CD34 defines an osteoprogenitor cell population in mouse bone marrow stromal cells

Bone marrow stromal cells (BMSCs, also known as bone marrow-derived mesenchymal stem cells) and their progenitors have been identified based on retrospective functional criteria. CD markers are employed to define cell populations with distinct functional characteristics. However, defining and prospective isolation of BMSCs and committed progenitors are lacking. Here, we compared the transcriptome profile of CD markers expressed at baseline and during the course of osteoblast and adipocyte differentiation of two well-characterized osteogenic-committed murine BMSCs (mBMSCBone) and adipogenic-committed mBMSCs (mBMSCAdipo), respectively. Bioinformatic analysis revealed the presence of a core set of canonical mBMSC CD markers with comparable expression levels in mBMSCBone and mBMSCAdipo at baseline and during their differentiation. We identified 11 CD markers that are differentially expressed between mBMSCAdipo and mBMSCBone. Among these, we identified osteoprogenitor-associated CD markers expressed only in mBMSCBone: CD34, CD54, CD73, CD132, CD200, CD227 and adipoprogenitor-associated CD markers expressed only in mBMSCAdipo: CD53, CD80, CD134, CD141 and CD212. FACS analysis confirmed these results. We selected CD34 for further analysis. CD34 was expressed at baseline of mouse stromal cell line ST2, primary mBMSCs, mBMSCBone and its expression decreased during osteoblast differentiation. FACS-sorted CD34+ primary mBMSCs exhibited higher expression of 70% osteoblast-associated genes, and formed significantly higher heterotopic bone in vivo when implanted subcutaneously in immune-deficient mice compared with CD34− primary mBMSCs. Our results demonstrate that a set of CD markers can distinguish osteoprogenitor versus adipoprogenitor populations of mBMSCs. CD34 is suitable for prospective isolation of mouse bone marrow osteoprogenitors

Safety and efficacy of self-administered inhaled loxapine (ADASUVE) in agitated patients outside the hospital setting : Protocol for a phase IV, single-arm, open-label trial

There is a need for fast-acting, non-injection antiagitation treatments that are well tolerated and can be used outside of healthcare facilities. In phase II/III trials, an inhaled formulation of loxapine (ADASUVE®), a well-established, first-generation antipsychotic agent, provided rapid control of mild to moderate agitation in the hospital setting. The present study was designed to investigate the safety and efficacy of inhaled loxapine when self-administered outside the hospital setting. This phase IV, multicentre, single-arm, open-label clinical trial is being conducted in five countries in Europe: Spain, Germany, Norway, Romania and Austria. The aim is to include approximately 500 patients with schizophrenia or bipolar disorder who previously received and responded well to inhaled loxapine in the hospital setting. Eligible patients will be followed up for 6 months from baseline. They will be given a 10 mg dose of inhaled loxapine to self-administer outside the hospital setting to treat an agitation episode, should one occur. Patients will also be given a short-acting beta-agonist bronchodilator for treatment of possible severe respiratory side effects. The primary endpoint is incidence of serious adverse events (AEs) and respiratory AEs of special interest related to use of inhaled loxapine outside the hospital setting. Secondary endpoints include incidence of other AEs, Clinical Global Impression-Improvement scores up to 2 hours after self-administration of inhaled loxapine, time to improvement of agitation, patient satisfaction with treatment, treatment outcomes according to agitation severity and concordance between the patient (or a family member/caregiver) and the physician in scoring of agitation severity and the decision to self-administer inhaled loxapine. The protocol received ethics committee approval in the participating countries between January and August 2016. The results of this study will be disseminated through one or more scientific papers. Trial registration number EudraCT2015-003331-36; NCT02525991; Pre-results

Optimal Fishing Mortalities with Age-Structured Bioeconomic Model - A Case of NEA Mackerel

The effects of random environmental impacts on optimal exploitation of a fish population are investigated using both optimization and simulation, based on a discrete-time age-structured bioeconomic model. The optimization problem is solved as a non-linear programming problem in GAMS. First, a basic model structure and 6 different scenarios, dealing with two interactions between fish and environment, are introduced. Based on the simplest scenario, eight different parameter combinations are tested. Then the optimization problem is solved for each of the 6 scenarios for a period of 100 years in order to gain long term insights. The main finding is that higher volatility from the environment leads to higher net profits but together with a lower probability of actually hitting the mean values. Simulations are conducted with different fixed fishing mortality levels under 6 scenarios. It seems that a constant fishing mortality around 0.06 is optimal. In the end, a comparison is made between historical and optimal harvest for a period of 40 years. It turns out that in more than 70% of the time, the optimal exploitation offered by our optimization model dominates the historical one, leading to 43% higher net profit and 34% lower fishing cost on average