Autologous chondrocyte implantation versus ACI using 3D-bioresorbable graft for the treatment of large full-thickness cartilage lesions of the knee

BACKGROUND: In autologous chondrocyte implantation (ACI), the periosteum patch which is sutured over the cartilage defect has been identified as a major source of complications such as periosteal hypertrophy. In the present retrospective study, we compared midterm results of first-generation ACI with a periosteal patch to second generation ACI using a biodegradable collagen fleece (BioSeed-C) in 82 patients suffering from chronic posttraumatic and degenerative cartilage lesions of the knee. METHODS: Clinical outcome was assessed in 42 patients of group 1 and in 40 patients of group 2 before implantation of the autologous chondrocytes and at a minimum follow-up of 2 years using the ICRS score, the modified Cincinnati score and the Lysholm score. RESULTS: Although patients treated with BioSeed-C had more previous surgical procedures on their respective knees, highly significant improvements (P < 0.001) were assessed in both groups at comparable outcome levels: the ICRS score improved from grade D (poor) preoperatively to grade C (fair); the modified Cincinnati knee score from 3.26 to 6.4 (group 1) and 3.3 and 6.88 (group 2). Lysholm score improved from 33 to 70 points (group 1) and from 47 to 78 points (group 2), respectively. Revision surgery was due to symptomatic periosteal hypertrophy (n = 4), graft failure (n = 3), plica syndrome (n = 2) synovectomy (n = 1) (group 1); and graft failure (n = 2), debridement (n = 1), synovectomy (n = 2) (group 2). CONCLUSION: These results suggest that BioSeed-C is an equally effective treatment option for focal degenerative chondral lesions of the knee in this challenging and complex patient profile

GRANIT project: a trap for gravitational quantum states of UCN

Previous studies of gravitationally bound states of ultracold neutrons showed the quantization of energy levels, and confirmed quantum mechanical predictions for the average size of the two lowest energy states wave functions. Improvements in position-like measurements can increase the accuracy by an order of magnitude only. We therefore develop another approach, consisting in accurate measurements of the energy levels. The GRANIT experiment is devoted to the study of resonant transitions between quantum states induced by an oscillating perturbation. According to Heisenberg's uncertainty relations, the accuracy of measurement of the energy levels is limited by the time available to perform the transitions. Thus, trapping quantum states will be necessary, and each source of losses has to be controlled in order to maximize the lifetime of the states. We discuss the general principles of transitions between quantum states, and consider the main systematical losses of neutrons in a trap.Comment: presented in ISINN 15 seminar, Dubn

Revisiting and modelling the woodland farming system of the early Neolithic Linear Pottery Culture (LBK), 5600–4900 B.C

International audienceThis article presents the conception and the conceptual results of a modelling representation of the farming systems of the Linearbandkeramik Culture (LBK). Assuming that there were permanent fields (PF) then, we suggest four ways that support the sustainability of such a farming system over time: a generalized pollarding and coppicing of trees to increase the productivity of woodland areas for foddering more livestock, which itself can then provide more manure for the fields, a generalized use of pulses grown together with cereals during the same cropping season, thereby reducing the needs for manure. Along with assumptions limiting bias on village and family organizations, the conceptual model which we propose for human environment in the LBK aims to be sustainable for long periods and can thereby overcome doubts about the PFs hypothesis for the LBK farming system. Thanks to a reconstruction of the climate of western Europe and the consequent vegetation pattern and productivity arising from it, we propose a protocol of experiments and validation procedures for both testing the PFs hypothesis and defining its eco-geographical area

Disaster Situation and Humanitarian Emergency – In-Between Responses to the Refugee Crisis in Germany

