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Background: Traditionally, surgical removal of glioblastoma is performed with general anaesthesia but a recent meta-analysis revealed that awake surgery in glioblastoma resulted in better surgical outcomes than non-awake surgery. Preoperative severe aphasia is one of the exclusion criteria for awake surgery because of difficulties in intraoperative interpretation of language deterioration and the distinction between preoperative vs. intraoperative induced paraphasias. As severe aphasia is common in glioblastoma patients, many potential patients who may benefit from awake surgery are excluded. Aims: We aim to investigate the feasibility of awake surgery in glioblastoma patients with severe aphasia using a patient-tailored approach with adapted intraoperative language tasks. We also examined the effect of awake surgery on language outcomes. Methods & Procedures: We discuss five case studies of patients elected for awake surgery with presumed glioblastoma in eloquent language areas and severe aphasia. Pre- and postoperatively, an extensive test-protocol was administered at different linguistic levels and modalities. A patient-tailored intraoperative language test-protocol was applied. Outcomes & Results: Preoperatively, all patients had severe impairments on all language and cognitive tests. Intraoperative language tasks for direct electrical stimulation and resection were selected and adapted to patients’ preoperative level. Despite preoperative severe aphasia, functional boundaries for critical language areas could be identified in each patient. Postoperatively, all patients had stable or improved language outcome. One of the patients recovered to maximum scores on nearly all language tests. Conclusions: Our cases demonstrate that awake surgery in severely aphasic glioblastoma patients is feasible and did not cause further deterioration of aphasia. An extensive preoperative neurolinguistic examination is necessary for adequate patient-tailored intraoperative monitoring with maximal tumour resection and to consequently increase the chance of language preservation and quality of life.

Tidal sand waves are large-scale bed forms found in shallow sandy seas, which show a migration of several meters per year. Field data from the Dutch part of the North Sea revealed a migration pattern causing bidirectional migration of sand waves over a sand bank, resulting in sand wave migration uphill from both sides of the sand bank. In order to understand the physical mechanisms behind this migration behaviour, we study the inclusion of a sand bank under a sand wave field using the numerical model Delft3D. First, the schematized model set-up (i.e. schematized bathymetry and simple tidal forcing) showed that the alteration of the tidal flow by a sand bank resulted in tide-averaged horizontal flow towards the top of the sand bank, causing the bidirectional migration of sand waves over the sand bank. Second, a case study was performed in which a more complex model set-up was used (bathymetry and tidal forcing identical to a study site in the North Sea where an offshore wind farm is developed). Here, the model results revealed migration directions comparable to field observations. The results open opportunities to explore modelling migration patterns of sand wave fields for offshore wind farm development in areas with complex bathymetric environments.

Installation and maintenance strategies regarding offshore wind farm operations involve extensive logistics. The main focus is the right temporal and spatial placement of personnel and equipment, while taking into account forecasted meteorological and ocean conditions. For these operations to be successful, weather windows characterized by certain permissive wave conditions are of enormous importance, whereas unforeseen events result in high cost and risk of safety. Numerical modelling of waves, water levels and current related variables has been used extensively to forecast ocean conditions. To account for the inherited model uncertainty, several error modelling techniques can be implemented for the numerical model forecasts to be corrected. In this study, various Bayesian Network (BN) models are incorporated, in order to enhance the accuracy of the significant wave height predictions and to be compared with other techniques, in conditions resembling the real-time nature of the application. The implemented BN models differ in terms of training and structure and provide overall the most satisfying performance. Supplementary, it is shown that the BN models illustrate significant advantages as both quantitative and conceptual tools, since they produce estimates for the underlying uncertainty of the phenomena, while providing information about the incorporated variables’ dependence relationships through their structure.

When building offshore wind turbines with monopile foundations, scour protection typically is placed to avoid scouring of the soil close to the monopile. An important aspect is that the scour protection itself causes erosion, inflicted by the local increase in current and/or wave velocities and in turn increased bed shear stresses. Scour of the edge material alongside the scour protection may cause deformations and failure of the scour protection of offshore wind turbine foundations. This can reduce the stability of the stone layer and cause exposure of cables running between the monopiles where they go from buried to the transition piece on the foundation. Although much information is available on the design of scour protection systems around monopiles, little is known on the mechanisms causing edge scour and the equilibrium stages of the edge scour process in steady current, waves and combined waves and current. This paper presents an extensive experimental campaign to explain the edge scour process in current and combined irregular waves and current, as well as tidal current. The three-dimensional flow field around the pile and scour protection is resolved by particle image velocimetry and bed shear stress measurements, showing a local increase in the flow velocities and bed shear stresses leading to increased sediment transport and scour. The governing process in steady current is a pair of symmetrical counter-rotating vortices emerging in the near bed region in the wake of the pile and scour protection, causing a significant downstream scour hole. It is found that the equilibrium scour hole depth and length scales with the pile diameter and the ratio between the thickness- and the width of the scour protection. In the second part of the present paper, the results from the experimental campaign are compared with the edge scour experienced in practice, outlined by a survey program of the offshore wind park Egmond Aan Zee and a published field investigation of Scroby Sands OWF by Whitehouse et al. (2011).

A 600 MW offshore wind farm is under construction in the Netherlands Exclusive Economic Zone at a site called Gemini situated 55 km north of the Wadden Sea island of Schiermonnikoog and 85 km from the nearest Dutch port of Eemshaven. This chapter investigates the option of introducing a multi-use design for the Gemini site by adding mussel cultivation (48 kt wet weight per year) and seaweed cultivation (480 kt wet weight per year) to the wind farm. An institutional analysis indicates a political will in the Netherlands to support the development of adding uses to offshore wind farms, but a number of implementation obstacles are also identified. Those obstacles include an absence of licences for multi-use production and legal restrictions against third-party access to wind farms. There is therefore a need for a regulatory framework for multi-use and trust-building among actors involved in multi-use installations. A financial and economic assessment, and a cost-benefit analysis also taking into account monetized changes in CO2 emissions, indicate that adding mussel cultivation to the wind farm is likely to be both financially and socio-economically viable. Including a seaweed cultivation function is probably not financially and socio-economically viable under current technical and economic conditions. Knowledge gaps and uncertainties in these assessments with respect to, for example, missing site-specific data and non-monetized externalities suggest further research, also including pilot cultivations of mussels and seaweed in planned single-use or multi-use installations.

European seas are encountering an upsurge in competing marine activities and infrastructures. Traditional exploitation such as fisheries, tourism, transportation, and oil production are accompanied by new sustainable economic activities such as offshore windfarms, aquaculture, and tidal and wave energy. One proposed solution to overcome possible competing claims at sea lies in combining these economic activities as part of Multi-Use Platforms at Sea (MUPS). MUPS can be understood as areas at sea, designated for a combination of activities, either completely integrated in a platform or in shared marine space. MUPS can potentially benefit from each other in terms of infrastructure, maintenance, etc. Developing MUPS in the marine environment demands adequate governance. In this article, we investigate four European sites to find out how governance arrangements may facilitate or complicate MUPs. In particular, we apply a framework specifying policy, economic, social, technical, environmental, and legal (PESTEL) factors to explore governance arrangements in four case study sites in different sea basins around Europe ( the Mediterranean Sea, the Atlantic Ocean, the North Sea, and the Baltic Sea). The article concludes with policy recommendations on a governance regime for facilitating the development of MUPS in the future.

Contains fulltext : 167803.pdf (Publisher’s version ) (Open Access) Background High fear of cancer recurrence (FCR) is an understudied topic in prostate cancer (PCa) survivors. This study aimed to detect the prevalence, consequences and characteristics associated with high FCR in PCa survivors. Material and methods This cross-sectional study included patients diagnosed with localized PCa and treated with curative radical prostatectomy between 1992 and 2012. We administered the Cancer Worry Scale (CWS) to assess FCR severity (primary outcome measure). Secondary outcomes included distress, quality of life (QOL), post-traumatic symptoms, and multidimensional aspects of FCR. chi(2)-tests, t-tests and Pearson's correlations examined the relationship between FCR and medical/demographic characteristics. MANOVA analyses and chi2-tests identified differences between PCa survivors with high and low FCR. Results Two hundred eighty-three PCa survivors (median age of 70.0 years) completed the questionnaires a median time of 7.1 years after surgery. About a third (36%) of all PCa survivors experienced high FCR. High FCR was associated with lower QOL, more physical problems, higher distress and more post-traumatic stress symptoms. PCa survivors with high FCR reported disease-related triggers (especially medical examinations), felt helpless and experienced problems in social relationships. High FCR was associated with a younger age and having received adjuvant radiotherapy. Conclusions Results illustrate that FCR is a significant problem in PCa survivors. Younger men and those treated with adjuvant radiotherapy are especially at risk. Those with high FCR experience worse QOL and higher symptom burden. Health care providers should pay specific attention to this problem and provide appropriate psychosocial care when needed.

European oceans are subject to rapid development. New activities such as aquaculture and ocean energy have gained importance. This triggers interest in ?multi-use platforms at sea? (MUPS), i.e., areas at sea in which different activities are combined. MUPS are complex features with regards to technology, governance, and financial, socioeconomic, and environmental aspects. To identify realistic and sustainable solutions and designs for MUPS, the MERMAID project applied a participatory design process (PDP) involving a range of stakeholders representing companies, authorities, researchers, and NGOs. This paper evaluates if and how the participatory design process contributed to the design of multi-use platforms. It is based on interviews with the managers of the case study sites and a questionnaire administered to all stakeholders participating in the PDP workshops. Analyzing the four case studies, we conclude that the participatory design process has had a valuable contribution to the development of the four different designs of MUPS, even though the preconditions for carrying out a participatory design process differed between sites. In all four cases, the process has been beneficial in generating new and shared knowledge. It brought new design issues to the table and increased knowledge and understanding among the different stakeholders. This research was funded under the Seventh Framework Program, Theme [OCEAN.2011-1]. “Innovative Multi-purpose off-shore platforms: planning, design and operation” Grant Agreement no.: 288710.

Experimental research during the past decade has greatly increased our understanding of the pathophysiology of traumatic brain injury (TBI) and allowed us to develop neuroprotective pharmacological therapies. Encouraging results of experimental pharmacological interventions, however, have not been translated into successful clinical trials, to date. Traumatic brain injury is now believed to be a progressive degenerative disease characterized by cell loss. The limited capacity for self-repair of the brain suggests that functional recovery following TBI is likely to require cellular transplantation of exogenous cells to replace those lost to trauma. Recent advances in central nervous system transplantation techniques involve technical and experimental refinements and the analysis of the feasibility and efficacy of transplantation of a range of stem cells, progenitor cells and postmitotic cells. Cellular transplantation has begun to be evaluated in several models of experimental TBI, with promising results. The following is a compendium of these new and exciting studies, including a critical discussion of the rationale and caveats associated with cellular transplantation techniques in experimental TBI research. Further refinements in future research are likely to improve results from transplantation-based treatments for TBI.

The epidermal growth factor receptor (EGFR) has been shown to play an important role in brain development, including stem and precursor cell survival, proliferation, differentiation, and migration. To further examine the temporal and spatial requirements of erbB signals in uncommitted neural stem cells (NSCs), we expressed the ligand-independent EGF receptor, EGFRvIII, in C17.2 NSCs. These NSCs are known to migrate and to evince a tropic response to neurodegenerative environments in vivo but for which an underlying mechanism remains unclear. We show that enhanced erbB signaling via constitutive kinase activity of EGFRvIII in NSCs sustains an immature phenotype and enhances NSC migration.

Background: Cerebral ischemia is considered a key factor in the development of secondary damage after Traumatic Brain Injury (TBI). Studies on Cerebral Blood Flow (CBF) have documented decreased flow in over 50% of patients with TBI, studied in the acute phase. Transcranial Doppler (TCD) sonography is a non-invasive technique, permitting frequent or continuous measurements of blood flow velocity in the basal cerebral arteries. Objectives: To investigate the potential of TCD to detect decreased blood flow velocity in the early phase after TBI; To investigate whether flow velocity differs between hemispheres in patients with focal lesions versus those with more diffuse injuries; To investigate if decreased blood flow velocity is indicative of cerebral ischemia, as evidenced by measurements of brain tissue pO2. Methods: TCD examinations were performed in 57 patients with severe TBI (GCS≤8) daily over a period of 10 days, with particular attention focused on the first 72 hours, during which period examinations were performed more frequently. A low flow velocity state (LFVS) was defined as a flow velocity≤35 cm/sec in one or both MCA's within 72 hours after trauma. PbrO2 was measured in 33 patients with an intraparenchymal Clark type electrode (Licox). Patients were differentiated into those with primarily unilateral pathology on the admission CT scan versus those with primarily more diffuse or bilateral pathology. Outcome was evaluated at six months after injury, according to the Glasgow Outcome Scale (GOS). Results: A low flow velocity state was observed in 63% of patients studied. Decreased flow was most pronounced during the first eight hours after injury and was accompanied by high pulsatility indices, especially at the side of the lesion. Flow velocity increased significantly after this time period. Initial Vmca values had a strong correlation with ipsilateral measured PbrO2 values (R=0.73). The occurrence of a LFVS was associated with poorer outcome (odds ratio 3.9). Conclusions: TCD studies show reduction of cerebral blood flow velocity in the acute phase after traumatic brain injury. Decreased flow velocity is most pronounced ipsilateral to focal pathology. A low flow velocity state is probably due to high peripheral resistance, and is indicative of ischemia, as demonstrated by the association with decreased PbrO2. A low flow velocity state is of prognostic value and identifies patients at increased risk for ischemia. Early TCD studies are recommended in TBI.

In this chapter, authors put forward a port layout design approach for an exposed container terminal. This is an unusual approach for this type of terminal because of the associated strict vessel motion criteria. Nevertheless, in view of increasingly bigger container ships that will respond less to environmental conditions, the proposed approach departs from traditional ideas on wave sheltering in ports. The chapter discusses associated advantages and disadvantages. Aside from potential economic benefits, advantages of such an approach could be smaller coastal impacts and larger sustainability . For the disadvantages we present possible directions in which we foresee that solutions could be found to overcome those (technical) limitations. After the remaining technical issues have been solved, and when the business plans of ports can facilitate this new approach, the concept of an open water port is expected to form a more sustainable alternative to traditional port layout design approaches.

Approximately 50% of severely head-injured patients suffer additional potentially life-threatening extracranial injuries such as multiple fractures, lung contusion, traumatic pneumothorax, and injury to intra-abdominal organs. Despite the high prevalence of multiple trauma in brain-injured patients, only a few studies have investigated the effect of extracranial injuries on the clinical course and outcome of patients with traumatic brain injury (TBI) (1, 2). Nevertheless, the prognosis and outcome have been shown to be worsened when multiple extracranial injuries are involved (1, 3). This exacerbation of injury is believed to be a consequence of secondary insults to the brain resulting from hypoxemia, hypotension, elevated intracranial pressure, insufficient cerebral perfusion pressure, hypercapnia, hyperthermia, hypo/hyperglycemia, hyponatremia, and sepsis (4-6) that can be caused by extracranial traumatic injuries. Although the uninjured brain can normally withstand these secondary insults by activating compensatory mechanisms, the brain is rendered vulnerable to secondary insults due to TBI-induced structural and metabolic deficits. Blood loss and subsequent systemic hypotension are major causes of secondary insult to the brain following TBI and occur more frequently in multiply injured patients (4, 7). Moreover, hypotension in the traumatically injured patient has been shown to be predictive for higher mortality and morbidity rates (8). Under laboratory conditions, experimentally induced hemorrhagic hypotension (HH) when superimposed on a traumatically injured brain has been shown to impair cerebral perfusion (9, 10) and reduce the amount of oxygen carriers contributing to the already reduced brain tissue oxygenation (11, 12). Additionally, secondary hypotension, with and without concomitant hypoxia, following TBI has been reported to impair systemic pressure autoregulation (13-15), impair cerebral autoregulation (15, 16), and aggravate TBI-induced structural damage as reflected by a significant increase in contusion volume (9, 17-19). Secondary hypoxia has also been reported to exacerbate acute sensorimotor and cognitive deficits following moderate fluid percussion (FP) brain injury in rats (20). To date, most preclinical pathophysiologic and pharmacologic studies have been conducted primarily in animals subjected to isolated TBI without HH, and a strong need exists to develop combined injury models to elucidate optimal treatment and management strategies for multiply-injured patients (see the excellent review in Ref. 21). Although several rodent models of combined injury (TBI with hypoxia, with and without HH) have been established (9, 15, 17, 20, 22, 23), experimental studies investigating the impact of superimposed HH have focused primarily on the pharmacologic restitution of mean arterial blood pressure (MABP) and/or cerebral perfusion pressure by infusing catecholamines (15, 24) and the evaluation of various resuscitation fluids (13, 25, 26). To date, the impact of hemorrhagic hypotension on neurologic and cognitive outcome following TBI has not been investigated. The present study was designed to reproduce the clinical scenario in which a TBI patient experiences an acute, transient (≤30 mins) arterial hemorrhage immediately following TBI. In one subgroup of brain-injured animals, lactated Ringer’s solution was infused to reverse the arterial hypotension whereas another subgroup was not fluid resuscitated. The impact of superimposed compensated or uncompensated HH on the acute pathologic response to TBI (brain edema formation at 24 hrs postinjury), long-term (5 month) neurobehavioral outcome variables, and hemispheric tissue loss after TBI was also evaluated in the current study.

OBJECTIVE: We have previously shown that constitutively active epidermal growth factor receptor signaling enhances the survival and motility of engrafted neural stem cells (NSCs) when transplanted into normal adult brain. In the present study, using the C17.2 NSC line stably transfected with the constitutively active epidermal growth factor receptor vlll, we sought to evaluate the phenotype of NSCs after engraftment into the milieu of traumatic head injury. METHODS: We performed intracerebral NSC transplantation with C17.2 NSCs over-expressing the active epidermal growth factor receptor vlll receptor into the ipsilateral (n = 17) or contralateral (n = 19) corpus callosum at 48 hours after severe experimental traumatic brain injury (TBI) or after sham injury (n = 12) in rats. RESULTS: All sham-injured animals (100%) showed NSC graft survival, compared with 65% of brain-injured animals receiving ipsilateral NSC transplants, and only 10% of brain-injured animals had surviving transplants after engraftment into the contralateral uninjured corpus callosum. A marked elevation of nerve growth factor (pg/mg protein) was observed at 72 hours after injury in the injured hemisphere (x = 80 ± 10 pg/mg) compared with the contralateral uninjured hemisphere (35 ± 0 pg/mg) (P < 0.05), and this elevation of nerve growth factor may have contributed to enhanced survival of engrafted NSCs. In uninjured control animals, NSC transplants proliferated actively, as evidenced by incorporation of bromodeoxyuridine. After TBI, however, transplanted NSCs failed to proliferate, regardless of the site of implantation. Morphologically, NSCs transplanted into the injured brain showed extensive process formation suggestive of a more differentiated phenotype, in contrast to NSCs engrafted into uninjured brain that appear undifferentiated, with round soma and no processes. NSCs transplanted into the corpus callosum of brain-injured animals also expressed NG2, a pro-oligodendrocyte marker that was not seen in cells transplanted into uninjured brain. Although migration of NSCs was much more pronounced in the uninjured brain, 2 weeks after TBI, NSCs transplanted into the ipsilateral corpus callosum were found to have migrated to the injury cavity. Moreover, NHSCs transplanted into the corpus callosum contralateral to the site of injury were observed crossing the corpus callosum by 2 weeks after transplantation. CONCLUSION: Our results suggest that the envionnent associated with acute experimental TBI can significantly modulate the phenotype and migratory patterns of the engrafted NSC. These findings have particularly impottant implcations for transplantation of NSCs into the traumatically injured nervous system.

The intensity of experimental and clinical research to identify a neuroprotective drug for the treatment of traumatic brain injury is motivated by the devastating morbidity and mortality of this condition. Encouraging experimental work has led so far to disappointing clinical trials and the identification of new potential therapeutic targets is critically dependent on a better understanding of the chronic pathophysiology triggered by the initial insult. Future advances in the pharmacological treatment of traumatic brain injury are likely to include the evaluation of sequentially timed therapies combining multiple and targeted agents, and manipulation of the newly discovered neurogenic potential of the adult brain together with the refinement of traditional interventions to block specific cytotoxic cascades.

A variety of pharmacological agents have been advocated to treat pain and agitation in the traumatic brain injury (TBI) patient. It is felt beneficial to minimize painful or noxious stimuli as well as agitation as they may potentially contribute to elevations in ICP, raises in blood pressure, body temperature elevations and resistance to controlled ventilation. Until recently the primary concern over the utilization of these agents has been related to their tendency to obscure the neurologic exam, with a secondary concern over potential adverse hemodymanic effects. In the previous edition of these guidelines,2 little information was provided regarding analgesic and sedation utilization in severe TBI. It was noted that there have been relatively few outcome studies and therefore “decisions about . . . use . . . and the choice of agents are left to the practitioner to make based on individual circumstances.”

Pooled data indicate that prophylactic hypothermia is not significantly associated with decreased mortality when compared with normothermic controls. However, preliminary findings suggest that a greater decrease in mortality risk is observed when target temperatures are maintained for more than 48 h. Prophylactic hypothermia is associated with significantly higher Glasgow Outcome Scale (GOS) scores when compared to scores for normothermic controls.