Exploring the Contribution of Innovation Intermediaries to the New Product Development (NPD) Process: a Typology and an Empirical Study

In the "knowledge economy" upheld by the European Lisbon strategy, knowledge-intensive services are considered a key driver for innovation and competitiveness. A category of knowledge-intensive services that has become of utmost importance in the last few decades is New Product Development (NPD) services, which interconnect distant knowledge domains with the client firms. In addition to NPD service providers, web-based innovation intermediaries have started to help innovative firms access dispersed bodies of knowledge. Despite the heterogeneity of their characteristics, however, a clear typology of the strategies used by traditional NPD service providers and web-based intermediaries to interact with their knowledge sources and with their clients is missing. This typology would be very useful for those firms that are willing to collaborate with innovation intermediaries because it could highlight the typologies of NPD problems different intermediaries are apt to address and the managerial challenges that working with them entails. Developing such a classification framework is the main goal of this paper. The typology proposed in this paper suggests that innovation intermediaries should be distinguished based on the following: (i) the way they Access their distributed knowledge sources and (ii) the way they Deliver value to their clients. By combining these two dimensions, 4 categories of innovation intermediaries are identified, which are named brokers, mediators, collectors and connectors. A multiple case study analysis involving 4 innovation intermediaries and 12 of their clients is presented in the paper. The analysis provides exploratory insights into (i) the typologies of NPD problems that each class of intermediaries addresses and (ii) the managerial challenges that working with each of them entails. These preliminary findings call for further theoretical and empirical research into the complex interaction among innovation intermediaries, their dispersed sources of knowledge and their clients

Influence of the heat treatment on the particles size and on the crystalline phase of TiO2 synthesized by the sol-gel method

Titanium biomaterials' response has been recognized to be affected by particles size, crystal structure, and surface properties. Chemical and structural properties of these nanoparticle materials are important, but their size is the key aspect. The aim of this study is the synthesis of TiO2 nanoparticles by the sol-gel method, which is an ideal technique to prepare nanomaterials at low temperature. The heat treatment can affect the structure of the final product and consequently its biological properties. For this reason, the chemical structure of the TiO2 nanoparticles synthesized was investigated after each heat treatment, in order to evaluate the presence of different phases formed among the nanoparticles. FTIR spectroscopy and XRD have been used to evaluate the different structures. The results of these analyses suggest that an increase of the calcination temperature induces the formation of mixed-crystalline-phases with different content of anatase and rutile phases. The results obtained by SEM measurements suggest that an increase in the particles size accompanied by a noticeable aggregation of TiO2 nanoparticles is due to high temperatures achieved during the thermal treatments and confirmed the presence of different content of the two crystalline phases of titanium dioxide

Tropospheric Ozone In A Mountain Forest Area: Spatial Distribution And Its Relation With Meteorology And Emission Sources

Biological injuries to forest ecosystems in two lateral valleys of Valtellina (Italy) have been studied. The selected areas are characterized by different forest novel decline symptoms and ozone concentration levels. Analyses of meteorological and air quality data collected by fixed and mobile stations located in the two valleys are presented. Ozone concentration has been measured both by passive samplers and continues analyzers and the ozone vertical gradient in one valley has been determined. In order to investigate the relation between emission sources, ambient ozone levels and plant biological injuries, a modeling research project has been started. As preliminary results the wind field obtained by the application of two diagnostic meteorological models, MINERVE and CALMET, and the computation of the biogenic emissions are presented. Some examples of spatial distribution and temporal trend of the most important pollutants emitted by plants are discussed

Laparoscopic paraesophageal hernia repair with absorbable mesh: a systematic review

