The long-term fate of the hip arthrodesis: does it remain a valid procedure for selected cases in the 21st century?

Even in current orthopaedic practice, some cases are still not suitable candidates for hip replacement and hip fusion remains the only option in these highly selected patients. In this retrospective study we describe the long-term clinical outcome, quality of life and radiological evaluation of all adjacent joints in a cohort of 47 hip fusions. The main objective of our study was to show the long-term effects of a fusion. Thirty patients were analysed after an average of 18.2 years (range 6.2–30.5 years) with a mean SMFA of 31.2 (range 9–70). The VAS for pain for the fused hip was an average 1.9 (range 0–8), for the contralateral hip 2.0 (0–8), for the ipsilateral knee 2.0 (0–8), for the contralateral knee 1.8 (0–8) and for the lower back 3.6 (0–8). Average walking distance was 115 minutes (range 10–unlimited). Although the hip arthrodesis has lost popularity, it still is an option for the young patient with severe hip disorders, while leaving the possibility to perform a THA at a later stage. If the arthrodesis is performed with an optimal alignment of the leg, complaints from the adjacent joints are minimal, even in the long-term, and an acceptable quality of life can be obtained. We believe that in highly selected cases a hip fusion, even in current practice, is still a valid option

Structural basis for delta cell paracrine regulation in pancreatic islets

International audienceLittle is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions

Delegation and coordination with multiple threshold public goods: experimental evidence

When multiple charities, social programs and community projects simultaneously vie for funding, donors risk mis-coordinating their contributions leading to an inefficient distribution of funding across projects. Community chests and other intermediary organizations facilitate coordination among donors and reduce such risks. To study this, we extend a threshold public goods framework to allow donors to contribute through an intermediary rather than directly to the public goods. Through a series of experiments, we show that the presence of an intermediary increases public good success and subjects’ earnings only when the intermediary is formally committed to direct donations to socially beneficial goods. Without such a restriction, the presence of an intermediary has a negative impact, complicating the donation environment, decreasing contributions and public good success.When multiple charities, social programs and community projects simultaneously vie for funding, donors risk mis-coordinating their contributions leading to an inefficient distribution of funding across projects. Community chests and other intermediary organizations facilitate coordination among donors and reduce such risks. To study this, we extend a threshold public goods framework to allow donors to contribute through an intermediary rather than directly to the public goods. Through a series of experiments, we show that the presence of an intermediary increases public good success and subjects’ earnings only when the intermediary is formally committed to direct donations to socially beneficial goods. Without such a restriction, the presence of an intermediary has a negative impact, complicating the donation environment, decreasing contributions and public good success

Mobilization of healthy donors with plerixafor affects the cellular composition of T-cell receptor (TCR)-αβ/CD19-depleted haploidentical stem cell grafts

Background: HLA-haploidentical hematopoietic stem cell transplantation (HSCT) is suitable for patients lacking related or unrelated HLA-matched donors. Herein, we investigated whether plerixafor (MZ), as an adjunct to G-CSF, facilitated the collection of mega-doses of hematopoietic stem cells (HSC) for TCR-αβ/CD19-depleted haploidentical HSCT, and how this agent affects the cellular graft composition. Methods: Ninety healthy donors were evaluated. Single-dose MZ was given to 30 ‘poor mobilizers’ (PM) failing to attain ≥40 CD34+ HSCs/μL after 4 daily G-CSF doses and/or with predicted apheresis yields ≤12.0x106 CD34+ cells/kg recipient’s body weight. Results: MZ significantly increased CD34+ counts in PM. Naïve/memory T and B cells, as well as natural killer (NK) cells, myeloid/plasmacytoid dendritic cells (DCs), were unchanged compared with baseline. MZ did not further promote the G-CSF-induced mobilization of CD16+ monocytes and the down-regulation of IFN-γ production by T cells. HSC grafts harvested after G-CSF + MZ were enriched in myeloid and plasmacytoid DCs, but contained low numbers of pro-inflammatory 6-sulfo-LacNAc+ (Slan)-DCs. Finally, children transplanted with G-CSF + MZ-mobilized grafts received greater numbers of monocytes, myeloid and plasmacytoid DCs, but lower numbers of NK cells, NK-like T cells and Slan-DCs. Conclusions: MZ facilitates the collection of mega-doses of CD34+ HSCs for haploidentical HSCT, while affecting graft composition

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis

Gaming the future of the ocean: the marine spatial planning challenge 2050

The authors present and discuss the conceptual and technical design of the game Marine Spatial Planning (MSP) Challenge 2050, developed with and for the Netherlands’ ministry of Infrastructure and Environment. The main question in this paper is: What constitutes the socio-technical complexity of marine areas and how can it be translated into a simulation model for serious game-play with marine spatial planners? MSP Challenge 2050 was launched in March 2014 in a two day session with twenty marine planners from six countries. It aims to initiate and support MSP in the various Atlantic regions by bringing policy-makers, stakeholders, scientists together in a ‘playful’ but realistic and meaningful environment. In the North Sea edition of the game, six countries make and implement plans for this sea basin over a period of 35 years, with cumulative effects of their sectoral and national decisions emerging. The authors conclude that the combined and iterative use of complexity modelling and gaming is effective from the perspectives of design (development of a MSP model), research (insight acquired on MSP) and policy (policy-oriented learning and analysis for MSP). Further development and global dissemination of MSP Challenge 2050, as well as research and data collection, is foreseen

Free and open source software development: the end of the teenage years

This thematic series of the Journal of Internet Services and Applications (JISA) presents a collection of articles around the broad topic of the development of Free and Open Source Software (FOSS). This series illustrates the diversity of topics that are related to FOSS – we received submissions from many different areas; for example, dealing with communication and coordination within FOSS communities, licensing, adoption of Kanban in FOSS settings, and the use of an open model in the editorship of standards. Moreover, the studies presented were conducted using data collected from different sources, including software repositories, mailing lists, interviews, questionnaires and field notes, and were analysed using quantitative and qualitative methods, including case studies and action research methods