Relevance The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting