Stepsize Learning for Policy Gradient Methods in Contextual Markov Decision Processes

Policy-based algorithms are among the most widely adopted techniques in model-free RL, thanks to their strong theoretical groundings and good properties in continuous action spaces. Unfortunately, these methods require precise and problem-specific hyperparameter tuning to achieve good performance, and tend to struggle when asked to accomplish a series of heterogeneous tasks. In particular, the selection of the step size has a crucial impact on their ability to learn a highly performing policy, affecting the speed and the stability of the training process, and often being the main culprit for poor results. In this paper, we tackle these issues with a Meta Reinforcement Learning approach, by introducing a new formulation, known as meta-MDP, that can be used to solve any hyperparameter selection problem in RL with contextual processes. After providing a theoretical Lipschitz bound to the difference of performance in different tasks, we adopt the proposed framework to train a batch RL algorithm to dynamically recommend the most adequate step size for different policies and tasks. In conclusion, we present an experimental campaign to show the advantages of selecting an adaptive learning rate in heterogeneous environments

<i>Fusarium roseum</i> var. <i>avenaceum</i> (Sacc.) Snyd. et Hans. agente di un « marciume molle» dei frutti di pomodoro in coltura protetta

The Authors report on the results of researches about a serious soft rot of greenhouse tomato fruits recently found in Sardinia (Italy). The disease symptoms and the characters of its causal agent, identified as Fusarium roseum var. avenaceum (Sacc.) Snyd. et Hans., are described. In laboratory, the influence of temperature, pH, and several culture media on growth and sporulation of the fungus, has been investigated. Artificial infection tests on tomato showed the high pathogenicity of the fungus to fruits only, but not to other plant organs

Effects of Tail Pinch on BDNF and trkB Expression in the Hippocampus of Roman Low- (RLA) and High-Avoidance (RHA) Rats

In this article, we describe the effects of tail pinch (TP), a mild acute stressor, on the levels of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor B (trkB) proteins in the hippocampus (HC) of the outbred Roman High- (RHA) and Low-Avoidance (RLA) rats, one of the most validated genetic models for the study of fear/anxiety- and stress-related behaviors. Using Western blot (WB) and immunohistochemistry assays, we show for the first time that TP induces distinct changes in the levels of BDNF and trkB proteins in the dorsal (dHC) and ventral (vHC) HC of RHA and RLA rats. The WB assays showed that TP increases BDNF and trkB levels in the dHC of both lines but induces opposite changes in the vHC, decreasing BDNF levels in RHA rats and trkB levels in RLA rats. These results suggest that TP may enhance plastic events in the dHC and hinder them in the vHC. Immunohistochemical assays, carried out in parallel to assess the location of changes revealed by the WB, showed that, in the dHC, TP increases BDNF-like immunoreactivity (LI) in the CA2 sector of the Ammon's horn of both Roman lines and in the CA3 sector of the Ammon's horn of RLA rats while, in the dentate gyrus (DG), TP increases trkB-LI in RHA rats. In contrast, in the vHC, TP elicits only a few changes, represented by decreases of BDNF- and trkB-LI in the CA1 sector of the Ammon's horn of RHA rats. These results support the view that the genotypic/phenotypic features of the experimental subjects influence the effects of an acute stressor, even as mild as TP, on the basal BDNF/trkB signaling, leading to different changes in the dorsal and ventral subdivisions of the HC

Drosophila mutant model of Parkinson's disease revealed an unexpected olfactory performance: Morphofunctional evidences

Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized by the clinical triad: tremor, akinesia, and rigidity. Several studies have suggested that PD patients show disturbances in olfaction as one of the earliest, nonspecific nonmotor symptoms of disease onset. We sought to use the fruit fly Drosophila melanogaster as a model organism to explore olfactory function in LRRK loss-of-function mutants, which was previously demonstrated to be a useful model for PD. Surprisingly, our results showed that the LRRK mutant, compared to the wild flies, presents a dramatic increase in the amplitude of the electroantennogram responses and this is coupled with a higher number of olfactory sensilla. In spite of the above reported results, the behavioural response to olfactory stimuli in mutant flies is impaired compared to that obtained in wild type flies. Thus, behaviour modifications and morphofunctional changes in the olfaction of LRRK loss-of-function mutants might be used as an index to explore the progression of parkinsonism in this specific model, also with the aim of studying and developing new treatment

Neuroplastic changes in c-Fos, ΔFosB, BDNF, trkB, and Arc expression in the hippocampus of male Roman rats: differential effects of sexual activity

Sexual activity causes differential changes in the expression of markers of neural activation (c-Fos and Delta FosB) and neural plasticity (Arc and BDNF/trkB), as determined either by Western Blot (BDNF, trkB, Arc, and Delta FosB) or immunohistochemistry (BDNF, trkB, Arc, and c-Fos), in the hippocam pus of male Roman high (RHA) and low avoidance (RLA) rats, two psychogenetically selected rat lines that display marked differences in sexual behavior (RHA rats exhibit higher sexual motivation and better copulatory performance than RLA rats). Both methods showed (with some differences) that sexual activity modifies the expression levels of these markers in the hippocampus of Roman rats depending on: (i) the level of sexual experience, that is, changes were usually more evident in sexually naive than in experienced rats; (ii) the hippocampal partition, that is, BDNF and Arc increased in the dorsal but tended to decrease in the ventral hippocampus; (iii) the marker considered, that is, in sexually experienced animals BDNF, c-Fos, and Arc levels were similar to those of controls, while Delta FosB levels increased; and (iv) the rat line, that is, changes were usually larger in RHA than RLA rats. These findings resemble those of early studies in RHA and RLA rats showing that sexual activity influences the expression of these markers in the nucleus accumbens, medial prefrontal cortex, and ventral tegmental area, and show for the first time that also in the hippocampus sexual activity induces neural activation and plasticity, events that occur mainly during the first phase of the acquisition of sexual experience and depend on the genotypic/phenotypic characteristics of the animals

Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosus

IntroductionThe pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined. MethodsTo identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s). ResultsWe enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients' sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients' sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-&amp; beta;2-glycoprotein-I (a &amp; beta;2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies. ConclusionIn conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include &amp; beta;2GPI

Impiego degli Inibitori della Pompa protonica (IPP) in Piemonte: indagine sulle abitudini prescrittive dei Medici di Medicina Generale

Proton Pump Inhibitors (PPIs) (Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole and Esomeprazole), one of the most commonly prescribed classes of medications in the primary care setting, are considered a major advance in the treatment of acid-peptic diseases. In Italy PPIs are reimbursed by National Health Service on the basis of CUF (Commissione Unica del Farmaco) 1 and 48 Notes. In 2002 and 2003 a significant increase in PPIs consumption and expenditure have been documented, showing differences between regions. The aim of this study is to investigate and monitor, at regional level, type and entity of PPIs use through a drug utilization study, evaluating prescribing behaviour and compliance of PPIs treatments with CUF Notes indications. The study has been carried out on a sample of 436 General Practitioners belonging to 22 Piemonte's ASL (Aziende Sanitarie Locali). The data analysis shows that acid-related pathologies are significantly more common in patients with at least 50 years of age and the most frequent condition is represented by gastroesophageal reflux disease. Despite the general conditions of PPIs use by General Practitioners in terms of duration and dosage of therapy result in most cases (from 49% to 80% for duration and from 54% to 97% for dosage) compliant with what proposed by CUF Notes, in some cases the same CUF Notes indications seem to be not observed. Consequently the Piemonte Region has decided to plan a guideline on PPIs rational use. Such guideline, expected to be introduced in the regional area, may also be considered as an instrument able to lead to a more appropriate expenditure for this drug class. Moreover, in order to control PPIs expenditure, pharmacoeconomic methodologies can be applied allowing to identify the most cost - effective active substance and therapeutic scheme, overcoming CUF Notes which consider all PPIs use under the same reimbursement conditions

The Matter of Future Heritage

In 2018, for the first time, the University of Bologna’s Board of PhD in Architecture and Design Culture assigned second-year PhD students the task of developing and managing an international conference and publishing its works. The organisers of the first edition of this initiative – Giacomo Corda, Pamela Lama, Viviana Lorenzo, Sara Maldina, Lia Marchi, Martina Massari and Giulia Custodi – have chosen to leverage the solid relationship between the Department of Architecture and the Municipality of Bologna to publish a call having to do with the European Year of Cultural Heritage 2018, in which the Municipality was involved. The theme chosen for the call, The Matter of Future Heritage, set itself the ambitious goal of questioning the future of a field of research – Cultural Heritage (CH) – that is constantly being &nbsp;redefined. A work that was made particularly complex in Europe by the development of the H2020 programme, where the topic entered, surprisingly, not as a protagonist but rather as an articulation of other subjects that in the vision of the programme seemed evidently more urgent and, one might say, dominant. The resulting tensions have been considerable and with both negative and positive implications, all the more evident if we refer to the issues that are closest to us namely the city and the landscape

Brain-reactive autoantibodies in neuropsychiatric systemic lupus erythematosus

IntroductionThe pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) is widely unknown, and the role of autoantibodies is still undetermined.MethodsTo identify brain-reactive autoantibodies possibly related to NPSLE, immunofluorescence (IF) and transmission electron microscopy (TEM) on rat and human brains were performed. ELISA was used to reveal the presence of known circulating autoantibodies, while western blot (WB) was applied to characterize potential unknown autoantigen(s).ResultsWe enrolled 209 subjects, including patients affected by SLE (n=69), NPSLE (n=36), Multiple Sclerosis (MS, n=22), and 82 age- and gender-matched healthy donors (HD). Autoantibody reactivity by IF was observed in almost the entire rat brain (cortex, hippocampus, and cerebellum) using sera from NPSLE and SLE patients and was virtually negative in MS and HD. NPSLE showed higher prevalence (OR 2.4; p = 0.047), intensity, and titer of brain-reactive autoantibodies than SLE patients. Most of the patient sera with brain-reactive autoantibodies (75%) also stained human brains. Double staining experiments on rat brains mixing patients’ sera with antibodies directed against neuronal (NeuN) or glial markers showed autoantibody reactivity restricted to NeuN-containing neurons. Using TEM, the targets of brain-reactive autoantibodies were located in the nuclei and, to a lesser extent, in the cytoplasm and mitochondria. Given the high degree of colocalization between NeuN and brain-reactive autoantibodies, we assumed NeuN was a possible autoantigen. However, WB analysis with HEK293T cell lysates expressing or not expressing the gene encoding for NeuN protein (RIBFOX3) showed that patients’ sera carrying brain-reactive autoantibodies did not recognize the NeuN corresponding band size. Among the panel of NPSLE-associated autoantibodies (e.g., anti-NR2, anti-P-ribosomal protein, antiphospholipid) investigated by ELISA assay, only the anti-β2-glycoprotein-I (aβ2GPI) IgG was exclusively found in those sera containing brain-reactive autoantibodies.ConclusionIn conclusion, SLE and NPSLE patients possess brain-reactive autoantibodies but with higher frequency and titers found in NPSLE patients. Although many target antigens of brain-reactive autoantibodies are still undetermined, they likely include β2GPI

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening