45% Deforestation is higher in villages in the north and southea

45%. Deforestation is higher in villages in the north and southeast of Sa Pa district, that are located at greater distance from the tourism centre. Land abandonment

is mostly observed in Sa Pa town and in the communes of Ta Phin, San Sa Ho, Lao Chai, Ta Van and Ban Ho (Fig. 1 and Fig. 3). In some villages (Sa Pa town; Ta Chai village, belonging to Ta Phin commune; Ly Lao Chai village, belonging to Lao Chai commune and Hoang Lien village, belonging to Ban Ho commune), more than 8% of the surface area was abandoned between 1993 and 2014. Over the period 1995–2009, the number of tourists in Sa Pa district has increased by 25 times (Fig. 1). Given the current economic policy, it is expected that the development of tourism activities will further increase in the future (Michaud and Turner, 2006). The statistical results indicate that the cultivation of cardamom is negatively click here associated with deforestation and expansion of arable land. This means that the involvement in cardamom cultivation (under forest) slows down deforestation and expansion of cultivated land, as cardamom plantations are not classified here as agricultural land. Cardamom production provides higher incomes than traditional crop farming (Sowerwine, 2004a). Recently, cardamom is emerging as an important learn more cash

crop in northern Vietnam that requires little investment and labour but may offer higher income levels (Tugault-Lafleur Org 27569 and Turner, 2009). Because

of the requirement of a dense forest canopy for optimal production, the villagers not only protect the remaining old forest but also allow regeneration of some of the swidden lands in order to create the necessary ecological conditions to plant and harvest cardamom (Sowerwine, 2004b). Its impact on forest conservation is similar to the system of shade coffee cultivation in forest that also contributed to a preservation of the afromontane forests in, e.g., the south of Ethiopia (Getahun et al., 2013). The role of ethnicity is complex. After controlling for biophysical and socio-economic settings, Hmong villages are characterized by higher expansion rates of arable land compared to Yao villages. This can be explained by the fact that Hmong villages are more densely populated than Yao villages (Jadin et al., 2013) so they need to expand their arable land more to supply the food demand. In villages with mixed ethnicities, the land abandonment rate is higher than in Yao villages, which can be explained by the fact that mixed ethnicities only occur in the accessible commune centres that are more involved in off-farm activities. The effect of preservation policy is certainly reflected in the difference in land cover changes inside and outside the National park. The estimated coefficients for the explanatory variable ‘Inside NP’ are negative for all land cover change categories whereby the ‘Outside NP’ is taken as a reference value.

, 2006) If venom is still measurable after antivenom has been ad

, 2006). If venom is still measurable after antivenom has been administered it is thought that this represents free venom and insufficient antivenom has been Talazoparib ic50 given. We have

previously made use of the same technique in vitro to show that the addition of increasing concentrations of antivenom to venom gives an exponential decrease in measurable free venom ( Isbister et al., 2007 and Isbister et al., 2011). The concentration of antivenom at which venom is no longer detectable can then be converted to a dose required for neutralisation. This approach appears to work well with Australian antivenoms where there is likely to be an excess of antivenom compared to venom, because the commercial antivenom is highly concentrated (O’Leary and Isbister, 2009) and the venom concentration Lumacaftor order in patients is low due to the small amount of venom delivered by elapids (Kulawickrama et al., 2010, Allen et al., 2012 and Isbister et al., 2012). Therefore, venom is rarely detectable after administration of even one vial of antivenom in Australian elapid envenoming

(Allen et al., 2012 and Isbister et al., 2012). In contrast to this, in many non-Australian snakes, and in particular vipers, the venom concentrations are much higher (10–100 fold) and they are not reduced to zero following the administration of antivenom in a proportion of cases (Phillips et al., 1988 and Ho et al., 1990). However, the persistence of venom, or in some cases recurrence of detectable venom, does not always appear to be associated with persistence of envenoming, such as coagulopathy. One explanation for this is that the venom being detected as “free”

venom is in fact bound venom or venom–antivenom (VAV) complexes where the ratio of antivenom to venom is low (1–1) so that the VAV complex can still bind to the enzyme immunoassay (EIA) microplate (Fig. 1A). The suggestion that the assay for free venom can also detect bound venom (or VAV) as well as free venom means that it is important to be able to detect bound venom or VAV complexes. Such Alanine-glyoxylate transaminase an assay would require an antibody to bind to the venom component of the VAV complex and an antibody to the antivenom (i.e. anti-horse antibodies for an equine antivenom). Fig. 1B shows such an assay where antibodies to the venom are attached to the microplate and conjugated anti-horse antibodies are used as the detecting antibody. The aim of this study was to develop an assay to measure the venom–antivenom (VAV) complex which will complement the free venom assay. We investigate the binding of venom and antivenom in vitro with the assay, which could potentially be used determine if antivenom has bound to venom in vivo.

