Evaluation of the Hepa Wash® treatment in pigs with acute liver failure

BACKGROUND Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. METHODS In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h. RESULTS All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed. CONCLUSIONS Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins.

Prediction of water–rock interaction and porosity evolution in a granitoid-hosted enhanced geothermal system, using constraints from the 5 km Basel-1 well

Numerical simulations based on plans for a deep geothermal system in Basel, Switzerland are used here to understand chemical processes that occur in an initially dry granitoid reservoir during hydraulic stimulation and long-term water circulation to extract heat. An important question regarding the sustainability of such enhanced geothermal systems (EGS), is whether water–rock reactions will eventually lead to clogging of flow paths in the reservoir and thereby reduce or even completely block fluid throughput. A reactive transport model allows the main chemical reactions to be predicted and the resulting evolution of porosity to be tracked over the expected 30-year operational lifetime of the system. The simulations show that injection of surface water to stimulate fracture permeability in the monzogranite reservoir at 190 °C and 5000 m depth induces redox reactions between the oxidised surface water and the reduced wall rock. Although new calcite, chlorite, hematite and other minerals precipitate near the injection well, their volumes are low and more than compensated by those of the dissolving wall-rock minerals. Thus, during stimulation, reduction of injectivity by mineral precipitation is unlikely. During the simulated long-term operation of the system, the main mineral reactions are the hydration and albitization of plagioclase, the alteration of hornblende to an assemblage of smectites and chlorites and of primary K-feldspar to muscovite and microcline. Within a closed-system doublet, the composition of the circulated fluid changes only slightly during its repeated passage through the reservoir, as the wall rock essentially undergoes isochemical recrystallization. Even after 30 years of circulation, the calculations show that porosity is reduced by only ∼0.2%, well below the expected fracture porosity induced by stimulation. This result suggests that permeability reduction owing to water–rock interaction is unlikely to jeopardize the long-term operation of deep, granitoid-hosted EGS systems. A peculiarity at Basel is the presence of anhydrite as fracture coatings at ∼5000 m depth. Simulated exposure of the circulating fluid to anhydrite induces a stronger redox disequilibrium in the reservoir, driving dissolution of ferrous minerals and precipitation of ferric smectites, hematite and pyrite. However, even in this scenario the porosity reduction is at most 0.5%, a value which is unproblematic for sustainable fluid circulation through the reservoir.

Sonic intelligence as a virtual therapeutic environment

This paper reports on the results of a research project, on comparing one virtual collaborative environment with a first-person visual immersion (first-perspective interaction) and a second one where the user interacts through a sound-kinetic virtual representation of himself (avatar), as a stress-coping environment in real-life situations. Recent developments in coping research are proposing a shift from a trait-oriented approach of coping to a more situation-specific treatment. We defined as real-life situation a target-oriented situation that demands a complex coping skills inventory of high self-efficacy and internal or external "locus of control" strategies. The participants were 90 normal adults with healthy or impaired coping skills, 25-40 years of age, randomly spread across two groups. There was the same number of participants across groups and gender balance within groups. All two groups went through two phases. In Phase I, Solo, one participant was assessed using a three-stage assessment inspired by the transactional stress theory of Lazarus and the stress inoculation theory of Meichenbaum. In Phase I, each participant was given a coping skills measurement within the time course of various hypothetical stressful encounters performed in two different conditions and a control group. In Condition A, the participant was given a virtual stress assessment scenario relative to a first-person perspective (VRFP). In Condition B, the participant was given a virtual stress assessment scenario relative to a behaviorally realistic motion controlled avatar with sonic feedback (VRSA). In Condition C, the No Treatment Condition (NTC), the participant received just an interview. In Phase II, all three groups were mixed and exercised the same tasks but with two participants in pairs. The results showed that the VRSA group performed notably better in terms of cognitive appraisals, emotions and attributions than the other two groups in Phase I (VRSA, 92%; VRFP, 85%; NTC, 34%). In Phase II, the difference again favored the VRSA group against the other two. These results indicate that a virtual collaborative environment seems to be a consistent coping environment, tapping two classes of stress: (a) aversive or ambiguous situations, and (b) loss or failure situations in relation to the stress inoculation theory. In terms of coping behaviors, a distinction is made between self-directed and environment-directed strategies. A great advantage of the virtual collaborative environment with the behaviorally enhanced sound-kinetic avatar is the consideration of team coping intentions in different stages. Even if the aim is to tap transactional processes in real-life situations, it might be better to conduct research using a sound-kinetic avatar based collaborative environment than a virtual first-person perspective scenario alone. The VE consisted of two dual-processor PC systems, a video splitter, a digital camera and two stereoscopic CRT displays. The system was programmed in C++ and VRScape Immersive Cluster from VRCO, which created an artificial environment that encodes the user's motion from a video camera, targeted at the face of the users and physiological sensors attached to the body.

