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Background: Use of donor granulocyte concentrate (GC) has been limited due to its short storage time of 6-24 h, which is partially due to residual red blood cells (RBCs) and platelets and the resulting lactate production leading to an acidotic milieu. To increase this storage time, we developed a closed system procedure compatible with standard blood bank technologies to remove RBC and platelets and to enrich the GC. Methods: Standard GCs (sGCs) were sedimented, washed twice with 0.9% sodium chloride (NaCl), and resuspended in blood group-identical fresh frozen plasma. The resulting purified GCs (pGCs) were then stored in platelet bags at a cell concentration of about 5 × 107 ± 1.8 × 107 leukocytes/ml without agitation at room temperature for up to 72 h. Cell count and viability, pH, blood gases, phagocytosis, and oxidative burst were monitored daily. Results: A significant reduction in RBC (98%) through sedimentation, and platelets (96%) by washing, purified the white blood cell (WBC) population and enriched the granulocytes to 96% of the WBC in the pGC. After 72 h of storage, over 90% of the initial WBC count of pGC remained, was viable (>97%), and the granulocytes exhibited a high phagocytosis and oxidative burst functionality, comparable to sGC after 24 h. Conclusion: Purification extends the maximum storage period of GC from 24 to 72 h and may therefore improve the availability of GC and its clinical use.

A granulocyte bioreactor for the extracorporeal treatment was developed to enhance the immune cell function in patients with severe sepsis. The influence of oxygenation on the used cells was tested in a prospective clinical study. Ten patients with severe sepsis were treated twice with the granulocyte bioreactor. The used cells were screened for functionality; values of blood gases, glucose and lactate were obtained from the recirculating bioreactor circuit. Five patients were treated with an oxygenator setup (Oxy group), five without oxygenator (Non-Oxy group). The overall in-hospital mortality was 50%. Significantly lower values of oxygen saturation, partial oxygen pressure, lactate, oxyburst and phagocytosis were seen in the Non-Oxy group compared with the Oxy group in the bioreactor circuit. Further studies with this approach are encouraged and should focus on the influence of oxygenation on production of reactive oxygen species and cytokines of used cells.

Im Rahmen dieser Dissertation wurde eine Methode zur Herstellung eines hochreinen, granulozytenreichen, funktionstüchtigen Leukozytenpräparats entwickelt. Unter Berücksichtigung des entwickelten Verfahrens konnten die physiologischen Bedingungen so geschaffen werden, dass die Lagerung von gereinigten Granulozytenkonzentraten mit therapeutisch wirksamen Gesamtzellzahlen über einen Zeitraum von 72 Stunden möglich wird. Das Aufreinigungs- und Lagerungsverfahren ist in einem geschlossenen Beutelsystem mit geringem Zeit- und Kostenaufwand durchführbar.

Table S1. AICc comparison of the statistical model for arrival in James Bay. The top 5 models are displayed, with the best model in boldface. Timing of arrival in James Bay is the response variable in all models. Departure refers to the last detection of an individual in Delaware Bay and tailwind refers to the tailwind the first 3h of the trajectory.; Fig S1. Locations of groupings of automated telemetry receivers in North America (see main text for details). The white dot indicates the capture site of Delaware Bay and the grey dot represents James Bay, located at the southern edge of the breeding grounds. The red dots indicate the fall detection sites of the Mingan Archipelago the Bay of Fundy. Maps created using R 3.3.3 using packages ggplot2, ggmap, raster and RgoogleMaps (image data providers: US Dept. of State Geographer © 2016); Fig S2. Estimates of the relationship between residual mass (relative body condition) and arrival dates to the sub-Arctic. Birds in a higher condition at the stopover site arrive earlier at the breeding grounds. Data points are estimates of linear mixed models (see main text for details), and the gray area represents 95% confidence intervals.

Brainstem descending control is crucial in maintaining the balance of excitation and inhibition in spinal sensory networks. In the adult, descending inhibition of spinal dorsal horn circuits arising from the brainstem rostroventral medial medulla (RVM) is targeted to neurons with a strong nociceptive C fibre input. Before the fourth postnatal week, the RVM exerts a net facilitation of spinal networks but it is not known if this is targeted to specific dorsal horn neuronal inputs. As the maturation from descending facilitation to inhibition occurs only after C fibre central synaptic maturation is complete, we hypothesized that RVM facilitation in young animals is targeted to A fibre afferent inputs. To test this, the RVM was stimulated while recording dorsal horn neuronal activity in vivo under isoflurane anaesthesia at postnatal day (P) 21 and P40 (adult). Electrical thresholds for A and C fibre evoked activity, spike counts and wind-up characteristics at baseline and during RVM stimulation (10-100 µA, 10 Hz) were compared. In adults, RVM stimulation selectively increased the threshold for C fibre evoked activity while at P21, it selectively decreased the threshold for A fibre evoked activity and these effects were correlated to the wind-up characteristics of the neuron. Thus, the postnatal shift in RVM control of dorsal horn circuits is not only directional but also modality specific, from facilitation of A fibre input in the young animal to inhibition of nociceptive C input in the adult, with additional contextual factors. The descending control of spinal sensory networks serves very different functions in young and adult animals.

This thesis presents new insights into fluid flow at Opouawe Bank, on the Hikurangi margin off New Zealand. Three case studies highlight different aspects of the gas migration system. The first study shows that seepage is driven by biogenic gas migration. Accumulating free gas underneath the base of gas hydrate stability is generated at a maximum depth of 1500-2100 m below the seafloor (mbsf). The flow is mostly focused along vertical conduits with some stratigraphically controlled flow along dipping horizons. Case study 2 links the vent systems with the tectonic framework. Gas migrates along extensional fractures systems that are elongated perpendicular to the ridge axis of Opouawe Bank. They are parallel to the main direction of compression induced by subduction and result from secondary longitudinal extension of the ridge. With declining overburden stress they develop into more pipe-like conduits in the shallow sediment at < 100 mbsf. Case study 3 investigated shallow gas migration. Differences in migration structures indicate different evolutionary stages of seep formation, from channeled gas flow, to gas trapping, and doming. Based on geo-mechanical quantifications, gas column heights necessary to create domes were calculated. Contrary to ongoing discussions, this study demonstrated that these doming features can evolve into seep sites without pockmark formation. The combined results of these case studies suggest that the exceptional observation of extensional gas migration structures may represent a common phenomenon at convergent margins. This has implications in the overall understanding of the stress regime of the accretionary prism. Furthermore, the study of seafloor doming yields a better understanding of gas migration and the stability of the seabed. This is relevant to improve the safety of oil and gas exploration operations and provides an additional tool to understand the mechanics of upward migrating gas through marine sediments.

The characteristic morphology of spreading, in the form of a recurring and parallel pattern of ridges and troughs, has been observed in numerous submarine landslides around the world. Limit equilibrium modelling of slope failure processes in the Storegga Slide had indicated that an increase in pore pressure is likely an important cause of spreading. In this study we explore the hypothesis that pore pressure generation in sub-seafloor sediments by shallow gas can promote the development of a weak layer above which submarine spreading can occur. We do this by analysing multibeam echosounder, sub-bottom and 2D multichannel seismic data acquired offshore the east coast of the North Island, New Zealand., peer-reviewed

Purpose: Granulocyte transfusions have been used to treat immune cell dysfunction in sepsis. A granulocyte bioreactor for the extracorporeal treatment of sepsis was tested in a prospective clinical study focusing on the dosage of norepinephrine in patients and influence on dynamic and cell based liver tests during extracorporeal therapies. Methods and Patients: Ten patients with severe sepsis were treated twice within 72 h with the system containing granulocytes from healthy donors. Survival, physiologic parameters, extended hemodynamic measurement, and the indocyanine green plasma disappearance rate (PDR) were monitored. Plasma of patients before and after extracorporeal treatments were tested with a cell based biosensor for analysis of hepatotoxicity. Results: The observed mortality rate was 50% during stay in hospital. During the treatments, the norepinephrine-dosage could be significantly reduced while mean arterial pressure was stable. In the cell based analysis of hepatotoxicity, the viability and function of sensor-cells increased significantly during extracorporeal treatment in all patients and the PDR-values increased significantly between day 1 and day 7 only in survivors. Conclusion. The extracorporeal treatment with donor granulocytes showed promising effects on dosage of norepinephrine in patients, liver cell function, and viability in a cell based biosensor. Further studies with this approach are encouraged.