Background: Laparoscopic repair is the standard of care for patients with paraesophageal hernia (PEH). Different prosthetic materials have been proposed to bolster the hiatus thus theoretically minimizing the probability for hernia recurrence. The use of non-absorbable mesh has been reported however, their safety profile has been questioned because the noteworthy mesh-related complication rate. Opposite, absorbable mesh (synthetic and biologic) seems associated with mitigated mesh-related complications and comparable hernia recurrence in the short- and medium-term. Methods: PubMed, MEDLINE, EMBASE, Scopus, Google Scholar, and ClinicalTrials.gov were executed according to the PRISMA statement until May 2022. Primary endpoints were technical details and surgical outcomes of adult patients (>= 18 years old) that underwent laparoscopic PEH repair and crural reinforcement with absorbable mesh. The ROBINS-I tool was used to assess the methodological quality of included studies. Results: Thirty-nine studies (3,103 patients) were included. The age of the patient population ranged from 18 to 93 years old and 62.8% were females. Posterior cruroplasty was performed in all patients. U-shape (83.7%), circumferential (8.1%), keyhole (5.4%) and starburst (2.8%) mesh configuration were described. Different methods for mesh fixation (sutures vs. fibrin glue vs. absorbable tacks) were adopted while Nissen (75.1%) and Toupet (21.1%) fundoplication were mainly fashioned. The overall postoperative complication rate was 2.5%. Pulmonary and cardiac complication rates were 1.8% and 0.9%, respectively while in-hospital mortality was 0.2%. Postoperative follow-up ranged from 12 to 166 months. Mesh-related complication rate was 0.06% (esophageal stricture related to fibrosis). Hernia recurrence rate was 12.7% while re-do surgery was required in 1.9% of patients. Postoperative dysphagia rate was 5.1%. Discussion: Consensus concerning the optimal mesh material for crural buttressing is lacking. Given the potential for tissue ingrowth rather than encapsulation and reduced degree of perivisceral inflammation, absorbable meshes are mostly preferred over non-absorbable meshes. The use of absorbable mesh seems safe and effective with low overall and mesh-related complications, acceptable recurrence rate and low need for re-do surgery in the short/medium-term. Because heterogeneity related to different hernia characteristics, intraoperative technical variations (i.e., method for mesh fixation, etc.), definition of hernia recurrence and diverse follow-up, a conclusive evidence is still to be defined

Usefulness of the maggic score in predicting the competing risk of non-sudden death in heart failure patients receiving an implantable cardioverter-defibrillator: A sub-analysis of the observo-icd registry

The role of prognostic risk scores in predicting the competing risk of non-sudden death in heart failure patients with reduced ejection fraction (HFrEF) receiving an implantable cardioverterdefibrillator (ICD) is unclear. To this goal, we evaluated the accuracy and usefulness of the MetaAnalysis Global Group in Chronic Heart Failure (MAGGIC) score. The present analysis included 1089 HFrEF ICD recipients enrolled in the OBSERVO-ICD registry (NCT02735811). During a median follow-up of 36 months (1st\u20133rd IQR 25\u201348 months), 193 patients (17.7%) experienced at least one appropriate ICD therapy, and 133 patients died (12.2%) without experiencing any ICD therapy. The frequency of patients receiving ICD therapies was stable around 17\u201319% across increasing tertiles of 3-year MAGGIC probability of death, whereas non-sudden mortality increased (6.4% to 9.8% to 20.8%, p < 0.0001). Accuracy of MAGGIC score was 0.60 (95% CI, 0.56\u20130.64) for the overall outcome, 0.53 (95% CI, 0.49\u20130.57) for ICD therapies and 0.65 (95% CI, 0.60\u20130.70) for non-sudden death. In patients with higher 3-year MAGGIC probability of death, the increase in the competing risk of non-sudden death during follow-up was greater than that of receiving an appropriate ICD therapy. Results were unaffected when analysis was limited to ICD shocks only. The MAGGIC risk score proved accurate and useful in predicting the competing risk of non-sudden death in HFrEF ICD recipients. Estimation of mortality risk should be taken into greater consideration at the time of ICD implantation

Human iPSC-Derived 3D Hepatic Organoids in a Miniaturized Dynamic Culture System

The process of identifying and approving a new drug is a time-consuming and expensive procedure. One of the biggest issues to overcome is the risk of hepatotoxicity, which is one of the main reasons for drug withdrawal from the market. While animal models are the gold standard in preclinical drug testing, the translation of results into therapeutic intervention is often ambiguous due to interspecies differences in hepatic metabolism. The discovery of human induced pluripotent stem cells (hiPSCs) and their derivatives has opened new possibilities for drug testing. We used mesenchymal stem cells and hepatocytes both derived from hiPSCs, together with endothelial cells, to miniaturize the process of generating hepatic organoids. These organoids were then cultivated in vitro using both static and dynamic cultures. Additionally, we tested spheroids solely composed by induced hepatocytes. By miniaturizing the system, we demonstrated the possibility of maintaining the organoids, but not the spheroids, in culture for up to 1 week. This timeframe may be sufficient to carry out a hypothetical pharmacological test or screening. In conclusion, we propose that the hiPSCderived liver organoid model could complement or, in the near future, replace the pharmacological and toxicological tests conducted on animals

Antiangiogenic activity of semisynthetic biotechnological heparins: low-molecular-weight-sulfated Escherichia coli K5 polysaccharide derivatives as fibroblast growth factor antagonists.

