Biomarkers in chronic obstructive pulmonary diseases. Clinical and functional correlations.

Asthma and chronic obstructive pulmonary disease (COPD) are two distinct lung diseases with distinctive clinical and inflammatory features. A proportion of asthmatic patients experience a fixed airflow obstruction that persists despite optimal pharmacologic treatment for reasons that are still largely unknown. We found that patients with asthma and COPD sharing a similar fixed airflow obstruction have an increased lung function decline and frequency of exacerbations. Nevertheless, the decline in lung function is associated with specific features of the underlying inflammation. Airway inflammation increases during asthma exacerbation and disease severity. Less is known about the correlations between symptoms and airway inflammation in COPD patients. We found that there is no correlation between symptoms and lung function in COPD patients. Nevertheless symptoms changes are associated with specific inflammatory changes: cough is associated with an increase of sputum neutrophils in COPD, dyspnoea is associated with an increase of eosinophils. The mechanisms of this correlation remain unknown. Neutrophils inflammation is associated with bacterial colonization in stable COPD. Is not known whether inhaled corticosteroids might facilitate bacterial colonization in COPD patients. We found that the use of inhaled corticosteroids in COPD patients is associated with an increase of airway bacterial load and with an increase of airway pathogen detection. Bacterial and viral infections are the main causes of COPD and asthma exacerbations. Impaired innate immune responses to rhinovirus infections have been described in adult patients with atopic asthma. Whether this impaired immune condition is present early in life and whether is modulated by a concomitant atopic condition is currently unknown. We found that deficient innate immune responses to rhinovirus infection are already present early in life in atopic patients without asthma and in asthmatic subjects. These findings generalize the scenario of increased susceptibility to viral infections to other Th2 oriented conditions.

I beni immateriali nella valutazione d'azienda

In seguito ad una disamina del materiale presente in letteratura, ci siamo chiesti se i numerosi investimenti pubblicitari, promozionali, di marketing e, per dirla in una parola sola “intangibili”, generassero un aumento del valore dell’impresa nel contesto valutativo oppure se dessero origine esclusivamente ad aumenti di fatturato. L’obiettivo più ambito consiste nel capitalizzare gli investimenti su attività intangibili come la costruzione del marchio, l’utilizzo di brevetti, le operazioni rivolte alla soddisfazione del cliente e tutto quanto si possa definire immateriale. Eppure coesistono nel mare magnum della stessa azienda. Fino a quando non si potrà inserire criteri di valutazione d’azienda delle performance di marketing non ci potrà essere crescita in quanto, le risorse, sono utilizzate senza un criterio di ritorno di investimento.

Transkriptom des Meristemgewebes des Kolumnarapfels

Kolumnare Apfelbäume (Malus x domestica) stellen aufgrund ihres auffälligen Phänotyps eine ökonomisch interessante Wuchsform dar. Diese extreme Form des Kurztriebwuchses zeichnet sich durch einen insgesamt sehr schlanken, säulenförmigen Habitus aus, welcher eine dichte Pflanzung und damit einhergehend Ertragssteigerungen im Vergleich zu normalwüchsigen Bäumen ermöglicht. Verursacht wird der Phänotyp durch die Anwesenheit eines einzelnen, dominanten Allels des Columnar (Co)-Gens. Bis auf die approximative Lokalisation des Gens auf Chromosom 10 ist über mögliche Identität und Funktion bislang nichts bekannt.rnIn der vorliegenden Arbeit wurde ein erster Versuch unternommen, mit Hilfe von Next Generation Sequencing (NGS) Technologien und RNA-Seq Einblicke in das Transkriptom des Sprossapikalmeristems (SAM) kolumnarer Apfelbäume zu gewinnen. So konnte gezeigt werden, dass unabhängig vom Zeitpunkt der Entnahme des Materials mehrere hundert Gene differentiell reguliert werden. Diese lassen sich funktional in mehrere überrepräsentierte Kategorien gruppieren, von denen sich einige wiederum mit dem kolumnaren Phänotyp assoziieren lassen. Durch den Einsatz weiterer Expressionsstudien (Microarrays, qRT-PCR) konnten frühere Ergebnisse bezüglich des Hormonhaushalts auf Genebene bestätigt und neue Erkenntnisse gewonnen werden, die eine mögliche Erklärung für den Phänotyp darstellen. Weiterhin ergab der Vergleich aller durchgeführten Expressionsstudien eine Anreicherung signifikant differentiell regulierter Gene auf Chromosom 10, was auf einen „selective sweep“ hindeutet. Eine potentielle epigenetische Regulation dieser Gene durch das Genprodukt von Co könnte daher möglich sein. Mehr als die Hälfte dieser Gene lassen sich darüber hinaus aufgrund ihrer Funktion direkt mit dem kolumnaren Phänotyp assoziieren.rnDiese Ergebnisse zeigen, dass die Anwesenheit des Co-Allels massive Veränderungen in der Genregulation des SAMs mit sich bringt, wobei einige dieser differentiell regulierten Gene mit großer Wahrscheinlichkeit an der Etablierung des kolumnaren Phänotyps beteiligt sind. Auch wenn die Funktion des Co-Genproduktes nicht abschließend geklärt werden konnte, sind doch anhand der Resultate schlüssige Hypothesen diesbezüglich möglich.rn

Un Mediolaniensis mos in epigrafia: l'officina epigrafica di Mediolanum

Si compie un'indagine al fine di determinare se all'interno dell'epigrafia romana fossero presenti precise specificità locali e quale livello di consapevolezza ne avessero i fruitori del mezzo epigrafico. Campione di indagine è l'orizzonte epigrafico di Mediolanum, di cui si definiscono le specificità - monumentali, impaginative, sintattiche, ma anche relative a maestranze e committenza - per confronto con le produzioni epigrafiche circostanti. Il quadro finale è quello di una produzione ben inserita negli orizzonti cisalpino e transpadano, ma che allo stesso tempo se ne differenzia per una serie di peculiarità, che in taluni casi sembrerebbero volutamente ricercate dai committenti.

Psychosocial correlates of rehabilitation from stroke: a longitudinal study

The general aim of this dissertation was to uncover the association between psychosocial factors and rehabilitation outcome after stroke. METHOD. A sample of patients with stroke (n=40) and their caregivers (n=36) were assessed at admission to and six months after discharge from rehabilitation hospital, using the following instruments: Structured Clinical Interview for DSM-IV, structured interview based on Diagnostic Criteria for Psychosomatic Research, Symptom Questionnaire, Psychosocial Index, Psychological Well-Being Scales, and Family Assessment Device. 40 subjects from the general population underwent the same psychological assessment. In addition, patients' functional status was measured using the Functional Independence Measure. RESULTS. Stroke survivors reported lower education and higher alcohol consumption than controls. No significant differences emerged between the two groups in the prevalence of psychiatric diagnoses or psychosomatic syndromes, however patients reported significantly higher levels of anxiety, depression, somatic symptoms, and lower autonomy than controls. Caregivers reported significantly higher scores in anxiety, depression, and somatic symptoms compared to normative data, while no impairments emerged in psychological well-being and family functioning. At six-month follow-up, in patients a significant decrease in smoking habit and an increase in DSM diagnoses were reported. Both stroke survivors and caregivers showed significant reductions in anxiety, with patients displaying also a decrease in somatic symptoms, an increase in stress and a deterioration in quality of life. Significant deteriorations in several aspects of family functioning was perceived only by patients. An association between patients' functional recovery in the cognitive domain and family behavior control emerged. For caregivers, family functioning significantly predicted hostility and somatic symptoms were associated with family affective involvement. CONCLUSIONS. These data highlight the utility in the Italian setting of the adoption of a psychosocial assessment and a family-systems approach in stroke rehabilitation, in order to development interventions properly targeted to the characteristics of patients and their family members.

Optimization of molecular and crystalline forms of drugs, agrochemicals, pesticides in relation to activity, bioavailability, patentability and to the fabrication of polymorphs, solvates, co-crystals with green chemistry methods

This doctorate was funded by the Regione Emilia Romagna, within a Spinner PhD project coordinated by the University of Parma, and involving the universities of Bologna, Ferrara and Modena. The aim of the project was: - Production of polymorphs, solvates, hydrates and co-crystals of active pharmaceutical ingredients (APIs) and agrochemicals with green chemistry methods; - Optimization of molecular and crystalline forms of APIs and pesticides in relation to activity, bioavailability and patentability. In the last decades, a growing interest in the solid-state properties of drugs in addition to their solution chemistry has blossomed. The achievement of the desired and/or the more stable polymorph during the production process can be a challenge for the industry. The study of crystalline forms could be a valuable step to produce new polymorphs and/or co-crystals with better physical-chemical properties such as solubility, permeability, thermal stability, habit, bulk density, compressibility, friability, hygroscopicity and dissolution rate in order to have potential industrial applications. Selected APIs (active pharmaceutical ingredients) were studied and their relationship between crystal structure and properties investigated, both in the solid state and in solution. Polymorph screening and synthesis of solvates and molecular/ionic co-crystals were performed according to green chemistry principles. Part of this project was developed in collaboration with chemical/pharmaceutical companies such as BASF (Germany) and UCB (Belgium). We focused on on the optimization of conditions and parameters of crystallization processes (additives, concentration, temperature), and on the synthesis and characterization of ionic co-crystals. Moreover, during a four-months research period in the laboratories of Professor Nair Rodriguez-Hormedo (University of Michigan), the stability in aqueous solution at the equilibrium of ionic co-crystals (ICCs) of the API piracetam was investigated, to understand the relationship between their solid-state and solution properties, in view of future design of new crystalline drugs with predefined solid and solution properties.

Comunicazione d'impresa in Alto Adige: Indagine sulle strategie di gestione del multilinguismo nelle PMI insediate in un territorio di contatto linguistico

La ricerca sulla comunicazione e gestione multilingue della conoscenza in azienda si è sinora concentrata sulle multinazionali o PMI in fase di globalizzazione. La presente ricerca riguarda invece le PMI in zone storicamente multilingui al fine di studiare se l’abitudine all’uso di lingue diverse sul mercato locale possa rappresentare un vantaggio competitivo. La tesi illustra una ricerca multimetodo condotta nel 2012-2013 in Alto Adige/Südtirol. Il dataset consiste in 443 risposte valide a un questionario online e 23 interviste con manager e imprenditori locali. Le domande miravano a capire come le aziende altoatesine affrontino la sfida del multilinguismo, con particolare attenzione ai seguenti ambiti: comunicazione multilingue, documentazione, traduzione e terminologia. I risultati delineano un quadro generale delle strategie di multilinguismo applicate in Alto Adige, sottolineandone punti di forza e punti deboli. Nonostante la presenza di personale multilingue infatti il potenziale vantaggio competitivo che ne deriva non è sfruttato appieno: le aziende si rivolgono ai mercati in cui si parla la loro stessa lingua (le imprese a conduzione italiana al mercato nazionale, quelle di lingua tedesca ad Austria e Germania). La comunicazione interna è multilingue solo nei casi in sia imprescindibile. Le “traduzioni fai-da-te” offrono l’illusione di gestire lingue diverse, ma il livello qualitativo rimane limitato. I testi sono sovente tradotti da personale interno privo di competenze specifiche. Anche nella cooperazione con i traduttori esterni si evidenza la mancata capacità di ottenere il massimo profitto dagli investimenti. La tesi propone delle raccomandazioni pratiche volte a ottimizzare i processi attuali e massimizzare la resa delle risorse disponibili per superare la sfida della gestione e comunicazione multilingue. Le raccomandazioni non richiedono investimenti economici di rilievo e sono facilmente trasferibili anche ad altre regioni multilingui/di confine, come ad altre PMI che impiegano personale plurilingue. Possono dunque risultare utili per un elevato numero di imprese.

Verso il consumo sostenibile: i prodotti biologici nelle abitudini alimentari degli italiani

Scegliere di consumare in modo sostenibile significa passare ad un nuovo modello di consumo. Tale modello richiede una maggiore consapevolezza e responsabilità da parte dei consumatori, unite all'adozione di nuovi stili di vita e di scelte d’acquisto, che permettano il raggiungimento di elevati livelli di benessere nel rispetto dell'ambiente. Un notevole sforzo è stato compiuto recentemente dai policy maker per incoraggiare il consumo sostenibile quali implementazioni dello sviluppo sostenibile. Ancora lunga, tuttavia, è la strada da percorrere per raggiungere pienamente questo obiettivo. Tra i prodotti sostenibili, il biologico si è rivelato di gran lunga il più rappresentativo: le statistiche di questo mercato mostrano, infatti, tendenze positive, sebbene il consumo risulti ancora eterogeneo e contenuto rispetto al consumo di alimenti convenzionali. Ciò mostra che il comportamento dei consumatori non è ancora abbastanza reattivo alle suddette politiche. Il presente studio si propone di contribuire alla ricerca sul consumo sostenibile approfondendo i fattori che incoraggiano o impediscono il consumo di prodotti alimentari biologici in Italia. Adottando un nuovo approccio si cerca di capire come i diversi segmenti di diete alimentari affrontino gli alimenti biologici in termini di consumi e di atteggiamenti. Un'analisi multivariata a più fasi è stata condotta su un campione di 3.004 consumatori. Un’analisi delle componenti principali non lineare è stata applicata alle variabili ordinali che misurano il consumo di ventuno categorie di alimenti. Successivamente è stata applicata la cluster analysis che ha dato luogo a quattro segmenti di abitudini alimentari. I prodotti biologici sono diventati parte delle abitudini alimentari in Italia in quasi un terzo della popolazione. Il consumo sembra essersi affermato soprattutto nel segmento con abitudini alimentari sane. Una scarsa attenzione ad una dieta sana, gli stili di vita, il reddito, l'accessibilità, la mancanza di consapevolezza condizionano le abitudini alimentari a scapito di un consumo più sostenibile.

Molekulare Analyse des Kolumnar-Gens beim Apfel (Malus x domestica)

Das Kolumnarwachstum beim Apfel (Malus x domestica) geht auf eine in den frühen 1960er Jahren entdeckte Zufallsmutation zurück. Die daraus resultierende Sprossmutante ist von großem wirtschaftlichem Interesse, da diese sehr kompakte Wuchsform unter anderem zu einer enormen Ertragssteigerung durch eine hohe Pflanzdichte der Bäume führt. Das Ziel der Arbeit ist die Entschlüsselung der molekularen Ursache dieser Mutation, die bisher weitgehend ungeklärt ist. Die Analyse wurde durch die Erstellung einer Referenzsequenz der Co-Zielregion einer kolumnaren Apfelsorte sowie durch die Konstruktion eng gekoppelter molekularer Marker realisiert. Durch die Konstruktion von genomischen Apfel-BAC-Bibliotheken mit mehrfacher Genomabdeckung und die Erstellung geeigneter Sonden wurde die Co-Region kloniert und deren Sequenz bestimmt. In Kombination zu dieser klassischen positionellen Klonierungsstrategie wurden genomische Illumina „mate pair“-Bibliotheken erstellt, sequenziert und bioinformatisch analysiert, um die genomische Region vollständig zu annotieren. Somit wurde eine vollständige genomische Referenz der Co-Region einer kolumnaren Apfelsorte erstellt, die die Grundlage für weitere Analysen bildet. Auf Basis dieser Referenz konnte die Co-Mutation in Form der Integration des LTR-Retrotransposons Gypsy-44 im kolumnaren Chromosom an Position 18,79 Mbp auf Chromosom 10 lokalisiert werden. Darüber hinaus konnten Transposon-basierende molekulare Marker erstellt werden, die eine verlässliche Genotypisierung von Apfelbäumen in Bezug auf das Kolumnarwachstum ermöglichen und dies unabhängig von der verwendeten Apfelsorte. Der genaue Wirkmechanismus von Gypsy-44, der zur Ausprägung dieses extremen Phänotyps führt, ist bislang unklar. Zusammenfassend lässt sich sagen, dass die molekulare Ursache für das kolumnare Wachstum aufgeklärt werden konnte und zudem die ersten molekularen Marker erstellt wurden, die eine sortenunabhängige Differenzierung zwischen kolumnaren und nicht kolumnaren Apfelbäumen ermöglichen.

Molecular genetic causes of columnar growth in apple (Malus x domestica)

The columnar growth habit of apple is interesting from an economic point of view as the pillar-like trees require little space and labor. Genetic engineering could be used to speed up breeding for columnar trees with high fruit quality and disease resistance. For this purpose, this study dealt with the molecular causes of this interesting phenotype. The original bud sport mutation that led to the columnar growth habit was found to be a novel nested insertion of a Gypsy-44 LTR retrotransposon on chromosome 10 at 18.79 Mb. This subsequently causes tissue-specific differential expression of nearby downstream genes, particularly of a gene encoding a 2OG-Fe(II) oxygenase of unknown function (dmr6-like) that is strongly upregulated in developing aerial tissues of columnar trees. The tissue-specificity of the differential expression suggests involvement of cis-regulatory regions and/or tissue-specific epigenetic markers whose influence on gene expression is altered due to the retrotransposon insertion. This eventually leads to changes in genes associated with stress and defense reactions, cell wall and cell membrane metabolism as well as phytohormone biosynthesis and signaling, which act together to cause the typical phenotype characteristics of columnar trees such as short internodes and the absence of long lateral branches. In future, transformation experiments introducing Gypsy-44 into non-columnar varieties or excising Gypsy-44 from columnar varieties would provide proof for our hypotheses. However, since site-specific transformation of a nested retrotransposon is a (too) ambitious objective, silencing of the Gypsy-44 transcripts or the nearby genes would also provide helpful clues.

Indagine sociolinguistica sulla minoranza linguistica storica francese in Piemonte: il caso delle valli valdesi

Au Piémont quatre minorités linguistiques historiques sont protégées par la loi: occitane, française, provençale et walser. Les municipalités francophones du Piémont sont vingt-huit, dont la plupart se trouve sur un territoire appelé « vallées vaudoises ». Le français est parlé comme un dialecte régional et il peut être considéré comme une variété de la langue, car il diffère du français de France pour son vocabulaire et sa prononciation. Le but de cette étude est celui d’examiner le degré de diffusion du français dans les vallées vaudoises, vérifier la présence d’initiatives de protection et l’engagement de la population. La présente étude est composée par sept parties. Le Chapitre 1 et 2 présentent l’état des recherches et définissent la méthode et le but de l’étude. Le Chapitre 3 présente un aperçu de l’histoire linguistique de la région, examine la situation linguistique actuelle notamment des minorités linguistiques historiques et du dialecte régional et analyse les lois qui protègent les minorités. Le Chapitre 4 décrit le territoire habité par la minorité française et présente un aperçu sur les événements historiques qui ont fait de ce territoire une communauté multilingue. Le Chapitre 5 analyse les compétences de la population, le degré de diffusion et les traits sociolinguistiques de la minorité. Le Chapitre 6 décrit les raisons de l’importance de la préservation du français dans les vallées vaudoises et présente un aperçu des initiatives de protection. La Conclusion présente les résultats et les possibles évolutions futures de l’étude. Afin d’atteindre l’objectif de l’étude, un sondage en ligne et plusieurs interviews ont été effectués ; ceux-ci ont permis d’obtenir des données ensuite analysées d’un point de vue statistique. En général, ce patrimoine est aujourd’hui très fragile ; cependant, un procès de revitalisation a commencé.

Inflammatory myofibroblastic tumour of the lung in a five-year-old girl

The inflammatory myofibroblastic tumour of the lung is considered a rare diagnosis of lung masses. We report the case of a five-year-old girl who presented with recurrent pyrexia, dry cough, and shortness of breath. Chest X-ray and computed tomography showed a total atelectasis of the left lower lobe and a segmental atelectasis of the left upper lobe. The mass was removed in toto, histopathology revealed the diagnosis of an inflammatory myofibroblastic tumour of the lung. The patient is without any signs of relapse 30 months after surgery.

Pond-Women Revelations: The Subaltern Registers in Maithil Women's Expressive Forms

Ponds are ubiquitous in the Maithil region of Nepal, and they figure prominently in folk narratives and ceremonial paintings produced by women there. I argue that in Maithil women's folktales, as in their paintings, the trope of ponds shifts the imaginative register toward women's perspectives and the importance of women's knowledge and influence in shaping Maithil society, even as this register shift occurs within plots featuring male protagonists. I argue further that in the absence of a habit of exegesis in their expressive arts, and given the cross-referential, dialogic nature of expressive practices, a methodology that draws into interpretive conversation the multitude of expressive forms exercised by Maithil women enhances analytical access to Maithil women's collective perspectives on their social and cosmological worlds.

A New Cryptically Dioecious Species of Bush Tomato (Solanum) From the Northern Territory, Australia

A new species of dioecious Solanum from the Australian “Dioicum Complex” of Solanum subgenus Leptostemonum is described. Solanum cowiei Martine sp. nov., is allied with other members of this problematic lineage, but differs in its slender leaves, limited armature and diminutive habit. The species was first segregated by botanists at the Northern Territory Herbarium as Solanum sp. Litchfield (I.D. Cowie 1428); and specimens representing this species have also been referred to by Symon as Solanum sp. Fitzmaurice River. Collections suggest that this is an endemic of the sub-arid tropical zone of the Northern Territory. SEM images support initial assumptions that the new species is cryptically dioecious via production of inaperturate pollen grains in morphologically hermaphrodite flowers.

Respiratory symptoms in preterm infants: burden of disease in the first year of life

Objective While respiratory symptoms in the first year of life are relatively well described for term infants, data for preterm infants are scarce. We aimed to describe the burden of respiratory disease in a group of preterm infants with and without bronchopulmonary dysplasia (BPD) and to assess the association of respiratory symptoms with perinatal, genetic and environmental risk factors. Methods Single centre birth cohort study: prospective recording of perinatal risk factors and retrospective assessment of respiratory symptoms during the first year of life by standardised questionnaires. Main outcome measures: Cough and wheeze (common symptoms), re-hospitalisation and need for inhalation therapy (severe outcomes). Patients: 126 preterms (median gestational age 28.7 weeks; 78 with, 48 without BPD) hospitalised at the University Children's Hospital of Bern, Switzerland 1999-2006. Results Cough occurred in 80%, wheeze in 44%, rehospitalisation in 25% and long term inhalation therapy in wheezers in 13% of the preterm infants. Using logistic regression, the main risk factor for common symptoms was frequent contact with other children. Severe outcomes were associated with maximal peak inspiratory pressure, arterial cord blood pH, APGAR and CRIB-Score. Conclusions Cough in preterm infants is as common as in term infants, whereas wheeze, inhalation therapy and re-hospitalisations occur more often. Severe outcomes are associated with perinatal risk factors. Preterm infants who did not qualify for BPD according to latest guidelines also showed a significant burden of respiratory disease in the first year of life.