Paths to Innovation in Supply Chains: The Landscape of Future Research

This chapter presents a Strategic Research and Innovation Agenda for supply chain and it is the result of an intensive work jointly performed involving a wide network of stakeholders from discrete manufacturing, process industry and logistics sector to put forward a vision to strengthen European Supply Chains for the next decade. The work is based on matching visions from literature and from experts with several iterations between desk research and workshops, focus groups and interviews. The result is a detailed analysis of the supply chain strategies identified as most relevant for the next years and definition of the related research and innovation topics as future developments and steps for the full implementation of the strategies, thus proposing innovative and cutting-edge actions to be implemented based on technological development and organisational change

Spirodela intermedia W. Koch

Concepción del UruguayLorentz, P. G.Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto Multidisciplinario de Biología Vegetal; Argentin

Adénopathies et fièvre chez une patiente VIH positive [Immunocompromised HIV patient with lymphadenopathy and fever].

The case of a immunocompromised HIV patient with fever and lymphadenopathy discussed in an anatomo-pathological round. This complex clinical case was used as an opportunity to discuss the broad differential diagnosis of fever in an immunocompromized individual with multiples lymphadenopathies. Clinical reasoning leading to the probable diagnosis based on clinical, biological and radiological informations is not only a difficult task for the speaker but also a rich source of learning opportunities for our medical community

Hypertension pulmonaire d'origine indéterminée chez un homme de 56 ans.. [Pulmonary hypertension of undertermined origine in a man aged 56...]

The case of a patient with severe pulmonary hypertension whose etiology has remained unknown until an autopsy was performed is discussed in a symposium of pathological anatomy. This case helped to address the diagnostic and therapeutic management of pulmonary hypertension. The broad differential diagnosis of this disease requires a diagnostic strategy to be developped. Clinical reasoning leading to a probable diagnosis based on clinical biological and radiological information is not only a difficult task for the speaker but also a rich source of learning opportunities for our medical community

A phase I trial of E7974 administered on days 1 and 15 of a 28-day cycle in patients with solid malignancies

2550 Background: E7974 is a synthetic hemiasterlin analogue exhibiting binding to a and β tubulin. It induces disruption of spindle formation and mitotic arrest characteristic of anti-tubulin cancer drugs. Unlike taxanes and vincas, E7974 is a poor substrate for the PgP drug efflux pump, potentially overcoming this common mechanism of drug resistance. E7974 demonstrates broad anti-tumor activity against a variety of human tumor xenografts. Methods: An accelerated phase I dose escalation design was used to determine the maximum tolerated dose (MTD) and pharmacokinetic (PK) profile of E7974 administered IV over 2–5 minutes on Days 1 and 15 of a 28-day cycle. Results: Seventeen patients (14 male, 3 female) with a median age of 59 yrs. (range: 42–77 yrs.) were treated at doses of 0.18 mg/m2, 0.25 mg/m2, 0.31 mg/m2, and 0.39 mg/m2. Patients with colorectal (6), esophageal (3), prostate (2), urothelial (2), NSCLC (2), and other (2) cancers were enrolled. At the 0.39 mg/m2 dose level, one patient experienced grade 3 neutropenia and 2 patients experienced grade 4 neutropenia. The 0.31 mg/m2 dose was declared the MTD. Additional drug related toxicities (grade 1–2) included fatigue (8 pts.), constipation (4 pts), neuropathy (3 pts.), diarrhea (2 pts.), flushing (2 pts.) and myalgia (1 pt.). One patient with esophageal cancer had a partial response at the 0.39 mg/m2 dose level and one patient with prostate cancer had &gt;50% decline in PSA and significant clinical benefit for &gt;4 months at the 0.31 mg/m2 dose level. Stable disease was seen in two patients, one with esophageal cancer (8 cycles) and one with colorectal cancer (4 cycles). The PK profile of E7974 was characterized by moderate to large distribution (Vss = 55 - 187 L), slow clearance (CL = 1.99 - 8.77 L/hr) and moderate to slow elimination (t1/2 = 11.9 - 31.6 hr). Approximately 26 - 85% of the administered dose of E7974 was recovered unchanged in the urine 48 hours post-dose. Conclusions: The recommended phase 2 dose of E7974 on days 1 and 15 of a 28-day schedule is 0.31mg/m2. Observed toxicities were manageable and reversible. No significant financial relationships to disclose. </jats:p