922 resultados para Number development


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We have used whole exome sequencing to compare a group of presentation t(4;14) with t(11;14) cases of myeloma to define the mutational landscape. Each case was characterized by a median of 24.5 exonic nonsynonymous single-nucleotide variations, and there was a consistently higher number of mutations in the t(4;14) group, but this number did not reach statistical significance. We show that the transition and transversion rates in the 2 subgroups are similar, suggesting that there was no specific mechanism leading to mutation differentiating the 2 groups. Only 3% of mutations were seen in both groups, and recurrently mutated genes include NRAS, KRAS, BRAF, and DIS3 as well as DNAH5, a member of the axonemal dynein family. The pattern of mutation in each group was distinct, with the t(4;14) group being characterized by deregulation of chromatin organization, actin filament, and microfilament movement. Recurrent RAS pathway mutations identified subclonal heterogeneity at a mutational level in both groups, with mutations being present as either dominant or minor subclones. The presence of subclonal diversity was confirmed at a single-cell level using other tumor-acquired mutations. These results are consistent with a distinct molecular pathogenesis underlying each subgroup and have important impacts on targeted treatment strategies. The Medical Research Council Myeloma IX trial is registered under ISRCTN68454111.

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Ageing and deterioration of infrastructure is a challenge facing transport authorities. In
particular, there is a need for increased bridge monitoring in order to provide adequate
maintenance and to guarantee acceptable levels of transport safety. The Intelligent
Infrastructure group at Queens University Belfast (QUB) are working on a number of aspects
of infrastructure monitoring and this paper presents summarised results from three distinct
monitoring projects carried out by this group. Firstly the findings from a project on next
generation Bridge Weight in Motion (B-WIM) are reported, this includes full scale field testing
using fibre optic strain sensors. Secondly, results from early phase testing of a computer
vision system for bridge deflection monitoring are reported on. This research seeks to exploit
recent advances in image processing technology with a view to developing contactless
bridge monitoring approaches. Considering the logistical difficulty of installing sensors on a
‘live’ bridge, contactless monitoring has some inherent advantages over conventional
contact based sensing systems. Finally the last section of the paper presents some recent
findings on drive by bridge monitoring. In practice a drive-by monitoring system will likely
require GPS to allow the response of a given bridge to be identified; this study looks at the
feasibility of using low-cost GPS sensors for this purpose, via field trials. The three topics
outlined above cover a spectrum of SHM approaches namely, wired monitoring, contactless
monitoring and drive by monitoring

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Rotational moulding is a unique manufacturing technique for the production of hollow plastic parts manufacturing. Moulds for rotational moulding are generally not standardized, such as for injection moulding, so each new mould must be completely manufactured except for a few ancillary parts like screws or clamps. The aim of this work has been to adapt and apply the advantages of rapid prototyping and electroforming technologies to try to achieve an innovative mould design for rotational moulding. The new innovative design integrates an electroformed shell, manufactured starting from a rapid prototyping mandrel, with different designed standard aluminium tools. The shell holder enables mould assembly with high precision a shell in a few minutes with the advantage of changing different geometries of the electroformed shells in the same tool. The overall mould cost is significantly decreased because it is only necessary to manufacture one or two shells each time, however the rest of the elements of the mould are standard and usable for an infinite number of shells, depending on size. The rapid prototyping of the mandrel enables a significant decrease the global cost of mould manufacturing as well. © 2008 Taylor & Francis Group.

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Today a number of studies are published on how organizational strategy is developed and how organizations contribute to local and regional development through the realization of these strategies. There are also many articles dealing with the success of a project by identifying the criteria and the factors that influence them. This article introduces the project-oriented strategic planning process that reveals how projects contribute to local and regional development and demonstrates the relationship between this approach and the regional competitiveness model as well as the KRAFT concept. There is a lot of research that focuses on sustainability in business. These studies argue that sustainability is very important to the success of a business in the future. The Project Excellence Model that analyses project success does not contain the sustainability criteria; the GPM P5 standard consists of sustainability components related either to the organizational level. To fill this gap a Project Sustainability Excellence Model (PSEM) was developed. The model was tested by interviews with managers of Hungarian for-profit and non-profit organizations. This paper introduces the PSEM and highlights the most important elements of the empirical analysis.

