Quantifying knowledge exchange in R&D networks: A data-driven model

We propose a model that reflects two important processes in R&D activities of firms, the formation of R&D alliances and the exchange of knowledge as a result of these collaborations. In a data-driven approach, we analyze two large-scale data sets extracting unique information about 7500 R&D alliances and 5200 patent portfolios of firms. This data is used to calibrate the model parameters for network formation and knowledge exchange. We obtain probabilities for incumbent and newcomer firms to link to other incumbents or newcomers which are able to reproduce the topology of the empirical R&D network. The position of firms in a knowledge space is obtained from their patents using two different classification schemes, IPC in 8 dimensions and ISI-OST-INPI in 35 dimensions. Our dynamics of knowledge exchange assumes that collaborating firms approach each other in knowledge space at a rate $\mu$ for an alliance duration $\tau$. Both parameters are obtained in two different ways, by comparing knowledge distances from simulations and empirics and by analyzing the collaboration efficiency $\mathcal{\hat{C}}_{n}$. This is a new measure, that takes also in account the effort of firms to maintain concurrent alliances, and is evaluated via extensive computer simulations. We find that R&D alliances have a duration of around two years and that the subsequent knowledge exchange occurs at a very low rate. Hence, a firm's position in the knowledge space is rather a determinant than a consequence of its R&D alliances. From our data-driven approach we also find model configurations that can be both realistic and optimized with respect to the collaboration efficiency $\mathcal{\hat{C}}_{n}$. Effective policies, as suggested by our model, would incentivize shorter R&D alliances and higher knowledge exchange rates.Comment: 35 pages, 10 figure

VALIDATION OF A MODIFIED MODEL OF TNBS-INDUCED COLITIS IN RATS. HOW TO INDUCE A CHEMICAL COLITIS IN RATS.

Background: there are no standard practice in the induction of colitis by 2,4,6-trinitrobenzene sulfonic (TNBS) acid. Usually, the repeated administration of TNBS is preferred, because it will result in a local Th1 response that has the characteristics of Crohn's disease. material and Methods: A total of 30 rats were randomized into two groups, consisting of a saline control group of ten rats and a TNBS groups of 20 rats. After the animals were anesthesized, 0,5 ml of either 0,9 % saline 8controls) or TNBS 50 mg/Kg dissolved in 50% ethanol were instilled into the colon through a rubber catheter. The experiment was repeated weekly for four weeks, then, the rats were killed at day 40, and the distal colon removed. results: At day 40, the bowel wall basically normal in the control group. In the TNBS group, the bowel lumen became narrow with tickened wall, and the mucosal surface presented adherent membrane with brown black, linear ulcers, proliferous lymphocites tissue, inflammatory granulomas and submucosal neutrophil infiltration. The median score of the severity of the colonic damage was 0 in the control group, and 4,75 (range 4-5) in the TNBS group; the mean weight of the rats was 180+35 g in the TNBS group, while it was 215+25 in the control group. Conclusions: The presented experiment is a cost-effective and safe method to induce Crohn-like colonic damage using a lower dose of TNBS, thus avoiding the risk of a massive loss of rats. This model is rather suitable for the assessment of the effects of potential therapeutic agent

NUTRITION, MALNUTRITION AND DIETARY INTERVENTIONS IN INFLAMMATORY BOWEL DISEASE

Inflammatory Bowel Disease (IBD), which includes both Crohn's disease (CD) and Ulcerative Colitis (UC), is a chronic idiopathic inflammatory disorder affecting the gastrointestinal tract. Diet, as a source of luminal antigens, is thought to be an important factor in the pathogenesis of IBD. often the nutritional status of patients is significantly compromised, particularly in CD. several factors, including drug-nutrient interactions, disease location, symptoms, and dietary restriction can lead to protein energy malnutrition and specific nutritional deficiencies. solid evidence regarding the accountability of certain dietary components in the etiology of IBD are lacking. With regard to malnutrition, its consequence are growth failure, weight loss, bone disease, and/or micronutrient deficiencies, although micronutrient deficiency in IBD in most cases does not tend to have any evident clinical manifestation, except with regardo of iron, folic acid, and vitamin B. Nutritional supplemantation is essential for patients with evidence of malnutrition to increase calorie, and protein intake. Nutritional supplementation can also have efficacy in the induction and maintenance of remission in adults with CD, however it does not replace other treatments. Aim of this review is to discuss the role of nutrition and nutrients' deficiencies in the clinical setting of IBD, and to analyze efficacy and safety of the dietary interventions in patients with IBD

Recurrent retroperitoneal abscess after biliary tract surgery in an elderly patient: a minimally invasive nonsurgical approach and its consequences: a case report

Abstract Introduction Hepatic abscess can be defined as an encapsulated collection of suppurative material within the liver parenchyma. Hepatic abscess can be distinguished as pyogenic, amebic, or fungal. Biliary tract disease remains the most common cause of hepatic abscess today, and the most common complications range from pleural effusion, empyema, and bronchohepatic fistula to subphrenic abscess and rupture into the peritoneal cavity, stomach, colon, vena cava, or kidney. A large abscess compressing the inferior vena cava and the hepatic veins may result in Budd-Chiari syndrome. In this report, we present a rare case of hepatic abscess with an unusual evolution that was treated with a noninvasive approach. Case presentation A 79-year-old Caucasian woman underwent endoscopic bile stone extraction and laparoscopic cholecystectomy. Six months later, a hepatic abscess in association with bilateral effusion was diagnosed. The prompt imaging-guided drainage solved the case. Three years later, she came to our attention complaining of dull, diffuse abdominal pain and high body temperature (38 °C). A retroperitoneal abscess was diagnosed that was spreading to the right lateral wall of the abdomen and extending across the muscular wall to the subcutaneous layer. The fluid collection also involved the right pleural cavity, forming an empyema. Also in this case, an imaging-guided drainage was performed, and the patient’s clinical picture resolved in a few days. The retroperitoneal abscess recurred 14 months later, and it was dealt with using the same treatment. Three months from the last follow-up, the patient came back to our attention with an evident swelling of her right lumbar region. Computed tomography revealed a right inferior lumbar hernia comprising adipose tissue and the right kidney. A surgical intervention was recommended to the patient, but, owing to her poor general health, she refused any invasive approach. Conclusions Retroperitoneal abscess is an uncommon complication of biliary tract surgery and represents a potential cause of death, especially in those patients with multiple diseases. Prompt drainage is crucial to the treatment. Failure in eliminating the primary infective focus could bring complications and, in general, a weakness of lumbar muscular wall, even resulting in a rare case of lumbar hernia

Advanced endoscopic imaging for surveillance for dysplasia and colorectal cancer in inflammatory bowel disease: Could the pathologist be further helped?

Patients with inflammatory bowel disease (IBD) have an increased risk of developing intestinal cancer. The magnitude of that increased risk as well as how best to mitigate it remain a topic of ongoing investigation in the field. It is important to quantify the risk of colorectal cancer in association with IBD. The reported risk varies widely between studies. This is partly due to the different methodologies used in the studies. Because of the limitations of surveillance strategies based on the detection of dysplasia, advanced endoscopic imaging and techniques involving the detection of alterations in mucosal antigens and genetic abnormalities are being investigated. Development of new biomarkers, predicting future occurrence of colonic neoplasia may lead to more biomarker-based surveillance. There are promising results that may lead to more efficient surveillance in IBD patients and more general acceptance of its use. A multidisciplinary approach, involving in particular endoscopists and pathologists, together with a centralized patient management, could help to optimize treatments and follow-up measures, both of which could help to reduce the IBD-associated cancer risk

Probiotics, prebiotics and symbiotics in inflammatory bowel diseases: state-of-the-art and new insights

Inflammatory bowel disease (IBD) consists of two distinct clinical forms, ulcerative colitis (UC) and Crohn s disease (CD), with unknown aetiology, which nevertheless are considered to share almost identical pathophysiological backgrounds. Up to date, a full coherent mechanistic explanation for IBD is still lacking, but people start to realize that the pathogenesis of IBD involves four fundamental components: the environment, gut microbiota, the immune system and the genome. As a consequence, IBD development might be due to an altered immune response and a disrupted mechanism of host tolerance to the non-pathogenic resident microbiota, leading to an elevated inflammatory response. Considering the available data arising from the scientific literature, here reviewed, in CD, a benefit of probiotics remains unproven; in UC, a benefit of probiotics remains unproven, even if E. coli Nissle 1917seems promising in maintaining remission and it could be considered an alternative in patients intolerant or resistant to 5-ASA preparations; in pouchitis, small controlled trials suggest a benefit from VSL no. 3 in the primary and secondary prevention of pouchitis; in IBD-associated conditions, a benefit of probiotics remains unproven. However, well-designed randomized control clinical trials are necessary to understand the undoubted role of these agents in the management of gut physiology in health and disease

Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial

Abstract Background Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4–6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. Methods This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. Discussion The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. Trial registration ARMANI is registered at ClinicalTrials.gov (NCT02934464, October 17, 2016) and EudraCT(2016–001783-12, April 202,016)