Innovation and economic performance of the firms in the service sector: relevant issues and open problems

This thesis is a collection of essays related to the topic of innovation in the service sector. The choice of this structure is functional to the purpose of single out some of the relevant issues and try to tackle them, revising first the state of the literature and then proposing a way forward. Three relevant issues has been therefore selected: (i) the definition of innovation in the service sector and the connected question of measurement of innovation; (ii) the issue of productivity in services; (iii) the classification of innovative firms in the service sector. Facing the first issue, chapter II shows how the initial width of the original Schumpeterian definition of innovation has been narrowed and then passed to the service sector form the manufacturing one in a reduce technological form. Chapter III tackle the issue of productivity in services, discussing the difficulties for measuring productivity in a context where the output is often immaterial. We reconstruct the dispute on the Baumol’s cost disease argument and propose two different ways to go forward in the research on productivity in services: redefining the output along the line of a characteristic approach; and redefining the inputs, particularly analysing which kind of input it’s worth saving. Chapter IV derives an integrated taxonomy of innovative service and manufacturing firms, using data coming from the 2008 CIS survey for Italy. This taxonomy is based on the enlarged definition of “innovative firm” deriving from the Schumpeterian definition of innovation and classify firms using a cluster analysis techniques. The result is the emergence of a four cluster solution, where firms are differentiated by the breadth of the innovation activities in which they are involved. Chapter 5 reports some of the main conclusions of each singular previous chapter and the points worth of further research in the future.

Clinicopathological and molecular characterization of gastroesophageal junction (GEJ) adenocarcinoma before age of 40 years

Gastroesophageal junction (GEJ) adenocarcinoma are uncommon before age of 40 years. While certain clinical, pathological and molecular features of GEJ adenocarcinoma in older patients have been extensively studied, these characteristics in the younger population remain to be determined. In the recent literature, a high sensitivity and specificity for the detection of dysplasia and esophageal adenocarcinoma was demonstrated by using multicolor fluorescence in situ hybridization (FISH) DNA probe set specific for the locus specific regions 9p21 (p16), 20q13.2 and Y chromosome. We evaluated 663 patients with GEJ adenocarcinoma and further divided them into 2 age-groups of and >or= 50 years, rispectively. FISH with selected DNA probe for Y chromosome, locus 9p21 (p16), and locus 20q13.2 was investigated with formalin fixed and parassin embedded tissue from surgical resections of 17 younger and 11 older patients. Signals were counted in > 100 cells with each given histopathological category. The chromosomal aberrations were then compared in the 2 age-groups with the focus on uninvolved squamous and columnar epithelium, intestinal metaplasia (Barrett's mucosa), glandular dysplasia, and adenocarcinoma. Comparisons were performed by the X2 test, Fisher's exact test, Student's t-test and Mann-Whitney U-test as appropriate. Survival was estimated by the Kaplan-Meier method with univariate analysis by the log-rank. Significance was taken at the 5% level. There was no difference in the surgical technique applied in both age groups and most patients underwent Ivor Lewis esophagectomy. Among clinical variables there was a higher incidence of smocking history in older patient group. We identified a progressive loss of Y chromosome from benign squamos epithelium to Barrett's mucosa and glandular dysplasia, and, ultimately, to a near complete loss in adenocarcinoma in both age groups. The young group revealed significantly more losses of 9p21 in both benign and neoplastic cells when compared to the older patients group. In addition, we demonstrated an increase in the percentage of cells showing gain of locus 20q13.2 with progression from benign epithelium through dysplasia to adenocarcinoma with almost the same trend in both the young and the older patients. When compared with the older age-group, younger patients with GEJ adenocarcinoma possess similar known demographics, environmental factors, clinical, and pathologic characteristics. The most commonly detected genetic aberrations of progressive Y chromosomal loss, 9p21 locus loss, and 20q13 gains were similar in the younger and older patients. However the rate of loss of 9p21 is significantly higher in young patients, in both the benign and the neoplastic cells. The loss of 9p21, and possibly, the subsequent inactivation of p16 gene may be one of the molecular mechanisms responsible for the accelerated neoplastic process in young patients.

Development of musculoskeletal models for the design and the pre-clinical validation of hip resurfacing prosthesis

Background. The surgical treatment of dysfunctional hips is a severe condition for the patient and a costly therapy for the public health. Hip resurfacing techniques seem to hold the promise of various advantages over traditional THR, with particular attention to young and active patients. Although the lesson provided in the past by many branches of engineering is that success in designing competitive products can be achieved only by predicting the possible scenario of failure, to date the understanding of the implant quality is poorly pre-clinically addressed. Thus revision is the only delayed and reliable end point for assessment. The aim of the present work was to model the musculoskeletal system so as to develop a protocol for predicting failure of hip resurfacing prosthesis. Methods. Preliminary studies validated the technique for the generation of subject specific finite element (FE) models of long bones from Computed Thomography data. The proposed protocol consisted in the numerical analysis of the prosthesis biomechanics by deterministic and statistic studies so as to assess the risk of biomechanical failure on the different operative conditions the implant might face in a population of interest during various activities of daily living. Physiological conditions were defined including the variability of the anatomy, bone densitometry, surgery uncertainties and published boundary conditions at the hip. The protocol was tested by analysing a successful design on the market and a new prototype of a resurfacing prosthesis. Results. The intrinsic accuracy of models on bone stress predictions (RMSE < 10%) was aligned to the current state of the art in this field. The accuracy of prediction on the bone-prosthesis contact mechanics was also excellent (< 0.001 mm). The sensitivity of models prediction to uncertainties on modelling parameter was found below 8.4%. The analysis of the successful design resulted in a very good agreement with published retrospective studies. The geometry optimisation of the new prototype lead to a final design with a low risk of failure. The statistical analysis confirmed the minimal risk of the optimised design over the entire population of interest. The performances of the optimised design showed a significant improvement with respect to the first prototype (+35%). Limitations. On the authors opinion the major limitation of this study is on boundary conditions. The muscular forces and the hip joint reaction were derived from the few data available in the literature, which can be considered significant but hardly representative of the entire variability of boundary conditions the implant might face over the patients population. This moved the focus of the research on modelling the musculoskeletal system; the ongoing activity is to develop subject-specific musculoskeletal models of the lower limb from medical images. Conclusions. The developed protocol was able to accurately predict known clinical outcomes when applied to a well-established device and, to support the design optimisation phase providing important information on critical characteristics of the patients when applied to a new prosthesis. The presented approach does have a relevant generality that would allow the extension of the protocol to a large set of orthopaedic scenarios with minor changes. Hence, a failure mode analysis criterion can be considered a suitable tool in developing new orthopaedic devices.

Longterm peripheral baroreflex and chemoreflex function after bilateral eversion carotid endarterectomy