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Land Ownership and Development: Evidence from Postwar Japan This paper analyzes the effect of land ownership on technology adoption and structural transformation. A large-scale land reform in postwar Japan enforced a large number of tenant farmers who were cultivating land to become owners of this land. I find that the municipalities which had many owner farmers after the land reform tended to experience a quick entry of new agricultural machines which became available after the reform. The adoption of the machines reduced the dependence on family labor, and led to a reallocation of labor from agriculture to industries and service sectors in urban centers when these sectors were growing. I also analyze the aggregate impact of labor reallocation on economic growth by using a simple growth model and micro data. I find that it increased GDP by about 12 percent of the GDP in 1974 during 1955-74. I also find a large and positive effect on agricultural productivity. Loyalty and Treason: Theory and Evidence from Japan's Land Reform A historically large-scale land reform in Japan after World War II enforced by the occupation forces redistributed a large area of farmlands to tenant farmers. The reform demolished hierarchical structures by weakening landlords' power in villages and towns. This paper investigates how the change in the social and economic structure of small communities affects electoral outcomes in the presence of clientelism. I find that there was a considerable decrease in the vote share of conservative parties in highly affected areas after the reform. I find the supporting evidence that the effect was driven by the fact that the tenant farmers who had obtained land exited from the long-term tenancy contract and became independent landowners. The effect was relatively persistent. Finally, I also find the surprising result that there was a decrease, rather than an increase, in turnout in these areas after the reform.  Geography and State Fragmentation We examine how geography affects the location of borders between sovereign states in Europe and surrounding areas from 1500 until today at the grid-cell level. This is motivated by an observation that the richest places in this region also have the highest historical border presence, suggesting a hitherto unexplored link between geography and modern development, working through state fragmentation. The raw correlations show that borders tend to be located on mountains, by rivers, closer to coasts, and in areas suitable for rainfed, but not irrigated, agriculture. Many of these patterns also hold with rigorous spatial controls. For example, cells with more rivers and more rugged terrain than their neighboring cells have higher border densities. However, the fragmenting effects of suitability for rainfed agriculture are reversed with such neighbor controls. Moreover, we find that borders are less likely to survive over time when they separate large states from small, but this size-difference effect is mitigated by, e.g., rugged terrain.

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La spectrométrie de masse mesure la masse des ions selon leur rapport masse sur charge. Cette technique est employée dans plusieurs domaines et peut analyser des mélanges complexes. L’imagerie par spectrométrie de masse (Imaging Mass Spectrometry en anglais, IMS), une branche de la spectrométrie de masse, permet l’analyse des ions sur une surface, tout en conservant l’organisation spatiale des ions détectés. Jusqu’à présent, les échantillons les plus étudiés en IMS sont des sections tissulaires végétales ou animales. Parmi les molécules couramment analysées par l’IMS, les lipides ont suscité beaucoup d'intérêt. Les lipides sont impliqués dans les maladies et le fonctionnement normal des cellules; ils forment la membrane cellulaire et ont plusieurs rôles, comme celui de réguler des événements cellulaires. Considérant l’implication des lipides dans la biologie et la capacité du MALDI IMS à les analyser, nous avons développé des stratégies analytiques pour la manipulation des échantillons et l’analyse de larges ensembles de données lipidiques. La dégradation des lipides est très importante dans l’industrie alimentaire. De la même façon, les lipides des sections tissulaires risquent de se dégrader. Leurs produits de dégradation peuvent donc introduire des artefacts dans l’analyse IMS ainsi que la perte d’espèces lipidiques pouvant nuire à la précision des mesures d’abondance. Puisque les lipides oxydés sont aussi des médiateurs importants dans le développement de plusieurs maladies, leur réelle préservation devient donc critique. Dans les études multi-institutionnelles où les échantillons sont souvent transportés d’un emplacement à l’autre, des protocoles adaptés et validés, et des mesures de dégradation sont nécessaires. Nos principaux résultats sont les suivants : un accroissement en fonction du temps des phospholipides oxydés et des lysophospholipides dans des conditions ambiantes, une diminution de la présence des lipides ayant des acides gras insaturés et un effet inhibitoire sur ses phénomènes de la conservation des sections au froid sous N2. A température et atmosphère ambiantes, les phospholipides sont oxydés sur une échelle de temps typique d’une préparation IMS normale (~30 minutes). Les phospholipides sont aussi décomposés en lysophospholipides sur une échelle de temps de plusieurs jours. La validation d’une méthode de manipulation d’échantillon est d’autant plus importante lorsqu’il s’agit d’analyser un plus grand nombre d’échantillons. L’athérosclérose est une maladie cardiovasculaire induite par l’accumulation de matériel cellulaire sur la paroi artérielle. Puisque l’athérosclérose est un phénomène en trois dimension (3D), l'IMS 3D en série devient donc utile, d'une part, car elle a la capacité à localiser les molécules sur la longueur totale d’une plaque athéromateuse et, d'autre part, car elle peut identifier des mécanismes moléculaires du développement ou de la rupture des plaques. l'IMS 3D en série fait face à certains défis spécifiques, dont beaucoup se rapportent simplement à la reconstruction en 3D et à l’interprétation de la reconstruction moléculaire en temps réel. En tenant compte de ces objectifs et en utilisant l’IMS des lipides pour l’étude des plaques d’athérosclérose d’une carotide humaine et d’un modèle murin d’athérosclérose, nous avons élaboré des méthodes «open-source» pour la reconstruction des données de l’IMS en 3D. Notre méthodologie fournit un moyen d’obtenir des visualisations de haute qualité et démontre une stratégie pour l’interprétation rapide des données de l’IMS 3D par la segmentation multivariée. L’analyse d’aortes d’un modèle murin a été le point de départ pour le développement des méthodes car ce sont des échantillons mieux contrôlés. En corrélant les données acquises en mode d’ionisation positive et négative, l’IMS en 3D a permis de démontrer une accumulation des phospholipides dans les sinus aortiques. De plus, l’IMS par AgLDI a mis en évidence une localisation différentielle des acides gras libres, du cholestérol, des esters du cholestérol et des triglycérides. La segmentation multivariée des signaux lipidiques suite à l’analyse par IMS d’une carotide humaine démontre une histologie moléculaire corrélée avec le degré de sténose de l’artère. Ces recherches aident à mieux comprendre la complexité biologique de l’athérosclérose et peuvent possiblement prédire le développement de certains cas cliniques. La métastase au foie du cancer colorectal (Colorectal cancer liver metastasis en anglais, CRCLM) est la maladie métastatique du cancer colorectal primaire, un des cancers le plus fréquent au monde. L’évaluation et le pronostic des tumeurs CRCLM sont effectués avec l’histopathologie avec une marge d’erreur. Nous avons utilisé l’IMS des lipides pour identifier les compartiments histologiques du CRCLM et extraire leurs signatures lipidiques. En exploitant ces signatures moléculaires, nous avons pu déterminer un score histopathologique quantitatif et objectif et qui corrèle avec le pronostic. De plus, par la dissection des signatures lipidiques, nous avons identifié des espèces lipidiques individuelles qui sont discriminants des différentes histologies du CRCLM et qui peuvent potentiellement être utilisées comme des biomarqueurs pour la détermination de la réponse à la thérapie. Plus spécifiquement, nous avons trouvé une série de plasmalogènes et sphingolipides qui permettent de distinguer deux différents types de nécrose (infarct-like necrosis et usual necrosis en anglais, ILN et UN, respectivement). L’ILN est associé avec la réponse aux traitements chimiothérapiques, alors que l’UN est associé au fonctionnement normal de la tumeur.

