3D-printed calcium phosphate scaffolds for bone regeneration: impact of geometry and treatment an in vivo study

The combination of the direct ink writing (DIW) manufacturing technique, also named robocasting, with the use of self-setting calcium phosphate inks based on α-tricalcium phosphate opens new possibilities in the field of bone regeneration: i) On one hand, the DIW fabrication process allows a precise control on the external shape and internal porosity of the scaffold. The porosity allows the colonization of the bone tissue and the shape control opens new perspectives in personalised medicine; ii) On the other hand, the use of self-setting α-TCP inks provide a micro/nano porosity and a high specific surface area (SSA) to the bone graft. Both factors have been identified as crucial for the bioactivity of the material. Since the fabrication time is a crucial factor for the successful translation of these technologies to the clinical field, and the hardening reaction of conventional self-setting inks is slow, recent investigations have developedan alternative setting procedure (hydrothermal) that considerably reduces the hardening step from 7 days to 30 minutes. Regarding the role of scaffold architecture in bone regeneration, it has been recently proved that the presence of concave surfaces enhances osteogenesis. However, since DIW is based on the extrusion of a paste through a needle, conventional DIW scaffolds are composed of extruded filaments with convex surfaces. Hence the interest in developing scaffolds with non-cylindrical strands, which have concave surfaces. The aim of this study was to assess the in-vivo performance of calcium phosphate scaffolds, analysing on one side the effect of the setting treatment, i.e., comparing the biomimetic setting with the hydrothermal setting treatment, and on the other side comparing cylindrical vs.non-cylindrical strands. The characterization of the scaffolds obtained with the two different treatments revealed that whereas the biomimetic treatment resulted in calcium deficient hydroxiapatatite (CDHA), the hydrothermal treatment led to the presence of small amounts of β-tricalcium phosphate. Biomimetic scaffolds consisted of plate-like crystals, with higher SSA and smaller microporosity than the hydrothermal scaffolds, made of needle-like crystals. The geometry of the strands(i.e. cylindrical vs non-cylindrical)did not havean influence on the material composition, microstructure and global porosity, but they did have an impact on the mechanical properties,with lower ultimate compressive strength for the structures with non-cylindrical strands. The scaffolds were implanted in the femoral condyles of 10 adult female New Zeeland rabbits and explanted after 8 weeks. The samples were embedded in resin and characterised by micro-computed tomography, scanning electron microscopy and optical microscopy afterGolden-Mason trichrome staining. All the samples presented the formation of new mature lamellar bone and a successful osteointegration. No statistically significant differences were observed between the samples studied in terms of the amount of newly formed bone, quantified from the SEM observation.Micro-CT allowed the assessment of bone formation in 3D, although difficulties related to image processing prevented the volumetric quantification that might have revealed significant differences. However, a clear tendency was found for new bone formation in constrained microenvironments, such as the contact zone between two strands or the concavities present in the non-cylindrical condition. Further data analysis will have to be carried out to assess the differences in the different sample conditions.Incomin

Inverse box-counting method: A fractal-based procedure to create biospheric landscape patterns

1st WSEAS International Conference on Landscape Architecture (LA 2008), Univ Algarve, Algarve, PORTUGAL, JUN 11-13, 2008International audiencePlanners and designers are interested in replicating biospheric landscape patterns to reclaim surface mines to match existing natural landscape patterns. One approach that shows promise is the use of fractal geometry to generate biospheric landscape patterns. While the measurement of the actual fractal dimension of a landscape can be difficult, a box-counting method was developed at INHP, Angers, France which approximates the spatial patterns of biospheric landscapes. Essentially the procedure entails covering a natural object/pattern with a regular grid of size r and then one simply counts the number of grid boxes, N(r), that contain some part of the object. The boxes are subdivided and the value of r is progressively reduced and N(r) is similarly re-measured until some of the boxes become empty (containing no landscape objects of interest). Then the fractal dimension of the object is approximated to be the log(N(r))/Iog(l/r). We illustrate this procedure by measuring and replicating a stand of trees in the Upper Peninsula of Michigan. Our study revealed a fractal number of 1.0 17 (p < 0.01), with a mean of 77.4 trees per 100 in by 100 in stand, and a standard deviation of 34.87 trees per stand