In 2015, the needs of hundreds of thousands of refugees who arrived in Germany could only be met by deploying all available civil protection units. This article presents procedures and practices of state and non-state formal actors in the field of civil protection and related crisis management structures implemented and established across the board in the municipalities, the Federal Government and mass shelters, in particular in Bavaria. From a disaster research and humanitarian studies perspective we use the concept of “patterns of interpretation” to analyse the application of the “humanitarian emergency” and the “disaster situation” procedures to discuss whether the situation can really be categorized as “either-or” or whether the coexistence of the two served a function in managing such a complex situation. Finally, we discuss some developments that occurred after 2015/16 and consider the extent to which these developments shift or expand the existing patterns of interpretation

Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2

<p>Abstract</p> <p>Background</p> <p>The autosomal recessively inherited ataxia with oculomotor apraxia 2 (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum AFP levels. AOA2 is caused by mutations within the senataxin gene (<it>SETX</it>). The majority of known mutations are nonsense, missense, and splice site mutations, as well as small deletions and insertions.</p> <p>Methods</p> <p>To detect mutations in patients showing a clinical phenotype consistent with AOA2, the coding region including splice sites of the <it>SETX </it>gene was sequenced and dosage analyses for all exons were performed on genomic DNA. The sequence of cDNA fragments of alternative transcripts isolated after RT-PCR was determined.</p> <p>Results</p> <p>Sequence analyses of the <it>SETX </it>gene in four patients revealed a heterozygous nonsense mutation or a 4 bp deletion in three cases. In another patient, PCR amplification of exon 11 to 15 dropped out. Dosage analyses and breakpoint localisation yielded a 1.3 kb LINE1 insertion in exon 12 (patient P1) and a 6.1 kb deletion between intron 11 and intron 14 (patient P2) in addition to the heterozygous nonsense mutation R1606X. Patient P3 was compound heterozygous for a 4 bp deletion in exon 10 and a 20.7 kb deletion between intron 10 and 15. This deletion was present in a homozygous state in patient P4.</p> <p>Conclusion</p> <p>Our findings indicate that gross mutations seem to be a frequent cause of AOA2 and reveal the importance of additional copy number analysis for routine diagnostics.</p

The role of c-FLIP splice variants in urothelial tumours

Deregulation of apoptosis is common in cancer and is often caused by overexpression of anti-apoptotic proteins in tumour cells. One important regulator of apoptosis is the cellular FLICE-inhibitory protein (c-FLIP), which is overexpressed, for example, in melanoma and Hodgkin's lymphoma cells. Here, we addressed the question whether deregulated c-FLIP expression in urothelial carcinoma impinges on the ability of death ligands to induce apoptosis. In particular, we investigated the role of the c-FLIP splice variants c-FLIPlong (c-FLIPL) and c-FLIPshort (c-FLIPS), which can have opposing functions. We observed diminished expression of the c-FLIPL isoform in urothelial carcinoma tissues as well as in established carcinoma cell lines compared with normal urothelial tissues and cells, whereas c-FLIPS was unchanged. Overexpression and RNA interference studies in urothelial cell lines nevertheless demonstrated that c-FLIP remained a crucial factor conferring resistance towards induction of apoptosis by death ligands CD95L and TRAIL. Isoform-specific RNA interference showed c-FLIPL to be of particular importance. Thus, urothelial carcinoma cells appear to fine-tune c-FLIP expression to a level sufficient for protection against activation of apoptosis by the extrinsic pathway. Therefore, targeting c-FLIP, and especially the c-FLIPL isoform, may facilitate apoptosis-based therapies of bladder cancer in otherwise resistant tumours

On-site data cast doubts on the hypothesis of shifting cultivation in the Late Neolithic (c. 4300-2400 cal. BC): Landscape management as an alternative paradigm

This article brings together in a comprehensive way, and for the first time, on- and off-site palaeoenvironmental data from the area of the Central European lake dwellings (a UNESCO World Cultural Heritage Site since 2011). The types of data considered are as follows: high-resolution off-site pollen cores, including micro-charcoal counts, and on-site data, including botanical macro- and micro-remains, hand-collected animal bones, remains of microfauna, and data on woodland management (dendrotypology). The period considered is the late Neolithic (c. 4300–2400 cal. BC). For this period, especially for its earlier phases, discussions of land-use patterns are contradictory. Based on off-site data, slash-and-burn – as known from tropical regions – is thought to be the only possible way to cultivate the land. On-site data however show a completely different picture: all indications point to the permanent cultivation of cereals (Triticum spp., Hordeum vulgare), pea (Pisum sativum), flax (Linum usitatissimum) and opium-poppy (Papaver somniferum). Cycles of landscape use are traceable, including coppicing and moving around the landscape with animal herds. Archaeobiological studies further indicate also that hunting and gathering were an important component and that the landscape was manipulated accordingly. Late Neolithic land-use systems also included the use of fire as a tool for opening up the landscape. Here we argue that bringing together all the types of palaeoenvironmental proxies in an integrative way allows us to draw a more comprehensive and reliable picture of the land-use systems in the late Neolithic than had been reconstructed previously largely on the basis of off-site data

Middle Neolithic farming of open-air sites in SE France: new insights from archaeobotanical investigations of three wells found at Les Bagnoles (L'Isle-sur-la-Sorgue, Dépt. Vaucluse, France)

Previous reviews of Middle Neolithic agricultural practice (4400–3500 cal bc) in southern France have highlighted a change in crop assemblages after 4000 cal bc, with a reduction of naked wheat and an increase of emmer and partly of einkorn. The recent investigation of three wells from the site of Les Bagnoles (4250–3800 cal bc) in the periphery of the southern Rhône valley yielded an unprecedented amount of waterlogged uncharred and charred plant macro remains that offer new insights into crop diversity and its changes over time. The results from the wells at Les Bagnoles were compared with other dated sunken features from open-air sites (in contrast to caves and rock shelters), with the aim of identifying patterns sug-gesting changes in the crop spectra between the early (MN1) and late (MN2) Middle Neolithic phases from taphonomically comparable contexts. The results from Les Bagnoles demonstrate that oil crops and pulses are underrepresented in dry sites and that they were a significant part of Middle Neolithic agriculture. They also indicate an increase in the representation of einkorn (instead of emmer) during MN2 that is also visible in other open-air sites. The comparison of the archaeobotani-cal results with silo storage capacity values as a proxy for average production capacity per household leads us to propose a possible drop in naked wheat productivity and opens new questions in factors affecting crop choice at the beginning of the 4th millennium cal bc

Caspase-8 activity has an essential role in CD95/Fas-mediated MAPK activation

Stimulation of CD95/Fas/APO-1 results in the induction of both apoptotic and non-apoptotic signaling pathways. The processes regulating these two opposing pathways have not been thoroughly elucidated to date. In this study, using quantitative immunoblots, imaging, and mathematical modeling, we addressed the dynamics of the DED proteins of the death-inducing signaling complex (DISC), procaspase-8, and cellular FLICE inhibitory proteins (c-FLIPs) to the onset of CD95-mediated ERK1/2 and p38 mitogen-activated protein kinase (MAPK) activation. We found that CD95 DISC-induced caspase-8 activity is important for the initiation of ERK1/2 and p38 MAPK activation. The long c-FLIP isoform, c-FLIPL, and the short c-FLIP isoform, c-FLIPR, inhibited MAPK induction by blocking caspase-8 processing at the DISC. Furthermore, we built a mathematical model describing CD95 DISC-mediated MAPK activation and apoptosis. The model quantitatively defined the dynamics of DED proteins, procaspase-8, and c-FLIP, which lead to caspase-8 activation and induction of apoptotic and non-apoptotic signaling pathways. In conclusion, the combination of biochemical analysis with mathematical modeling provides evidence for an important role of caspase-8 in CD95-mediated activation of MAPKs, while c-FLIP exerts a regulatory function in this process