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The numbers of water-borne oomycete propagules in outdoor reservoirs used in horticultural nurseries within the UK are investigated in this study. Water samples were recovered from 11 different horticultural nurseries in the southern UK during Jan-May in two ‘cool’ years (2010.and 2013; winter temperatures 2.0 and 0.4oC below UK Met Office 30 year winter average respectively) and two ‘warm’ years (2008 and 2012; winter temperatures 1.2 and 0.9oC above UK Met Office 30 year winter average respectively). Samples were analysed for total number of oomycete colony forming units (CFU), predominantly members of the families Saprolegniaceae and Pythiaceae, and these were combined to give monthly mean counts. The numbers of CFU were investigated with respect to prevailing climate in the region: mean monthly air temperatures calculated by using daily observations from the nearest climatological station. The investigations show that the number of CFU during spring can be explained by a linear first-order equation and a statistically significant r2 value of 0.66 with the simple relationship: [CFU] = a(T-Tb )-b, where a is the rate of inoculum development with temperature T, and b is the baseload population at temperatures below Tb. Despite the majority of oomycete CFU detected being non-phytopathogenic members of the Saprolegniaceae, total oomycete CFU counts are still of considerable value as indicators of irrigation water treatment efficacy and cleanliness of storage tanks. The presence/absence of Pythium spp. was also determined for all samples tested, and Pythium CFU were found to be present in the majority, the exceptions all being particularly cold months (January and February 2010 and January 2008). A simple scenario study (+2 deg C) suggests that abundance of water-borne oomycetes during spring could be affected by increased temperatures due to climate change.

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Morphogens are signalling molecules that play a significant role in modulation of cell fate and development. Hedgehog proteins (Hh) are morphogens that have been shown to be involved in the development of immune cells. In this study, it is demonstrated that treatment of B cells with rShh, can increase B cell activation and also promote survival of B cells at 18hours post-stimulus. Also, at this time point, there was found to be an increase in secretion of antibody isotypes and IL-6. By 40hours post-stimulus, it was observed that the level of B cell activation was apparently arrested in treated B cells, whereas the level of activation continued to rise in untreated B cells. Interestingly, it was observed that there was an increase in the percentage of; CD23-CD25+ B cells when B cells were treated with rShh and this was accompanied by an increase in apoptosis. Consistent with this finding in relation to apoptosis, there was an increased expression of the pro-apoptotic protein Bnip3 in B cells treated with rShh by 40hours post-stimulus. It was observed that there were three subsets of B cells arising in our culture at 40hours, which were all found to possess different characteristics. It was demonstrated that treatment with rShh can increase B cell differentiation towards FO-I at 18hours post-stimulus. By 40hours post-stimulus, Hh signalling can divert differentiation away from the FO-I B cell towards the T2-MZP, which was accompanied by an increase in IL-10 secretion. Gene expression analysis revealed that Hh signalling could modulate a number of molecules involved in delivering the BCR signal into the cells such as Btk, Nfatc1 and Traf2. Additionally, deletion of Dhh, showed that there was a skewed peripheral B cell development in the Dhh-/- mice. Overall, our data demonstrate that Hh signalling can regulate the development of B cells in response to an activation stimulus by strengthening the BCR signalling pathway.

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The current study was carried out to evaluate the impact of a well-being curriculum based on existing knowledge of themes within PP, which contribute to well-being. The Positive Well-Being Curriculum consists of twelve ninety minute sessions delivered weekly during a school term. The twelve well-being sessions fit into four domains: positive experience, positive emotions, positive relationships, achievement and meaning (Seligman, 2007). The objectives of the study were to test the practical implications of running a well-being curriculum, to develop a range of activities within each domain and to evaluate the impact on student well-being with regard to life satisfaction, positive affectivity and subjective happiness. A pilot was carried out as preparation for the main mixed method intervention study, which was conducted in two London primary schools. Pre and post data was collected using standardised measures, focus groups and one to one interviews. Findings from the pilot demonstrated a significant increase in well-being as demonstrated by increases in: life satisfaction, positive affect and subjective happiness. Additional information was gathered which informed the content and implementation of the curriculum in the main study. The experience of taking part in the study as evidenced through qualitative and quantitative results, indicate that the Positive Well-being Curriculum was perceived by participating teachers and children to contribute positively to the well-being of the children. These findings would be of interest to educational psychologists as there is an increasing interest by schools to include creative and validated resources to support and enhance the well-being of all children. A number of useful insights were developed about the usefulness of the curriculum for children in a variety of educational settings.

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This work supported drafting project management guidance for the Iowa Department of Transportation (DOT). The goal is to incorporate a greater focus on project management in their project development process. A technical advisory committee (TAC) was assembled to accomplish this effort. The TAC took into consideration the current status of project management with the Iowa DOT, their experience during the demonstration workshop held in Iowa as part of the implementation assistance they received, the project management peer exchange hosted by the Iowa DOT, and additional examples of project management that were presented. With this basis, the TAC participated in a number of discussions to develop draft guidance for the foundation of a Project Management Office (PMO) within the Iowa DOT. The final report describes the process that was used in establishing this guidance. The report details the decisions and decision process that the TAC employed in this endeavor and provides additional thoughts and insight into the draft guidance. Appendix A includes the draft guidance in the form of PMO function details and detailed lists of project management roles and responsibilities. Appendix B includes a starter list of project management resources for the PMO.

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Pour ce projet, nous avons développé une plateforme pour l’analyse pangénomique de la méthylation de l’ADN chez le bovin qui est compatible avec des échantillons de petites tailles. Cet outil est utilisé pour étudier les caractéristiques génétiques et épigénétiques (méthylation de l’ADN) des gamètes soumis aux procédures de procréation médicalement assisitée et des embryons précoces. Dans un premier temps, une plateforme d’analyse de biopuces spécifiques pour l’étude de la méthylation de l’ADN chez l’espèce bovine a été développée. Cette plateforme a ensuite été optimisée pour produire des analyses pangénomiques de méthylation de l’ADN fiables et reproductibles à partir d’échantillons de très petites tailles telle que les embryons précoces (≥ 10 ng d’ADN a été utilisé, ce qui correspond à 10 blastocystes en expansion). En outre, cet outil a permis d’évaluer de façon simultanée la méthylation de l’ADN et le transcriptome dans le même échantillon, fournissant ainsi une image complète des profils génétiques et épigénétiques (méthylation de l’ADN). Comme preuve de concept, les profils comparatifs de méthylation de l’ADN spermatique et de blastocystes bovins ont été analysés au niveau de l’ensemble du génome. Dans un deuxième temps, grâce à cette plateforme, les profils globaux de méthylation de l’ADN de taureaux jumeaux monozygotes (MZ) ont été analysés. Malgré qu’ils sont génétiquement identiques, les taureaux jumeaux MZ ont des descendants avec des performances différentes. Par conséquent, l’hypothèse que le profil de méthylation de l’ADN spermatique de taureaux jumeaux MZ est différent a été émise. Dans notre étude, des différences significatives entre les jumeaux MZ au niveau des caractéristiques de la semence ainsi que de la méthylation de l’ADN ont été trouvées, chacune pouvant contribuer à l’obtention de performances divergentes incongrues des filles engendrées par ces jumeaux MZ. Dans la troisième partie de ce projet, la même plateforme a été utilisée pour découvrir les impacts d’une supplémentation à forte concentration en donneur de méthyle universel sur les embryons précoces bovins. La supplémentation avec de grandes quantités d’acide folique (AF) a été largement utilisée et recommandée chez les femmes enceintes pour sa capacité bien établie à prévenir les malformations du tube neural chez les enfants. Cependant, plus récemment, plusieurs études ont rapporté des effets indésirables de l’AF utilisé à des concentrations élevées, non seulement sur le développement de l’embryon, mais aussi chez les adultes. Au niveau cellulaire, l’AF entre dans le métabolisme monocarboné, la seule voie de production de S-adénosyl méthionine (SAM), un donneur universel de groupements méthyles pour une grande variété de biomolécules, y compris l’ADN. Par conséquent, pour résoudre cette controverse, une forte dose de SAM a été utilisée pour traiter des embryons produits in vitro chez le bovin. Ceci a non seulement permis d’influencer le phénotype des embryons précoces, mais aussi d’avoir un impact sur le transcriptome et le méthylome de l’ADN. En somme, le projet en cours a permis le développement d’une plateforme d’analyse de la méthylation de l’ADN à l’échelle du génome entier chez le bovin à coût raisonnable et facile à utiliser qui est compatible avec les embryons précoces. De plus, puisque c’est l’une des premières études de ce genre en biologie de la reproduction bovine, ce projet avait trois objectifs qui a donné plusieurs nouveaux résultats, incluant les profils comparatifs de méthylation de l’ADN au niveau : i) blastocystes versus spermatozoïdes ; ii) semence de taureaux jumeaux MZ et iii) embryons précoces traités à de fortes doses de SAM versus des embryons précoces non traités.

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Background to the Momentum project : PSS1 (Sept 2014 - July 2016): funded by HEFCE to promote Postgraduate Education and Employability. A discussion of group demographics, student experience, employer feedback, and enterprise creation through the establishment of the University of Worcester Business Incubator. The presentation concludes with a number of lessons learned from the project.

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Gluten sensitive consumers and people suffering from coeliac disease account for up to 6% of the general population (Catassi et al., 2013). These consumers must avoid foods which contain gluten and related proteins found in wheat, rye or barley. Beer is produced from barley malt and therefore contains hordeins, (gluten like proteins). Beers labelled as gluten-free must contain below 10 mg/kg hordeins (10 mg/kg hordeins = 20 mg/kg gluten under current regulations) to be considered safe for gluten sensitive consumers. Currently there are a limited number of methods available for reducing beer hordeins, the studies outlined in this thesis provide a range of tools for the beverage industry to reduce the hordein content of beer It is well known, that during malting and brewing hordeins are reduced, but they still remain in beer at levels above 10 mg/kg. During malting, hordeins are broken down to form new proteins in the growing plant. Model malting and brewing systems were developed and used to test, how the modification of the malting process could be used to reduce beer hordeins. It was shown, that by using a controlled malting and brewing regime, a range of barley cultivars produced beer with significant differences in levels of hordeins. Beer hordeins ranged from 10 mg/kg to 60 mg/kg. Another study revealed that when malting was prolonged, to maximise breakdown of proteins, beer hordeins can be reduced by up to 44%. The natural breakdown of hordein during malting enhanced in a further study, when a protease was added to support the hordein degradation during steeping and germination. The enzyme addition resulted in a 46% reduction in beer hordeins 2 when compared to the control. All of the malt treatments had little or no impact on malt quality. The hordein levels can also be reduced during the beer stabilisation process. Levels of beer hordein were tested after stabilisation using two different concentrations of silica gel and tannic acid. Silica gel was very effective in reducing beer hordeins, 90% of beer hordeins were removed compared to the control beer. Beer hordeins could be reduced to below 10 mg/kg and the beer qualities such as foam, colour and flavour were not affected. Tannic acid also reduced beer hordein by up to 90%, but it reduced foam stability and affected beer flavours. A further study described treatment of beer with microbial transglutaminase (mTG), to create bonds between hordein proteins, which increased particle size and allowed removal during filtration. The addition of the mTG led to a reduction of the beer hordein by up to 96% in beer, and the impact on the resulting beer quality was minimal. These studies provide the industry with a toolbox of methods leading to the reduction of hordein in the final beer without negatively affecting beer quality.

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Purpose – The aim of this study is to investigate the role of key strategic factors in new service development (NSD). In particular, the role of service development strategy, a formalised development process, integrated development teams and customer co-creation were investigated and the results were compared with managers' beliefs. Design/methodology/approach – The study used a sample of more than 500 service development projects to test a NSD conceptual model. Regression analysis was used to test the relative importance of the key strategic factors, and the results were compared with managers' beliefs. Findings – The results show that managers believe that customer co-creation is most important in order to succeed with NSD. However, contrary to management belief, a service development strategy is the “missing link” in improving NSD performance. In addition, the research highlighted an interaction effect between integrated development teams and customer co-creation, which means that project managers should focus on individual competencies on the development team and how they interact with customers throughout the NSD process. Originality/value – For a long time, NSD has failed to receive the attention it deserves, not just in practice but also in service research. This study shows that the number of new services put on the market and then withdrawn because of low sales remains as high as 43 per cent. This paper contributes knowledge on how to reduce the number of failures in NSD by pointing out the key strategic factors that influence NSD performance.