Hydrothermal processing of 3D-printed calcium phosphate scaffolds enhances bone formation in vivo: a comparison with biomimetic treatment

Hydrothermal (H) processes accelerate the hydrolysis reaction of a-tricalcium phosphate (a-TCP) compared to the long-established biomimetic (B) treatments. They are of special interest for patient-specific 3D-printed bone graft substitutes, where the manufacturing time represents a critical constraint. Altering the reaction conditions has implications for the physicochemical properties of the reaction product. However, the impact of the changes produced by the hydrothermal reaction on the in vivo performance was hitherto unknown. The present study compares the bone regeneration potential of 3D-printed a-TCP scaffolds hardened using these two treatments in rabbit condyle monocortical defects. Although both consolidation processes resulted in biocompatible scaffolds with osseointegrative and osteoconductive properties, the amount of newly formed bone increased by one third in the hydrothermal vs the biomimetic samples. B and H scaffolds consisted mostly of high specific surface area calcium-deficient hydroxyapatite (38 and 27 m2 g-1, respectively), with H samples containing also 10 wt.% ß-tricalcium phosphate (ß-TCP). The shrinkage produced during the consolidation process was shown to be very small in both cases, below 3%, and smaller for H than for B samples. The differences in the in vivo performance were mainly attributed to the distinct crystallisation nanostructures, which proved to have a major impact on permeability and protein adsorption capacity, using BSA as a model protein, with B samples being highly impermeable. Given the crucial role that soluble proteins play in osteogenesis, this is proposed to be a relevant factor behind the distinct in vivo performances observed for the two materials. Statement of significance The possibility to accelerate the consolidation of self-setting calcium phosphate inks through hydrothermal treatments has aroused great interest due to the associated advantages for the development of 3D-printed personalised bone scaffolds. Understanding the implications of this approach on the in vivo performance of the scaffolds is of paramount importance. This study compares, for the first time, this treatment to the long-established biomimetic setting strategy in terms of osteogenic potential in vivo in a rabbit model, and relates the results obtained to the physicochemical properties of the 3D-printed scaffolds (composition, crystallinity, nanostructure, nanoporosity) and their interaction with soluble proteins.Peer ReviewedPostprint (published version

Current Trends in the Russian Financial System

The papers in the present SUERF Study is a selection of the papers presented at a SUERF Workshop and Special OeNB East Jour Fixe held at Oesterreichische Nationalbank in Vienna on 23 January 2009. In his opening remarks (chapter 2), Ewald Nowotny, Governor of the Oesterreichische Nationalbank referred to Austrian banks? engagement with neighbouring Central and Eastern European Countries. The current crisis should not make people forget the fact that Austrian banks? deep engagement with the neighbouring countries is one of the success stories in Austrian economic history. Since the fall of the Berlin Wall, Austrian banks have become one of the driving forces of the process of structural adjustment, modernization of business practices, and deepening of financial intermediation in the region. At end 2007, in Central Europe, the share of Austrian banks surpassed a fifth of aggregate sector assets, in Southeastern Europe even a third of the respective total. A considerable share of the earnings of Austrian banks comes from banking activities in Central and Eastern Europe. Austrian bankers can claim to be among the pioneer foreign investors in Russia, Ukraine, Kazakstan and Belarus. The international financial crisis has from September 2008 demonstrated Russia?s structural vulnerability. The comprehensive countermeasures by the Russian authorities to assist the banking sector and the economy are characterized by the Governor as worthy endeavours. Chapter 3 is based on the keynote speech by Pekka Sutela, BOFIT, Bank of Finland ?Russian Finance: Drag or Booster for Future Growth?? The author praises the Russian authorities for having made prudent decisions in recent years. The Putin-Kudrin regime chose a stability-oriented macro policy. The very strong increase in the global oil price up to 2008 implied a strong growth in the value of Russian exports and lead to an impressive GDP growth. The author uses the term ?windfall?. The Russian Government decided to pay back practically all foreign debt, much of it ahead of schedule. The regime wanted to bring back what they see as Russian sovereignty and in particular to avoid being dependent on IMF or other foreign financiers. Their policy contributed strongly to an improvement of Russia?s general credit-worthiness and to a growth in foreign reserves. During the 1990s, lack of trust in the rouble had as consequence that the US dollar was applied to a considerable extent in payments between Russians. The stability oriented policy after 2001 contributed to a de-dollarization of the economy up to 2008. It follows from the stability-oriented policy that Russia was relatively well prepared when it was hit by the global financial crisis in 2007?2008. In the autumn of 2008, however, the general public started to withdraw bank deposits and the relative share of foreign exchange deposits increased again. The public shifted towards foreign currency cash assets. The author explains that Russia has a dual economy. The natural resource based sectors are clearly globally competitive but the sectors outside the resource sectors are not. The big resource based companies have relied on foreign markets for their financial needs. The home market is primarily serviced by domestic banks. At the end of September 2008, government-controlled banks had 47.8% of all bank assets. The state maintains banking sector stability primarily through state banks. The author?s answer to the question in the headline is: ?The Russian financial system is rather a drag than a booster for future growth?. In addition, it is unlikely that Russia will become a regional financial centre or an inventionbased society in the foreseeable future. Chapter 4 by Stephan Barisitz, Oesterreichische Nationalbank, is ?Russian Banking in Recent Years: Gaining Depth in a Fragile Environment.? The author shows tables with macroeconomic, monetary and financial indicators for Russia for the years 2002?2008. Key observations are: Strong economic growth, strong dependence on oil prices, inflation problems, recent volatility of private capital in- and outflows. Banking development initially featured rather slow recovery from the financial crisis of 1998, coupled with sluggish reforms. This was followed by a stepped-up pace of institutional and structural adjustments in 2003?2005, which brought about major improvements of banking activities and of the regulatory framework. The return on equity (ROE) of banks was in 2006?2007 above 20%. The solvency ratio of banks declined steadily up to 2008 due to strong growth in bank assets. The oil price driven improvements in Russia?s terms of trade over the period 1998 to 2008 combined with political stability, prudent macroeconomic policies and some successful institutional and structural reforms have supported Russian economic expansion. Not only exports, but also consumption, have driven strong GDP growth. Financial intermediation continued to deepen swiftly in Russia up to the fall of 2008, despite important repercussions of the US subprime crisis. As the interbank market tightened during 2008 and capital outflows increased, Central Bank of Russia reacted quickly with repeated liquidity interventions. Following the continuous oil price decline and pressures on the rouble, Central Bank of Russia intervened extensively in the foreign exchange market and draw down foreign exchange reserves. The controlled depreciation strategy initiated in November 20078 has not stopped the decline in foreign exchange reserves. Due to the still sizable foreign reserves, the relatively high profitability of banking activity and the satisfactory capital adequacy level as shock absorbing factors, Russia seems to be in a better position to handle the financial crisis than many other countries. Chapter 5 by Alexander Lehmann, European Bank for Reconstruction and Development has the headline ?Banks and Financial Reform: Their Role in Sustaining Russia?s Growth.? The paper focuses on the strength of the link between economic growth and financial development. Even in East European transition countries where a positive correlation between finance and growth developed in the 1990s, there was little microeconomic evidence that the financial sector actively supported growth. Investments were overwhelmingly financed through retained earnings, and what little external finance was raised came from foreign direct investment. Around year 2000, this changed. Regulatory improvements, better enforcement and rapid development of individual institutions meant that the financial sector undoubtedly has supported economic growth since year 2000. The disruption to credit growth since 2008 and the simultaneous downturn of the Russian real economy has made the link abundantly clear. EBRD evaluates the progress in structural reforms in transition countries by means of ?transition scores?. The author shows an exhibit which illustrates the development of the EBRD transition score for Russia from 1989 to 2006. It shows that the fastest progress took place from 1995 to 2003. The improvements in the regulatory framework for banking activity supported financial intermediation and Russian banks expanded their balance sheets and diversified into lending to retail customers and SMEs. For corporate investment as a whole, however, the share of new investment financed through bank credit remained relatively small. The sectors that saw sharp increases in investment and accounted for the bulk of capital spending, predominantly benefited from internal cash flows, or benefited from public support or ownership. Chapter 6 by Cyril Pineau-Valencienne, CEO, CPV Conseil, is ?Russian financial institutions and the oil and gas sector: funding and recycling.? The paper first outlines the importance of the oil and gas sector for the Russian economy. Capital expenditures in the sector grew strongly from 1999 to 2007. The huge investments were to a large extent financed by internal operating cash flows and by borrowing in international financial markets. The big oil and gas companies are important customers for foreign banks. The companies also have their own so-called raw material banks but these banks have not played a major role as related parties in the financing of the investments of these groups. The willingness of the oil and gas companies to incur debt denominated in foreign currency must be understood in the light of their revenue structure. Contracts in the global energy markets are primarily denominated in US-dollars and the companies are therefore to a considerable extent able to match currency revenues from exports with currency payments of principal and interest. Recycling of funds related to the oil and gas sector has partly been carried out by the state and by the sovereign funds controlled by the state. Revenue from export duties has been accumulated in the funds and applied in accordance with the funds? investment strategies. Chapter 7 is based on the presentation by Zuzana Fungácová, BOFIT, Bank of Finland ?Risk-taking by Russian banks: do location, ownership and size matter?? The paper is co-authored by Laura Solanko. The rapid growth of the assets of Russian banks has in the last 6?7 years contributed to a decrease in the capital adequacy ratio, thus influencing the ability of banks to cope with risk. In the paper, the authors investigate the relationship between bank characteristics and risk-taking. The banks are divided into different subgroups by size, ownership and location. The authors distinguish between state-controlled, foreign-controlled and domestic private banks. Risk is measured in two different ways: By group-wise comparisons of financial risk ratios i.e. accounting data, and by regression analysis of bank insolvency risk as measured by a Z-score indicator. The average level of financial ratios are all well above the regulatory minima set by Central Bank of Russia. Large banks in Russia have higher insolvency risk than small ones. Foreign-owned banks exhibit higher insolvency risk than domestic banks. State-controlled banks are on average more stable than the private domestic banks. Similar to the case of foreign banks, large state-controlled banks are more stable than the others. Regional banks are significantly more prone to risk-taking than their counterparts in Moscow. Chapter 8 is based on the keynote speech ?Russia?s Financial Crisis: Causes, Consequences, and Prospects? by Zeljko Bogetic, World Bank, Moscow. Until mid-2008, Russia was viewed as a ?safe haven? during turbulent times in global financial markets. Record high oil prices, strong macroeconomic fundamentals, lack of exposure of Russian banks to the US sub-prime mortgage markets, strong ratings and a strong appreciating currency explained the confidence in Russia. After mid-2008 Russia was hit. There was an oil price shock, a sudden stop in capital flows, and a sharp tightening of external borrowing conditions. The paper contains a diagram that documents an almost perfect correlation of the Russian stock index RTS with the price of oil. From the peaks in May-June 2008 to the end of the year, the RTS moved from 2400 to 440 and the oil price from USD 144 per barrel to USD 45 per barrel. The non-oil external current account deficit continued to deteriorate very fast in 2008 as import volumes grew faster than non-oil exports. Incoming FDIs declined and worsened the composition of capital flows towards borrowing. While public external debt remained moderate, private (corporate and bank) debt grew rapidly. In the balance sheets of Russian banks, the loan-deposit ratio increased from approximately 107% in 2005 to 127% in the autumn of 2008, making the banking sector more exposed to the interbank market and to rollover risk. As response to the crisis, the Russian authorities have loosened their monetary stance and provided fiscal support to ease the liquidity crisis. The exchange rate has continuously been managed with progressive widening of the bi-currency corridor. After a gradual depreciation since November 2008, the rouble was devalued in mid January 2009. The speaker described the 2009 outlook for the Russian economy as very uncertain. It is likely that the twin surpluses on the Government budget and the balance of payments current account will disappear, but thanks to the prudent macroeconomic policies in recent years, these deficits can be financed for some time. The speaker reflected on the social impact of the crisis. If the recession in 2009 becomes deeper, it might require an introduction of a fiscal stimulus package focusing on domestic demand and the poorer segments of the population, including strengthening of the unemployment, training and social assistance and possibly well designed public works. Chapter 9 is based on the presentation by Peter Havlik, The Vienna Institute for International Economic Studies (WIIW) ?Russian Economy and the Global Turmoil.? The paper contains very illustrative exhibits that show the development of Russian GDP, exports, imports, inflation, money supply, stock prices and nominal and real exchange rates. Among the Putin administration?s key achievements, he lists improved living standards, rising employment, more FDI inflows, repayment of external debt, ballooning foreign exchange reserves, restoring stability, stronger role of the state but also deteriorating external relations. Despite strong economic fundamentals, Russia has been seriously hit by the global crisis. The Medvedev administration faces serious challenges. It plans to use industrial policy instruments in order to reduce the dependence on energy proceeds. The Government offers targeted support to various public-private partnership projects in the automotive, aviation, shipbuilding and selected high-tech industries. According to the speaker, some of the envisaged industrial policy tools could well be in conflict with WTO rules and make Russia?s WTO accession more difficult. Chapter 10 is based on the workshop contribution by Debora Revoltella, UniCredit Group ?The Russian Banking Sector: What to Expect? The paper is co-authored by Vladimir V.Osakovsky and Valery Invushin. It is divided in three sections: 1) The past: Russian economic renaissance, 2) The crisis: Politics and Economics join forces, and 3) Longer term prospects are brighter. Up to 2008, Russia enjoyed strong growth in domestic investment, consumption and GDP. Prudent fiscal policy and massive capital inflows helped to amass the world?s third largest international reserves. The country was, however, exposed to global commodities prices, a demographic crisis, a rigid labour market and an increasing dependence on foreign sources of funding. The crisis in 2008 was triggered by collapse of global commodities prices, massive capital flight, failures of some large market participants and general loss of confidence abroad and at home. As reaction to the challenges posed by the crisis, the Government and Central bank of Russia initiated corporate debt refinancing assistance, liquidity infusion into the banking system and fiscal stimuli. The authors expect a major restructuring of the Russian banking sector including a considerable reduction of the number of financial institutions

3D printing with star-shaped strands: a new approach to enhance in vivo bone regeneration

Concave surfaces have shown to promote bone regeneration in vivo. However, bone scaffolds obtained by direct ink writing, one of the most promising approaches for the fabrication of personalized bone grafts, consist mostly of convex surfaces, since they are obtained by microextrusion of cylindrical strands. By modifying the geometry of the nozzle, it is possible to print 3D structures composed of non-cylindrical strands and favor the presence of concave surfaces. In this work, we compare the in vivo performance of 3D-printed calcium phosphate scaffolds with either conventional cylindrical strands or star-shaped strands, in a rabbit femoral condyle model. Monocortical defects, drilled in contralateral positions, are randomly grafted with the two scaffold configurations, with identical composition. The samples are explanted eight weeks post-surgery and assessed by µ-CT and resin-embedded histological observations. The results reveal that the scaffolds containing star-shaped strands have better osteoconductive properties, guiding the newly formed bone faster towards the core of the scaffolds, and enhance bone regeneration, although the increase is not statistically significant (p > 0.05). This new approach represents a turning point towards the optimization of pore shape in 3D-printed bone grafts, further boosting the possibilities that direct ink writing technology offers for patient-specific applications.Peer ReviewedPostprint (published version

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts