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The rapid growth of digital technologies and the extraordinary amount of data that devices and applications collect each day are increasingly driving companies to radically transform the business architecture through which they create and appropriate value. However, companies may fail to extract value from digital transformation due to the disconnection between strategy formulation and strategy implementation. Through the analysis of three case studies of firms that digitally transformed their business—namely ABB, CNH Industrial, and Vodafone—this article presents a framework than can help companies implement their digital transformation strategy and thereby renovate their business model.

The importance of DHA to support fetal development and maternal health is well established. In this study, we applied the natural abundance approach to determine the contribution of 200 mg/d of DHA supplement to the plasma DHA pool in nineteen healthy pregnant women. Women received DHA, from week 20 until delivery, from an algal source (n 13, Algae group) or from fish oil (n 6, Fish group) with slightly different content of 13C. We measured plasma phospholipids DHA 13C:12C ratio (reported as δ13C) prior to supplementation (T0), after 10 (T1) and 90 days (T2) and prior to delivery (T3). The δ13C of DHA in algae and fish supplements were −15·8 (sd 0·2) mUr and −25·3 (sd 0·2) mUr (P < 0·001). DHA δ13C in the Algae group increased from −27·7 (sd 1·6) mUr (T0) to −21·9 (sd 2·2) mUr (T3) (P < 0·001), whereas there were not significant changes in the Fish group (–27·8 (sd 0·9) mUr at T0 and −27·3 (sd 1·1) mUr at T3, P = 0·09). In the Algae group, 200 mg/d of DHA contributed to the plasma phospholipid pool by a median value of 53 % (31–75 % minimum and maximum). This estimation was not possible in the Fish group. Our results demonstrate the feasibility of assessing the contribution of DHA from an algal source to the plasma DHA pool in pregnant women by the natural abundance approach. Plasma δ13C DHA did not change when consuming DHA of fish origin, with almost the same δ13C value of that of the pre-supplementation plasma δ13C DHA.

Objectives To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). Methods We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)>10H) and the 24 months neurodevelopment. Results Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. NIRS>10H in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p>10H were found to have lower systemic oxygenation than their counterparts with rScO2 Conclusions NIRS>10H in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values.

BACKGROUND Early continuous positive airway pressure (CPAP) and surfactant replacement are effective treatments for neonatal respiratory distress syndrome (RDS). CPAP is the first line in preterm infants needing respiratory support, with surfactant replacement in case of CPAP failure (CPAP-F). OBJECTIVES To analyze incidence and factors associated with CPAP-F in preterm infants with RDS. DESIGN, SETTING AND PATIENTS Single-center retrospective database analysis (2004-2017) of inborn infants, gestational age (GA) 24 + 0/7-31 + 6/7 weeks, not intubated on admission to the neonatal intensive care unit, managed with CPAP. CPAP-F was defined as intubation and surfactant administration in the first 72 h of life; CPAP success (CPAP-S) was CPAP alone without need for additional RDS treatments. Demographic, respiratory, and clinical data associated with CPAP-F were studied using logistic regression analysis. RESULTS A total of 562 infants met the inclusion criteria: 252 (44.8%) were CPAP-F and 310 (55.2%) were CPAP-S. The CPAP-F, compared to CPAP-S group, had lower GA and birth weight, and were less likely to receive antenatal steroids or to be vaginal births. Logistic regression showed that the fraction of inspired oxygen (FiO2 ) ≥ 0.23 between 180 and 240 min of life (FiO2 180-240 min) was the strongest factor associated with CPAP-F (odds ratio: 16.01 [95% confidence interval: 10.34-24.81]). CONCLUSION FiO2 180-240 min was highly predictive of CPAP-F in preterm infants. With this model for surfactant administration/CPAP-F, 11.2% of infants would have unnecessarily received treatment, but importantly, 27.7% would have been treated much earlier, with a potential reduction in air leaks and duration of mechanical ventilation.

Background: Brain injury, impaired brain maturation, and long-term neurodevelopmental disorders are common in infants with congenital heart diseases (CHD). We aimed to assess whether plasma glial fibrillary acidic protein (GFAP) can predict neurodevelopmental anomalies in CHD infants operated on cardiopulmonary bypass (CPB). Methods: We measured plasma GFAP in 38 infants at multiple CPB phases. Cognitive, neuropsychological, and psychopathological functioning were assessed 5.7 ± 2.2 years after surgery. We identified an impaired global neurodevelopmental index (NDI) when at least two domains were abnormal. The relationships between NDI, GFAP, and clinical variables were explored with non-supervised feature selection methods and modeled with a nested non-linear logistic regression. Results: Intelligence quotient scores were within the normal range in 84% of children, whereas 58% showed an abnormal NDI, with the greatest impairments in the psychopathological area. The plasma GFAP peak was 0.95 (0.44–1.57) ng/mL, and it was correlated with age, weight, duration of surgery phases, and CPB minimum temperature. In the regression model, the GFAP peak was associated with an impaired NDI with a possible flexible point toward NDI impairment at 0.49 ng/mL, keeping constant ICU stay, CPB duration, CHD anatomy, weight, and CPB minimum temperature. Conclusion: GFAP is a promising early marker of abnormal long-term neuropsychological development.

The paper investigates the incentives of Salop-type oligopolistic firms to cooperate and the architecture of the resulting collaboration networks. We find that when spillovers are exogenous, firm profits are not affected by the network structure. On the contrary, with endogenous spillovers (absorptive capacity) firms tend to form less dense networks. We also seek out the architecture of socially efficient networks, showing that social welfare is maximised in the complete network. Also, given the network structure we conclude that a Salop industry could be characterized by a general tendency to under-connection.

Summary Background Blood urea is considered a marker of amino acid utilization in preterm infants on routine parenteral nutrition. However, the association between blood urea and intravenous amino acid intake remains debated. Aims To evaluate the association between blood urea and both nutrition and clinical data, in a large cohort of preterm infants. Methods Consecutively admitted preterm infants with a gestational age of less than 32 weeks and a birth weight lower than 1250 g on routine parenteral nutrition from the first hour of life were studied. Clinical and nutrition data collected hourly during the hospitalization were used in multiple linear regression analysis. Results We studied 674 patients and 1863 blood urea determinations. Blood urea concentration was positively associated with blood creatinine concentration, intravenous amino acid intake, patent ductus arteriosus and respiratory distress syndrome, and negatively associated with intravenous non-protein energy intakes, daily weight change, gestational age, being small for gestational age, antenatal steroids therapy and reverse flow in the umbilical artery (p Conclusions From a nutrition perspective, in our large cohort of small preterm infants blood urea was positively correlated with intravenous amino acid intake and negatively correlated with intravenous non-protein energy intake. This is in line with current knowledge in human physiology and suggest that a reduction of intravenous amino acid intake based on blood urea concentrations was justified.

Summary Background & aims Preterm infants are at increased risk of long-term neurodevelopmental disabilities (NDD). Long chain n-3 fatty acids play a key role during the development of the central nervous system and some studies in preterm infants showed benefits of docosahexaenoic acid and arachidonic acid supplementation for visual and cognitive development. In recent years fish oil has been added to the fat blend of intravenous (IV) lipid emulsions (LE) but to date scanty data are available on neurodevelopmental outcome of preterm infants that received fish oil containing LE. We studied the effect of fish oil containing IV LE vs standard IV LE on neurodevelopment in a large cohort of preterm infants who received routine parenteral nutrition (PN) from birth. Methods We retrospectively reviewed the neurodevelopmental outcome of 477 preterm infants (birth weight (BW): 400–1249 g and gestational age (GA) at birth: 24+0 - 35+6 weeks (W)) admitted to our NICU between Oct-2008 and June-2017, who received routine PN with different LE, with and without fish oil (IV-FO vs CNTR). We compared neurodevelopment at 2 years corrected age by the Bayley III development scale and the incidence of NDD. Results Demographics, birth data and the incidence of the main clinical short-term outcomes of prematurity were similar in the two groups (IV-FO: n = 178, GA 197 ± 14 days, BW 931 ± 182 g; CNTR: n = 192, GA 198 ± 15 days, BW 944 ± 194 g). No differences were found in maternal demographics nor in parental education between the two groups. Cognitive score was not significantly different between IV-FO and CNTR (92 ± 15 vs 93 ± 13, p = 0.5). No differences were found in motor and language scores, and in the incidence of NDD in the two groups. Conclusions Contrary to our hypothesis, the use of fish oil containing LE in a large cohort of preterm infants on routine PN did not result in better neurodevelopment. Large randomized controlled trials powered for neurodevelopment are needed to clarify the impact of the widely used fish oil containing LE on neurodevelopment of preterm infants.

