Optimisation of Low-Thrust and Hybrid Earth-Moon Transfers

This paper presents an optimization procedure to generate fast and low-∆v Earth-Moon transfer trajectories, by exploiting the multi-body dynamics of the Sun-Earth-Moon system. Ideal (first-guess) trajectories are generated at first, using two coupled planar circular restricted three-body problems, one representing the Earth-Moon system, and one representing the Sun-Earth. The trajectories consist of a first ballistic arc in the Sun-Earth system, and a second ballistic arc in the Earth-Moon system. The two are connected at a patching point at one end (with an instantaneous ∆v), and they are bounded at Earth and Moon respectively at the other end. Families of these trajectories are found by means of an evolutionary optimization method. Subsequently, they are used as first-guess for solving an optimal control problem, in which the full three-dimensional 4-body problem is introduced and the patching point is set free. The objective of the optimisation is to reduce the total ∆v, and the time of flight, together with introducing the constraints on the transfer boundary conditions and of the considered propulsion technology. Sets of different optimal trajectories are presented, which represents trade-off options between ∆v and time of flight. These optimal transfers include conventional solar-electric low-thrust and hybrid chemical/solar-electric high/low-thrust, envisaging future spacecraft that can carry both systems. A final comparison is made between the optimal transfers found and only chemical high-thrust optimal solutions retrieved from literature

What are the causes of hypomagnesemia?

The causes of magnesium depletion and hypomagnesemia are decreased gastrointestinal (GI) absorption and increased renal loss. Decreased GI absorption is frequently due to diarrhea, malabsorption, and inadequate dietary intake. Common causes of excessive urinary loss are diuresis due to alcohol, glycosuria, and loop diuretics. Medical conditions putting persons at high risk for hypomagnesemia are alcoholism, congestiveheart failure, diabetes, chronic diarrhea, hypokalemia, hypocalcemia, and malnutrition (strength of recommendation: C, based on expert opinion, physiology, and case series). Evidence suggests that magnesium deficiency is both more common and more clinically significant than generally appreciated

Effects of sex hormones on bronchial reactivity during the menstrual cycle

Background: Many asthmatic women complain of symptom exacerbations in particular periods, i.e. during pregnancy and menstrual cycles (perimenstrual asthma: PMA)". The goal of this study was to study the effect of the luteal and follicular phases of the menstrual cycle on bronchial reactivity (BR) in a group of asthmatic women. Methods: For this purpose, 36 pre-menopausal women were enrolled and underwent testing for resting pulmonary function, measurement of the diffusing capacity of the lung for carbon monoxide (DLCO), and airway responsiveness to methacholine in the follicular and luteal phases of their menstrual cycles. We also measured plasma hormone levels and levels of cyclic adenosine monophosphate (cAMP; a mediator of bronchial smooth muscle contraction) and testosterone in induced sputum samples. Results: Our study showed that about 30% of the asthmatic women had decreased PC20FEV1.0 in the follicular phase of menstrual cycle with a significant correlation between PC20FEV1.0 and serum testosterone levels. Moreover, marked increases in sputum testosterone levels (mean = 2.6-fold increase) together with significant increases in sputum cAMP concentrations (mean = 3.6-fold increases) were observed during the luteal phase of asthmatic patients, suggesting that testosterone contributes to the pathophysiology of PMA. We excluded the possibility that testosterone directly inhibits phosphodiesterase (PDE) activity as incubating PDE with testosterone in vitro did not reduce PDE catalytic activity. Conclusions: In conclusion, our data show that PC20FEV1.0 was decreased in the follicular phase of the menstrual cycle in about 30% of women and was associated with lower cAMP levels in sputum samples, which may contribute to bronchoconstriction. Our results also suggest a link between PMA and testosterone levels. However, whether these findings are of clinical significance in terms of the management of asthma or asthma worsening during the menstrual cycle needs further investigation

Pattern of statin use in southern Italian primary care: Can prescription databases be used for monitoring long-term adherence to the treatment?