Fractures in Children and Adolescents

Fractures of the growing bone require fixation techniques, which preclude any injury to the growth plate regions. This requirement is met by Elastic Stable Intramedullary Nails (ESIN) which are positioned between both metaphyseal regions. Pronounced malposition and/or shortening, open fractures and fractures with impending skin perforation are indications for clavicle nailing in adolescents. Retrograde nailing with two elastic nails, inserted from lateral, is the method of choice for stabilization of humerus fractures. In radial neck fractures with severe tilting of the radial head, a retrograde nail may reduce and fix the head. In Monteggia lesions, the ulna fracture is reduced and fixed with an antegrade nail. Forearm fractures with unacceptable axial deviation are reduced and fixed with one antegrade nail in the ulna and a retrograde nail in the radius. Ascending elastic nailing is done for femur shaft and proximal femur fractures. The medial and lateral entry sites are located above the distal physis. End caps are used to prevent shortening in spiral and multiple segment fractures. Fractures of the distal third of the femur are nailed in a descending technique. The entry sites of two nails are located on the lateral cortex below the greater trochanter. Combined tibia and fibula fractures, open fractures and unstable fracture types such as spiral and multifragmental tibia fractures are good indications for ESIN. Descending nailing is the method of choice. The nail entry points are medially and laterally distal to the apophysis of the proximal tibia. Thorough knowledge of each fracture type, fracture location and age specific healing pattern is necessary for safe and effective treatment of pediatric fractures

Who gets the high quality jobs ten years after compulsory school?

Good work quality is crucial for employee well-being and health. Indicators of work quality are, among others, aspects of one’s work organization and learning opportunities. Based on the Job-Demands Control model we investigate if a) young employees are confronted with different combinations of job characteristics, b) cluster membership is predicted through socio-demographic and educational factors as well as positive self-evaluations and health, and c) cluster membership leads to different associations with job-related and general well-being. Based on TREE (Transition from Education to Employment) data we found three clusters of job characteristics, i.e. high resources – low demands, medium resources – medium demands, and low resources – high demands. Likelihood to be in a more favourable group was higher for females and young employees who reported more positive self-evaluations and higher learning efforts after compulsory school. Young employees in more favourable groups also reported higher levels of job-related and general well-being.

Dynamic computer simulation of electrophoretic enantiomer migration order and separation in presence of a neutral cyclodextrin

One-dimensional dynamic computer simulation was employed to investigate the separation and migration order change of ketoconazole enantiomers at low pH in presence of increasing amounts of (2-hydroxypropyl)-β-cyclodextrin (OHP-β-CD). The 1:1 interaction of ketoconazole with the neutral cyclodextrin was simulated under real experimental conditions and by varying input parameters for complex mobilities and complexation constants. Simulation results obtained with experimentally determined apparent ionic mobilities, complex mobilities, and complexation constants were found to compare well with the calculated separation selectivity and experimental data. Simulation data revealed that the migration order of the ketoconazole enantiomers at low (OHP-β-CD) concentrations (i.e. below migration order inversion) is essentially determined by the difference in complexation constants and at high (OHP-β-CD) concentrations (i.e. above migration order inversion) by the difference in complex mobilities. Furthermore, simulations with complex mobilities set to zero provided data that mimic migration order and separation with the chiral selector being immobilized. For the studied CEC configuration, no migration order inversion is predicted and separations are shown to be quicker and electrophoretic transport reduced in comparison to migration in free solution. The presented data illustrate that dynamic computer simulation is a valuable tool to study electrokinetic migration and separations of enantiomers in presence of a complexing agent.

Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant.

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event-free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety-one of 167 patients (55%) failed front-line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up-front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post-IST failure (P 0·73). Acute graft-versus-host disease (GVHD) grade II-IV was 8% in MFD graft vs. 25% for HSCT post-IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post-IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first-line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option.

Dendritic spine morphology determines membrane-associated protein exchange between dendritic shafts and spine heads.

The purpose of this study was to examine whether variability in the shape of dendritic spines affects protein movement within the plasma membrane. Using a combination of confocal microscopy and the fluorescence loss in photobleaching technique in living hippocampal CA1 pyramidal neurons expressing membrane-linked GFP, we observed a clear correlation between spine shape parameters and the diffusion and compartmentalization of membrane-associated proteins. The kinetics of membrane-linked GFP exchange between the dendritic shaft and the spine head compartment were slower in dendritic spines with long necks and/or large heads than in those with short necks and/or small heads. Furthermore, when the spine area was reduced by eliciting epileptiform activity, the kinetics of protein exchange between the spine compartments exhibited a concomitant decrease. As synaptic plasticity is considered to involve the dynamic flux by lateral diffusion of membrane-bound proteins into and out of the synapse, our data suggest that spine shape represents an important parameter in the susceptibility of synapses to undergo plastic change.

Simple measures of climate, soil properties and plant traits predict national-scale grassland soil carbon stocks

Soil carbon (C) storage is a key ecosystem service. Soil C stocks play a vital role in soil fertility and climate regulation, but the factors that control these stocks at regional and national scales are unknown, particularly when their composition and stability are considered. As a result, their mapping relies on either unreliable proxy measures or laborious direct measurements. Using data from an extensive national survey of English grasslands, we show that surface soil (0–7 cm) C stocks in size fractions of varying stability can be predicted at both regional and national scales from plant traits and simple measures of soil and climatic conditions. Soil C stocks in the largest pool, of intermediate particle size (50–250 μm), were best explained by mean annual temperature (MAT), soil pH and soil moisture content. The second largest C pool, highly stable physically and biochemically protected particles (0·45–50 μm), was explained by soil pH and the community abundance-weighted mean (CWM) leaf nitrogen (N) content, with the highest soil C stocks under N-rich vegetation. The C stock in the small active fraction (250–4000 μm) was explained by a wide range of variables: MAT, mean annual precipitation, mean growing season length, soil pH and CWM specific leaf area; stocks were higher under vegetation with thick and/or dense leaves. Testing the models describing these fractions against data from an independent English region indicated moderately strong correlation between predicted and actual values and no systematic bias, with the exception of the active fraction, for which predictions were inaccurate. Synthesis and applications. Validation indicates that readily available climate, soils and plant survey data can be effective in making local- to landscape-scale (1–100 000 km2) soil C stock predictions. Such predictions are a crucial component of effective management strategies to protect C stocks and enhance soil C sequestration.

Size parameters, size-class distribution and area-number relationship of microscopic charcoal: relevance for fire reconstruction

Charcoal analysis was conducted on sediment cores from three lakes to assess the relationship between the area and number of charcoal particles. Three charcoal-size parameters (maximum breadth, maximum length and area) were measured on sediment samples representing various vegetation types, including shrub tundra, boreal forest and temperate forest. These parameters and charcoal size-class distributions do not differ statistically between two sites where the same preparation technique (glycerine pollen slides) was used, but they differ for the same core when different techniques were applied. Results suggest that differences in charcoal size and size-class distribution are mainly caused by different preparation techniques and are not related to vegetation-type variation. At all three sites, the area and number concentrations of charcoal particles are highly correlated in standard pollen slides; 82–83% of the variability of the charcoal-area concentration can be explained by the particle-number concentration. Comparisons between predicted and measured area concentrations show that regression equations linking charcoal number and area concentrations can be used across sites as long as the same pollen-preparation technique is used. Thus it is concluded that it is unnecessary to measure charcoal areas in standard pollen slides – a time-consuming and tedious process.

Lateral impact in closed head injury: A substantially increased risk for diffuse axonal injury—A preliminary study

OBJECTIVE: Assessment, whether location of impact causing different facial fracture patterns was associated with diffuse axonal injury in patients with severe closed head injury. METHODS: Retrospectively all patients referred to the Trauma Unit of the University Hospital of Zurich, Switzerland between 1996 and 2002 presenting with severe closed head injuries (Abbreviated Injury Scale (AIS) (face) of 2-4 and an AIS (head and neck) of 3-5) were assessed according to the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS). Facial fracture patterns were classified as resulting from frontal, oblique or lateral impact. All patients had undergone computed tomography. The association between impact location and diffuse axonal injury when correcting for the level of consciousness (using the Glasgow scale) and severity of injury (using the ISS) was calculated with a multivariate regression analysis. RESULTS: Of 200 screened patients, 61 fulfilled the inclusion criteria for severe closed head injury. The medians (interquartile ranges 25;75) for GCS, AIS(face) AIS(head and neck) and ISS were 3 (3;13), 2 (2;4), 4 (4;5) and 30 (24;41), respectively. A total of 51% patients had frontal, 26% had an oblique and 23% had lateral trauma. A total of 21% patients developed diffuse axonal injury (DAI) when compared with frontal impact, the likelihood of diffuse axonal injury increased 11.0 fold (1.7-73.0) in patients with a lateral impact. CONCLUSIONS: Clinicians should be aware of the substantial increase of diffuse axonal injury related to lateral impact in patients with severe closed head injuries.

ROSINA/DFMS and IES observations of 67P: Ion-neutral chemistry in the coma of a weakly outgassing comet

Context. The Rosetta encounter with comet 67P/Churyumov-Gerasimenko provides a unique opportunity for an in situ, up-close investigation of ion-neutral chemistry in the coma of a weakly outgassing comet far from the Sun. Aims. Observations of primary and secondary ions and modeling are used to investigate the role of ion-neutral chemistry within the thin coma. Methods. Observations from late October through mid-December 2014 show the continuous presence of the solar wind 30 km from the comet nucleus. These and other observations indicate that there is no contact surface and the solar wind has direct access to the nucleus. On several occasions during this time period, the Rosetta/ROSINA/Double Focusing Mass Spectrometer measured the low-energy ion composition in the coma. Organic volatiles and water group ions and their breakup products (masses 14 through 19), CO2+ (masses 28 and 44) and other mass peaks (at masses 26, 27, and possibly 30) were observed. Secondary ions include H3O+ and HCO+ (masses 19 and 29). These secondary ions indicate ion-neutral chemistry in the thin coma of the comet. A relatively simple model is constructed to account for the low H3O+/H2O+ and HCO+/CO+ ratios observed in a water dominated coma. Results from this simple model are compared with results from models that include a more detailed chemical reaction network. Results. At low outgassing rates, predictions from the simple model agree with observations and with results from more complex models that include much more chemistry. At higher outgassing rates, the ion-neutral chemistry is still limited and high HCO+/CO+ ratios are predicted and observed. However, at higher outgassing rates, the model predicts high H3O+/H2O+ ratios and the observed ratios are often low. These low ratios may be the result of the highly heterogeneous nature of the coma, where CO and CO2 number densities can exceed that of water.

Joy, Schadenfreude, Sorrow, and Resentment as Responses Restoring Balance in Cognitive Units

Based on Heider’s (1958) balance theory we hypothesize that emotional responses to other persons’ outcomes depend on attitudes towards these persons. Positive attitudes towards others lead to empathic responses to their outcomes– joy after a success and sorrow after a failure. Negative attitudes result in paradoxical responses – negative to a success (resentment) and positive to a failure (schadenfreude). These emotions function as responses restoring balance within cognitive units consisting of the perceiver, other persons and their outcomes. Three studies supported these hypotheses and showed that deservingness considerations play a weaker role in shaping emotional responses of joy and sorrow to others’ outcomes when strong interpersonal attitudes are involved. However, deservingness plays an independent role in shaping the emotional response of resentment.

