A rapid impact assessment approach for decision support in food policy

Under the pressure of many alternative stakeholders’ demands, the food policy maker needs to consider regulatory decisions in order to grant a safe final product for the consumer, as well as to foster the improvement of the agro-food supply system. However, current ex-ante impact assessment systems present many evaluation shortcomings due to the intrinsic difficulty of: modelling impact phenomena, establishing reliable time-related parameters and predicting food supply network actors’ behaviour. Considering these issues the present doctoral thesis proposes an alternative assessment approach, based on a mix of qualitative and quantitative elements, able to rapidly obtain impacts and display them in an intuitively comprehensible visualization. Main features of the created model are: the consequentiality between food sector enterprises’ compliance with new policies and the calculation of potential macro impacts, the highly disaggregated multi-level government impacts data collection, the structured procedure in analysing the numerous impact categories and the indication of inputs uncertainty. Results from two case studies (Directive 2009/128/EC of the 21st of October 2009 ‘establishing a framework for Community action to achieve the sustainable use of pesticides’ and European Commission Proposal of 30th January 2008 for a Regulation ‘on the provision of food information to consumers – allergens focus’), a simulation and direct interviews to prospective users of the model (European Commission Departments members), revealed the complementary role of the rapid assessment approach in respect of part of the current impact assessment system. Finally a dedicated software illustrates how the rapid assessment approach could serve policy makers in supporting their decisions when dealing with food regulations’ outcomes improvement.Eine effiziente Bewertungsmethode zur Unterstützung der Entscheidungsfindung in der Ernährungspolitik Unter dem Druck der verschiedenen Ansprüche der Akteure der Lebens- mittelwertschöpfungskette sind Entscheidungsträger der Ernährungspolitik gezwungen Entscheidungen zu treffen, die sowohl die Lebensmittelsicherheit der Endprodukte für den Verbraucher berücksichtigen als auch der Verbesserung der Wertschöpfungskette des Agribusiness Rechnung tragen. Bestehende ex-ante Bewertungssysteme weisen verschiedene Mängel auf, die auf Schwierigkeiten innerhalb des Systems zurückzuführen sind: Modellierung der Bewertungsphänomene, Etablierung verlässlicher zeit-bezogener Parameter und Vorhersage des Verhaltens von Akteuren der Wertschöpfungskette. Unter Berücksichtigung dieser Probleme beschäftigt sich diese Doktorarbeit mit möglichen Lösungsansätzen. Schwerpunkt bildet die Entwicklung eines alternativen, effizienten Bewertungsansatzes, welcher auf qualitativen als auch quantitativen Komponenten basiert. Dies ermöglicht es, Einflussfaktoren effizient und effektiv zu identifizieren und visualizieren. Im Mittelpunkt des erarbeiteten Modells stehen die Zusammenhänge zwischen der Compliance der Ernährungsindustrie und potentiellen Einflussfaktoren, disaggregierte Datenerhebung auf mehreren Ebenen, strukturierte Vorgehensweise in der Analyse potentieller Einflussfaktoren und Ausweisung von Unsicherheitsfaktoren. Ergebnisse liefern zwei Fallstudien (Richtlinie 2009/128/EG über‚ einen Aktionsrahmen der Gemeinschaft für die nachhaltige Verwendung von Pestiziden‘ und Vorschlag für eine Verordnung (2008) betreffend ‚die Information der Verbraucher über Lebensmittel – Fokus auf Allergene‘), eine Simulation sowie Tiefeninterviews mit zukünftigen Nutzern der effizienten Bewertungsmethode (Generaldirektionen Mitglieder). Es zeigt sich, dass die effiziente Bewertungsmethode komplementär zum derzeitigen Bewertungsmechanismus gesehen werden kann. Abschließend illustriert eine Softwareanwendung, wie die effiziente Bewertungsmethode zukünftig politische Entscheidungsträger in ihrer Entscheidungsfindung bezüglich Lebensmittelgesetzen und –richtlinien unterstützen könnte.Un sistema rapido di valutazione degli impatti per il supporto alle decisioni nelle politiche agro-alimentari Sotto la spinta di diversi gruppi di pressione, quali i consumatori, le industrie manifatturiere agro-alimentari e l‟opinione pubblica, il decisore politico si trova a prendere scelte atte a garantire sia la sanità del prodotto finale che lo sviluppo e l‟innovazione delle reti di offerta agro-alimentari. Tuttavia gli odierni sistemi di valutazione ex-ante degli impatti delle politiche agro-alimentari presentano molteplici problemi di analisi legati alla modellizzazione delle particolarità dei fenomeni sottastanti gli impatti, alla determinazione di parametri con variabilità temporale e alla previsione dei comportamenti degli attori economici del settore. Considerando le difficoltà sopra elencate, il presente lavoro propone un approccio di valutazione alternativo; tale sistema, in parte basato su informazioni qualitative ed in parte su informazioni quantitative, permette di ottenere velocemente i potenziali impatti ex-ante presentandoli con un‟interfaccia di facile ed intuitiva comprensibilità. Le caratteristiche principali del modello sottostante il sistema di valutazione creato sono: la consequenzialità tra la conformità delle imprese agro-alimentari alle norme di nuove politiche e il calcolo degli impatti a livello aggregato, la raccolta disaggregata dei dati di impatto a diversi livelli di governo del territorio, la procedura strutturata nel considerare le molteplici categorie di impatto e l‟indicatore di incertezza connessa agli inputs immessi. Il test del sistema di valutazione attraverso due casi studio (Direttiva 2009/128/CE „Istituzione di un quadro per l‟azione comunitaria ai fini dell‟utilizzo sostenibile dei pesticidi‟ e Proposta di Regolamento della Commissione (2008) „relativo alla fornitura di informazioni alimentari ai consumatori – focus sugli allergeni‟), una simulazione ed interviste dirette ad utilizzatori potenziali del modello (membri di specifici Direttorati Generali della Commissione Europea), hanno rivelato la complementarietà tra l‟approccio di valutazione espresso in questo studio e i sistemi di valutazione di impatto esistenti. Un software dedicato dimostra infine come l‟approccio di valutazione rapida possa servire il decisore politico aiutandolo nel miglioramento degli esiti delle politiche agro-alimentari

