47 research outputs found

    Inferring causal molecular networks: empirical assessment through a community-based effort

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    Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks

    Inferring causal molecular networks: empirical assessment through a community-based effort

    Get PDF
    It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense

    Occupational allergy to food-derived allergens

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    Although most cases of food allergy are related to food ingestion, occupational exposure to foods by contact or inhalation may also lead to adverse reactions, inducing contact urticaria or dermatitis, asthma, rhinitis, hypersensitivity pneumonitis, and anaphylaxis. Almost 10–25% of cases of allergic occupational asthma and rhinitis are due to food products. Animal and vegetal high-molecular weight proteins derived from aerosolized foods during food processing or handling at the workplace, as well as additives used as preservatives and antioxidants, and food contaminants, are the main causal agents. Farmers who grow and harvest crops and workers employed in food processing, storage and packing, and those involved in food preparation and transport are considered at increased risk for developing food-induced occupational asthma and rhinitis. Bakers’ asthma is the most frequent type of occupational asthma all around the world. Seafood processing industry is also at higher risk for asthma and rhinitis. A proportion of cases of asthma and rhinitis in food industry is also related to latex gloves used during food processing. The diagnosis of food-related occupational asthma and rhinitis includes a careful clinical and occupational history, respiratory functional assessment and measurement of non-specific bronchial hyperresponsiveness, immunologic assessment and specific inhalation challenge. The management includes environmental interventions aimed to avoid or reduce exposure to the offending agent, pharmacologic therapy, and allergen immunotherapy when available. Only few cases of food-induced occupational anaphylaxis have been described. The management of these emergencies should follow the current guidelines on anaphylaxis. The worker should be educated in managing future possible episodes that may also occur out of the workplace, by instance after accidental ingestion of the culprit allergen, and to carry 2 pre-loaded adrenaline delivery systems and a MedicAlert bracelet

    Respiratory occupational allergies: the experience of the Hospital Operative Unit of Occupational Medicine in Lombardy from 1990 to 1998

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    A retrospective study on occupational rhinitis and asthma diagnosed in 7 occupational health institutes in Lombardia (North-West Italy) was performed using a standardized card. 141 cases of rhinitis and 281 cases of asthma due to sensitization to occupational agents were analyzed and their clinical characteristics, aetiology, diagnostic methods and associated allergic diseases were determined. In this population the most frequent agents of occupational rhinitis were wheat flour and latex, whereas those of occupational asthma were latex and isocyanate. More than half of the subjects had more than one clinical manifestation of allergy. In 92 out of the 281 asthmatic patients rhinitis was the first clinical manifestation, particularly in subjects sensitized to high molecular weight substances, and preceded, asthma by 12 months as a mean. Specific bronchial provocation tests were useful for the diagnosis of asthma in 153 of the asthmatic patients and 45 of them had an isolated late bronchial reaction following the specific stimulus. At diagnosis 61 subjects (21.7%) had FEV1 < 80% of predicted; factors associated to ventilatory impairment were sensitization to high molecular weight substances, duration of exposure to the sensitizing agent, persistence of exposure after onset of symptoms

    Espettorato indotto e patologie dell'apparato respiratorio

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    Induced sputum is a nonivasive technique useful to assess airway inflammation. Sputum is induced through the inhalation of ultrasonic nebulized hypertonic saline solution and pre-treatment of the subject with b2 agonist is recommended to avoid bronchoconstriction. After the inhalation period the subject is invited to cough and to produce sputum. The sample is sent to the laboratory within 2 hours where it is solubilised in order to evaluate total cells and differential inflammatory cell count. Sputum of a healthy subject is mainly constituted by macrophages and neutrophils while eosinophils, lymphocytes and epithelial cells are only rarely present. Most asthmatic subjects have an increase of eosinophils in their sputum samples but neutrophilic or paucigranular patterns are also found in asthmatics' airways. Sputum eosinophils are usually predictors of a good response to inhaled or systemic corticosteroid therapy, whereas the presence of neutrophils in induced sputum, suggests a different therapeutic choice since neutrophils are not responsive to steroids. Furthermore, neutrophils are the most represented inflammatory cells in the sputum samples of subjects with chronic obstructive pulmonary disease (COPD). Total cells and sputum neutrophils increase during disease exacerbation. In the sputum of COPD subjects, the presence of eosinophils can precede an exacerbation and envisages a favourable response to steroids. Soluble mediators can be measured in the supernatant of processed induced sputum samples, particularly many cytokines, chemokines and other markers of inflammation and oxidative stress, but none of them seems to be particularly useful for the diagnosis or for the follow-up of patients with respiratory diseases. The majority of studies on induced sputum are conducted on asthmatic and COPD subjects but the scarce invasiveness of the procedure also allows its application in other pulmonary diseases such as eosinophilic bronchitis, cystic fibrosis, interstitial lung diseases

    Dermopatie professionali: analisi della casistica diagnosticata presso l’Istituto Scientifico di Pavia della Fondazione Maugeri nel periodo gennaio 1996 – aprile 2002

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    Le dermopatie costituiscono una percentuale notevole (almeno il 10-30%) delle malattie professionali. I compiti della medicina del lavoro nei confronti di tali patologie vanno dalla definizione della diagnosi, alla identificazione degli agenti e delle modalità d’esposizione responsabili, all’adozione di misure terapeutiche e preventive, ad adempimenti di natura medico-legale. In tale contesto, abbiamo ritenuto utile svolgere un’indagine retrospettiva sulle dermopatie occupazionali diagnosticate presso il nostro Istituto negli ultimi anni. I nostri dati indicano che, nonostante alcuni progressi compiuti negli ultimi anni in ambito preventivo, le dermopatie professionali continuano ad essere di frequente riscontro nella pratica clinica. Nella presente casistica, tali malattie sono state diagnosticate soprattutto nelle donne e in soggetti attorno ai 40 anni; nessuna età lavorativa è risultata tuttavia risparmiata. La casistica conferma l’elevata frequenza in Italia di allergopatie cutanee professionali (DAC, orticaria da contatto, angioedema), già segnalata in passato. Queste malattie possono presentarsi in associazione tra loro e/o con asma bronchiale
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