Introduction The “eversion” technique for carotid endarterectomy (e-CEA), that involves the transection of the internal carotid artery at the carotid bulb and its eversion over the atherosclerotic plaque, has been associated with an increased risk of postoperative hypertension possibly due to a direct iatrogenic damage to the carotid sinus fibers. The aim of this study is to assess the long-term effect of the e-CEA on arterial baroreflex and peripheral chemoreflex function in humans. Methods A retrospective review was conducted on a prospectively compiled computerized database of 3128 CEAs performed on 2617 patients at our Center between January 2001 and March 2006. During this period, a total of 292 patients who had bilateral carotid stenosis ≥70% at the time of the first admission underwent staged bilateral CEAs. Of these, 93 patients had staged bilateral e-CEAs, 126 staged bilateral s- CEAs and 73 had different procedures on each carotid. CEAs were performed with either the eversion or the standard technique with routine Dacron patching in all cases. The study inclusion criteria were bilateral CEA with the same technique on both sides and an uneventful postoperative course after both procedures. We decided to enroll patients submitted to bilateral e-CEA to eliminate the background noise from contralateral carotid sinus fibers. Exclusion criteria were: age >70 years, diabetes mellitus, chronic pulmonary disease, symptomatic ischemic cardiac disease or medical therapy with b-blockers, cardiac arrhythmia, permanent neurologic deficits or an abnormal preoperative cerebral CT scan, carotid restenosis and previous neck or chest surgery or irradiation. Young and aged-matched healthy subjects were also recruited as controls. Patients were assessed by the 4 standard cardiovascular reflex tests, including Lying-to-standing, Orthostatic hypotension, Deep breathing, and Valsalva Maneuver. Indirect autonomic parameters were assessed with a non-invasive approach based on spectral analysis of EKG RR interval, systolic arterial pressure, and respiration variability, performed with an ad hoc software. From the analysis of these parameters the software provides the estimates of spontaneous baroreflex sensitivity (BRS). The ventilatory response to hypoxia was assessed in patients and controls by means of classic rebreathing tests. Results A total of 29 patients (16 males, age 62.4±8.0 years) were enrolled. Overall, 13 patients had undergone bilateral e-CEA (44.8%) and 16 bilateral s-CEA (55.2%) with a mean interval between the procedures of 62±56 days. No patient showed signs or symptoms of autonomic dysfunction, including labile hypertension, tachycardia, palpitations, headache, inappropriate diaphoresis, pallor or flushing. The results of standard cardiovascular autonomic tests showed no evidence of autonomic dysfunction in any of the enrolled patients. At spectral analysis, a residual baroreflex performance was shown in both patient groups, though reduced, as expected, compared to young controls. Notably, baroreflex function was better maintained in e-CEA, compared to standard CEA. (BRS at rest: young controls 19.93 ± 2.45 msec/mmHg; age-matched controls 7.75 ± 1.24; e-CEA 13.85 ± 5.14; s-CEA 4.93 ± 1.15; ANOVA P=0.001; BRS at stand: young controls 7.83 ± 0.66; age-matched controls 3.71 ± 0.35; e-CEA 7.04 ± 1.99; s-CEA 3.57 ± 1.20; ANOVA P=0.001). In all subjects ventilation (VÝ E) and oximetry data fitted a linear regression model with r values > 0.8. Oneway analysis of variance showed a significantly higher slope both for ΔVE/ΔSaO2 in controls compared with both patient groups which were not different from each other (-1.37 ± 0.33 compared with -0.33±0.08 and -0.29 ±0.13 l/min/%SaO2, p<0.05, Fig.). Similar results were observed for and ΔVE/ΔPetO2 (-0.20 ± 0.1 versus -0.01 ± 0.0 and -0.07 ± 0.02 l/min/mmHg, p<0.05). A regression model using treatment, age, baseline FiCO2 and minimum SaO2 achieved showed only treatment as a significant factor in explaining the variance in minute ventilation (R2= 25%). Conclusions Overall, we demonstrated that bilateral e-CEA does not imply a carotid sinus denervation. As a result of some expected degree of iatrogenic damage, such performance was lower than that of controls. Interestingly though, baroreflex performance appeared better maintained in e-CEA than in s-CEA. This may be related to the changes in the elastic properties of the carotid sinus vascular wall, as the patch is more rigid than the endarterectomized carotid wall that remains in the e-CEA. These data confirmed the safety of CEA irrespective of the surgical technique and have relevant clinical implication in the assessment of the frequent hemodynamic disturbances associated with carotid angioplasty stenting.

Mechanisms of cell senescence: p21 and DNA damage response in aging and longevity

Theory of aging postulates that aging is a remodeling process where the body of survivors progressively adapts to internal and external damaging agents they are exposed to during several decades. Thus , stress response and adaptation mechanisms play a fundamental role in the aging process where the capability of adaptating effects, certainly, also is related the lifespan of each individual. A key gene linking aging to stress response is indeed p21, an induction of cyclin-dependent kinase inhibitor which triggers cell growth arrest associated with senescence and damage response and notably is involved in the up-regulation of multiple genes that have been associated with senescence or implicated in age-related . This PhD thesis project that has been performed in collaboration with the Roninson Lab at Ordway Research Institute in Albany, NY had two main aims: -the testing the hypothesis that p21 polymorphisms are involved in longevity -Evaluating age-associated differences in gene expression and transcriptional response to p21 and DNA damage In the first project, trough PCR-sequencing and Sequenom strategies, we we found out that there are about 30 polymorphic variants in the p21 gene. In addition, we found an haplotpype located in -5kb region of the p21 promoter whose frequency is ~ 2 fold higher in centenarians than in the general population (Large-scale analysis of haplotype frequencies is currently in progress). Functional studies I carried out on the promoter highilighted that the ―centenarian‖ haplotype doesn’t affect the basal p21 promoter activity or its response to p53. However, there are many other possible physiological conditions in which the centenarian allele of the p21 promoter may potentially show a different response (IL6, IFN,progesterone, vitamin E, Vitamin D etc). In the second part, project #2, trough Microarrays we seeked to evaluate the differences in gene expression between centenarians, elderly, young in dermal fibroblast cultures and their response to p21 and DNA damage. Microarray analysis of gene expression in dermal fibroblast cultures of individuals of different ages yielded a tentative "centenarian signature". A subset of genes that were up- or downregulated in centenarians showed the same response to ectopic expression of p21, yielding a putative "p21-centenarian" signature. Trough RQ-PCR (as well Microarrays studies whose analysis is in progress) we tested the DNA damage response of the p21-centenarian signature genes showing a correlation stress/aging in additional sets of young and old samples treated with p21-inducing drug doxorubicin thus finding for a subset of of them , a response to stress age-related.

