Mean field games: prospects and intuitions

Mean field games is a branch of game theory that deals with large symmetrical games. Born in 2006, it is now a lively research topic that poses tough mathematical challenges and already features a broad range of applications. Among the challenges, a system of coupled PDE plays the major role, while current mean field games models deal with crowds behaviour, traffic flows, macroeconomics dynamics and cancer evolution. Our work has a dual aim: to highlight the core intuitions of this approach and to present some of its prospects as an applied tool. To do this, we merge the Mean Field Games analytic backbone by P. Cardaliaguet with some of the applications by O. Guéant, J-M. Lasry and P-L. Lions. The first part of our work introduces the main intuitions behind the mean field game solution, such as the limit game definition, the forward-backward reasoning and the fixed point nature of the mean field. We then solve a {single-shot} game via the mean field approach and present a numerical simulation of the results. The second part shows how the same steps can be employed in the continuous time case to obtain the coupled PDE formulation. In this general problem setting, we prove an important existence and uniqueness theorem for the mean field solution and characterize this latter as an epsilon-Nash equilibrium. In the last part we focus on the prospects for this recent theory, presenting some economics related applications. After a brief model of imitative preferences, we discuss an heterogeneous agents, human capital based growth model, highlighting how easily real-like scenarios can give birth to new unconventional PDE systems

A Recommendation and Risk Classification System for Connecting Rough Sleepers to Essential Outreach Services

Rough sleeping is a chronic problem faced by some of the most disadvantaged people in modern society. This paper describes work carried out in partnership with Homeless Link, a UK-based charity, in developing a data-driven approach to assess the quality of incoming alerts from members of the public aimed at connecting people sleeping rough on the streets with outreach service providers. Alerts are prioritised based on the predicted likelihood of successfully connecting with the rough sleeper, helping to address capacity limitations and to quickly, effectively, and equitably process all of the alerts that they receive. Initial evaluation concludes that our approach increases the rate at which rough sleepers are found following a referral by at least 15\% based on labelled data, implying a greater overall increase when the alerts with unknown outcomes are considered, and suggesting the benefit in a trial taking place over a longer period to assess the models in practice. The discussion and modelling process is done with careful considerations of ethics, transparency and explainability due to the sensitive nature of the data in this context and the vulnerability of the people that are affected.Comment: 10 pages, 5 figures, 5 table

Polypharmacy and malnutrition in older people: A narrative review

Polypharmacy is the simultaneous use of multiple medicines, usually more than five. Polypharmacy is highly prevalent among older individuals and is associated with several adverse health outcomes, including frailty. The role of polypharmacy in nutritional status seems to be crucial: although a clear association between polypharmacy and malnutrition has been widely reported in older people, the magnitude of the effect of increased number of drugs in combination with their type on the risk for malnutrition remains to be largely explored. Therefore, this review aims to discuss the association between polypharmacy and malnutrition in older people and to provide suggestions for its management. Polypharmacy is prevalent among malnourished frail patients, and the relative contribution of comorbidities and polypharmacy to malnutrition is difficult to be determined. Several mechanisms by which commonly used medications have the potential to affect nutritional status have been identified and described. Deprescribing (i.e., a systematic process of identification and discontinuation of drugs or a reduction of drug regimens) could be an essential step for minimizing the effects of polypharmacy on malnutrition. In this regard, the literature suggests that in older patients taking several medications, the best method to solve this problem is the comprehensive geriatric assessment, based on a holistic approach, including drug review, to find potential unnecessary and inappropriate medications. Nutritional and deprescribing interventions must be tailored to patient needs and to the local context to overcome barriers when applied in different settings

Markers for the detection of Lewy body disease versus Alzheimer's disease in mild cognitive impairment: a systematic review and meta-analysis

Background Mild cognitive impairment (MCI) may evolve into dementia. Early recognition of possible evolution to Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) is of importance, but actual diagnostic criteria have some limitations. In this systematic review and meta-analysis, we aimed to find the most accurate markers that can discriminate patients with DLB versus AD, in MCI stage. Methods We searched several databases up to 17 August 2023 including studies comparing markers that may distinguish DLB-MCI from AD-MCI. We reported data regarding sensitivity, specificity, and the area under the curves (AUCs) with their 95% confidence intervals (CIs). Results Among 2219 articles initially screened, eight case-control studies and one cohort study were included for a total of 832 outpatients with MCI. The accuracy of cerebrospinal fluid (CSF) markers was the highest among the markers considered (AUC > 0.90 for the CSF markers), with the AUC of CSF A beta 42/A beta 40 of 0.94. The accuracy for clinical symptom scales was very good (AUC = 0.93), as evaluated in three studies. Although limited to one study, the accuracy of FDG-PET (cingulate island sign ratio) was very good (AUC = 0.95) in discriminating DLB from AD in MCI, while the accuracy of SPECT markers and EEG frequencies was variable. Conclusions Few studies have assessed the accuracy of biomarkers and clinical tools to distinguish DLB from AD at the MCI stage. While results are promising for CSF markers, FDG-PET and clinical symptoms scales, more studies, particularly with a prospective design, are needed to evaluate their accuracy and clinical usefulness

Tgf-β1 transcriptionally promotes 90K expression: possible implications for cancer progression.

The 90K protein, also known as Mac-2 BP or LGALS3BP, can activate the immune response in part by increasing major histocompatibility (MHC) class I levels. In studies on a non-immune cell model, the rat FRTL-5 cell line, we observed that transforming growth factor (TGF)-β1, like γ-interferon (IFN), increased 90K levels, despite its immunosuppressive functions and the ability to decrease MHC class I. To explain this paradoxical result, we investigated the mechanisms involved in the TGF-β1 regulation of 90K expression with the aim to demonstrate that TGF-β1 utilizes different molecular pathways to regulate the two genes. We found that TGF-β1 was able to increase the binding of Upstream Stimulatory Factors, USF1 and USF2, to an E-box element, CANNTG, at -1926 to -1921 bp, upstream of the interferon response element (IRE) in the 90K promoter. Thyrotropin (TSH) suppressed constitutive and γ-IFN-induced 90K expression by decreasing USF binding to the E-box. TGF-β1 was able to overcome TSH suppression at the transcriptional level by increasing USF binding to the E-box. We suggest that the ability of TGF-β1 to increase 90K did not result in an increase in MHC class I because of a separate suppressive action of TGF-β1 directly on the MHC class I gene. We propose that the increased levels of 90K may play a role, rather than in immune response, in the context of the TGF-β1-induced changing of the cellular microenvironment that predisposes to cell motility and cancer progression. Consistently, analyzing the publicly available cancer patient data sets cBioPortal, we found that 90K expression directly correlated with TGF-β1 and USFs and that high levels of 90K were significantly associated with increased mortality in patients affected by different types of cancer

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific data- bases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was euro2,558.91 and euro3,287.40 for subjects with micro- prolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after ini- tial treatment were euro798.13 and euro1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of euro3,201.15 compared to bromocriptine, based on a willingness-to-pay of euro40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic sur- gery was more cost-effective than cabergoline, with an ICER of euro44,846.64. Considering a willingness-to-pay of euro40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis

IntroductionWorldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries.MethodsFour investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool.Resultsoverall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1–74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97–100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis.ConclusionsOur study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality