New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

BACKGROUND: Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. METHODS: Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. RESULTS: Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max = 3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated hemispheric atrophy at 14 days (1.3 ± 4.0 mm(3), n = 7 vs. 12.1 ± 3.8 mm(3), n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate administration was also neuroprotective and attenuated the deficit (median = 1, min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1, max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 ± 12.2 mm(3), n = 12 vs. 29.6 ± 25.4 mm(3), n = 12, p < 0.05). CONCLUSIONS: The beneficial effect of lactate is long-lasting: lactate protects the mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke.

In Search of Corporate Renewal: How to Benefit from Corporate Venturing?

Despite the rapid change in today's business environment there are relatively few studies about corporate renewal. This study aims for its part at filling that research gap by studying the concepts of strategy, corporate renewal, innovation and corporate venturing. Its purpose is to enhance our understanding of how established companies operating in dynamic and global environment can benefit from their corporate venturing activities. The theoretical part approaches the research problem in corporate and venture levels. Firstly, it focuses on mapping the determinants of strategy and suggests using industry, location, resources, knowledge, structure and culture, market, technology and business model to assess the environment and using these determinants to optimize speed and magnitude of change.Secondly, it concludes that the choice of innovation strategy is dependent on the type and dimensions of innovation and suggests assessing market, technology, business model as well as novelty and complexity related to each of them for choosing an optimal context for developing innovations further. Thirdly, it directsattention on processes through which corporate renewal takes place. On corporate level these processes are identified as strategy formulation, strategy formation and strategy implementation. On the venture level the renewal processes are identified as learning, leveraging and nesting. The theoretical contribution of this study, the framework of strategic corporate venturing, joins corporate and venture level management issues together and concludes that strategy processes and linking processes are the mechanism through which continuous corporate renewaltakes place. The framework of strategic corporate venturing proposed by this study is a new way to illustrate the role of corporate venturing as a purposefullybuilt, different view of a company's business environment. The empirical part extended the framework by enhancing our understanding of the link between corporate renewal and corporate venturing in its real life environment in three Finnish companies: Metso, Nokia and TeliaSonera. Characterizing companies' environmentwith the determinants of strategy identified in this study provided a structured way to analyze their competitive position and renewal challenges that they arefacing. More importantly the case studies confirmed that a link between corporate renewal and corporate venturing exists and found out that the link is not as straight forward as indicated by the theory. Furthermore, the case studies enhanced the framework by indicating a sequence according to which the processes work. Firstly, the induced strategy processes strategy formulation and strategy implementation set the scene for corporate venturing context and management processes and leave strategy formation for the venture. Only after that can strategies formed by ventures come back to the corporate level - and if found viable in the corporate level be formalized through formulation and implementation. With the help of the framework of strategic corporate venturing the link between corporaterenewal and corporate venturing can be found and managed. The suggested response to the continuous need for change is continuous renewal i.e. institutionalizing corporate renewal in the strategy processes of the company. As far as benefiting from venturing is concerned the answer lies in deliberately managing venturing in a context different to the mainstream businesses and establishing efficientlinking processes to exploit the renewal potential of individual ventures.

Choice of Optimal MembraneProcesses for Economical Treatment of Paper Machine Clear Filtrate

In this thesis membrane filtration of paper machnie clear filtrate was studied. The aim of the study was to find membrane processes which are able to produce economically water of sufficient purity from paper machine white water or its saveall clarified fractions for reuse in the paper machnie short circulation. Factors affecting membrane fouling in this application were also studied. The thesis gives an overview af experiments done on a laboratory and a pilot scale with several different membranes and membrane modules. The results were judged by the obtained flux, the fouling tendency and the permeate quality assessed with various chemical analyses. It was shown that membrane modules which used a turbulence promotor of some kind gave the highest fluexes. However, the results showed that the greater the reduction in the concentration polarisation layer caused by increased turbulence in the module, the smaller the reductions in measured substances. Out of the micro-, ultra- and nanofiltration membranes tested, only nanofiltration memebranes produced permeate whose quality was very close to that of the chemically treated raw water used as fresh water in most paper mills today and which should thus be well suited for reuse as shower water both in the wire and press section. It was also shown that a one stage nanofiltration process was more effective than processes in which micro- or ultrafiltration was used as pretreatment for nanofiltration. It was generally observed that acidic pH, high organic matter content, the presence of multivalent ions, hydrophobic membrane material and high membrane cutoff increased the fouling tendency of the membranes.

MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial.

PURPOSE: Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen. EXPERIMENTAL DESIGN: Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m(2) per day)/one week off] or Arm B [3 weeks on (80 mg/m(2) per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O(6)-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR. RESULTS: Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8-3.2 vs. B: 2.0 months; 95% CI, 1.8-3.5] and overall survival [A: 9.8 months (95% CI, 6.7-13.0) vs. B: 10.6 months (95% CI, 8.1-11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8-7.4) versus 1.8 months (95% CI, 1.8-2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation. CONCLUSIONS: Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation.

Predicting diffusion of innovations with self-organisation and machine learning

The main subject of this master's thesis was predicting diffusion of innovations. The prediction was done in a special case: product has been available in some countries, and based on its diffusion in those countries the prediction is done for other countries. The prediction was based on finding similar countries with Self-Organizing Map~(SOM), using parameters of countries. Parameters included various economical and social key figures. SOM was optimised for different products using two different methods: (a) by adding diffusion information of products to the country parameters, and (b) by weighting the country parameters based on their importance for the diffusion of different products. A novel method using Differential Evolution (DE) was developed to solve the latter, highly non-linear optimisation problem. Results were fairly good. The prediction method seems to be on a solid theoretical foundation. The results based on country data were good. Instead, optimisation for different products did not generally offer clear benefit, but in some cases the improvement was clearly noticeable. The weights found for the parameters of the countries with the developed SOM optimisation method were interesting, and most of them could be explained by properties of the products.

Multifactor Performance Study on Complex Systems for the Benefit of Management

The primary objective is to identify the critical factors that have a natural impact on the performance measurement system. It is important to make correct decisions related to measurement systems, which are based on the complex business environment. The performance measurement system is combined with a very complex non-linear factor. The Six Sigma methodology is seen as one potential approach at every organisational level. It will be linked to the performance and financial measurement as well as to the analytical thinking on which the viewpoint of management depends. The complex systems are connected to the customer relationship study. As the primary throughput can be seen in a new well-defined performance measurement structure that will also be facilitated as will an analytical multifactor system. These critical factors should also be seen as a business innovation opportunity at the same time. This master's thesis has been divided into two different theoretical parts. The empirical part consists of both action-oriented and constructive research approaches with an empirical case study. The secondary objective is to seek a competitive advantage factor with a new analytical tool and the Six Sigma thinking. Process and product capabilities will be linked to the contribution of complex system. These critical barriers will be identified by the performance measuring system. The secondary throughput can be recognised as the product and the process cost efficiencies which throughputs are achieved with an advantage of management. The performance measurement potential is related to the different productivity analysis. Productivity can be seen as one essential part of the competitive advantage factor.

Les vaccins contre le zona : efficacité, sécurité, et rapport coût/bénéfices [Vaccines against Herpes zoster: Effectiveness, safety, and cost/benefit ratio].

CONTEXT: A vaccination against herpes zoster and its complication is available in France since June 2015. Its exact benefit for public health is still controversial and its level of protection is not optimal. All those reasons seem to suggest a low acceptation rate from general practitioners. OBJECTIVE: To evaluate the effectiveness, the safety, and the cost/benefit ratio of the vaccination against herpes zoster in people aged 50 year or over. DOCUMENTARY SOURCE: Systematic review in Medline and PubMed with research by key words: "herpes zoster vaccine", "zoster vaccine" and "post herpetic neuralgia vaccine". SELECTION OF STUDIES: Randomized and observational studies published in English and French language have been selected by two readers. RESULTS: On 1886 articles identified, 62 studies were included in this systematic review of which 21 randomized trials, 21 observational studies, and 17 medico-economic studies concerned the unadjuvanted vaccine. Considered studies showed an effectiveness of 50% against herpes zoster and 60% on post-herpetic neuralgia incidence of the unadjuvanted vaccine. Five randomized controlled studies were identified for the adjuvanted vaccine. The overall effectiveness of this vaccine was > 90% whatever the age of subjects including those over age 70 and 80. The medico-economic studies conducted in many countries have shown that vaccine policies were beneficial in individuals aged 60 years or over. LIMITATION OF THE WORK: Most of data of effectiveness, and tolerance result from 2 large controlled studies only (SPS and ZEST) for the unadjuvanted vaccine and only one for the adjuvanted vaccine. CONCLUSION: Despite controversy and few uncertainties, the vaccine significantly reduces herpes zoster and its complication incidence. In terms of public health objectives, it reduces the burden of the disease and has a positive medico-economic impact. Preliminary data concerning the adjuvanted vaccine, whilst very promising, are still too limited. Up to now, no group of people with particularly high risk of herpes zoster-related complication who will beneficiate the most of the vaccination has been identified yet and only an age criteria has been considered for the recommendation.

Cost-benefit analysis of an enhanced recovery protocol for pancreaticoduodenectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) programmes have been shown to decrease complications and hospital stay. The cost-effectiveness of such programmes has been demonstrated for colorectal surgery. This study aimed to assess the economic outcomes of a standard ERAS programme for pancreaticoduodenectomy. METHODS: ERAS for pancreaticoduodenectomy was implemented in October 2012. All consecutive patients who underwent pancreaticoduodenectomy until October 2014 were recorded. This group was compared in terms of costs with a cohort of consecutive patients who underwent pancreaticoduodenectomy between January 2010 and October 2012, before ERAS implementation. Preoperative, intraoperative and postoperative real costs were collected for each patient via the hospital administration. A bootstrap independent t test was used for comparison. ERAS-specific costs were integrated into the model. RESULTS: The groups were well matched in terms of demographic and surgical details. The overall complication rate was 68 per cent (50 of 74 patients) and 82 per cent (71 of 87 patients) in the ERAS and pre-ERAS groups respectively (P = 0·046). Median hospital stay was lower in the ERAS group (15 versus 19 days; P = 0·029). ERAS-specific costs were euro922 per patient. Mean total costs were euro56 083 per patient in the ERAS group and euro63 821 per patient in the pre-ERAS group (P = 0·273). The mean intensive care unit (ICU) and intermediate care costs were euro9139 and euro13 793 per patient for the ERAS and pre-ERAS groups respectively (P = 0·151). CONCLUSION: ERAS implementation for pancreaticoduodenectomy did not increase the costs in this cohort. Savings were noted in anaesthesia/operating room, medication and laboratory costs. Fewer patients in the ERAS group required an ICU stay.

Cardiovascular risk among hypertensive adolescents and the potential benefit of a screen-and-treat strategy.

To evaluate whether screening for hypertension should start early in life, information on the risk of diseases associated with the level of blood pressure in childhood or adolescence is needed. The study by Leiba et al. that is reported in the current issue of Pediatric Nephrology demonstrates convincingly that hypertensive adolescents are at higher risk of cardiovascular death than normotensive adolescents. Nevertheless, it can be shown that this excess risk is not sufficient to justify a screen-and-treat strategy. Since the large majority of cardiovascular deaths occur among normotensive adolescents, measures for primordial prevention of cardiovascular diseases could have a much larger impact at the population level.

Brideshead Revisited (1945) by Evelyn Waugh (1903-1966): the benefit of an Arcadian experience in confronting the human tragedy

As the frontispiece of Book One of Evelyn Waugh’s Brideshead Revisited, the phrase ‘Et in Arcadia ego’ announces the author’s intention of making the classical Arcadian theme a key reference in a text that speaks of nostalgia for a joyful past in times marked by sadness and pain. However, an interpretation may be approached from several directions even within the classical tradition. Thus, without ignoring philological or artistic aspects of the topic, this article focuses on a close study of the author’s most original message: the notion that a youthful Arcadian experience confers on young men and women a ‘residue of happiness’ able to sustain their future development and assist them in dealing with the challenges of personal tragedy.

Economical and operational analysis of outsourced warehouse function

The target of the thesis was to find out has the decision to outsource part of Filtronic LK warehouse function been profitable. Furthermore, another thesis target was to demonstrate current logistics processes between TPLP and company and find out the targets for developing these processes. The decision to outsource part of logistical funtions have been profitable during the first business year. Partnership includes always business risks. Risk increases high asset specific investments. In the other hand investment to partnership increases mutual trust and commitment between parties. By developing partnership risks and opportunitic behaviour can be decreased. The potential of managing material and data flows between logistic service provider and company observed. By analyzing inventory effiency were highlighted the need for decreasing the capital invested to inventories. The recommendations for managing outsourced logistical funtions were established such as improving partnership, process development, performance measurement and invoice checking.