Generation and Diffusion of Innovations in a District Innovation System: The Case of Ink-Jet Printing

[EN] This paper provides an in-depth case study of the ink-jet printing (IJP) technology that emerged from the ceramic industry in a Spanish region (Castellon) in the first decade of 2000. We propose an analytical framework that combines the theoretical perspectives of Industrial Districts and Innovation Systems, and exploit a qualitative methodology that includes information from patent and scientific article databases and 21 in-depth interviews. Our results show that IJP is a major innovation that breaks with the tradition of machinery innovations in this industry in Spain. Micro-level evidences show the complex external and internal relationships in the sharing of knowledge and innovation process, being the role of internal ties, trust, secrecy and strong in-house R&D strategies determinants of the IJP innovationThis work was supported by ITC-AICE and the Quevedo Program of the Spanish Ministry of Science and Innovation Education and Culture through Project no. PB97-0804, and by the Agencia Española de Cooperación Internacional through the Project RedINNOVAReig-Otero, Y.; Edwards Schachter, ME.; Feliú-Mingarro, C.; Fernandez De Lucio, I. (2014). Generation and Diffusion of Innovations in a District Innovation System: The Case of Ink-Jet Printing. Journal of Technology Management and Innovation. 9(2):56-76. https://doi.org/10.4067/S0718-27242014000200005S56769

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients

Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when = 50 years and symptomatic for <= 7days were included. The intervention consisted of 200-300mL of CP with a predefined minimum level of antibodies. Primary endpoints were a 5-point disease severity scale and a composite of hospitalization or death by 28 days. Amongst the 797 patients included, 390 received CP and 392 placebo; they had a median age of 58 years, 1 comorbidity, 5 days symptoms and 93% had negative IgG antibody-test. Seventy-four patients were hospitalized, 6 required mechanical ventilation and 3 died. The odds ratio (OR) of CP for improved disease severity scale was 0.936 (credible interval (CI) 0.667-1.311); OR for hospitalization or death was 0.919 (CI 0.592-1.416). CP effect on hospital admission or death was largest in patients with <= 5 days of symptoms (OR 0.658, 95%CI 0.394-1.085). CP did not decrease the time to full symptom resolution

Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial

PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer

A combination of ascorbic acid and α-tocopherol to test the effectiveness and safety in the fragile X syndrome: study protocol for a phase II, randomized, placebo-controlled trial

BACKGROUND: Fragile X syndrome (FXS) is an inherited neurodevelopmental condition characterised by behavioural, learning disabilities, phisical and neurological symptoms. In addition, an important degree of comorbidity with autism is also present. Considered a rare disorder affecting both genders, it first becomes apparent during childhood with displays of language delay and behavioural symptoms. Main aim: To show whether the combination of 10 mg/kg/day of ascorbic acid (vitamin C) and 10 mg/kg/day of α-tocopherol (vitamin E) reduces FXS symptoms among male patients ages 6 to 18 years compared to placebo treatment, as measured on the standardized rating scales at baseline, and after 12 and 24 weeks of treatment. Secondary aims: To assess the safety of the treatment. To describe behavioural and cognitive changes revealed by the Developmental Behaviour Checklist Short Form (DBC-P24) and the Wechsler Intelligence Scale for Children–Revised. To describe metabolic changes revealed by blood analysis. To measure treatment impact at home and in an academic environment. METHODS/DESIGN: A phase II randomized, double-blind pilot clinical trial. Scope: male children and adolescents diagnosed with FXS, in accordance with a standardized molecular biology test, who met all the inclusion criteria and none of the exclusion criteria. Instrumentation: clinical data, blood analysis, Wechsler Intelligence Scale for Children–Revised, Conners parent and teacher rating scale scores and the DBC-P24 results will be obtained at the baseline (t0). Follow up examinations will take place at 12 weeks (t1) and 24 weeks (t2) of treatment. DISCUSSION: A limited number of clinical trials have been carried out on children with FXS, but more are necessary as current treatment possibilities are insufficient and often provoke side effects. In the present study, we sought to overcome possible methodological problems by conducting a phase II pilot study in order to calculate the relevant statistical parameters and determine the safety of the proposed treatment. The results will provide evidence to improve hyperactivity control and reduce behavioural and learning problems using ascorbic acid (vitamin C) and α-tocopherol (vitamin E). The study protocol was approved by the Regional Government Committee for Clinical Trials in Andalusia and the Spanish agency for drugs and health products. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01329770 (29 March 2011

Lesión cribiforme en la cara de un varón de 44 años de edad

El acantoma de la vaina pilosa es un tumor benignode piel muy poco frecuente. Suele presentarse comouna pápula asintomática, con un orificio central y lalocalización más frecuente es la cara. Presentamos unnuevo caso de acantoma de vaina pilosa, apoartandoimagen dermatoscópica del tumor

Lesión cribiforme en la cara de un varón de 44 años de edad

El acantoma de la vaina pilosa es un tumor benignode piel muy poco frecuente. Suele presentarse comouna pápula asintomática, con un orificio central y lalocalización más frecuente es la cara. Presentamos unnuevo caso de acantoma de vaina pilosa, apoartandoimagen dermatoscópica del tumor

High intensity interval training improves glucose metabolism in diabetic mice despite limited mitochondrial adaptations

National audienceRecent studies have proved in patients with type 2 diabetes the positive effects of High Intensity Interval Training (HIIT) programs on hyperglycemia and muscle mitochondrial capacity. The aim of this work was to compare the effects of HIIT with a traditional Moderate Intensity Continuous Training (MICT) on glucose metabolism and mitochondrial function in diabetic mice. 25 db/db mice aged 6 weeks were subdivided into MICT group, HIIT group, or control group (CON). Animals in the training groups ran on a treadmill 5 days/week during 10 weeks. In vivo, ex vivo and post-mortem biochemical measurements were performed at the end at the end of the protocol. HIIT lowered fasting glycemia (-40% vs CON) and HbA1c (-20% vs CON), and improved response to starch and insulin tolerance tests vs CON group. No changes were noted in MICT group regarding the glucose homeostasis. 24h respiratory exchange ratio was increased in HIIT (+6% vs CON) and MICT group (+4% vs CON) after the training program but without any changes in 24h total energy expenditure. ETC protein content was increased in HIIT vs CON, whereas other mitochondrial density markers were unchanged. Western blot analysis revealed a significant increase of muscle Glut4 content and higher Akt phosphorylation ratios only in HIIT group. This study showed that HIIT may improve glucose metabolism more efficiently than traditional MICT in diabetic mice by mechanisms independent of mitochondrial adaptations. As already reported in the literature, intact leptin signaling might be necessary for exercise-induced adaptation of mitochondrial function through AMPK and Sirt1 in the muscl

High intensity interval training improves glucose metabolism in diabetic mice despite limited mitochondrial adaptations

National audienceRecent studies have proved in patients with type 2 diabetes the positive effects of High Intensity Interval Training (HIIT) programs on hyperglycemia and muscle mitochondrial capacity. The aim of this work was to compare the effects of HIIT with a traditional Moderate Intensity Continuous Training (MICT) on glucose metabolism and mitochondrial function in diabetic mice. 25 db/db mice aged 6 weeks were subdivided into MICT group, HIIT group, or control group (CON). Animals in the training groups ran on a treadmill 5 days/week during 10 weeks. In vivo, ex vivo and post-mortem biochemical measurements were performed at the end at the end of the protocol. HIIT lowered fasting glycemia (-40% vs CON) and HbA1c (-20% vs CON), and improved response to starch and insulin tolerance tests vs CON group. No changes were noted in MICT group regarding the glucose homeostasis. 24h respiratory exchange ratio was increased in HIIT (+6% vs CON) and MICT group (+4% vs CON) after the training program but without any changes in 24h total energy expenditure. ETC protein content was increased in HIIT vs CON, whereas other mitochondrial density markers were unchanged. Western blot analysis revealed a significant increase of muscle Glut4 content and higher Akt phosphorylation ratios only in HIIT group. This study showed that HIIT may improve glucose metabolism more efficiently than traditional MICT in diabetic mice by mechanisms independent of mitochondrial adaptations. As already reported in the literature, intact leptin signaling might be necessary for exercise-induced adaptation of mitochondrial function through AMPK and Sirt1 in the muscl