Qualification and Quantification of Fairness for Sustainable Mobility Policies

The adoption of new mobility technologies on a large-scale plays a crucial role to promote a green transition in the mobility field. Nonetheless, the acceptance of new mobility solutions implies radical changes in the everyday lives of individuals and, thus, it can be hampered by many different factors besides transport habits, such as socio-economic individual features. For this reason, it is essential to design human-centered policies directly addressing such barriers, avoiding the unwanted effect of amplifying inequalities at the edges of society. To this end, we propose a data-driven approach to embed socio-economic factors in the design of new mobility strategies that quantitatively account for fairness in a control-oriented and dynamic fashion. The formalization (and the inclusion in the approach) of the concepts of doxastic equality and equity allows us to mitigate epistemic exclusions, assessing system fairness. Thus, by combining tools from the control framework with those of philosophy, our approach offers an actionable tool for the support of the design of fair policies to foster the adoption of sustainable mobility habits.</p

Mechanical ventilation and volutrauma: study in vivo of a healthy pig model

Mechanical ventilation is essential in intensive care units. However, it may itself induce lung injury. Current studies are based on rodents, using exceptionally large tidal volumes for very short periods, often after a "priming" pulmonary insult. Our study deepens a clinically relevant large animal model, closely resembling human physiology and the ventilator setting used in clinic settings. Our aim was to evaluate the pathophysiological mechanisms involved in alveolo/capillary barrier damage due to mechanical stress in healthy subjects. We randomly divided 18 pigs (sedated with medetomidine/tiletamine-zolazepam and anesthetised with thiopental sodium) into three groups (n=6): two were mechanically ventilated (tidal volume of 8 or 20 ml/kg), the third breathed spontaneously for 4 hours, then animals were sacrifi ced (thiopental overdose). We analyzed every 30' hemogasanalysis and the main circulatory and respiratory parameters. Matrix gelatinase expression was evaluated on bronchoalveolar lavage fl uid after surgery and before euthanasia. On autoptic samples we performed zymographic analysis of lung, kidney and liver tissues and histological examination of lung. Results evidenced that high V T evoked profound alterations of lung mechanics and structure, although low V T strategy was not devoid of side effects, too. Unexpectedly, also animals that were spontaneously breathing showed a worsening of the respiratory functions

Current models of care for the management of HIV patients with comorbidities in England: a survey

Introduction: The number of people aged ]50 living with HIV in the UK is rapidly increasing. Effective treatment means HIV is usually well controlled; however, there has been an increase in individuals experiencing comorbid conditions associated with ‘‘normal’’ ageing. This aim of this study was to find out what models of care are currently in place for the management of patients with comorbidities. Materials and methods: A link to an online questionnaire was sent via the British HIV Association (BHIVA) Audit Committee to one HIV clinician in each HIV unit in England. Results: Forty-four units responded. Only 11 units (25%) provided specialized clinics for the management of comorbidities. These included: 1) Specialist clinics for the management of a non-infectious comorbidity (any age) e.g. a liver or renal clinic (n10). These clinics utilized in-person appointments (n3), or a combination of virtual and in-person appointments (n7). They were managed by an HIV clinician and non-HIV clinician together (n8), HIV clinician with an interest in the specialist area (n4) or specialist with an interest in HIV (n4). 2) Services for HIV patients with multiple comorbidities (any age) (n2). 3) Dedicated clinics for older people (n5) with eligibility determined by age (]50 years) or the presence of a comorbidity. Additionally, two HIV units employed a GP on site and two had set up a locally enhanced service providing enhanced primary care for HIV-positive patients. Six HIV units ran nurse-led clinics for patients with comorbid conditions. Co-ordination of care for patients with comorbid conditions was conducted by an HIV specialist doctor (n27), the patient’s GP (n18), HIV specialist nurse (n11) or the patient themselves (n9). Eleven clinics reported using case management for patients with multiple comorbid conditions. Self-management support (e.g. nurse-led or as part of an expert patient programme) for patients with comorbid conditions was provided at 18 HIV units. Conclusions: Only a quarter of the clinics surveyed had set up clinics for the management of comorbidities in people living with HIV. While a variety of different approaches were used, services were usually focused on the management of one comorbidity, and few provided services for multiple comorbidities. This is an increasing priority in the context of an ageing population. P162 Th