Bovine Staphylococcus aureus: Subtyping, evolution, and zoonotic transfer.

Staphylococcus aureus is globally one of the most important pathogens causing contagious mastitis in cattle. Previous studies using ribosomal spacer (RS)-PCR, however, demonstrated in Swiss cows that Staph. aureus isolated from bovine intramammary infections are genetically heterogeneous, with Staph. aureus genotype B (GTB) and GTC being the most prominent genotypes. Furthermore, Staph. aureus GTB was found to be contagious, whereas Staph. aureus GTC and all the remaining genotypes were involved in individual cow disease. In addition to RS-PCR, other methods for subtyping Staph. aureus are known, including spa typing and multilocus sequence typing (MLST). They are based on sequencing the spa and various housekeeping genes, respectively. The aim of the present study was to compare the 3 analytic methods using 456 strains of Staph. aureus isolated from milk of bovine intramammary infections and bulk tanks obtained from 12 European countries. Furthermore, the phylogeny of animal Staph. aureus was inferred and the zoonotic transfer of Staph. aureus between cattle and humans was studied. The analyzed strains could be grouped into 6 genotypic clusters, with CLB, CLC, and CLR being the most prominent ones. Comparing the 3 subtyping methods, RS-PCR showed the highest resolution, followed by spa typing and MLST. We found associations among the methods but in many cases they were unsatisfactory except for CLB and CLC. Cluster CLB was positive for clonal complex (CC)8 in 99% of the cases and typically positive for t2953; it is the cattle-adapted form of CC8. Cluster CLC was always positive for t529 and typically positive for CC705. For CLR and the remaining subtypes, links among the 3 methods were generally poor. Bovine Staph. aureus is highly clonal and a few clones predominate. Animal Staph. aureus always evolve from human strains, such that every human strain may be the ancestor of a novel animal-adapted strain. The zoonotic transfer of IMI- and milk-associated strains of Staph. aureus between cattle and humans seems to be very limited and different hosts are not considered as a source for mutual, spontaneous infections. Spillover events, however, may happen.

Influence of noninjecting and injecting drug use on mortality, retention in the cohort, and antiretroviral therapy, in participants in the Swiss HIV Cohort Study.

OBJECTIVES We studied the influence of noninjecting and injecting drug use on mortality, dropout rate, and the course of antiretroviral therapy (ART), in the Swiss HIV Cohort Study (SHCS). METHODS Cohort participants, registered prior to April 2007 and with at least one drug use questionnaire completed until May 2013, were categorized according to their self-reported drug use behaviour. The probabilities of death and dropout were separately analysed using multivariable competing risks proportional hazards regression models with mutual correction for the other endpoint. Furthermore, we describe the influence of drug use on the course of ART. RESULTS A total of 6529 participants (including 31% women) were followed during 31 215 person-years; 5.1% participants died; 10.5% were lost to follow-up. Among persons with homosexual or heterosexual HIV transmission, noninjecting drug use was associated with higher all-cause mortality [subhazard rate (SHR) 1.73; 95% confidence interval (CI) 1.07-2.83], compared with no drug use. Also, mortality was increased among former injecting drug users (IDUs) who reported noninjecting drug use (SHR 2.34; 95% CI 1.49-3.69). Noninjecting drug use was associated with higher dropout rates. The mean proportion of time with suppressed viral replication was 82.2% in all participants, irrespective of ART status, and 91.2% in those on ART. Drug use lowered adherence, and increased rates of ART change and ART interruptions. Virological failure on ART was more frequent in participants who reported concomitant drug injections while on opiate substitution, and in current IDUs, but not among noninjecting drug users. CONCLUSIONS Noninjecting drug use and injecting drug use are modifiable risks for death, and they lower retention in a cohort and complicate ART.