A comparative analysis of Alexandrium catenella/tamarense blooms in Annaba Bay (Algeria) and Thau lagoon (France); phosphorus limitation as a trigger.

Environmental conditions ultimately leading to blooms of the toxic dinoflagellate Alexandrium catenella/tamarense were investigated at two Mediterranean sites (Annaba Bay, Algeria and Thau lagoon, France). Three years were examined in details: 1992 (a pre-Alexandrium period), 2002 (a year with the first bloom in Annaba) and 2010 (a year with a major bloom in Annaba). Most conditions were similar, but ammonium concentrations were much higher in Annaba (up to 100µM) than in Thau (up to 10µM). First records of A. catenella/tamarense were in 1995 for Thau and 2002 for Annaba, and coincided with soluble reactive phosphorus (SRP) decreasing below a concentration of about 1µM. No other environmental variable could be related to those blooms. Thus, it is likely that the large reductions in SRP at both sites led to phosphorus limitation of a certain number of phytoplankton species and favored the development of A. catenella/tamarense.

Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis.

Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care.