Cranioplasty with Adipose-Derived Stem Cells, Beta-Tricalcium Phosphate Granules and Supporting Mesh : Six-Year Clinical Follow-Up Results

Several alternative techniques exist to reconstruct skull defects. The complication rate of the cranioplasty procedure is high and the search for optimal materials and techniques continues. To report long-term results of patients who have received a cranioplasty using autologous adipose-derived stem cells (ASCs) seeded on beta-tricalcium phosphate (betaTCP) granules. Between 10/2008 and 3/2010, five cranioplasties were performed (four females, one male; average age 62.0 years) using ASCs, betaTCP granules and titanium or resorbable meshes. The average defect size was 8.1 x 6.7 cm(2). Patients were followed both clinically and radiologically. The initial results were promising, with no serious complications. Nevertheless, in the long-term follow-up, three of the five patients were re-operated due to graft related problems. Two patients showed marked resorption of the graft, which led to revision surgery. One patient developed a late infection (7.3 years post-operative) that required revision surgery and removal of the graft. One patient had a successfully ossified graft, but was re-operated due to recurrence of the meningioma 2.2 years post-operatively. One patient had an uneventful clinical follow-up, and the cosmetic result is satisfactory, even though skull x-rays show hypodensity in the borders of the graft. Albeit no serious adverse events occurred, the 6-year follow-up results of the five cases are unsatisfactory. The clinical results are not superior to results achieved by conventional cranial repair methods. The use of stem cells in combination with betaTCP granules and supporting meshes in cranial defect reconstruction need to be studied further before continuing with clinical trials.Peer reviewe

Genome-Wide Meta-Analysis of Sciatica in Finnish Population

Sciatica or the sciatic syndrome is a common and often disabling low back disorder in the working-age population. It has a relatively high heritability but poorly understood molecular mechanisms. The Finnish population is a genetic isolate where small founder population and bottleneck events have led to enrichment of certain rare and low frequency variants. We performed here the first genome-wide association (GWAS) and meta-analysis of sciatica. The meta-analysis was conducted across two GWAS covering 291 Finnish sciatica cases and 3671 controls genotyped and imputed at 7.7 million autosomal variants. The most promising loci (pPeer reviewe

Independent monitoring and the new pandemic agreement

Negotiations are underway at the WHO for a legally binding instrument for pandemic prevention, preparedness and response. As seen in the International Health Regulations, however, countries signing up to an agreement is no guarantee of its effective implementation. We, therefore, investigated the potential design features of an accountability framework for the proposed pandemic agreement that could promote countries’ compliance with it. We reviewed the governance of a number of international institutions and conducted over 40 interviews with stakeholders and experts to investigate how the pandemic agreement could be governed.We found that enforcement mechanisms are a key feature for promoting the compliance of countries with the obligations they sign up for under international agreements but that they are inconsistently applied. It is difficult to design enforcement mechanisms that successfully avoid inflicting unintended harm and, so, we found that enforcement mechanisms generally rely on soft political levers rather than hard legal ones to promote compliance. Identifying reliable information on states’ behaviour with regard to their legal obligations requires using a diverse range of information, including civil society and intergovernmental organisations, and maintaining legal, financial, and political independence.We, therefore, propose that there should be an independent mechanism to monitor states’ compliance with and reporting on the pandemic agreement. It would mainly triangulate a diverse range of pre-existing information and have the authority to receive confidential reports and seek further information from states. It would report to a high-level political body to promote compliance with the pandemic agreement

Translocation of an arctic seashore plant reveals signs of maladaptation to altered climatic conditions

Ongoing anthropogenic climate change alters the local climatic conditions to which species may be adapted. Information on species' climatic requirements and their intraspecific variation is necessary for predicting the effects of climate change on biodiversity. We used a climatic gradient to test whether populations of two allopatric varieties of an arctic seashore herb (Primula nutans ssp.finmarchica) show adaptation to their local climates and how a future warmer climate may affect them. Our experimental set-up combined a reciprocal translocation within the distribution range of the species with an experiment testing the performance of the sampled populations in warmer climatic conditions south of their range. We monitored survival, size, and flowering over four growing seasons as measures of performance and, thus, proxies of fitness. We found that both varieties performed better in experimental gardens towards the north. Interestingly, highest up in the north, the southern variety outperformed the northern one. Supported by weather data, this suggests that the climatic optima of both varieties have moved at least partly outside their current range. Further warming would make the current environments of both varieties even less suitable. We conclude that Primula nutans ssp. finmarchica is already suffering from adaptational lag due to climate change, and that further warming may increase this maladaptation, especially for the northern variety. The study also highlights that it is not sufficient to run only reciprocal translocation experiments. Climate change is already shifting the optimum conditions for many species and adaptation needs also to be tested outside the current range of the focal taxon in order to include both historic conditions and future conditions