Takahe seep, located on the Opouawe Bank, Hikurangi Margin, is characterized by a well-defined subsurface seismic chimney structure ca. 80,500 m2 in area. Sub-seafloor geophysical data based on acoustic anomaly layers indicated the presence of gas hydrate and free gas layers within the chimney structure. Reaction-transport modeling was applied to porewater data from 11 gravity cores to constrain methane turnover rates and benthic methane fluxes in the upper 10 m. Model results show that methane dynamics were highly variable due to transport and dissolution of ascending gas. The dissolution of gas (up to 3761 mmol m−2 yr−1) dwarfed the rate of methanogenesis within the simulated sediment column (2.6 mmol m−2 yr−1). Dissolved methane is mainly consumed by anaerobic oxidation of methane (AOM) at the base of the sulfate reduction zone and trapped by methane hydrate formation below it, with maximum rates in the central part of the chimney (946 and 2420 mmol m−2 yr−1, respectively). A seep-wide methane budget was constrained by combining the biogeochemical model results with geophysical data and led to estimates of AOM rates, gas hydrate formation and benthic dissolved methane fluxes of 3.68 × 104 mol yr−1, 73.85 × 104 mol yr−1and 1.19 × 104 mol yr−1, respectively. A much larger flux of methane probably escapes in gaseous form through focused bubble vents. The approach of linking geochemical model results with spatial geophysical data put forward here can be applied elsewhere to improve benthic methane turnover rates from limited single spot measurements to larger spatial scales.

Introduction: Clinical assessments should meet the general psychometric properties of reliability and validity. Furthermore there are requirements in matters of diagnostic validity and usability. In regards to patients with severe brain damage, both issues can mainly be implemented by detecting and assessing returning abilities as early as possible, in order to use them for treatment planning. Main aim of this article is to investigate whether the newly developed and validated interprofessional Basel Vegetative State Assessment (BAVESTA) meets these practice criteria. Method: Data were collected as part of validity assessment of BAVESTA. Using the Glasgow Coma Scale as a reference, predictive parameters and measures of effect are calculated. Moreover, expert users were interviewed and results are presented in a descriptive way. Results: With a sensitivity of 0.84 and a specificity of 0.85, the BAVESTA can be regarded as suitable in differentiating between vegetative state and further states of remission such as the minimally conscious state. Expert users regard BAVESTA as eligible for mapping rehabilitative process of patients with severely impaired consciousness. They agree upon the fact that all relevant areas are covered by BAVESTA. Discussion: The BAVESTA displays high levels of differentiation, in regards to both sensitivity and specificity. However, measures of effect ought generally to be regarded with caution, as reference standards have not been developed for the area of rehabilitation. Considering time expenditure, BAVESTA is rated as only marginally feasible by expert users. It should be continued to investigate BAVESTA in regards to its diagnostic quality, integrating electrophysical diagnostic tools as reference standards.

Assessing the process of vegetative state is difficult. There are no observational tools so far which are sensitive enough to register the subtle changes in vegetative states. Besides, it is necessary to distinguish between measurements of consciousness and of functions. The »Basel Vegetative State Assessment« (BAVESTA) has been developed since 2007; its reliability and validity were examined in this study. Its main purpose is to bridge the gap between tools measuring the level of consciousness and tools observing functional capacities of a patient. Method: BAVESTA has been developed with the collaboration of experts and potential users. It has been applied at the vegetative state REHAB centre Basel for five years, in order to assess its validity. BAVESTA has been implemented in 126 patients with different aetiopathogeneses, for process evaluation and comparison with four further, well-established tools. Analyses: Cronbach’s alpha, interrater-reliability, retest-reliability, concurrent and prognostic validity were examined. Results: BAVESTA has been proven to be a reliable and valid assessment tool. It is able to consistently measure the subtle changes during the process of rehabilitation in vegetative state patients. Discussion: The results support that BAVESTA is a reliable and valid observational assessment tool. The validation process was undertaken at a rehabilitation centre with a highly specialized ward on patients with vegetative state. Hence, it remains unclear whether BAVESTA is generally comprehensive for users outside this centre. Furthermore, clinical day-to-day difficulties resulted in a considerable amount of missing data. Conclusion: BAVESTA bridges the gap between assessment of consciousness and of functions. Further institutions should investigate its validity.

Introduction: Clinical assessments should meet the general psychometric properties of reliability and validity. Furthermore there are requirements in matters of diagnostic validity and usability. In regards to patients with severe brain damage, both issues can mainly be implemented by detecting and assessing returning abilities as early as possible, in order to use them for treatment planning. Main aim of this article is to investigate whether the newly developed and validated interprofessional Basel Vegetative State Assessment (BAVESTA) meets these practice criteria. Method: Data were collected as part of validity assessment of BAVESTA. Using the Glasgow Coma Scale as a reference, predictive parameters and measures of effect are calculated. Moreover, expert users were interviewed and results are presented in a descriptive way. Results: With a sensitivity of 0.84 and a specificity of 0.85, the BAVESTA can be regarded as suitable in differentiating between vegetative state and further states of remission such as the minimally conscious state. Expert users regard BAVESTA as eligible for mapping rehabilitative process of patients with severely impaired consciousness. They agree upon the fact that all relevant areas are covered by BAVESTA. Discussion: The BAVESTA displays high levels of differentiation, in regards to both sensitivity and specificity. However, measures of effect ought generally to be regarded with caution, as reference standards have not been developed for the area of rehabilitation. Considering time expenditure, BAVESTA is rated as only marginally feasible by expert users. It should be continued to investigate BAVESTA in regards to its diagnostic quality, integrating electrophysical diagnostic tools as reference standards.

The continental margins of southern Italy are located along converging plate boundaries, which are affected by intense seismicity and volcanic activity. Most of the coastal areas experienced severe earthquakes, landslides, and tsunamis in historical and/or modern times. The most prominent example is the Messina earthquake of Dec. 28, 1908 (Ms=7.3; 80,000 casualties), which was characterized by the worst tsunami Italy experienced in the historical time (~2000 casualties). It is, however, still unclear, whether this tsunami was triggered by a sudden vertical movement along a major fault during the earthquake or as a result of a giant marine slide initiated by the earthquake. The recurrence rates of major landslides and therefore the risk associated with landslides is also unknown. Based on detailed bathymetric data sets collected by Italian colleagues in the frame of the MaGIC Project (Marine Geohazards along the Italian Coast), we collected seismic data (2D and 3D) and gravity cores in three working areas (The Messina Straits, off Eastern Sicily, the Gioia Basin). A dense grid of new 2D-seismic data in the Messina Straits will allow to map fault patterns in great detail. One interesting outcome in this context is the identification of a set of normal faults striking in an EW-direction, which is almost perpendicular to the previously postulated faults. This EW-striking faults seem to be active. The area off eastern Sicily is characterized by numerous landslides and a complex deformation pattern. A 3D-seismic data set has been collected during the cruise using the so called P-cable in order to investigate these deformation patterns in detail. The new data will be the basis for a risk assessment in the working areas., peer-reviewed

Introduction: Valid measurement instruments are necessary to evaluate the rehabilitation progress of brain-injured patients with severe disorders of consciousness such as persistent vegetative state and minimally conscious state. Method: Instruments and validation studies were identified by searching the databases MEDLINE, DIMDI, PEDro, OT Seeker, CINAHL, PsychInfo and PsychIndex and German journals according to following inclusion criteria: 1) the instrument should cover behavioural change in the rehabilitation of patients with persistent vegetative state and minimally conscious state, 2) it should be available as German version and 3) data on at least one psychometric property must be reported. A critical appraisal of the psychometric quality was carried out based on the identified validation studies. Results: 13 out of 28 instruments met the inclusion criteria. From these six were used to detect functional changes in everyday life and seven recorded the state of consciousness. The Glasgow Coma Instrument, the Early Functional Ability Assessment, the Functional Independent Measure and the Barthel Index demonstrated good metric properties. For the other instruments only in a few properties were reported. Conclusion: The Glasgow Coma Scale can be recommended for the assessment of coma depth in acute care, and the Functional Independent Measure to evaluate the progress of rehabilitation. Because only a few instruments were appropriately tested on reliability and validity, further validation studies are necessary.

This research focused on prestressed concrete bulb-T (PCBT) beams made composite with a cast-in-place concrete deck and continuous over several spans through the use of continuity diaphragms. The current design procedure in AASHTO states that a continuity diaphragm is considered to be fully effective if a compressive stress is present in the bottom of the diaphragm when the superimposed permanent load, settlement, creep, shrinkage, 50% live load, and temperature gradient are summed, or if the beams are stored at least 90 days when continuity is established. It is more economical to store beams for fewer days, so it is important to know the minimum number of days that beams must be stored to satisfy AASHTO requirements. In addition, if the beams are stored for 90 days before erection, the positive moment detail must have a factored nominal strength (fMn) greater than 1.2 times the cracking moment (Mcr). In 2005, Newhouse tested the positive moment diaphragm reinforcement detail that is currently being adopted by VDOT. The first objective of this research was to determine if the detail was adequate if beams are stored for 90 days. The second objective was to determine if, based on AASHTO requirements, beams could be stored for fewer than 90 days. After the analysis of all PCBT beam sizes and a wide variety of span lengths and beam spacings, it can be concluded that Newhouse's detail, four No. 6 bars bent 180 and extended into the diaphragm, is adequate for all beams except for the PCBT-77, PCBT-85, and the PCBT-93 when the beams are stored for a minimum of 90 days. For these three beam sizes, three possible solutions are presented: one with two additional bent strands extended into the continuity diaphragm, one with an additional hairpin bar extended into the diaphragm, and one with L-shaped mild reinforcing bars extended into the diaphragm. To determine the minimum number of storage days required to satisfy AASHTO's requirement for compression at the bottom of the diaphragm, a parametric study was performed. The PCA Method was used in this analysis with the updated AASHTO LRFD creep, shrinkage, and prestress loss models. The parametric study included all sizes of PCBT beams, with two beam spacings, three span lengths and two beam concrete strengths for each size. Both two-span and three-span cases were analyzed. It was concluded that about half of the cases result in a significant reduction in the minimum number of storage days if the designer is willing to perform a detailed analysis. The other half of the cases must be stored for 90 days because the total moment in the diaphragm will never become negative and satisfy the AASHTO requirement. In general, narrower beam spacing and higher concrete compressive strength results in shorter required storage duration. A recommended quick check is to sum the thermal, composite dead load, and half of the live load restraint moments. The beam must be stored 90 days if that sum is positive, and a more detailed time-dependent analysis will indicate a shorter than 90 day storage period if that sum is negative. Virginia Department of Transportation 83136 Federal Highway Administration 83136

This research document focuses on prestressed PCBT girders made composite with a cast-in-place concrete deck and continuous over several spans through the use of continuity diaphragms. The current design procedure in AASHTO states that a continuity diaphragm is considered to be fully effective if a compressive stress develops in the bottom of the diaphragm when the superimposed permanent load, settlement, creep, shrinkage, 50 percent live load, and temperature gradient are summed, or if the girders are stored at least 90 days when continuity is established. It is more economical to store girders for fewer days, so it is important to know the minimum number of days that girders must be stored to satisfy AASHTO requirements. In 2005, Charles Newhouse developed the positive moment diaphragm reinforcement detail that is currently being adopted by VDOT. This thesis concludes that Newhouse's detail, four No. 6 bars bent 180° and extended into the diaphragm, is adequate for all girders except for the PCBT-77, PCBT-85, and the PCBT-93 when the girders are stored for a minimum of 90 days. It is recommended that two additional bent strands be extended into the continuity diaphragm for these three girder sizes. It was also concluded that about half of the cases result in a significant reduction in the minimum number of storage days if the designer is willing to perform a detailed analysis. The other half of the cases must be stored for 90 days because the total moment in the diaphragm will never become negative and satisfy the AASHTO requirement. In general, narrower girder spacing and higher concrete compressive strength results in shorter required storage duration. The PCA Method was used in this analysis with the updated AASHTO LRFD creep, shrinkage, and prestress loss models. A recommended quick check is to sum the thermal, composite dead load, and half of the live load restraint moments. The girder must be stored 90 days if that sum is positive, and a more detailed time-dependent analysis would result in a shorter than 90 day storage period if that sum is negative. Master of Science