An E-platform for Supporting Sustainability Developments with Special Reference to Latin America

Due to raising pressures from civil society, consumers, businesses and public institutions, appropriate methodological, technological and organizational innovations acquired a central role for the establishment of global sustainable food supply chains. This paper presents an-line software able to support the implementation of sustainable policies for two highly traded products between Latina America and Europe that still raise environmental, social and economic concerns, namely soymeal and beef. The E-Platform propose itself as a synthesis of both scientific and management requirements, therefore combining complex analysis methods as life cycle analysis in the back-end and implementation and monitoring modules in the front-end. The system, currently in its test phase in Brazil, Argentina and Mexico, has its primary objectives in facilitating the implementation of new sustainable production policies, in opening access to new markets and in complying with stringent requirements minimizing the certification costs and time investments for the actors of the supply chain

Not only a problem of fatigue and sleepiness: Changes in psychomotor performance in Italian nurses across 8-h rapidly rotating shifts

Although many studies have detailed the consequences of shift work in nurses concerning health, fatigue, sleepiness, or medical errors, no study has been carried out trying to disentangle the contribution of sleepiness and fatigue associated to shift work from the attentional performance. The aim of this pilot study is (A) to investigate the effects of an 8-h rapidly rotating shift on fatigue and sleepiness among staff nurses and (B) how these factors affect their psychomotor performance. Fourteen nurses were selected for a within-subject cross-sectional study according to this sequence of shifts: morning–afternoon–night, which were compared as function of tiredness, sleepiness, and performance at the Psychomotor Vigilance Task (PVT). Subsequently, a within-subject Analysis of Covariance (ANCOVA) evaluated if the observed differences between shifts persist when the contribution of sleepiness is controlled. Our results clearly indicate that night shifts are associated with significant greater sleepiness and tiredness, and worsened performance at the PVT. As hypothesized, ANCOVA showed that these differences disappear when the contribution of sleepiness is controlled. Results point to a lower psychomotor performance in night compared to day shifts that depends on sleepiness. Hence, interventions to minimize the consequences of the night shift should consider a reduction of sleepiness

Nurses and Night Shifts. Poor Sleep Quality Exacerbates Psychomotor Performance

In Europe, 40% of health-care employees are involved in shift work. The altered sleep/wake rhythm of night-shift nurses is also associated with deteriorated cognitive efficiency. In this study, we examine the effects of the night shift on psychomotor performance, sleepiness, and tiredness in a large sample of shift-working nurses and evaluated if poor sleep quality, sex, age, or years on the job could impact on a better adaptation to shift work. Eighty-six nurses with 8-h-rapidly-rotating-shifts were evaluated at the end of three shifts (morning/afternoon/night) for sleepiness and tiredness. Sleepiness, as measured by the Karolinska Sleepiness Scale, and tiredness, as measured by the Tiredness Symptoms Scale, were more pronounced after the night shift. These increases were paralleled by lower attentional performance on the psychomotor vigilance task (PVT) after the night shift. While sex, age, and years on the job did not affect PVT performance after the night shift, lower sleep quality (Pittsburgh Sleep Quality, PSQI > 5) was associated with decreased performance. The high prevalence of altered sleep quality showed that nurses, and shift workers in general, are at risk for a poor sleep quality. The evaluation of sleep quality through PSQI could represent a rapid, inexpensive tool to assess health-care workers assigned to rotating night shifts or to evaluate nurses who coped poorly with night-shift work

Exon-trapping assay improves clinical interpretation of COL11A1 and COL11A2 intronic variants in stickler syndrome type 2 and otospondylomegaepiphyseal dysplasia

Stickler syndrome (SS) is a hereditary connective tissue disorder affecting bones, eyes, and hearing. Type 2 SS and the SS variant otospondylomegaepiphyseal dysplasia (OSMED) are caused by deleterious variants in COL11A1 and COL11A2, respectively. In both genes, available database information indicates a high rate of potentially deleterious intronic variants, but published evidence of their biological effect is usually insufficient for a definite clinical interpretation. We report our previously unpublished intronic variants in COL11A1 (c.2241 + 5G>T, c.2809 − 2A>G, c.3168 + 5G>C) and COL11A2 (c.4392 + 1G>A) identified in type 2 SS/OSMED individuals. The pathogenic effect of these variants was first predicted in silico and then investigated by an exon-trapping assay. We demonstrated that all variants can induce exon in-frame deletions, which lead to the synthesis of shorter collagen XI α1 or 2 chains. Lacking residues are located in the α-triple helical region, which has a crucial role in regulating collagen fibrillogenesis. In conclusion, this study suggests that these alternative COL11A1 and COL11A2 transcripts might result in aberrant triple helix collagen. Our approach may help to improve the diagnostic molecular pathway of COL11-related disorder

Recurrent, founder and hypomorphic variants contribute to the genetic landscape of Joubert syndrome

Background Joubert syndrome (JS) is a neurodevelopmental ciliopathy characterised by a distinctive mid-hindbrain malformation, the 'molar tooth sign'. Over 40 JS-associated genes are known, accounting for two-thirds of cases.Methods While most variants are novel or extremely rare, we report on 11 recurring variants in seven genes, including three known 'founder variants' in the Ashkenazi Jewish, Hutterite and Finnish populations. We evaluated variant frequencies in similar to 550 European patients with JS and compared them with controls (>15 000 Italian plus gnomAD), and with an independent cohort of similar to 600 JS probands from the USA.Results All variants were markedly enriched in the European JS cohort compared with controls. When comparing allele frequencies in the two JS cohorts, the Ashkenazim founder variant (TMEM216 c.218G>T) was significantly enriched in American compared with European patients with JS, while MKS1 c.1476T>G was about 10 times more frequent among European JS. Frequencies of other variants were comparable in the two cohorts. Genotyping of several markers identified four novel European founder haplotypes. Two recurrent variants (MKS1 c.1476T>G and KIAA0586 c.428delG), have been detected in homozygosity in unaffected individuals, suggesting they could act as hypomorphic variants. However, while fibroblasts from a MKS1 c.1476T>G healthy homozygote showed impaired ability to form primary cilia and mildly reduced ciliary length, ciliary parameters were normal in cells from a KIAA0586 c.428delG healthy homozygote.Conclusion This study contributes to understand the complex genetic landscape of JS, explain its variable prevalence in distinct geographical areas and characterise two recurrent hypomorphic variants