The thermal dehydration of aluminum trihydroxide (gibbsite) can l

The thermal dehydration of aluminum trihydroxide (gibbsite) can lead to the formation of χ, κ, ρ, η or θ transition aluminas, depending on the heating rate, the dwell temperature and the atmosphere in contact with the solid phase [1], [2] and [3]. The thermal dehydration of boehmite can afford γ, η, δ, or θ phases, depending on the conditions of dehydration, the particle size and degree of crystallinity of the starting boehmite. Pseudoboehmite, a poorly Pifithrin-�� concentration ordered

form of boehmite with a small primary particle size, is often a preferred precursor to transition aluminas, because it typically affords derivatives with relatively high surface areas and pore volumes. Particularly, γ alumina (γ-Al2O3) is formed from well ordered boehmite at a temperature over 500 °C, depending on the particle size. Pseudoboehmite can be transformed

to η alumina upon dehydration [1], [2] and [3]. Carboxylate-alumoxanes are prepared from the reaction of boehmite [Al(O)(OH)]n with carboxylic Ibrutinib chemical structure acid (HO2CR). Although, they are given the general formula, [Al(O)x(OH)y(O2CR)z]n where 2x + y + z = 3 and R = C1–C14 [1], carboxylate-alumoxanes are in fact alumina nanoparticles between 5 and 200 nm in diameter. The surface of the nanoparticle is covered with covalently bound carboxylate groups [4] and [5]. Some of the simple carboxylic acids which have been used are: acetic acid, methoxyacetic acid, methoxy (ethoxy) acetic acid, methoxy (ethoxy ethoxy) acetic acid, hexanoic acid etc. Some of the carboxylic acids containing other functionalized groups are: 4-hydroxybenzoic acid, 4-aminobenzoic acid, methacrylic acid, hydroxylacetic acid, aminoacetic acid, 6-aminohexanoic acid, lactic acid, l-lysine etc [4]. Carboxylate-alumoxanes have found applications in a variety of interesting fields, such as the following: synthesis of metal doped aluminum oxides, catalyst components, preparation of ceramic membranes, synthesis of hollow alumina spheres, strengthening of porous alumina ceramics, and fabrication of fiber reinforced ceramic matrix composites, fabrication of biocompatible nanocomposites, polymeric Isoconazole nanocomposites, performance improvements

of lithium batteries, non-skid and non-flammable coatings and MRI contrast agents [6] and [7]. In this sense, we have developed a method for the control of the porosity and pore size distribution on the synthesis of γ-alumina: reacting boehmite with a mixture of carboxylic acids from the extract of rosin, to produce carboxylate-alumoxane nanoparticles; drying the carboxylate-alumoxane nanoparticles; and firing the dried nanoparticles at a temperature of 650 °C. The rosin, main components of the colophony extract, is a mixture of isomeric cyclic carboxylic acids with the general formula C19H29COOH and it is produced by heating fresh liquid oleoresin to vaporize the volatile liquid terpene components [8] and [9].

Three patients had a combination of the symptoms Mean NIHSS on a

Three patients had a combination of the symptoms. Mean NIHSS on admission was 4 (min: 0, max: 8). Cerebral Magnetic Resonance Imaging with diffusion-weighted sequences documented the presence of ischemic areas in 7 patients in the corresponding omolateral carotid territory.