Summary Objectives To study the association of hypertriglyceridemia and of lipid tolerance with clinical and nutritional data in preterm infants receiving routine parenteral nutrition. Design We retrospectively studied 672 preterm infants (gestational age 250 mg⋅dL−1. Lipid tolerance was defined as the ratio of plasma triglycerides to the intravenous lipid intake at the time of sampling. Variables associated to hypertriglyceridemia and to lipid tolerance were identified by multiple logistic and linear regression analyses. Results Hypertriglyceridemia occurred in 200 preterm infants (30%), ranging from 67% at 23 weeks to 16% at 31 weeks' gestation. In 138 infants (69%) hypertriglyceridemia occurred at a lipid intake of 2.5 g⋅kg−1 or less. Lipid tolerance was reduced especially in infants of less than 28 weeks’ gestation (14.3 ± 9.3 vs 18.8 ± 10.2, respectively, p Conclusion Preterm infants on routine parenteral nutrition were able to tolerate markedly lower intravenous lipid intakes than the recommended target values of current guidelines. Lipid tolerance was associated with some of the major complication of prematurity, possibly at risk of developing hypertriglyceridemia.

Variability in the efficacy, safety, and quality of probiotic formulations depends on many factors, including process conditions used by manufacturers. Developing reliable analytical tools is therefore essential to quickly monitor manufacturing differences in probiotic samples for their quality assessment. Here, multi-strain probiotics from two production sites and countries were investigated by proteomics and physico-chemistry approaches in relation to the protective effect on gut barrier. Proteomic analyses showed differences in protein abundances, identities, and origins of two series of VSL#3 samples from different sites. Even though both formulations were qualitatively similar in thermal and colloidal profiles, significant differences were quantitatively observed in terms of maximum decomposition temperature Tmax (p

High dietary intakes of phytosterols (Phyto), such as those consumed by vegans and vegetarians, are not recommended for cholesterol-lowering in pregnant women (PW) because the safety of their use during pregnancy has not been fully established [1]. Information on Phyto in pregnancy is very limited.To characterize the maternal-fetal gradient of free and esterified Phyto at the time of delivery in humans.PW who had a term delivery at the Obstetrics and Gynecology Unit of the University Hospital of Padua (Padua, Italy), between November 2016 and March 2017, participated in the study. Fatty acids (FA), cholesterol (Chol), Chol metabolites (7-dehydrocholesterol, 7-DHChol; lathosterol, Latho; 7α-hydroxycholesterol, 7α-OHChol), and Phyto (campesterol, Camp; stigmasterol, Stigma; sitosterol, Sito) were measured in both maternal (MB) and cord blood (CB) at the time of delivery. Non-pregnant adult volunteers (Ref-NA) served as a reference.Thirty-four term PW and 12 Ref-NA signed informed consent and were studied. Plasma total Phyto concentrations in CB were up to 20-fold lower than in MB (p 0.05). Positive and significant correlations were found between total Phyto of MB-CB pairs (p 0.01), and between total FA and Camp of MB (p 0.05). Interestingly, free Chol to Chol ester ratio of CB did not differ from that of MB, and free Phyto to Phyto ester ratios were higher in CB than in MB (p 0.001). No differences were found between Phyto concentrations of MB and Ref-NA. However, free Chol to Chol ester ratio, and free Phyto to Phyto ester ratios were higher in MB than in Ref-NA (p 0.05). Chol synthesis, as indicated by 7-DHChol to 7α-OHChol, Latho to 7α-OHChol, and Latho to Sito ratios, was greatest in CB and lowest in Ref-NA.Our data suggest that free Phyto cross the human placenta more easily than Phyto ester. An elevated Stigma to Chol ratio in CB than in MB was also described for the first time. The impact of these findings on the neonatal outcomes remains to be elucidated.

Variation of the isotopic abundance of selected nutrients and molecules has been used for pharmacological and kinetics studies under the premise that the administered molecule has a different isotopic enrichment from the isotopic background of the recipient subject. The aim of this study is to test the feasibility of assessing the contribution of exogenous surfactant phospholipids to the endogenous alveolar pool in vivo after exogenous surfactant replacement therapy in rabbits. The study consisted in measuring the consistency of 13 C/12 C ratio of disaturated-phosphatidylcholine palmitate (DSPC-PA) in 7 lots of poractant alfa, produced over a year, and among bronchoalveolar lavages of 20 rabbits fed with a standard chow. A pilot study was performed in a rabbit model of lavage-induced surfactant deficiency: 7 control rabbits and 4 treated with exogenous surfactant. The contribution of exogenous surfactant to the alveolar pool was assessed after intra-tracheal administration of 200 mg/kg of poractant alfa. The 13 C content of DSPC-PA was measured by isotope ratio mass spectrometry. The mean DSPC-PA 13 C/12 C ratio of the 7 lots of poractant alfa was -18.8‰ with a SD of 0.1‰ (range: -18.9‰; -18.6‰). The mean 13 C/12 C ratio of surfactant DSPC recovered from the lung lavage of 20 rabbits was -28.8 ± 1.2‰ (range: -31.7‰; -25.7‰). The contribution of exogenous surfactant to the total alveolar surfactant could be calculated in the treated rabbits, and it ranged from 83.9% to 89.6%. This pilot study describes a novel method to measure the contribution of the exogenous surfactant to the alveolar pool. This method is based on the natural variation of 13 C, and therefore it does not require the use of chemically synthetized tracers. This method could be useful in human research and especially in surfactant replacement studies in preterm infants.

The manufacturing processes of commercial probiotic strains may be affected in different ways in the attempt to optimize yield, costs, functionality, or stability, influencing gene expression, protein patterns, or metabolic output. Aim of this work is to compare different samples of a high concentration (450 billion bacteria) multispecies (8 strains) formulation produced at two different manufacturing sites, United States of America (US) and Italy (IT), by applying a combination of functional proteomics, metabolomics, and in vivo analyses. Several protein-profile differences were detected between IT- and US-made products, with Lactobacillus paracasei, Streptococcus thermophilus, and Bifidobacteria being the main affected probiotics/microorganisms. Performing proton nuclear magnetic spectroscopy (1H-NMR), some discrepancies in amino acid, lactate, betaine and sucrose concentrations were also reported between the two products. Finally, we investigated the health-promoting and antiaging effects of both products in the model organism Caenorhabditis elegans. The integration of omics platforms with in vivo analysis has emerged as a powerful tool to assess manufacturing procedures.

We develop a model to examine the link formation and the stability of networks in a Hotelling-type oligopoly. We find that with two firms, the link formation depends on the degree of vertical differentiation regardless of the degree of horizontal differentiation, while, with a greater number of firms, link formation occurs when firms feature high horizontal differentiation but low vertical differentiation.

Background Respiratory Distress Syndrome (RDS) is a prematurity-related breathing disorder caused by a quantitative deficiency of pulmonary surfactant. Surfactant replacement therapy is effective for RDS newborns, although treatment failure has been reported. The aim of this study is to trace exogenous surfactant by 13C variation and estimate the amount reaching the lungs at different doses of the drug. Methods Forty-four surfactant-depleted rabbits were obtained by serial bronchoalveolar lavages (BALs), that were merged into a pool (BAL pool) for each animal. Rabbits were in nasal continuous positive airway pressure and treated with 0, 25, 50, 100 or 200 mg/kg of poractant alfa by InSurE. After 90 min, rabbits were depleted again and a new pool (BAL end experiment) was collected. Disaturated-phosphatidylcholine (DSPC) was measured by gas chromatography. DSPC-Palmitic acid (PA) 13C/12C was analyzed by isotope ratio mass spectrometry. One-way non-parametric ANOVA and post-hoc Dunn’s multiple comparison were used to assess differences among experimental groups. Results Based on DSPC-PA 13C/12C in BAL pool and BAL end experiment, the estimated amount of exogenous surfactant ranged from 61 to 87% in dose-dependent way (p

In case of hypertriglyceridemia (HiTG) during parenteral nutrition (PN), the 2018 European Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines recommend an intravenous (IV) lipid titration, but its consequences in small preterm infants are largely unknown. We compared macronutrient and energy intakes, growth, diseases associated with prematurity, and neurodevelopment in small preterm infants on PN who developed (cases) or did not develop HiTG (controls, CNTR).We retrospectively reviewed data of preterm infants with a birth weight (BW)1250 g consecutively admitted to our neonatal intensive care unit (2004-2016) who received routine PN. HiTG infants were defined by at least 1 triglyceride (TG) measurement250 mg/dL during the first 10 days of life. Patients with and without HiTG were match-paired for BW and gestational age.A total of 658 infants were analyzed and 196 (30%) had HiTG. One hundred thirty-six HiTG patients were matched with 136 CNTR. In the first 10 days of life, IV lipid, non-protein energy and total energy intakes, but not IV amino acids and carbohydrates, were significantly lower in HiTG infants. We found no differences between groups in diseases associated with prematurity. Anthropometry at 36 weeks (W), anthropometry at 2-year (Y) corrected age (CA), and neurodevelopment at 2Y CA were not different.Growth, diseases associated with prematurity, and neurodevelopment at 2Y CA in HiTG infants were similar to CNTR. This occurred despite a statistically significant albeit small reduction in IV lipid and non-protein energy intakes due to a strict TG monitoring and IV lipid titration at TG levels250 mg/dL.

Amyloid-treated microglia prime and sustain neuroinflammatory processes in the central nervous system activating different signalling pathways inside the cells. Since a key role for PARP-1 has been demonstrated in inflammation and in neurodegeneration, we investigated PARylated proteins in resting and in β-amyloid peptide treated BV2 microglial cells. A total of 1158 proteins were identified by mass spectrometry with 117 specifically modified in the amyloid-treated cells. Intervention of PARylation on the proteome of microglia showed to be widespread in different cellular districts and to affect various cellular pathways, highlighting the role of this dynamic post-translational modification in cellular regulation. Ubiquitination is one of the more enriched pathways, encompassing PARylated proteins like NEDD4, an E3 ubiquitine ligase and USP10, a de-ubiquitinase, both associated with intracellular responses induced by β-amyloid peptide challenge. PARylation of NEDD4 may be involved in the recruiting of this protein to the plasma membrane where it regulates the endocytosis of AMPA receptors, whereas USP10 may be responsible for the increase of p53 levels in amyloid stimulated microglia. Unfolded protein response and Endoplasmic Reticulum Stress pathways, strictly correlated with the Ubiquitination process, also showed enrichment in PARylated proteins. PARylation may thus represent one of the molecular switches responsible for the transition of microglia towards the inflammatory microglia phenotype, a pivotal player in brain diseases including neurodegenerative processes. The establishment of trials with PARP inhibitors to test their efficacy in the containment of neurodegenerative diseases may be envisaged.