Psychological treatments and psychotherapies in the neurorehabilitation of pain. Evidences and recommendations from the italian consensus conference on pain in neurorehabilitation

BACKGROUND: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. OBJECTIVES: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. METHODS: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. RESULTS: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive-Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post-Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache. CONCLUSIONS: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the pape

Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients

<p>Abstract</p> <p>Background</p> <p>MicroRNAs are highly conserved, noncoding RNAs involved in post-transcriptional gene silencing. They have been shown to participate in a wide range of biological processes, including myogenesis and muscle regeneration. The goal of this study is to test the hypothesis that myo-miRs (myo = muscle + miR = miRNA) expression is altered in muscle from patients affected by myotonic dystrophy type 1 (DM1), the most frequently inherited neuromuscular disease in adults. In order to gain better insights about the role of miRNAs in the DM1 pathogenesis, we have also analyzed the muscular expression of miR-103 and miR-107, which have been identified <it>in silico </it>as attractive candidates for binding to the <it>DMPK </it>mRNA.</p> <p>Methods</p> <p>To this aim, we have profiled the expression of miR-133 (miR-133a, miR-133b), miR-1, miR-181 (miR-181a, miR-181b, miR-181c) and miR-206, that are specifically induced during myogenesis in cardiac and skeletal muscle tissues. miR-103 and miR-107, highly expressed in brain, heart and muscle have also been included in this study. QRT-PCR experiments have been performed on RNA from vastus lateralis biopsies of DM1 patients (n = 7) and control subjects (n = 4). Results of miRNAs expression have been confirmed by Northern blot, whereas <it>in situ </it>hybridization technique have been performed to localize misexpressed miRNAs on muscle sections from DM1 and control individuals.</p> <p>Results</p> <p>Only miR-206 showed an over-expression in 5 of 7 DM1 patients (threshold = 2, fold change between 1.20 and 13.22, average = 5.37) compared to the control group. This result has been further confirmed by Northern blot analysis (3.37-fold overexpression, <it>R</it>²= 0.89). <it>In situ </it>hybridization localized miR-206 to nuclear site both in normal and DM1 tissues. Cellular distribution in DM1 tissues includes also the nuclear regions of centralized nuclei, with a strong signal corresponding to nuclear clumps.</p> <p>Conclusions</p> <p>This work provides, for the first time, evidences about miRNAs misexpression in DM1 muscle tissues, adding a new element in the pathogenesis of this complex genetic disease.</p

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations. It focuses on genetic newborn screening and artificial intelligence-based tools which will be applied to a large European population of about 25.000 infants. The neonatal screening strategy will be based on targeted sequencing, while whole genome sequencing will be offered to all enrolled infants who may show early symptoms but have resulted negative at the targeted sequencing-based newborn screening. We will leverage artificial intelligence-based algorithms to identify patients using Electronic Health Records (EHR) and to build a repository "symptom checkers" for patients and healthcare providers. S4C will design an equitable, ethical, and sustainable framework for genetic newborn screening and new digital tools, corroborated by a large workout where legal, ethical, and social complexities will be addressed with the intent of making the framework highly and flexibly translatable into the diverse European health systems

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior

Purpose We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. Methods We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. Results These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. Conclusion These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis