Co2-dependent vasomotor reactivity of cerebral arteries in patients with severe traumatic brain injury: time course and effect of augmentation of cardiac output with dobutamine

Failing cerebral blood flow (CBF) autoregulation may contribute to cerebral damage after traumatic brain injury (TBI). The purpose of this study was to describe the time course of CO(2)-dependent vasoreactivity, measured as CBF velocity in response to hyperventilation (vasomotor reactivity [VMR] index). We included 13 patients who had had severe TBI, 8 of whom received norepinephrine (NE) based on clinical indication. In these patients, measurements were also performed after dobutamine administration, with a goal of increasing cardiac output by 30%. Blood flow velocity was measured with transcranial Doppler ultrasound in both hemispheres. All patients except one had an abnormal VMR index in at least one hemisphere within the first 24 h after TBI. In those patients who did not receive catecholamines, mean VMR index recovered within the first 48 to 72 h. In contrast, in patients who received NE within the first 48 h period, VMR index did not recover on the second day. Cardiac output and mean CBF velocity increased significantly during dobutamine administration, but VMR index did not change significantly. In conclusion, CO(2) vasomotor reactivity was abnormal in the first 24 h after TBI in most of the patients, but recovered within 48 h in those patients who did not receive NE, in contrast to those eventually receiving the drug. Addition of dobutamine to NE had variable but overall insignificant effects on CO(2) vasomotor reactivity.

Variable ECG signs of ischemia during controlled occlusion of the left and right coronary artery in humans

Infarct size (IS) increases with vascular occlusion time, area at risk for infarction, lack of collateral supply, absence of preconditioning, and myocardial demand for O2 supply. ECG S-T segment elevation is used as a measure of severity of ischemia and a surrogate for IS. This study in 50 patients with coronary artery disease undergoing a first 120-s balloon occlusion of a stenosis sought to determine whether S-T segment elevation, corrected for the above-mentioned variables, in the left coronary artery (LCA group, n = 36) is different from that in the right coronary artery (RCA group, n = 14) territory. After consideration of all known determinants of IS, particularly mass at risk and collateral supply, the LCA territory is more sensitive than the RCA region to a 2-min period of myocardial ischemia.

Increased sensitivity in mapping task demand in visuospatial processing using reaction-time-dependent hemodynamic response predictors in rapid event-related fMRI

Searching for the neural correlates of visuospatial processing using functional magnetic resonance imaging (fMRI) is usually done in an event-related framework of cognitive subtraction, applying a paradigm comprising visuospatial cognitive components and a corresponding control task. Besides methodological caveats of the cognitive subtraction approach, the standard general linear model with fixed hemodynamic response predictors bears the risk of being underspecified. It does not take into account the variability of the blood oxygen level-dependent signal response due to variable task demand and performance on the level of each single trial. This underspecification may result in reduced sensitivity regarding the identification of task-related brain regions. In a rapid event-related fMRI study, we used an extended general linear model including single-trial reaction-time-dependent hemodynamic response predictors for the analysis of an angle discrimination task. In addition to the already known regions in superior and inferior parietal lobule, mapping the reaction-time-dependent hemodynamic response predictor revealed a more specific network including task demand-dependent regions not being detectable using the cognitive subtraction method, such as bilateral caudate nucleus and insula, right inferior frontal gyrus and left precentral gyrus.

Randomized controlled trial comparing a variable-thread novel tapered and a standard tapered implant: interim one-year results

STATEMENT OF PROBLEM: A tapered implant with continuously changing threads purported to provide stable tissue support and allow immediate function has been developed. Treatment success and stabilization of supporting tissues over time require documentation. PURPOSE: The purpose of this prospective, randomized, controlled, multicenter study was to evaluate changes in bone level and soft tissue behavior between the novel implant (NobelActive/NA) and a standard tapered implant (NobelReplace Tapered Groovy/NR) with regard to immediate function. MATERIAL AND METHODS: A total of 177 patients randomly allocated to 3 treatment groups (2 different test implant groups: NA Internal (n=117; internal connection) and External (n=82), and 1 standard treatment group, NR (n=126)) received 325 implants. Implants were placed into healed sites, and all but 6 implants were immediately nonocclusally loaded. Clinical and radiographic evaluations of treatment success, crestal bone levels, and soft tissue changes were performed at the time of placement and after 3, 6, and 12 months. Log-Rank test was used to analyze the differences in survival rate. Marginal bone level was compared using the Kruskal-Wallis test and Mann-Whitney U-test (alpha=.05). RESULTS: One-year cumulative survival rates were comparable (96.6% for NA Internal; 96.3% for NA External; 97.6% for NR; P=.852; Log-Rank). Mean (SD) change in bone level was -0.95 mm (1.37) for NA Internal, -0.64 mm (0.97) for NA External, and -0.63 mm (1.18) for NR (P=.589; Kruskal-Wallis). Stable soft tissues and significantly increased papilla scores (P<.001; Wilcoxon signed-rank) were observed for all implant types. CONCLUSIONS: The novel implants showed high survival rates as well as stable bone and soft tissue levels after 1 year, and may be recommended for clinical use, even under immediate function.

Expression Analysis of the Theileria parva Subtelomere-Encoded Variable Secreted Protein Gene Family

Background The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs) form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm. Methodology/Principal Findings We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals. Conclusions Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic proteins.

The von Mises-Fisher distribution of the first exit point from the hypersphere of the drifted Brownian motion and the density of the first exit time

A characterization is provided for the von Mises–Fisher random variable, in terms of first exit point from the unit hypersphere of the drifted Wiener process. Laplace transform formulae for the first exit time from the unit hypersphere of the drifted Wiener process are provided. Post representations in terms of Bell polynomials are provided for the densities of the first exit times from the circle and from the sphere.

GPS-only gravity field determination from GOCE data

The Gravity field and steady-state Ocean Circulation Explorer (GOCE) is now in orbit for more than four years. This is longer than the originally planned lifetime of the satellite and after three years on the same altitude the satellite has been lowered to 235 km in several steps. In the frame of the GOCE High-level Processing Facility the Astronomical Institute of the University of Bern (AIUB) is responsible for the determination of the official Precise Science Orbit (PSO) product. Kinematic GOCE orbits are part of this product and are used by several institutions in- and outside the HPF for determining the low degrees of the Earth’s gravity field. AIUB GOCE GPS-only gravity field solutions using the Celestial Mechanics Approach and covering the Release 4 period as well as a more recent time interval at the lower orbit altitude are shown and discussed. Special attention is paid to the impact of systematic deficiencies in the kinematic orbits on the resulting gravity fields, e.g., related to the geomagnetic equator, and on possibilities to get rid of them.

Time of emergence of trends in ocean biogeochemistry

For the detection of climate change, not only the magnitude of a trend signal is of significance. An essential issue is the time period required by the trend to be detectable in the first place. An illustrative measure for this is time of emergence (ToE), that is, the point in time when a signal finally emerges from the background noise of natural variability. We investigate the ToE of trend signals in different biogeochemical and physical surface variables utilizing a multi-model ensemble comprising simulations of 17 Earth system models (ESMs). We find that signals in ocean biogeochemical variables emerge on much shorter timescales than the physical variable sea surface temperature (SST). The ToE patterns of pCO2 and pH are spatially very similar to DIC (dissolved inorganic carbon), yet the trends emerge much faster – after roughly 12 yr for the majority of the global ocean area, compared to between 10 and 30 yr for DIC. ToE of 45–90 yr are even larger for SST. In general, the background noise is of higher importance in determining ToE than the strength of the trend signal. In areas with high natural variability, even strong trends both in the physical climate and carbon cycle system are masked by variability over decadal timescales. In contrast to the trend, natural variability is affected by the seasonal cycle. This has important implications for observations, since it implies that intra-annual variability could question the representativeness of irregularly sampled seasonal measurements for the entire year and, thus, the interpretation of observed trends.

Oxygen isotope record of oceanic and high-pressure metasomatism: a P-T-time-fluid path for the Monviso eclogites (Italy)

Fluids are considered a fundamental agent for chemical exchanges between different rock types in the subduction system. Constraints on the sources and pathways of subduction fluids thus provide crucial information to reconstruct subduction processes. The Monviso ophiolitic sequence is composed of mafic, ultramafic and minor sediments that have been subducted to ~80 km depth. In this sequence, both localized fluid flow and channelized fluids along major shear zones have been documented. We investigate the timing and source of the fluids that affected the dominant mafic rocks using microscale U-Pb dating of zircon and oxygen isotope analysis of mineral zones (garnet, zircon and antigorite) in high pressure rocks with variable degree of metasomatic modification. In mafic eclogites, Jurassic zircon cores are the only mineralogical relicts of the protolith gabbros and retain δ18O values of 4.5–6 ‰, typical of mantle melts. Garnet and metamorphic zircon that grew during prograde to peak metamorphism display low δ18O values between 0.2 and 3.8 ‰, which are likely inherited from high-temperature alteration of the protolith on the sea floor. This is corroborated by δ18O values of 3.0 and 3.6 ‰ in antigorite from surrounding serpentinites. In metasomatised eclogites within the Lower Shear Zone, garnet rim formed at the metamorphic peak shows a shift to higher δ18O up to 6‰. The age of zircons in high-pressure veins and metasomatised eclogites constrains the timing of fluid flow at high pressure at around 45–46 Ma. Although the oxygen data do not contradict previous reports of interaction with serpentinite-derived fluids, the shift to isotopically heavier oxygen compositions requires contribution from sediment-derived fluids. The scarcity of metasediments in the Monviso sequence suggests that such fluids were concentrated and fluxed along the Lower Shear Zone in a sufficient amount to modify the oxygen composition of the eclogitic minerals.

Polydnavirus of the parasitic wasp Chelonus inanitus (Braconidae): characterization, genome organization and time point of replication

Ultrastructural analysis of the polydnavirus of the braconid wasp Chelonus inanitus revealed that virions consist of one cylindrical nucleocapsid enveloped by a single unit membrane. Nucleocapsids have a constant diameter of 33.7 +/- 1.4 nm and a variable length of between 8 and 46 nm. Spreading of viral DNA showed that the genome consists of circular dsDNA molecules of variable sizes and measurement of the contour lengths indicated sizes of between 7 and 31 kbp. When virions were exposed to osmotic shock conditions to release the DNA, only one circular molecule was released per particle suggesting that the various DNA molecules are singly encapsidated in this bracovirus. The viral genome was seen to consist of at least 10 different segments and the aggregate genome size is in the order of 200 kbp. By partial digestion of viral DNA with HindIII or EcoRI in the presence of ethidium bromide and subsequent ligation with HindIII-cut pSP65 or EcoRI-cut pSP64 and transfection into Escherichia coli, libraries of 103 HindIII and 23 EcoRI clones were obtained. Southern blots revealed that complete and unrearranged segments were cloned with this approach, and restriction maps for five segments were obtained. Part of a 16.8 kbp segment was sequenced, found to be AT-rich (73%) and to contain six copies of a 17 bp repeated sequence. The development of the female reproductive tract in the course of pupal-adult development of the wasp was investigated and seen to be strictly correlated with the pigmentation pattern. By the use of a semiquantitative PCR, replication of viral DNA was observed to initiate at a specific stage of pupal-adult development.

Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis

BACKGROUND Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effective post-remission therapy is urgently needed. Although often no post-remission therapy is given to elderly patients, it might include chemotherapy or allogeneic haemopoietic stem cell transplantation (HSCT) following reduced-intensity conditioning. We aimed to assess the comparative value of allogeneic HSCT with other approaches, including no post-remission therapy, in patients with acute myeloid leukaemia aged 60 years and older. METHODS For this time-dependent analysis, we used the results from four successive prospective HOVON-SAKK acute myeloid leukaemia trials. Between May 3, 2001, and Feb 5, 2010, a total of 1155 patients aged 60 years and older were entered into these trials, of whom 640 obtained a first complete remission after induction chemotherapy and were included in the analysis. Post-remission therapy consisted of allogeneic HSCT following reduced-intensity conditioning (n=97), gemtuzumab ozogamicin (n=110), chemotherapy (n=44), autologous HSCT (n=23), or no further treatment (n=366). Reduced-intensity conditioning regimens consisted of fludarabine combined with 2 Gy of total body irradiation (n=71), fludarabine with busulfan (n=10), or other regimens (n=16). A time-dependent analysis was done, in which allogeneic HSCT was compared with other types of post-remission therapy. The primary endpoint of the study was 5-year overall survival for all treatment groups, analysed by a time-dependent analysis. FINDINGS 5-year overall survival was 35% (95% CI 25-44) for patients who received an allogeneic HSCT, 21% (17-26) for those who received no additional post-remission therapy, and 26% (19-33) for patients who received either additional chemotherapy or autologous HSCT. Overall survival at 5 years was strongly affected by the European LeukemiaNET acute myeloid leukaemia risk score, with patients in the favourable risk group (n=65) having better 5-year overall survival (56% [95% CI 43-67]) than those with intermediate-risk (n=131; 23% [19-27]) or adverse-risk (n=444; 13% [8-20]) acute myeloid leukaemia. Multivariable analysis with allogeneic HSCT as a time-dependent variable showed that allogeneic HSCT was associated with better 5-year overall survival (HR 0·71 [95% CI 0·53-0·95], p=0·017) compared with non-allogeneic HSCT post-remission therapies or no post-remission therapy, especially in patients with intermediate-risk (0·82 [0·58-1·15]) or adverse-risk (0.39 [0·21-0·73]) acute myeloid leukaemia. INTERPRETATION Collectively, the results from these four trials suggest that allogeneic HSCT might be the preferred treatment approach in patients 60 years of age and older with intermediate-risk and adverse-risk acute myeloid leukaemia in first complete remission, but the comparative value should ideally be shown in a prospective randomised study. FUNDING None.