All patients presented hemodynamic internal carotid stenosis consistent with the clinical symptoms. Heterogeneous, mostly hypoechoic, complicated plaques were detected find more in all cases. Moreover, high-resolution B-Mode imaging performed with high frequency probes and spatial compound to better visualize plaque surface and texture, demonstrated an extensive rupture of the surface with structure fissurations (Fig. 1), intraoperatively confirmed. Ultrasound B-Mode imaging also allowed the detection of an abnormal motion of the soft parts of the plaques, in particular nearby the sites of plaque rupture. In two cases, real-time B-Mode imaging demonstrated an endothelial floating flap represented by the ruptured cap of the plaque, mobile

in the lumen, and thus confirming the high potential embolic risk of these lesions (Fig. 2). Mobile clots were also visualized from the surface at the site of plaque rupture in two cases (Fig. 3). Contrast ultrasound imaging detected a high density of microvessels in the plaque tissue consisting with relevant neoangiogenesis, as already described elsewhere [2] and [3] in acute symptomatic plaques. Furthermore, contrast ultrasound allowed a better visualization of the plaque extension and surface, better demonstrating INK 128 price the rupture extended deeply from the surface to the core of the plaque. In one

case, a small ulceration with a mobile clot was also identified. All patients were immediately and successfully submitted to CEA: mean NIHSS at discharge was 2 (min: 0, max: 4). Stroke remains a leading cause of disability and death worldwide [4]. About one-third of ischemic strokes arise from carotid atherosclerotic GPX6 plaques, embolization representing the main pathophysiological explanation. For this reason, the identification of vulnerable lesions represents the fundamental step to select patients at risk of cerebrovascular ischemic events from carotid disease where the surgical procedure is indicated. This is a particularly relevant hot topic in literature since optimal management of asymptomatic carotid stenosis still remains controversial [5], while the beneficial effect of CEA is recognized worldwide in symptomatic patients for hemodynamic stenosis. However, the timing of surgery in acute cerebrovascular events is still controversial. At present, early CEA is indeed the most appropriate strategy to prevent further carotid cerebrovascular events.

Therefore, the research on non-toxic antifouling coatings should

Therefore, the research on non-toxic antifouling coatings should be stimulated, implemented and refined. These new technologies may provide

GDC-0941 nmr a valuable contribution to a sustainable coexistence of productive activities and nature conservation. “
“A straw poll of reasonably educated people virtually anywhere today would, I might guess, show that all had ticked the box which suggested it was important to protect the blue whale (Balaenoptera musculus). At ∼190 tonnes and 33 m in length, this is the largest animal that has ever lived on Earth, but only 1% of its ancient numbers, or between 5000 and 12,000 individuals, survive today as remnants from an earlier whaling era. It is so big, its tongue weighs as much as an elephant – ∼5 tonnes! I would also guess today that the same attitude would be mainly reflected, but with the exception of a few whaling nations, in any poll relating to marine mammals in general – virtually all whales, dolphins, the walrus, seals and sea lions and sea otters.

All are ‘big’ and, generally, ‘cute’. Although as demonstrated recently in the killing of a young man on Svalbard by a polar bear, maybe not so ‘cuddly’, in a conservation sense. The mTOR inhibitor same would apply to many sea birds, especially the not quite so big penguins. And ask any of the one million strong bird watching fraternity in the United Kingdom and all would agree that it was right to protect fish eating ospreys, two chicks of which were successfully hatched to a pair in Kielder Water and Forest Park in Northumberland in June 2011 making this the first place in England to have two breeding osprey families in 170 years. Impressive, ioxilan and worthy of 24-h ranger protection. Throughout the tropics there are hermatypic coral reefs. The Great Barrier Reef of Australia, which at over 2,000 km long, is so big ‘it can be seen from outer space’,

and has a committee and swathes of legislation in place to achieve its protection. Today, there are more than 300 marine protected areas in Australia covering a sea area of 463,000 km2. Similarly, in April 2010, the Chagos Archipelago (also known as the British Indian Ocean Territory), in the Indian Ocean, was declared a fully no-take marine protected area by the British Government. Encompassing an area of 544,000 km2 – larger than, for example, France – the Chagos Archipelago Marine Reserve is the biggest such area in the world (Sheppard, 2011). Before the sovereignty of Hong Kong was returned to China on 1 July 1997, the (colonial) government of the time also enabled the passing of legislation resulting in the designation on 31 May 1995 of the Marine Parks Bill, which resulted in the formal establishment, on 14 July 1996, of marine parks and a single reserve in the waters of the then colony.