Continuity and Change in New Products

This doctoral dissertation is triggered by an emergent problem: how can firms reinvent themselves? Continuity- and change-oriented decisions fundamentally shape overtime the activities and potential revenues of organizations and other adaptive systems, but both types of actions draw upon limited resources and rely on different organizational routines and capabilities. Most organizations appear to have difficulties in making tradeoffs, so that it is easier to overinvest in one of them than to successfully achieve a mixture of both. Nevertheless, theory and empirical evidence suggest that too little of either may reduce performance, indicating a need to learn more about how organizations reconcile these tensions. In the first paper, I moved from the consideration that rapid changes in competitive environments increasingly require firms to be “ambidextrous” implementing organizational mechanisms and structures that allow continuity- and change-oriented activities to be engaged at the same time. More specifically, I show that continuity- and change-related decisions can’t be confined either inside or outside the firm, but span overtime across distinct decision domains located within and beyond the organizational boundaries. Reconciling static and dynamic perspectives of ambidexterity, I conceptualize a firm’s strategy as a bundle of decisions about product attributes and components of the production team, proposing a multidimensional and dynamic model of structural ambidexterity that explains why and how firms could manage conflicting pressures for continuity and change in the context of new products. In the second study I note how rigorous systematic evidence documenting the success of ambidextrous organizations is lacking, and there has been very little investigation of how firms deal with continuity and change in new products. How to manage the transition form a successful product to another? What to change and what to keep? Incumbents that deal with series of products over time need to update their offerings in order to have the most relevant attributes to prospect clients without disappoint the current customer base. They need to both match and anticipate consumers’ preferences, blending something old with something new to satisfy the current demand and enlarge the herd by appealing to newer audiences. This paper contributes to strategic renewal and ambidexterity-related research with the first empirically assessment of a positive consumer response to ambidexterity in new products. Also, this study provides a practical method to monitor overtime the degree to which a brand or a firm is continuity- or change- oriented and evaluate different strategy profiles across two decision domains that play a pivotal role in new products: product attributes and components of the production team.

Local home bias: Theory and new empirical evidence from Italy

This thesis examines the literature on local home bias, i.e. investor preference towards geographically nearby stocks, and investigates the role of firm’s visibility, profitability, and opacity in explaining such behavior. While firm’s visibility is expected to proxy for the behavioral root originating such a preference, firm’s profitability and opacity are expected to capture the informational one. I find that less visible, and more profitable and opaque firms, conditionally to the demand, benefit from being headquartered in regions characterized by a scarcity of listed firms (local supply of stocks). Specifically, research estimates suggest that firms headquartered in regions with a poor supply of stocks would be worth i) 11 percent more if non-visible, non-profitable and non-opaque; ii) 16 percent more if profitable; and iii) 28 percent more if both profitable and opaque. Overall, as these features are able to explain most, albeit not all, of the local home bias effect, I reasonably argue and then assess that most of the preference for local is determined by a successful attempt to exploit local information advantage (60 percent), while the rest is determined by a mere (irrational) feeling of familiarity with the local firm (40 percent). Several and significant methodological, theoretical, and practical implications come out.

Evaluation of the photosynthetic efficiency of sweet sorghum under drought and cold conditions

Sweet sorghum, a C4 crop of tropical origin, is gaining momentum as a multipurpose feedstock to tackle the growing environmental, food and energy security demands. Under temperate climates sweet sorghum is considered as a potential bioethanol feedstock, however, being a relatively new crop in such areas its physiological and metabolic adaptability has to be evaluated; especially to the more frequent and severe drought spells occurring throughout the growing season and to the cold temperatures during the establishment period of the crop. The objective of this thesis was to evaluate some adaptive photosynthetic traits of sweet sorghum to drought and cold stress, both under field and controlled conditions. To meet such goal, a series of experiments were carried out. A new cold-tolerant sweet sorghum genotype was sown in rhizotrons of 1 m3 in order to evaluate its tolerance to progressive drought until plant death at young and mature stages. Young plants were able to retain high photosynthetic rate for 10 days longer than mature plants. Such response was associated to the efficient PSII down-regulation capacity mediated by light energy dissipation, closure of reaction centers (JIP-test parameters), and accumulation of glucose and sucrose. On the other hand, when sweet sorghum plants went into blooming stage, neither energy dissipation nor sugar accumulation counteracted the negative effect of drought. Two hybrids with contrastable cold tolerance, selected from an early sowing field trial were subjected to chilling temperatures under controlled growth conditions to evaluate in deep their physiological and metabolic cold adaptation mechanisms. The hybrid which poorly performed under field conditions (ICSSH31), showed earlier metabolic changes (Chl a + b, xanthophyll cycle) and greater inhibition of enzymatic activity (Rubisco and PEPcase activity) than the cold tolerant hybrid (Bulldozer). Important insights on the potential adaptability of sweet sorghum to temperate climates are given.

Strategic decision making in international firms: effect of top management team internationalization on international strategic decision process

In this research project, I have integrated two research streams on international strategic decisions making in international firms: upper echelons or top management teams (TMT) internationalization research and international strategic decision making process research. Both research streams in international business literature have evolved independently, but there is a potential in combining these two streams of research. The first empirical paper “TMT internationalization and international strategic decision making process: a decision level analysis of rationality, speed, and performance” explores the influence of TMT internationalization on strategic decision rationality and speed and, subsequently, their effect on international strategic decision effectiveness (performance). The results show that the internationalization of TMT is positively related to decision effectiveness and this relationship is mediated by decision rationality while the hypotheses regarding the association between TMT internationalization and decision speed, and the mediating effect of speed were not supported. The second paper “TMT internationalization and international strategic decision rationality: the mediating role of international information” of my thesis is a simple but logical extension of first paper. The first paper showed that TMT Internationalization has a significant positive effect on international strategic decision rationality. The second paper explicitly showed that TMT internationalization affect on international strategic decision rationality comes from two sources: international experience (personal international knowledge and information) and international information collected from managerial international contacts. For this research project, I have collected data from international software firms in Pakistan. My research contributes to the literature on upper echelons theory and strategic decision making in context of international business and international firms by explicitly examining the link between TMT internationalization and characteristics of strategic decisions making process (i.e. rationality and speed) in international firms and their possible mediating effect on performance.

Effects and Modes od Action of Canopy Management Practices on Vine Physiology and Berry Composition in Organically-Cultivated cv. Sangiovese (Vitis Vinifera L.)

In organic and biodynamic vineyards, canopy management practices should be carefully and timely modulated, particularly in a context of climate change, for successfully achieving balanced plants, ventilated and exposed berries, elevated grape and wine quality. In 2013 and 2014, characterized by contrasting climatic conditions, the implications of post-veraison (late) or pea-size trimming, post-veraison or pre-harvest late defoliations and shoot-positioning (post-veraison) were assessed against long-shoots non treated controls, under field conditions on organically-cultivated cv. Sangiovese. The key agronomic and enological relevance of late trimming and defoliations clearly emerged in both seasons. Berry skin phenolics (e.g. anthocyanins, flavonols) increased markedly, without changes in technological parameters. In case of early trimming, such positive effects were observed only in 2013. Maintaining long shoots for shading decreased anthocyanins, flavonols and total phenolics concentrations and promoted the production of compact bunches. Experimental data strongly designated late trimming, a practice proved to contain yield and bunch compactness, as a valuable alternative to cluster thinning. Late trimming, defoliations and shoot positioning reduced the severity of Botrytis cluster rot. The highest levels of berry skins phenolic compounds in late trimmed and defoliated plants could have contributed control the severity of this pathogen. The enological benefits induced by late trimming and defoliations and shoot positioning emerged in both young and aged wines. For the first time, cell cultures from cv. Sangiovese berry tissues were obtained and enabled to investigate, in controlled conditions, the relations between mechanisms regulating secondary metabolism in grapevine cells and changes induced by environmental and agronomic factors. The Doctoral Dissertation strongly highlights the need to consider, for a proper interpretation of the multiple modifications induced by canopy management strategies, physiological mechanisms other than the canonic source-sink relationships, in particular their impact on the vine hormonal status.