Towards Sustainable Fisheries Management: International Examples of Innovation

Fisheries change often carries its own financial rewards. Many reforms and changes which support conservation also result in higher profits and revenue streams for the involved businesses. This makes fisheries a potentially attractive investment arena for many commercial investors, once reform projects are properly structured and agreed upon between conservationists and the involved businesses. As commercial investors and social investors become more involved in the field of fisheries, the scale of the impacts that can be achieved is expected to expand. Foundations in the field are now looking to support this transition from fisheries conservation as a purely philanthropic investment to a blended conservation and business investment by encouraging non-profits, social change leaders and business entrepreneurs to create innovatively structured projects that can both build value for private investors and improve the speed and scale of fisheries conservation impacts. This report aims to support this transition, by providing information about and high-lighting the work of those at the forefront of innovative fisheries finance

Financing Fisheries Change: Learning from Case Studies

The fields of fisheries sustainability and conservation have evolved and grown considerably over the past decade. This evolution, its broad scope and the scale of capital needed for support will require project developers to seek the support and guidance of an array of investors, both in the non-profit and for-profit sectors. Non-profits, social change leaders and business entrepreneurs will need to work together to create innovatively structured projects that can both build value for private investors and improve the speed and scale of fisheries conservation impacts. This report presents case studies of groups who have incorporated innovative financing structures and partnerships into their strategies, and analyzes the lessons learned to offer investors and NGOs guidance for future projects. The 11 cases presented are divided into three groups depending on how conservation and financing strategies are tied together. The groups are:Assuring conservation through ownership: Using equity for asset purchase with an exit strategy.Promoting conservation through targeted lending: Filling credit gaps with debt instruments.Enabling conservation by combining services and capital: Incubating and providing information, connections and financing to promote business developmen

Dysfonctionnement systémique de la différenciation ostéoblastique des cellules souches adipeuses des patients atteints de myélome multiple

International audienceMultiple myeloma is characterized by bone lesions linked to increased osteoclast and decreased osteoblast activities. In particular, the osteoblast differentiation of bone marrow-derived stem cells (MSC) is impaired. Among the potential therapeutic tools for counteracting bone lesions, adipose-derived stem cells (ASC) could represent an appealing source for regenerative medicine due to their similar characteristics with MSC. Our study is among the first giving detailed insights into the osteoblastogenic capacities of ASC isolated by fat aspiration from myeloma patients (MM-ASC) compared to healthy subjects (HD-ASC). We showed that MM-ASC and HD-ASC exhibited comparable morphology, proliferative capacity, and immunophenotype. Unexpectedly, although normal in adipocyte differentiation, MM-ASC present a defective osteoblast differentiation, as indicated by less calcium deposition, decreased alkaline phosphatase activity, and downregulation of RUNX2 and osteocalcin. Furthermore, these ASC-derived osteoblasts displayed enhanced senescence, as shown by an increased β-galactosidase activity and cell cycle inhibitors expression (p16 INK4A , p21 WAF1/CIP1 .), associated with a markedly increased expression of DKK1, a major inhibitor of osteoblastogenesis in multiple myeloma. Interestingly, inhibition of DKK1 attenuated senescence and rescued osteoblast differentiation, highlighting its key role. Our findings show, for the first time, Cells 2019, 8, 441 2 of 16 that multiple myeloma is a systemic disease and suggest that ASC from patients would be unsuitable for tissue engineering designed to treat myeloma-associated bone disease.Le myélome multiple est caractérisé par des lésions osseuses liées à une augmentation de l'activité ostéoclastique et à une diminution de l'activité ostéoblastique. En particulier, la différenciation ostéoblastique des cellules souches issues de la moelle osseuse (CSM) est altérée. Parmi les outils thérapeutiques potentiels pour contrer les lésions osseuses, les cellules souches dérivées de l'adipeux (CSA) pourraient représenter une source intéressante pour la médecine régénérative en raison de leurs caractéristiques similaires à celles des cellules MSC. Notre étude est l'une des premières à donner un aperçu détaillé des capacités ostéoblastogènes de l'ASC isolée par aspiration graisseuse chez les patients atteints de myélome (MM-ASC) par rapport aux sujets sains (HD-ASC). Nous avons montré que le MM-ASC et le HD-ASC présentaient une morphologie, une capacité proliférative et un immunophénotype comparables. De façon inattendue, bien que normal dans la différenciation adipocytaire, le MM-ASC présente une différenciation ostéoblastique défectueuse, comme l'indiquent la diminution des dépôts de calcium, la diminution de l'activité des phosphatases alcalines et la régulation négative de RUNX2 et de l'ostéocalcine. De plus, ces ostéoblastes dérivés de l'ASC présentaient une sénescence accrue, comme en témoigne l'augmentation de l'activité de la β-galactosidase et de l'expression des inhibiteurs du cycle cellulaire (p16 INK4A, p21 WAF1/CIP1 .), associée à une expression nettement accrue du DKK1, un inhibiteur majeur de l'ostéoblastogenèse dans les myélomes multiples. Il est intéressant de noter que l'inhibition du DKK1 a atténué la sénescence et sauvé la différenciation des ostéoblastes, soulignant son rôle clé. Nos résultats montrent, pour la première fois, que le myélome multiple est une maladie systémique et suggèrent que les cellules 2019, 8, 441 2 sur 16 ne conviennent pas au génie tissulaire conçu pour traiter les maladies osseuses associées au myélome

Stem cell transplantation in multiple myeloma and other plasma cell disorders (report from an EBMT preceptorship meeting)

The European Society for Blood and Marrow Transplantation Chronic Malignancies Working Party held a preceptorship meeting in Turin, Italy on 25-26 September 2014, to discuss the role of stem cell transplantation (SCT) in the treatment of multiple myeloma and other plasma cell disorders. Scientists and clinicians working in the field gathered to discuss a variety of topics including the results of recent clinical trials, basic research, the concept of minimal residual disease, and immune modulation. As individual presentations revealed, important advances have occurred in our understanding of the pathophysiology of myeloma and the role that SCT, along with other forms of immunotherapy, plays in treating it. Each presentation stimulated discussion and exchange of ideas among the attendants. We decided to summarize and, importantly, to update the meeting proceedings in this review to share stimulating discussions and ideas on potentially novel treatment strategies among clinicians

Association between response kinetics and outcomes in relapsed/refractory multiple myeloma: analysis from TOURMALINE-MM1

© The Author(s) 2018.The association between depth of response in multiple myeloma (MM) and long-term outcomes is well recognized [1,2,3]. Thus, clinicians and patients are often encouraged by a rapid decrease of M-protein when treatment is initiated, and achieving ≥very-good partial response (VGPR) by 4 months of initial diagnosis has been associated with decreased mortality [4]. However, little is known about the association between response kinetics and outcomes. While some reports suggest that early responders may have compromised long-term outcomes compared with late responders [5, 6], these studies were limited, confined to frontline setting only, and based in the era prior to novel-agent availability.TOURMALINE-MM1 was sponsored by Millennium Pharmaceuticals Inc. Writing assistance for this manuscript was provided by Jane Saunders, FireKite (an Ashfield Company, part of UDG Healthcare PLC) and was funded by Millennium Pharmaceuticals Inc

Efficacy and Outcome of Allogeneic Transplantation in IgD and Nonsecretory Myeloma. A Report on Behalf of the Myeloma Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation

AbstractWe have recently reported on the outcome of autologous transplantation in the rare myelomas (IgD, IgE, IgM, and nonsecretory [NS]) but there is no real information on the outcome of these conditions after allogeneic transplantation. We used the European Group for Blood and Marrow Transplantation myeloma database to compare the outcomes after allogeneic transplantation of 1354 common myelomas (IgG, IgA, and light chain myeloma) with the outcome in 26 IgD myelomas and 52 NS myelomas. There was little difference between common and the IgD and NS myeloma patients with respect to prognostic factors although the IgD group had a higher beta 2 microglobulin at diagnosis, shorter time to transplantation, and more T cell depletion. IgD and NS patients had a significantly greater achievement of complete remission at conditioning but this did not translate into equivalent progression-free survival and overall survival for the IgD patients although the NS outcome was very similar to that of common myeloma. The PFS and OS of IgD, common, and NS myelomas appear similar after allogeneic transplantation, despite a tendency for higher early relapse rate in IgD myeloma. Allogeneic transplantation may, therefore, be an option to investigate in prospective observational studies

Cobalamin deficiency resulting in a rare haematological disorder: a case report

INTRODUCTION: We present the case of a patient with a cobalamin deficiency resulting in pancytopaenia, emphasizing the importance to define, diagnose and treat cobalamin deficiency. CASE PRESENTATION: A 52-year-old man from the Democratic Republic of Congo presented to the emergency department with shortness of breath and a sore tongue. Physical examination was unremarkable. His haemoglobin was low and the peripheral blood smear revealed pancytopaenia with a thrombotic microangiopathy. The findings were low cobalamin and folate levels, and high homocysteine and methylmalonate levels. Pernicious anaemia with chronic atrophic gastritis was confirmed by gastric biopsy and positive antiparietal cell and anti-intrinsic factor antibodies. Cobalamin with added folate was given. Six months later, the patient was asymptomatic. CONCLUSION: Cobalamin deficiency should always be ruled out in a patient with pancytopaenia. Our case report highlights a life-threatening cobalamin deficiency completely reversible after treatment

Melphalan 140mg/m2 or 200mg/m2 for autologous transplantation in myeloma: results from the Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study. A report by the EBMT Chronic Malignancies Working Party

Melphalan at a dose of 200mg/m2 is standard conditioning prior to autologous haematopoietic stem cell transplantation for multiple myeloma, but a dose of 140mg/m2 is often used in clinical practice in patients perceived to be at risk of excess toxicity. To determine if melphalan 200 and melphalan 140 are equally effective and tolerable in clinically relevant patient subgroups we analysed 1964 first single autologous transplantation episodes using a series of Cox proportional-hazards models. Overall survival, progression-free survival, cumulative incidence of relapse, non-relapse mortality, haematopoietic recovery and second primary malignancy rates were not significantly different between the melphalan 140 (n=245) and melphalan 200 (n=1719) groups. Multivariable subgroup analysis showed that disease status at transplantation interacted with overall survival, progression-free survival, and cumulative incidence of relapse, with a significant advantage associated with melphalan 200 in patients transplanted in less than partial response (adjusted hazard ratios for melphalan 200 versus melphalan 140: 0.5, 0.54, and 0.56). In contrast, transplantation in very good partial or complete response significantly favoured melphalan 140 for overall survival (adjusted hazard ratio: 2.02). Age, renal function, prior proteasome inhibitor treatment, gender, or Karnofsky score did not interact with overall/progression-free survival or relapse rate in the melphalan dose groups. There were no significant survival or relapse rate differences between melphalan 200 and melphalan 140 patients with high-risk or standard-risk chromosomal abnormalities. In conclusion, remission status at the time of transplantation may favour melphalan 200 or melphalan 140 for key transplant outcomes (NCT01362972)