132 research outputs found
Cynicism about change, work engagement, and job satisfaction of Public Sector Nurses
This paper uses the job demands‐resources theory to examine the consequences of changes on nursing work. Data were collected from 220 public sector nurses in Australia to test the model. We conducted a two‐wave data collection process where independent variables (organisational change, workload, job control, nursing administrative stressors, cynicism about organisational change, and demographic variables) were collected in Time 1. The dependent variables (nursing work engagement and job satisfaction) were collected 6 months later. Changes to nursing work were found to cause high workload and an increase of administrative stressors that leads to an increase in nurses’ change cynicism. Job control was needed to cope with the increase in workload and reduction in cynicism about change. Cynicism about organisational change was found to have a direct negative effect on nurses’ engagement which in turn was found to negatively impact job satisfaction. Our contribution to theory and practice arises from the discovery that the connections between organisational change, work environment variables, and job outcomes of nurses are more complicated than previous research suggests. Theoretical and practical implications will be discussed
Participation in change, job characteristics, and hedonic well‐being of senior public managers: The moderation effect of change information
This study contributes to Hobfoll\u27s Conservation of Resources theory by testing a moderated mediation model of the relationship between participation in change and senior managers’ hedonic well‐being. Using data collected from 266 Australian senior managers employed in the Commonwealth and State public sector, we tested the interaction of participation in change and change information with job satisfaction, an example of hedonic well‐being at work. Findings from the path analysis produced two new insights. First, both participation in change and information about change are key resources that senior managers can deploy to protect and enhance their job satisfaction. Second, information about change has a buffering effect on the indirect relationship between participation in change and job satisfaction through job control. These two findings have practical implications indicating that it is important to train and equip senior managers in the adoption of effective strategies to acquire job resources in assisting them deal with change induced job demands
Participation in change, job characteristics, and hedonic well‐being of senior public managers: The moderation effect of change information
This study contributes to Hobfoll\u27s Conservation of Resources theory by testing a moderated mediation model of the relationship between participation in change and senior managers’ hedonic well‐being. Using data collected from 266 Australian senior managers employed in the Commonwealth and State public sector, we tested the interaction of participation in change and change information with job satisfaction, an example of hedonic well‐being at work. Findings from the path analysis produced two new insights. First, both participation in change and information about change are key resources that senior managers can deploy to protect and enhance their job satisfaction. Second, information about change has a buffering effect on the indirect relationship between participation in change and job satisfaction through job control. These two findings have practical implications indicating that it is important to train and equip senior managers in the adoption of effective strategies to acquire job resources in assisting them deal with change induced job demands
Dissociating motor impairment from five-choice serial reaction time task performance in a mouse model of Angelman syndrome
Angelman syndrome (AS) is a single-gene neurodevelopmental disorder associated with cognitive and motor impairment, seizures, lack of speech, and disrupted sleep. AS is caused by loss-of-function mutations in the UBE3A gene, and approaches to reinstate functional UBE3A are currently in clinical trials in children. Behavioral testing in a mouse model of AS (Ube3am–/p+) represents an important tool to assess the effectiveness of current and future treatments preclinically. Existing behavioral tests effectively model motor impairments, but not cognitive impairments, in Ube3am–/p+ mice. Here we tested the hypothesis that the 5-choice serial reaction time task (5CSRTT) can be used to assess cognitive behaviors in Ube3am–/p+ mice. Ube3am–/p+ mice had more omissions during 5CSRTT training than wild-type littermate controls, but also showed impaired motor function including open field hypoactivity and delays in eating pellet rewards. Motor impairments thus presented an important confound for interpreting this group difference in omissions. We report that despite hypoactivity during habituation, Ube3am–/p+ mice had normal response latencies to retrieve rewards during 5CSRTT training. We also accounted for delays in eating pellet rewards by assessing omissions solely on trials where eating delays would not impact results. Thus, the increase in omissions in Ube3am–/p+ mice is likely not caused by concurrent motor impairments. This work underscores the importance of considering how known motor impairments in Ube3am–/p+ mice may affect behavioral performance in other domains. Our results also provide guidance on how to design a 5CSRTT protocol that is best suited for future studies in Ube3a mutants
Feedback-optimized parallel tempering Monte Carlo
We introduce an algorithm to systematically improve the efficiency of
parallel tempering Monte Carlo simulations by optimizing the simulated
temperature set. Our approach is closely related to a recently introduced
adaptive algorithm that optimizes the simulated statistical ensemble in
generalized broad-histogram Monte Carlo simulations. Conventionally, a
temperature set is chosen in such a way that the acceptance rates for replica
swaps between adjacent temperatures are independent of the temperature and
large enough to ensure frequent swaps. In this paper, we show that by choosing
the temperatures with a modified version of the optimized ensemble feedback
method we can minimize the round-trip times between the lowest and highest
temperatures which effectively increases the efficiency of the parallel
tempering algorithm. In particular, the density of temperatures in the
optimized temperature set increases at the "bottlenecks'' of the simulation,
such as phase transitions. In turn, the acceptance rates are now temperature
dependent in the optimized temperature ensemble. We illustrate the
feedback-optimized parallel tempering algorithm by studying the two-dimensional
Ising ferromagnet and the two-dimensional fully-frustrated Ising model, and
briefly discuss possible feedback schemes for systems that require
configurational averages, such as spin glasses.Comment: 12 pages, 14 figure
First-order transition of tethered membranes in 3d space
We study a model of phantom tethered membranes, embedded in three-dimensional
space, by extensive Monte Carlo simulations. The membranes have hexagonal
lattice structure where each monomer is interacting with six nearest-neighbors
(NN). Tethering interaction between NN, as well as curvature penalty between NN
triangles are taken into account. This model is new in the sense that NN
interactions are taken into account by a truncated Lennard-Jones potential
including both repulsive and attractive parts. The main result of our study is
that the system undergoes a first-order crumpling transition from low
temperature flat phase to high temperature crumpled phase, in contrast with
early numerical results on models of tethered membranes.Comment: 5 pages, 6 figure
Characterization and Comparison of 2 Distinct Epidemic Community-Associated Methicillin-Resistant Staphylococcus aureus Clones of ST59 Lineage.
Sequence type (ST) 59 is an epidemic lineage of community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal cassette mec (SCCmec) VT, and is frequently isolated from patients with severe disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a frequent colonizer of healthy children. Isolates of both clones were characterized by their ability to adhere to respiratory A549 cells, cytotoxicity to human neutrophils, and nasal colonization of a murine and murine sepsis models. Genome variation was determined by polymerase chain reaction of selected virulence factors and by multi-strain whole genome microarray. Additionally, the expression of selected factors was compared between the 2 clones. The Taiwan clone showed a much higher cytotoxicity to the human neutrophils and caused more severe septic infections with a high mortality rate in the murine model. The clones were indistinguishable in their adhesion to A549 cells and persistence of murine nasal colonization. The microarray data revealed that the Taiwan clone had lost the ø3-prophage that integrates into the β-hemolysin gene and includes staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for human immune evasion, scn and chps. Production of the virulence factors did not differ significantly in the 2 clonal groups, although more α-toxin was expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and an animal infection model. The evolutionary acquisition of PVL, the higher expression of α-toxin, and possibly the loss of a large portion of the β-hemolysin-converting prophage likely contribute to its higher pathogenic potential than the Asian-Pacific clone
Combination Antifungal Therapy for Cryptococcal Meningitis
Background
Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days.
Methods
We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks.
Results
A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (−0.42 log10 colony-forming units [CFU] per milliliter per day vs. −0.31 and −0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy.
Conclusions
Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found
TAK1 Is Required for Survival of Mouse Fibroblasts Treated with TRAIL, and Does So by NF-κB Dependent Induction of cFLIPL
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known as a “death ligand”—a member of the TNF superfamily that binds to receptors bearing death domains. As well as causing apoptosis of certain types of tumor cells, TRAIL can activate both NF-κB and JNK signalling pathways. To determine the role of TGF-β-Activated Kinase-1 (TAK1) in TRAIL signalling, we analyzed the effects of adding TRAIL to mouse embryonic fibroblasts (MEFs) derived from TAK1 conditional knockout mice. TAK1−/− MEFs were significantly more sensitive to killing by TRAIL than wild-type MEFs, and failed to activate NF-κB or JNK. Overexpression of IKK2-EE, a constitutive activator of NF-κB, protected TAK1−/− MEFs against TRAIL killing, suggesting that TAK1 activation of NF-κB is critical for the viability of cells treated with TRAIL. Consistent with this model, TRAIL failed to induce the survival genes cIAP2 and cFlipL in the absence of TAK1, whereas activation of NF-κB by IKK2-EE restored the levels of both proteins. Moreover, ectopic expression of cFlipL, but not cIAP2, in TAK1−/− MEFs strongly inhibited TRAIL-induced cell death. These results indicate that cells that survive TRAIL treatment may do so by activation of a TAK1–NF-κB pathway that drives expression of cFlipL, and suggest that TAK1 may be a good target for overcoming TRAIL resistance
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