In the mucoperiosteum, the recruitment of BMDCs is increased upon

In the mucoperiosteum, the recruitment of BMDCs is increased upon wounding, whilst these cells are already present in the skin. These differences might be related to the larger repair capacity of oral mucosa.16 Much more myofibroblasts were present in the mucoperiosteal wounds than in the skin wounds. This could be related to the different course of wound healing in both tissues. The skin of rats is very loose and can contract

easily. Contraction will therefore not generate a high tension within the wound tissue, which limits BLZ945 concentration myofibroblast differentiation.29 The mucoperiosteum, however, is tightly attached to the palatal bone by Sharpey’s fibres.16 Therefore, contraction will generate higher mechanical tension, and hence more myofibroblasts appear.30 However, less than 10% of the myofibroblasts in both wound types is derived from BMDCs. This is similar to another study performed in mice.7 Myofibroblasts can originate from circulating fibrocytes which are part of the haematopoietic lineage but also have mesenchymal properties.31 GSK1120212 Activated fibroblasts were also present in both types of wounds, as detected by staining for HSP47, a chaperone protein in collagen synthesis. This population of cells

probably includes the myofibroblasts, which are also producing large amounts of collagen. This is supported by double-staining for αSMA and HSP47 (data not shown). Especially in skin, the population of activated fibroblasts is much larger than that of myofibroblasts, both in the wound and in normal tissue. These cells might be more important in the healing of these

easily contracting wounds than the myofibroblasts. In contrast, in mucoperiosteal wounds, the population of activated fibroblasts was only slightly larger than that of myofibroblasts. The largest population of BMDCs is that of CD68-positive myeloid cells, notably Parvulin macrophages. In skin wounds, this population is about 40% of the total bone marrow-derived population. This is to be expected since bone marrow ablation followed by bone marrow grafting replaces most of the haematopoietic stem cells. Part of the local population of macrophages might already have been replaced by haematopoietic precursors in the recovery period after bone marrow transplantation, especially in the skin. In conclusion, the data indicate that a much larger population of local BMDCs is present in the skin than in the mucoperiosteum. The skin population of BMDCs seems to be able to resolve tissue damage, as no further BMDCs are recruited upon wounding at two weeks after wounding. In contrast, the small population of BMDCs in the mucoperiosteum is replenished with cells from the bone marrow during at the same time point. This might partly explain the rapid wound healing reported in oral mucosal wounds. Other important factors seem to be the growth factors present in saliva and the specific properties of oral fibroblasts.

O espectro de anormalidades neurológicas que ocorrem na doença he

O espectro de anormalidades neurológicas que ocorrem na doença hepática pode variar desde sutis alterações na concentração

e atenção até deficiências graves que conduzem à morte15 and 20. Inconsistências nos critérios diagnósticos e de métodos entre estudos têm contribuído para as grandes variações referidas na prevalência de disfunção cognitiva em pacientes com doença hepática4. Estas inconsistências dificultam a learn more realização de estimativas precisas da prevalência e incidência desse quadro21 and 22. No maior estudo realizado até esta data (n = 165) esta disfunção foi observada em 62,4% dos pacientes21. Mas em 2 outros estudos sobre este problema de pesquisa encontrou-se uma prevalência de encefalopatia hepática mínima de 48%, usando-se como critério a pontuação para encefalopatia hepática através da Wechsler adult intelligence scale-performance 17 e avaliação por espectroscopia cerebral 4. Os 2 valores não http://www.selleckchem.com/products/lee011.html foram compatíveis com o valor estimado no presente estudo, através do MEEM, porém, os critérios de avaliação foram diferentes. Os pacientes com doença mais grave (Child C) apresentam maiores déficits cognitivos, como se observou no presente estudo, o que é compatível com

a literatura, onde se supõe que os pacientes com doença mais grave apresentam maior comprometimento em testes de memória 4 and 19. O uso de testes cognitivos também permite a identificação de padrões específicos de comprometimento cognitivo em pacientes com doença hepática 23. McCrea et al. observaram disfunção relativamente seletiva da atenção Cepharanthine e habilidades motoras em um grupo

de cirróticos, na ausência de qualquer anormalidade da memória, linguagem ou habilidades visuais-espaciais 23. É preciso destacar que o maior declínio no desempenho do teste com o aumento da idade provavelmente relaciona-se também ao déficit cognitivo associado ao envelhecimento. Além do fator idade, há também uma relação bem estabelecida na literatura da associação entre alcoolismo crônico, por si só independente da hepatopatia concomitante, e disfunção cognitiva 24 and 25. O comprometimento cognitivo observado em pacientes com alcoolismo sem doença hepática demonstrável cursa frequentemente com déficit de funções executivas, de planejamento, resolução de problemas e memória 24, enquanto os pacientes com a doença neurodegenerativa de Wenicke-Korsakoff geralmente exibem principalmente prejuízos na memória 26. Apesar do grande número de estudos em pacientes com alcoolismo, têm sido relativamente poucos os trabalhos que averiguaram especificamente a contribuição da doença hepática no espectro de alterações cognitivas observadas nos alcoolistas 15.

Ettinger et al [16] reported the results of a phase II study of<

Ettinger et al. [16] reported the results of a phase II study of

AMR as a second-line therapy for patients with platinum-refractory SCLC. In total, 75 American and European patients were enrolled, of whom, 67 (89.3%) were pretreated with a chemotherapy regimen including etoposide. The confirmed ORR of AMR therapy was 21.3% (95% CI, 12.7–32.3%) and the median PFS was 3.2 months (95% CI, 2.4–4.0 months). These efficacy data are similar to those of the patients previously treated with etoposide in the present Japanese study. BIBF 1120 Therefore, previous chemotherapy with etoposide, but not ethnic differences, may have influenced the efficacy of AMR therapy. Preclinical studies [17], [18], [19] and [20] have suggested that treatment with topoisomerase I inhibitors results in downregulation of the topoisomerase I target and reciprocal upregulation of topoisomerase II, thereby causing hypersensitivity to topoisomerase II inhibitors. Conversely, treatment with topoisomerase II inhibitors results in downregulation of topoisomerase II and upregulation of topoisomerase I. These results may explain why prior treatment with etoposide was associated with a

lower response to AMR therapy in the present study. Although etoposide plus cisplatin (EP) is considered the standard first-line chemotherapy Selleck Forskolin for patients with extensive-stage SCLC in Western countries, irinotecan, a topoisomerase I inhibitor, plus cisplatin (IP) is generally used for Japanese patients, which is based on the results of a previous phase III study comparing IP with EP for extensive-stage SCLC (JCOG9511) [2]. AMR may also play an important role in the treatment

of refractory SCLC, especially for patients previously treated with IP. In a recent Japanese phase III study comparing AMR plus cisplatin (AP) with IP for the treatment of extensive-stage SCLC (JCOG0509) [21], similar PFS periods were found for AP and IP (median, 5.1 v 5.7 months), but AP was inferior to IP in terms Immune system of OS (median, 15.3 v 18.0 months). Over 90% patients in both groups received subsequent chemotherapy. The most commonly administered drugs after the termination of treatment were topotecan in the AP group and AMR in the IP group. Subsequent chemotherapy with AMR may have contributed to the longer OS period in the IP group. The most common severe toxicity associated with AMR therapy in the present study was myelosuppression in the form of neutropenia. No treatment-related death was observed, which was probably because of the reasonable protocol-specified dose reductions and/or treatment delays. However, patients experienced febrile neutropenia more frequently in the present study (26.8%) than in previous studies (5.0–13.8%) [9], [13] and [16]. According to the guidelines of the American Society of Clinical Oncology, prophylactic G-CSF use is clinically effective when the risk of febrile neutropenia is 20% [22].

A fundamental problem in wavelet analysis is the selection of the

A fundamental problem in wavelet analysis is the selection of the mother wavelet function. For analysing the echo envelope of the acoustic signal, Ostrovsky & Tęgowski (2010) applied six differently defined mother functions. The use of so many different functions did not yield a larger amount of information, however. In the present case, the number of wavelet mother functions was reduced to two: one symmetric and the other asymmetric. The Mexican Hat (mexh) Metformin manufacturer was selected as the symmetric wavelet mother function, while the family of Daubechies wavelets exemplifies the asymmetric mother functions. A wavelet

of the order of 7 (db7) was selected from this family. In order to account for wavelet asymmetry, profiles were analysed in both directions, in the same direction as the measurements according to (db7 +) and in the opposite direction (db7 −). The following parameters were determined for each of the transforms: – wavelet energies for a given scaling parameter (EMVj, wav, ELTj, wav, ESTj, wav): The use of a fractal dimension in the analysis of bottom bathymetry should result from the following assumptions (Herzfeld et al. 1995): – bathymetry has a non-trivial structure at every scale;

It is evident that the bathymetry of a water body formed by numerous geological processes has a non-trivial structure and that it cannot be described by simple geometric figures. The work involving the analysis of bathymetric profiles from the eastern Pacific (Herzfeld et al. 1995) indicates that bathymetry can be treated as a fractal because the assumption that DH > DT is fulfilled; selleck monoclonal antibody however, the assumptions of self-similarity are not satisfied when the image scale is being changed. The fractal dimension is considered to be an appropriate parameter for describing the morphological diversification of bottom surfaces ( Wilson et al. 2007).

In the case of a flat bottom, the fractal dimension calculated for the bathymetric Erastin profile should take a value equal to unity; as irregularities in the seafloor appear and their magnitudes change, its value will rise. In this work, the fractal dimension was determined using indirect methods, such as the box dimension, semivariogram analysis of spectral parameters and wavelet analysis. For determining the box fractal dimension of the deviations from the bathymetric profile segments (DMVbox, DLTbox, DSTbox), the definition given by Hastings & Sugihara (1994) was used: equation(14) Dbox=limΔs→0log10NΔs−log10Δs, where N(Δs) determines the number of squares covering a depth profile of a side length Δs. In case of the bathymetric profiles, both the length and depth have the same dimension. The proposed procedure for determining this parameter consists of four consecutive steps: – normalisation of the distance, taking the unit profile length to be 256 m; Application of a uniform standardisation is valid, taking a standard distance and depth of 256 m, equal to the length of the analysed section.

1) Although the expression of pSmad 1/5/8 was decreased in cases

1). Although the expression of pSmad 1/5/8 was decreased in cases of non-unions compared to fracture callus, it was still present in osteoblasts and hypertrophic chondrocytes of non-unions (Table 2 and Fig. 1, Fig. 2 and Fig. 3), confirming our previous report showing active BMP signaling in non-unions [8]. The expression of noggin and gremlin was present in all cell types of all specimens. On the other hand, BMP3 (generally referred to as a BMP-inhibitor)

and chordin were not expressed in chondrocytes (hypertrophic and non-hypertrophic) of non-unions. Results of the expression of Smad-6 and Smad-7 were mixed. Although both Smad-6 and Smad-7 are inhibitors, their expression did not follow the same pattern. When comparing sections http://www.selleckchem.com/products/dabrafenib-gsk2118436.html of fracture callus with those of non-unions, our results showed increased expression of Smad-6 in osteoblasts, hypertrophic and non-hypertrophic chondrocytes of non-unions, Smad-7 showed equal expression in osteoblasts of both fracture callus and non-unions, while decreased expression in hypertrophic and non-hypertrophic chondrocytes of non-unions. Representative staining images are shown in Fig. 2 and Fig. 3. In general, results of double and triple immunofluorescence staining showed co-localization of BMP ligands with inhibitors, in all sections of both fracture callus and non-unions. There was also decreased staining of BMP2

in the non-unions (representative images are shown in Fig. 4, Fig. 5, Fig. 6, Fig. 7 and Fig. 8). A summary of the expression data is shown in Table 2. The results of this study AG-14699 support our hypothesis that the balance between expression of endogenous BMP ligands and BMP-inhibitors in non-unions is different than in normal fracture healing. Specifically, our results show that in chondrocytes, expression of BMP2 was markedly decreased in non-unions and that of BMP7 was almost completely absent. On the other hand, expression of BMP-inhibitors (noggin, gremlin, Smad-6 and Smad-7) was almost the same in osteoblasts, chondrocytes and fibroblasts Oxalosuccinic acid of both fracture callus

and non-unions. Although these data are consistent with our hypothesis, we had expected that this “imbalance” was due to an increased expression of BMP-inhibitors in non-unions. The current data suggest, however, that it is due to decreased expression of BMPs. In our previous study on delayed and non-unions, we demonstrated that BMP2, BMP4 and BMP7, BMPRs and pSmad 1/5/8 were present in most non-unions in osteoblasts and fibroblasts [8]. However, in that study, we did not specifically analyze the expression of these BMP-related proteins in cartilage cells and we did not compare our findings with those of normal fracture healing. The concept of imbalance between BMP ligands and their antagonists, being a potential cause of the development of non-unions, was first suggested by Niikura et al.