Objectives: We sought to evaluate the prescribing pattern of statins according to national and regional health policy interventions and to assess specifically the adherence to the therapy in outpatient setting in Southern Italy. Methods: A population-based study was performed on persons ≥15 years old, living in the catchment area of Caserta (Southern Italy), and registered in Arianna database between 2004 and 2010. Prevalence and incidence of new treatments with statins were calculated for each year and stratified by drug. Adherence to therapy was measured by Medication Possession Ratio. Sub-analyses by individual compound and type of cardiovascular prevention were performed. Results: From 2004 to 2010, the one-year prevalence of statin use increased from 44.9/1,000 inhabitants to 79.8/1,000, respectively, consistently with the incidence of new use from 16.2/1,000 to 19.5/1,000, except a slight decrease after criteria reimbursement revision

Low-Thrust to Solar-Sail Trajectories: A Homotopic Approach

This paper describes a novel method to compute minimum-time solar-sail trajectories starting from a given low-thrust solution. The method is based on the use homotopy and numerical continuation. Homotopy is used to link the low-thrust with the solar-sail optimal control problem. Numerical continuation is used to compute the optimal solar-sail solution, starting from a given low-thrust planar solution, which is normally easy to find. Planar solar sail trajectories are computed by means of the homotopic approach. These solutions are used to compute, in a single shooting approach, three-dimensional solar-sail trajectories, for transfer scenarios involving a small change of the orbital inclination. The proposed homotopic approach is tested against a conventional approach, based on the use of a genetic algorithm. Numerical test cases are performed both on Earth-Mars and Earth-Apophis rendezvous. The results show that the proposed method is advantageous, in terms of accuracy of the solution and computational time

Advancing Personalized Medicine in the Treatment of Locally Advanced Rectal Cancer

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, distant tumor recurrence remains a concern, prompting the exploration of total neoadjuvant therapy (TNT) as a comprehensive treatment strategy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Nonoperative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving complete clinical response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for the assessment of treatment response. This review synthesizes current evidence on TNT, ICIs, NOM, and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application

Preparation and rheological properties of whey protein emulsion fluid gels

The research uses a novel approach to tackle structuring in liquids through shear-gel technology, resulting in advanced material properties.</p

Case Report: Circulating Myeloid-Derived Suppressive-Like Cells and Exhausted Immune Cells in Non-Small Cell Lung Cancer Patients Treated With Three Immune Checkpoint Inhibitors

none12noImmune checkpoint inhibition induced a great step forward in the treatment of non-small cell lung cancer patients. In cancer immune microenvironment many checkpoints were studied and their involvement could represent a mechanism of resistance to cancer immunotherapy. For this reason, the inhibition of multiple immune checkpoints is under development. However, myeloid-derived suppressor cells (MDSC) and exhausted immune cells could limit the efficacy of cancer immunotherapy. We analyzed the variation of circulating immune suppressive-like cell subsets and exhausted immune cells in three non-small cell lung cancer patients treated with the combination of anti-CTLA-4 plus anti-PD-1 plus anti-LAG-3 at T0 (baseline), T1 (after 2 months) and T2 (after 4 months). We also describe the clinical and radiological course of the disease during this treatment in all three patients. We observed both clinical differences and changes in the composition of immune suppressive-like cell subsets and exhausted immune cells between the patients receiving the same schedule of treatment with immune checkpoint inhibitors. The study on a wider patient population and experimental model design could help to clarify the kinetics of these cell subpopulations with the perspective to find new targets for treatment or new biomarkers for resistance to cancer immunotherapy.openBronte G.; Verlicchi A.; De Matteis S.; Rossi A.; Affatato A.; Sullo F.G.; Gianni C.; Canale M.; Burgio M.A.; Delmonte A.; Milella M.; Crino L.Bronte, G.; Verlicchi, A.; De Matteis, S.; Rossi, A.; Affatato, A.; Sullo, F. G.; Gianni, C.; Canale, M.; Burgio, M. A.; Delmonte, A.; Milella, M.; Crino, L

Melanoma metastasis mimicking gastric cancer: a challenge that starts from diagnosis

The gastrointestinal tract is an uncommon site of metastasis in melanoma. However, when the primary melanoma cannot be found, the diagnosis of gastric melanoma by endoscopic biopsy is problematic mainly because some tumors are amelanotic and do not contain melanin granules detectable by microscopy. A 56-year-old Caucasian man with melanoma was referred to us following an initial histopathological diagnosis via gastroscopy of poorly differentiated primary gastric carcinoma. A computerized tomography (CT) scan showed metastatic disease and on the basis of this information we started palliative chemotherapy. However, the atypical presentation of the disease with subcutaneous metastases prompted us to make a more in-depth evaluation. Immunohistochemical evaluation modified the diagnosis to melanoma. After only one cycle of chemotherapy, treatment was changed to dabrafenib + trametinib, which was better tolerated and initially induced a partial response. The patient is currently in good clinical condition 20 months after diagnosis. Our case report highlights the difficulty in diagnosing melanoma of the gastrointestinal tract and indicates the need for pathologists and clinicians to consider such a possibility when they are faced with a diagnosis of poorly differentiated gastric cancer and unusual sites of metastasis