OBJECTIVE: Low-molecular-weight heparin (LMWH) exerts antitumor activity in clinical trials. The K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor. Chemical and enzymatic modifications of K5 polysaccharide lead to the production of biotechnological heparin-like compounds. We investigated the fibroblast growth factor-2 (FGF2) antagonist and antiangiogenic activity of a series of LMW N,O-sulfated K5 derivatives. METHODS AND RESULTS: Surface plasmon resonance analysis showed that LMW-K5 derivatives bind FGF2, thus inhibiting its interaction with heparin immobilized to a BIAcore sensor chip. Interaction of FGF2 with tyrosine-kinase receptors (FGFRs), heparan sulfate proteoglycans (HSPGs), and alpha(v)beta3 integrin is required for biological response in endothelial cells. Similar to LMWH, LMW-K5 derivatives abrogate the formation of HSPG/FGF2/FGFR ternary complexes by preventing FGF2-mediated attachment of FGFR1-overexpressing cells to HSPG-bearing cells and inhibit FGF2-mediated endothelial cell proliferation. However, LMW-K5 derivatives, but not LMWH, also inhibit FGF2/alpha(v)beta3 integrin interaction and consequent FGF2-mediated endothelial cell sprouting in vitro and angiogenesis in vivo in the chick embryo chorioallantoic membrane. CONCLUSIONS: LMW N,O-sulfated K5 derivatives affect both HSPG/FGF2/FGFR and FGF2/alpha(v)beta3 interactions and are endowed with FGF2 antagonist and antiangiogenic activity. These compounds may provide the basis for the design of novel LMW heparin-like angiostatic compounds

Alcohol-related liver disease phenotype impacts survival after an acute variceal bleeding episode

[Background & Aims] Alcohol-related hepatitis (AH) encompasses a high mortality. AH might be a concomitant event in patients with acute variceal bleeding (AVB). The current study aimed to assess the prevalence of AH in patients with AVB and to compare the clinical outcomes of AH patients to other alcohol-related liver disease (ALD) phenotypes and viral cirrhosis.[Methods] Multicentre, observational study including 916 patients with AVB falling under the next categories: AH (n = 99), ALD cirrhosis actively drinking (d-ALD) (n = 285), ALD cirrhosis abstinent from alcohol (a-ALD) (n = 227) and viral cirrhosis (n = 305). We used a Cox proportional hazards model to calculate adjusted hazard ratio (HR) of death adjusted by MELD.[Results] The prevalence of AH was 16% considering only ALD patients. AH patients exhibited more complications. Forty-two days transplant-free survival was worse among AH, but statistical differences were only observed between AH and d-ALD groups (84 vs. 93%; p = 0.005), when adjusted by MELD no differences were observed between AH and the other groups. At one-year, survival of AH patients (72.7%) was similar to the other groups; when adjusted by MELD mortality HR was better in AH compared to a-ALD (0.48; 0.29–0.8, p = 0.004). Finally, active drinkers who remained abstinent presented better survival, independently of having AH.[Conclusions] Contrary to expected, AH patients with AVB present no worse one-year survival than other patients with different alcohol-related phenotypes or viral cirrhosis. Abstinence influences long-term survival and could explain these counterintuitive results.Meritxell Ventura-Cots is a recipient of Juan Rodés grant from the Instituto de Salud Carlos III (ISCIII), Joan Genescà is a recipient of grants PI18/00947 and PI21/00691 from ISCIII.Peer reviewe

Preemptive-TIPS improves outcome in high-risk variceal bleeding : An observational study

Objective Patients admitted with acute variceal bleeding (AVB) and Child Pugh C score (CP\u2010C) or Child Pugh B plus active bleeding at endoscopy (CP\u2010B+AB) are at high risk for treatment failure, rebleeding and mortality. Preemptive TIPS (p\u2010TIPS) has been shown to improve survival in these patients but its use in clinical practice has been challenged and not routinely incorporated. The present study aimed to further validate the role of preemptive TIPS in a large number of high\u2010risk patients. Design Multicenter, international, observational study including 671 patients from 34 centers admitted for AVB and high\u2010risk of treatment failure. Patients were managed according to current guidelines and use of drugs and endoscopic therapy (D+E) or preemptive TIPS (p\u2010TIPS) was based on individual center policy. Results p\u2010TIPS in the setting of AVB is associated with a lower mortality in Child C patients compared to D+E (1 year mortality 22% vs 47% in D+E group; P=0.002). Mortality rate in CP\u2010B+AB patients was low and p\u2010TIPS did not improve it. In CP\u2010C and CP\u2010B +AB patients, p\u2010TIPS reduces treatment failure and rebleeding (1 year CIF\u2010probability of remaining free of the composite endpoint: 92% vs 74% in the D+E group; P=0.017), development of \u201cde novo\u201d or worsening of previous ascites without increasing rates of hepatic encephalopathy. Conclusion p\u2010TIPS must be the treatment of choice in CP\u2010C patients with AVB. Due to the strong benefit in preventing further bleeding and ascites, p\u2010TIPS could be a good treatment strategy for CP\u2010B+AB patients