ATPase activity of DFCP1 controls selective autophagy

Cellular homeostasis is governed by removal of damaged organelles and protein aggregates by selective autophagy mediated by cargo adaptors such as p62/SQSTM1. Autophagosomes can assemble in specialized cup-shaped regions of the endoplasmic reticulum (ER) known as omegasomes, which are characterized by the presence of the ER protein DFCP1/ZFYVE1. The function of DFCP1 is unknown, as are the mechanisms of omegasome formation and constriction. Here, we demonstrate that DFCP1 is an ATPase that is activated by membrane binding and dimerizes in an ATP-dependent fashion. Whereas depletion of DFCP1 has a minor effect on bulk autophagic flux, DFCP1 is required to maintain the autophagic flux of p62 under both fed and starved conditions, and this is dependent on its ability to bind and hydrolyse ATP. While DFCP1 mutants defective in ATP binding or hydrolysis localize to forming omegasomes, these omegasomes fail to constrict properly in a size-dependent manner. Consequently, the release of nascent autophagosomes from large omegasomes is markedly delayed. While knockout of DFCP1 does not affect bulk autophagy, it inhibits selective autophagy, including aggrephagy, mitophagy and micronucleophagy. We conclude that DFCP1 mediates ATPase-driven constriction of large omegasomes to release autophagosomes for selective autophagy

Polycystic ovary syndrome and hyperglycaemia in pregnancy. A narrative review and results from a prospective Danish cohort study

Insulin resistance is common in polycystic ovary syndrome (PCOS). PCOS may be associated with increased risk of gestational diabetes mellitus (GDM).To 1) review literature regarding PCOS and hyperglycaemia in pregnancy and 2) present original data from Odense Child Cohort (OCC) regarding GDM in PCOS.Literature search including original studies from 2000-18. OCC included 2,548 pregnant women, 9.5 % (n=241) had PCOS. Fasting plasma glucose was measured in 1,519 and 659 oral glucose tolerance tests were performed (with risk factor for GDM, n= 384, without risk factors, n=275), applying two different GDM criteria RESULTS: 30 studies were eligible using 12 different sets of diagnostic criteria for GDM. Ten studies included n > 50, control group, assessment of GDM and BMI. Results were not uniform, but supported that higher BMI, higher age, Asian ethnicity, and fertility treatment increased the risk of GDM in PCOS. In OCC, women with PCOS and controls had similar prevalences of GDM independent of different sets of criteria for GDM.PCOS may not be an individual risk factor for GDM. Pregnancies in PCOS are characterized by factors known to increase risk of GDM, especially high BMI and fertility treatment

Developmental and Tumor Angiogenesis Requires the Mitochondria-Shaping Protein Opa1

While endothelial cell (EC) function is influenced by mitochondrial metabolism, the role of mitochondrial dynamics in angiogenesis, the formation of new blood vessels from existing vasculature, is unknown. Here we show that the inner mitochondrial membrane mitochondrial fusion protein optic atrophy 1 (OPA1) is required for angiogenesis. In response to angiogenic stimuli, OPA1 levels rapidly increase to limit nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) signaling, ultimately allowing angiogenic genes expression and angiogenesis. Endothelial Opa1 is indeed required in an NFκB-dependent pathway essential for developmental and tumor angiogenesis, impacting tumor growth and metastatization. A first-in-class small molecule-specific OPA1 inhibitor confirms that EC Opa1 can be pharmacologically targeted to curtail tumor growth. Our data identify Opa1 as a crucial component of physiological and tumor angiogenesis

Assessment of diagnostic criteria for multifocal motor neuropathy in patients included in the Italian database

Background and purposeThis study aimed to assess the diagnostic criteria, ancillary investigations and treatment response using real-life data in multifocal motor neuropathy (MMN) patients.MethodsClinical and laboratory data were collected from 110 patients enrolled in the Italian MMN database through a structured questionnaire. Twenty-six patients were excluded due to the unavailability of nerve conduction studies or the presence of clinical signs and symptoms and electrodiagnostic abnormalities inconsistent with the MMN diagnosis. Analyses were conducted on 73 patients with a confirmed MMN diagnosis and 11 patients who did not meet the diagnostic criteria.ResultsThe European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria were variably applied. AUTHOR:When applying the American Association of Electrodiagnostic Medicine criteria, an additional 17% of patients fulfilled the criteria for probable/definite diagnosis whilst a further 9.5% missed the diagnosis. In 17% of the patients only compound muscle action potential amplitude, but not area, was measured and subsequently recorded in the database by the treating physician. Additional investigations, including anti-GM1 immunoglobulin M antibodies, cerebrospinal fluid analysis, nerve ultrasound and magnetic resonance imaging, supported the diagnosis in 46%-83% of the patients. Anti-GM1 immunoglobulin M antibodies and nerve ultrasound demonstrated the highest sensitivity. Additional tests were frequently performed outside the EFNS/PNS guideline recommendations.ConclusionsThis study provides insights into the real-world diagnostic and management strategies for MMN, highlighting the challenges in applying diagnostic criteria

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery