An age-related increase in resistance to DNA damage-induced apoptotic cell death is associated with development of DNA repair mechanisms

Neurons in the developing brain die via apoptosis after DNA damage, while neurons in the adult brain are generally resistant to these insults. The basis for this resistance is a matter of conjecture. We report here that cerebellar granule neurons (CGNs) in culture lose their competence to die in response to DNA damage as a function of time in culture. CGNs at either 1 day in vitro (DIV) or 7 DIV were treated with the DNA damaging agents camptothecin, UV or gamma-irradiation and neuronal survival measured. The younger neurons were effectively killed by these agents, while the older neurons displayed a significant resistance to killing. Neuronal survival did not change with time in culture when cells were treated with C2-ceramide or staurosporine, agents which do not target DNA. The resistance to UV irradiation developed over time in culture and was not due to changes in mitotic rate. Increases in DNA strand breakage, up-regulation of the levels of both p53 and its phosphorylated form and nuclear translocation of p53 were equivalent in both older and younger neurons, indicating a comparable p53 stress response. In addition, we show that treatment of older neurons with pharmacological inhibitors of distinct components of the DNA repair machinery promotes the accumulation of DNA damage and sensitizes these cells to the toxic effects of UV exposure. These data demonstrate that older neurons appear to be more proficient in DNA repair in comparison to their younger counterparts, and that this leads to increased survival after DNA damage.

Are HRM practices related with patient mortality in NHS hospitals?:A study examining the underlying reasons for such an association

This thesis will report details of two studies conducted within the National Health Service in the UK that examined the association between HRM practices related to training and appraisal with health outcomes within NHS Trusts. Study one represents the organisational analysis of 61 NHS Trusts, and will report training and appraisal practices were significantly associated with lower patient mortality. Specifically, the research will show significantly lower patient mortality within NHS Trusts that: a) had achieved Investors in People accreditation; b) had a formal strategy document relating to training; c) had tailored training policy documents across occupational groups; d) had integrated training and appraisal practices; e) had a high percentage of staff receiving either an appraisal or updated personal development plan. There was also evidence of an additive effect where NHS Trusts that displayed more of these characteristics had significantly lower patient mortality. Study one in this thesis will also report significantly lower patient mortality within the NHS Trusts where there was broad level representation for the HR function. Study two will report details of a study conducted to examine the potential reasons why HR practices may be related to hospital performance. Details are given of the results of a staff attitudinal survey within five NHS Trusts. This study examined will show that a range of developmental activity, the favourability of the immediate work environment (in relation to social support and role stressors) and motivational outcomes are important antecedents to citizenship behaviours. Furthermore, the thesis will report that principles of the demand-control model were adopted to examine the relationship between workplace support and role stressors, and workplace support, influence, and an understanding of role expectation help mitigate against the negative effects of work demands upon motivational outcomes.

Relaxation procedures for an iterative MFS algorithm for the stable reconstruction of elastic fields from Cauchy data in two-dimensional isotropic linear elasticity

We investigate two numerical procedures for the Cauchy problem in linear elasticity, involving the relaxation of either the given boundary displacements (Dirichlet data) or the prescribed boundary tractions (Neumann data) on the over-specified boundary, in the alternating iterative algorithm of Kozlov et al. (1991). The two mixed direct (well-posed) problems associated with each iteration are solved using the method of fundamental solutions (MFS), in conjunction with the Tikhonov regularization method, while the optimal value of the regularization parameter is chosen via the generalized cross-validation (GCV) criterion. An efficient regularizing stopping criterion which ceases the iterative procedure at the point where the accumulation of noise becomes dominant and the errors in predicting the exact solutions increase, is also presented. The MFS-based iterative algorithms with relaxation are tested for Cauchy problems for isotropic linear elastic materials in various geometries to confirm the numerical convergence, stability, accuracy and computational efficiency of the proposed method.

Reconstruction of an unsteady flow from incomplete boundary data:Part I. Theory

Purpose – To propose and investigate a stable numerical procedure for the reconstruction of the velocity of a viscous incompressible fluid flow in linear hydrodynamics from knowledge of the velocity and fluid stress force given on a part of the boundary of a bounded domain. Design/methodology/approach – Earlier works have involved the similar problem but for stationary case (time-independent fluid flow). Extending these ideas a procedure is proposed and investigated also for the time-dependent case. Findings – The paper finds a novel variation method for the Cauchy problem. It proves convergence and also proposes a new boundary element method. Research limitations/implications – The fluid flow domain is limited to annular domains; this restriction can be removed undertaking analyses in appropriate weighted spaces to incorporate singularities that can occur on general bounded domains. Future work involves numerical investigations and also to consider Oseen type flow. A challenging problem is to consider non-linear Navier-Stokes equation. Practical implications – Fluid flow problems where data are known only on a part of the boundary occur in a range of engineering situations such as colloidal suspension and swimming of microorganisms. For example, the solution domain can be the region between to spheres where only the outer sphere is accessible for measurements. Originality/value – A novel variational method for the Cauchy problem is proposed which preserves the unsteady Stokes operator, convergence is proved and using recent for the fundamental solution for unsteady Stokes system, a new boundary element method for this system is also proposed.

