Insertion of the CXC chemokine ligand 9 (CXCL9) into the mouse hepatitis virus genome results in protection from viral-induced encephalitis and hepatitis.

The role of the CXC chemokine ligand 9 (CXCL9) in host defense following infection with mouse hepatitis virus (MHV) was determined. Inoculation of the central nervous system (CNS) of CXCL9-/- mice with MHV resulted in accelerated and increased mortality compared to wild type mice supporting an important role for CXCL9 in anti-viral defense. In addition, infection of RAG1-/- or CXCL9-/- mice with a recombinant MHV expressing CXCL9 (MHV-CXCL9) resulted in protection from disease that correlated with reduced viral titers within the brain and NK cell-mediated protection in the liver. Survival in MHV-CXCL9-infected CXCL9-/- mice was associated with reduced viral burden within the brain that coincided with increased T cell infiltration. Similarly, viral clearance from the livers of MHV-CXCL9-infected mice was accelerated but independent of increased T cell or NK cell infiltration. These observations indicate that CXCL9 promotes protection from coronavirus-induced neurological and liver disease

The impact and significance of tephra deposition on a Holocene forest environment in the North Cascades, Washington, USA

High-resolution palaeoecological analyses (stratigraphy, tephra geochemistry, radiocarbon dating, pollen and ordination) were used to reconstruct a Holocene vegetation history of a watershed in the Pacific Northwest of America to evaluate the effects and duration of tephra deposition on a forest environment and the significance of these effects compared to long-term trends. Three tephra deposits were detected and evaluated: MLF-T158 and MLC-T324 from the climactic eruption of Mount Mazama, MLC-T480 from a Late Pleistocene eruption of Mount Mazama and MLC-T485 from a Glacier Peak eruption. Records were examined from both the centre and fringe of the basin to elucidate regional and local effects. The significance of tephra impacts independent of underlying long-term trends was confirmed using partial redundancy analysis. Tephra deposition from the climactic eruption of Mount Mazama approximately 7600 cal. years BP caused a significant local impact, reflected in the fringe location by changes to open habitat vegetation (Cyperaceae and Poaceae) and changes in aquatic macrophytes (Myriophyllum spicatum, Potamogeton, Equisetum and the alga Pediastrum). There was no significant impact of the climactic Mazama tephra or other tephras detected on the pollen record of the central core. Changes in this core are potentially climate driven. Overall, significant tephra fall was demonstrated through high resolution analyses indicating a local effect on the terrestrial and aquatic environment, but there was no significant impact on the regional forest dependent of underlying environmental changes

Tacrolimus in pediatric renal transplantation

Tacrolimus was used as the primary immunosuppressive agent in 69 pediatric renal transplantations between December 17, 1989, and June 30, 1995. Children undergoing concomitant or prior liver and/or intestinal transplantation were excluded from analysis. The mean recipient age was 10.3±5.0 years (range, 0.7-17.5 years). Seventeen (24.6%) children were undergoing retransplantation, and six (8.7%) had a panel reactive antibody level of 40% or higher. Thirty-nine (57%) cases were with cadaveric kidneys, and 30 (43%) were with living donors. The mean donor age was 28.0±14.7 years (range, 1.0-50.0 years), and the mean cold ischemia time for the cadaveric kidneys was 27.0±9.4 hr. The antigen match was 2.7±1.2, and the mismatch was 3.1±1.2. All patients received tacrolimus and steroids, without antibody induction, and 26% received azathioprine as well. The mean follow-up was 32±20 months. One- and 4-year actuarial patient survival rates were 100% and 95%. One- and 4-year actuarial graft survival rates were 99% and 85%. The mean serum creatinine level was 1.2±0.8 mg/dl, and the calculated creatinine clearance was 82±26 ml/min/1.73 m2. The mean tacrolimus dose was 0.22±0.14 mg/kg/day, and the level was 9.5±4.8 ng/ml. The mean prednisone dose was 2.1±4.9 mg/day (0.07±0.17 mg/kg/day), and 73% of successfully transplanted children were off prednisone. Seventy-nine percent were not taking any antihypertensive medications. The mean serum cholesterol level was 158±54 mg/dl. The incidence of delayed graft function was 4.3%. The incidence of rejection was 49%, and the incidence of steroid-resistant rejection was 6%. The incidence of rejection decreased to 27% in the most recent 26 cases (January 1994 through June 1995). The incidence of new-onset diabetes was 10.1%; six of the seven affected children were able to be weaned off insulin. The incidence of cytomegalovirus disease was 13%, and that of posttransplant lymphoproliferative disorder was 10%; the incidence of posttransplant lymphoproliferative disorder in the last 40 transplants was 5% (two cases). All of the children who developed posttransplant lymphoproliferative disorder are alive and have functioning allografts. Based on this data, we believe that tacrolimus is a superior immunosuppressive agent in pediatric renal transplant patients, with excellent short- and medium-term patient and graft survival, an ability to withdraw steroids in the majority of patients, and, with more experience, a decreasing rate of rejection and vital complications

Seeking Optimum System Settings for Physical Activity Recognition on Smartwatches

Physical activity recognition (PAR) using wearable devices can provide valued information regarding an individual's degree of functional ability and lifestyle. In this regards, smartphone-based physical activity recognition is a well-studied area. Research on smartwatch-based PAR, on the other hand, is still in its infancy. Through a large-scale exploratory study, this work aims to investigate the smartwatch-based PAR domain. A detailed analysis of various feature banks and classification methods are carried out to find the optimum system settings for the best performance of any smartwatch-based PAR system for both personal and impersonal models. To further validate our hypothesis for both personal (The classifier is built using the data only from one specific user) and impersonal (The classifier is built using the data from every user except the one under study) models, we tested single subject validation process for smartwatch-based activity recognition.Comment: 15 pages, 2 figures, Accepted in CVC'1

Posttransplant lymphoproliferative disorders in adult and pediatric renal transplant patients receiving tacrolimus-based immunosuppression

Between March 27, 1989 and December 31, 1997, 1316 kidney transplantations alone were performed under tacrolimus-based immunosuppression at our center. Posttransplant lymphoproliferative disorders (PTLD) developed in 25 (1.9%) cases; the incidence in adults was 1.2% (15/1217), whereas in pediatric patients it was 10.1% (10/99; P<.0001). PTLD was diagnosed 21.0±22.5 months after transplantation, 25.0±24.7 months in adults and 14.4±18.2 months in pediatric patients. Of the 4 adult cases in whom both the donor and recipient Epstein Barr virus (EBV) serologies were known, 2 (50%) were seropositive donor → seronegative recipient. Of 7 pediatric cases in whom both the donor and recipient EBV serologies were known, 6 (86%) were EBV seropositive donor → seronegative recipient. Acute rejection was observed before the diagnosis of PTLD in 8 (53%) of 15 adults and 3 (30%) of 10 pediatric patients. Initial treatment of PTLD included a marked decrease or cessation of immunosuppression with concomitant ganciclovir therapy; two adults and two pediatric patients required chemotherapy. With a mean follow-up of 24.9 ±30.1 months after transplantation, the 1- and 5-year actuarial patient and graft survival rates in adults were 93% and 86%, and 80% and 60%, respectively. Two adults died, 3.7 and 46.2 months after transplantation, of complications related to PTLD, and 10 (including the 2 deaths) lost their allograft 3.7-84.7 months after transplantation. In children, the 1- and 5-year actuarial patient and graft survival rates were 100% and 100%, and 100% and 89%, respectively. No child died; one child lost his allograft 41.3 months after transplantation. One child had presumed recurrent PTLD that responded to discontinuation of tacrolimus and reinitiation of antiviral therapy. The mean serum creatinine level in adults was 2.5±1.2 mg/dl, and in children, it was 1.3±0.6 mg/dl. Under tacrolimus-based immunosuppression, PTLD is less common after renal transplantation in adults than in children, but PTLD in children is associated with more favorable outcomes than in adults

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

Levosimendan for the prevention of acute organ dysfunction in sepsis

BACKGROUND Levosimendan is a calcium-sensitizing drug with inotropic and other properties that may improve outcomes in patients with sepsis. METHODS We conducted a double-blind, randomized clinical trial to investigate whether levosimendan reduces the severity of organ dysfunction in adults with sepsis. Patients were randomly assigned to receive a blinded infusion of levosimendan (at a dose of 0.05 to 0.2 μg per kilogram of body weight per minute) for 24 hours or placebo in addition to standard care. The primary outcome was the mean daily Sequential Organ Failure Assessment (SOFA) score in the intensive care unit up to day 28 (scores for each of five systems range from 0 to 4, with higher scores indicating more severe dysfunction; maximum score, 20). Secondary outcomes included 28-day mortality, time to weaning from mechanical ventilation, and adverse events. RESULTS The trial recruited 516 patients; 259 were assigned to receive levosimendan and 257 to receive placebo. There was no significant difference in the mean (±SD) SOFA score between the levosimendan group and the placebo group (6.68±3.96 vs. 6.06±3.89; mean difference, 0.61; 95% confidence interval [CI], −0.07 to 1.29; P=0.053). Mortality at 28 days was 34.5% in the levosimendan group and 30.9% in the placebo group (absolute difference, 3.6 percentage points; 95% CI, −4.5 to 11.7; P=0.43). Among patients requiring ventilation at baseline, those in the levosimendan group were less likely than those in the placebo group to be successfully weaned from mechanical ventilation over the period of 28 days (hazard ratio, 0.77; 95% CI, 0.60 to 0.97; P=0.03). More patients in the levosimendan group than in the placebo group had supraventricular tachyarrhythmia (3.1% vs. 0.4%; absolute difference, 2.7 percentage points; 95% CI, 0.1 to 5.3; P=0.04). CONCLUSIONS The addition of levosimendan to standard treatment in adults with sepsis was not associated with less severe organ dysfunction or lower mortality. Levosimendan was associated with a lower likelihood of successful weaning from mechanical ventilation and a higher risk of supraventricular tachyarrhythmia. (Funded by the NIHR Efficacy and Mechanism Evaluation Programme and others; LeoPARDS Current Controlled Trials number, ISRCTN12776039.

Joint actions with large partners and small-firm ambidexterity in asymmetric alliances:The mediating role of relational identification

This study investigates the role of relational identification in the relation between joint actions and small-firm ambidexterity in asymmetric alliances. Using survey data on Chinese high-technology firms, we find that joint problem-solving and joint sensemaking are both positively associated with small firm's relational identification. We also find a positive relationship between small firm's relational identification and knowledge exploration and exploitation. More importantly, we show that relational identification mediates the relationships between joint actions (i.e., joint problem-solving and joint sensemaking) and small-firm ambidexterity, except for the relationship between joint sensemaking and small-firm knowledge exploitation. This study advances our understanding of the association between joint actions and ambidexterity by providing a social identification explanation