Public and private hospital services reform:an investigation in Iranian hospitals

This research aimed to present a model of efficiency for selected public and private hospitals of East Azerbaijani province of Iran by making use of DEA approach in order to recognize and suggest the best practice standards. In other words, its aim was to suggest a suitable context to develop efficient hospital systems while maintaining the quality of care at minimum expenditures. It is recommended for inefficient hospitals to make use of the followings: transferring, selling, or renting idle/unused beds; transferring excess doctors and nurses to the efficient hospitals or other health centers; pensioning off, early retirement clinic officers, technicians/technologists, and other technical staff. The saving obtained from the above approaches could be used to improve remuneration for remaining staff and quality of health care services of hospitals, rural and urban health centers, support communities to start or sustain systematic risk and resource pooling and cost sharing mechanisms for protecting beneficiaries against unexpected health care costs, compensate the capital depreciation, increasing investments, and improve diseases prevention services and facilities in the provincial and national levels.

An iterative method for the reconstruction of a stationary flow

In this article, an iterative algorithm based on the Landweber-Fridman method in combination with the boundary element method is developed for solving a Cauchy problem in linear hydrostatics Stokes flow of a slow viscous fluid. This is an iteration scheme where mixed well-posed problems for the stationary generalized Stokes system and its adjoint are solved in an alternating way. A convergence proof of this procedure is included and an efficient stopping criterion is employed. The numerical results confirm that the iterative method produces a convergent and stable numerical solution. © 2007 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2007

Nonlinear integral equation methods for the reconstruction of an acoustically sound-soft obstacle

The problem considered is that of determining the shape of a planar acoustically sound-soft obstacle from knowledge of the far-field pattern for one time-harmonic incident field. Two methods, which are based on the solution of a pair of integral equations representing the incoming wave and the far-field pattern, respectively, are proposed and investigated for finding the unknown boundary. Numerical resultsare included which show that the methods give accurate numerical approximations in relatively few iterations.

Reconstruction of an acoustically sound-soft obstacle from one incident field and the far field pattern

The problem considered is that of determining the shape of a plane acoustically sound-soft obstacle from the knowledge of the far-field pattern for one time-harmonic incident field. An iterative procedure is proposed based on two boundary integrals representing the incident field and the far-field pattern, respectively. Numerical examples are included which show that the procedure gives accurate numerical approximations in relatively few iterations.

An iterative method for reconstruction of temperature

An iterative method for the reconstruction of a stationary three-dimensional temperature field, from Cauchy data given on a part of the boundary, is presented. At each iteration step, a series of mixed well-posed boundary value problems are solved for the heat operator and its adjoint. A convergence proof of this method in a weighted L 2-space is include

Local resources and procurement practices in humanitarian supply chains:an empirical examination of large-scale house reconstruction projects

Different procurement decisions taken by relief organizations can result in considerably different implications in regards to transport, storage, and distribution of humanitarian aid and ultimately can influence the performance of the humanitarian supply chain and the delivery of the humanitarian aid. In this article, we look into what resources are needed and how these resources evolve in the delivery of humanitarian aid. Drawing on the resource-based view of the firm, we develop a framework to categorize the impact of local resources on the configuration of humanitarian supply chains. In contrast to other papers, the importance of localizing the configuration of the humanitarian supply chain is not only conceptually recognized, but empirical investigations are also provided. In terms of methodology, this article is based on the analysis of secondary data from two housing reconstruction projects. Findings indicate that the use of local resources in humanitarian aid has positive effects on programs' overall supply chain performance and these effects are not only related to the macroeconomic perspective, but benefits expand to improvements related to the use of knowledge. At the same time, it was found that local sourcing often comes with a number of problems. For example, in one of the cases, significant problems existed, which were related to the scarcity of local supplies. Both housing reconstruction projects have indicated the continuous need for changes throughout the programs as a dynamic supply chain configuration is important for the long-term sustainability of reconstruction aid. © 2014 Decision Sciences Institute.

An artificial neural network stratifies the risks of reintervention and mortality after endovascular aneurysm repair:a retrospective observational study

Background Lifelong surveillance after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) is considered mandatory to detect potentially life-threatening endograft complications. A minority of patients require reintervention but cannot be predictively identified by existing methods. This study aimed to improve the prediction of endograft complications and mortality, through the application of machine-learning techniques. Methods Patients undergoing EVAR at 2 centres were studied from 2004-2010. Pre-operative aneurysm morphology was quantified and endograft complications were recorded up to 5 years following surgery. An artificial neural networks (ANN) approach was used to predict whether patients would be at low- or high-risk of endograft complications (aortic/limb) or mortality. Centre 1 data were used for training and centre 2 data for validation. ANN performance was assessed by Kaplan-Meier analysis to compare the incidence of aortic complications, limb complications, and mortality; in patients predicted to be low-risk, versus those predicted to be high-risk. Results 761 patients aged 75 +/- 7 years underwent EVAR. Mean follow-up was 36+/- 20 months. An ANN was created from morphological features including angulation/length/areas/diameters/ volume/tortuosity of the aneurysm neck/sac/iliac segments. ANN models predicted endograft complications and mortality with excellent discrimination between a low-risk and high-risk group. In external validation, the 5-year rates of freedom from aortic complications, limb complications and mortality were 95.9% vs 67.9%; 99.3% vs 92.0%; and 87.9% vs 79.3% respectively (p0.001) Conclusion This study presents ANN models that stratify the 5-year risk of endograft complications or mortality using routinely available pre-operative data.

Towards the strategic adoption of Lean in aviation Maintenance Repair and Overhaul (MRO) industry:an empirical study into the industry's Lean status

Purpose - Despite many Maintenance Repair and Overhaul (MRO) organisations alluding their positive business performances to the adoption Lean initiatives, there is a paucity of direct literature that validates this assertion. Thus, the purpose of this paper is to study empirically via the use of an industry-wide survey to establish and extent of Lean adoption and to verify its suitability in mitigating prevalent MRO challenges. Design/methodology/approach - The empirical study contained in this paper is facilitated by an industry-wide survey to collect data from several firms across the MRO spectrum. The analysed responses from industry leaders, professionals and executives synthesised with existing literature was used in ascertaining the extent of Lean adoption within the operational framework of the industry. Findings - The empirical study helped in validating the suitability of Lean in MRO context. However, it was also observed that the focus of its application was skewed towards its production-orientated functions more than its service-orientated functions. Nonetheless, this paper presents results of the positive influence of Lean in MRO context. Research limitations/implications - This empirical study presented in this paper was carried out within a framework of key characteristics of operation. Although this approach is sufficient in assessing the industry's Lean status, further assessment can also be achieved within the context of relevant performance metrics which was not included in this paper. Practical implications - By exploring the industry's Lean status within the context of operational characteristics of operation, this study provides MRO practitioners with more awareness into some of the critical factors required for successful holistic Lean realisation. Social implications - The state-of-the-art of Lean within the aviation MRO context established through this research also contributes to the wider product-centric service environment by providing a platform that facilitates strategy development which ensures Lean success within this environment. Originality/value - Apart from validating the suitability of Lean in MRO contexts, by establishing the extent of Lean adoption within the context of the operational framework, this paper provides a clearer insight as to how successful Lean implementation can be achieved via a holistic implementation strategy balanced between the product-centric and service-centric aspects of the industry.

An in vitro comparison of the incorporation, growth, and chondrogenic potential of human bone marrow versus adipose tissue mesenchymal stem cells in clinically relevant cell scaffolds used for cartilage repair

Aim. To compare the incorporation, growth, and chondrogenic potential of bone marrow (BM) and adipose tissue (AT) mesenchymal stem cells (MSCs) in scaffolds used for cartilage repair. Methods. Human BM and AT MSCs were isolated, culture expanded, and characterised using standard protocols, then seeded into 2 different scaffolds, Chondro-Gide or Alpha Chondro Shield. Cell adhesion, incorporation, and viable cell growth were assessed microscopically and following calcein AM/ethidium homodimer (Live/Dead) staining. Cell-seeded scaffolds were treated with chondrogenic inducers for 28 days. Extracellular matrix deposition and soluble glycosaminoglycan (GAG) release into the culture medium was measured at day 28 by histology/immunohistochemistry and dimethylmethylene blue assay, respectively. Results. A greater number of viable MSCs from either source adhered and incorporated into Chondro-Gide than into Alpha Chondro Shield. In both cell scaffolds, this incorporation represented less than 2% of the cells that were seeded. There was a marked proliferation of BM MSCs, but not AT MSCs, in Chondro-Gide. MSCs from both sources underwent chondrogenic differentiation following induction. However, cartilaginous extracellular matrix deposition was most marked in Chondro- Gide seeded with BM MSCs. Soluble GAG secretion increased in chondrogenic versus control conditions. There was no marked difference in GAG secretion by MSCs from either cell source. Conclusion. Chondro-Gide and Alpha Chondro Shield were permissive to the incorporation and chondrogenic differentiation of human BM and AT MSCs. Chondro-Gide seeded with BM MSCs demonstrated the greatest increase in MSC number and deposition of a cartilaginous tissue.