Destructive de-energizing relationships: How thriving buffers their effect on performance.

PublishedThis is the author accepted manuscript. The final version is available from American Psychological Association via the DOI in this record.In this paper, we establish the relationship between de-energizing relationships and individual performance in organizations. To date, the emphasis in social network research has largely been on positive dimensions of relationships despite literature from social psychology revealing the prevalence and detrimental impact of de-energizing relationships. In 2 field studies, we show that de-energizing relationships in organizations are associated with decreased performance. In Study 1, we investigate how de-energizing relationships are related to lower performance using data from 161 people in the information technology (IT) department of an engineering firm. In Study 2, in a sample of 439 management consultants, we consider whether the effects of de-energizing relationships on performance may be moderated by the extent to which an individual has the psychological resource of thriving at work. We find that individuals who are thriving at work are less susceptible to the effects of de-energizing relationships on job performance. We close by discussing implications of this research

Predicting calvarial morphology in sagittal craniosynostosis

Early fusion of the sagittal suture is a clinical condition called, sagittal craniosynostosis. Calvarial reconstruction is the most common treatment option for this condition with a range of techniques being developed by different groups. Computer simulations have a huge potential to predict the calvarial growth and optimise the management of this condition. However, these models need to be validated. The aim of this study was to develop a validated patient-specific finite element model of a sagittal craniosynostosis. Here, the finite element method was used to predict the calvarial morphology of a patient based on its preoperative morphology and the planned surgical techniques. A series of sensitivity tests and hypothetical models were carried out and developed to understand the effect of various input parameters on the result. Sensitivity tests highlighted that the models are sensitive to the choice of input parameter. The hypothetical models highlighted the potential of the approach in testing different reconstruction techniques. The patient-specific model highlighted that a comparable pattern of calvarial morphology to the follow up CT data could be obtained. This study forms the foundation for further studies to use the approach described here to optimise the management of sagittal craniosynostosis

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.

Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B

BACKGROUND: Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS: In this phase 3, double-blind trial, we randomly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necroinflammatory score, without worsening of fibrosis). RESULTS: Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated (70 percent), as compared with 174 of 287 such patients in the lamivudine group (61 percent, P=0.01). More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus (HBV) DNA levels according to a polymerase-chain- reaction assay (90 percent vs. 72 percent, P<0.001) and normalization of alanine aminotransferase levels (78 percent vs. 71 percent, P = 0.045). The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine (5.0 vs. 4.5 log [on a base-10 scale] copies per milliliter, P<0.001). There was no evidence of resistance to entecavir. Safety and adverse-event profiles were similar in the two groups. CONCLUSIONS: Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue, the rates of histologic improvement, virologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine. The safety profile of the two agents was similar, and there was no evidence of viral resistance to entecavir. Copyright © 2006 Massachusetts Medical Society.published_or_final_versio

Influence of long-range dipolar interactions on the phase stability and hysteresis shapes of ferroelectric and antiferroelectric multilayers

Phase transition and field driven hysteresis evolution of a two-dimensional Ising grid consisting of ferroelectric-antiferroelectric multilayers that take into account the long range dipolar interactions were simulated by a Monte-Carlo method. Simulations were carried out for a 1+1 bilayer and a 5+5 superlattice. Phase stabilities of components comprising the structures with an electrostatic-like coupling term were also studied. An electrostatic-like coupling, in the absence of an applied field, can drive the ferroelectric layers towards 180º domains with very flat domain interfaces mainly due to the competition between this term and the dipole-dipole interaction. The antiferroelectric layers do not undergo an antiferroelectric-to-ferroelectric transition under the influence of an electrostatic-like coupling between layers as the ferroelectric layer splits into periodic domains at the expense of the domain wall energy. The long-range interactions become significant near the interfaces. For high periodicity structures with several interfaces, the interlayer long-range interactions substantially impact the configuration of the ferroelectric layers while the antiferroelectric layers remain quite stable unless these layers are near the Neel temperature. In systems investigated with several interfaces, the hysteresis loops do not exhibit a clear presence of antiferroelectricity that could be expected in the presence of anti-parallel dipoles, i. e., the switching takes place abruptly. Some recent experimental observations in ferroelectric-antiferroelectric multilayers are discussed where we conclude that the different electrical properties of bilayers and superlattices are not only due to strain effects alone but also long-range interactions. The latter manifests itself particularly in superlattices where layers are periodically exposed to each other at the interfaces

Intake of heterocyclic aromatic amines and the risk of prostate cancer in the EPIC-Heidelberg cohort

BACKGROUND: Heterocyclic amines (HCA) are positively associated with prostate cancer risk in animal models. Because of mostly inconsistent results of epidemiological studies, we examined the association between intake of HCA and prostate cancer risk. METHODS: In the EPIC-Heidelberg cohort, detailed information on diet, anthropometry, and lifestyle was assessed between 1994 and 1998. Dietary HCA intake was estimated using information on meat consumption, cooking methods, and preferred degree of browning. During 104,195 person-years of follow-up, 337 incident cases of prostate cancer (123 advanced cases) were identified among 9,578 men with valid dietary information. Multivariate Cox proportional hazards regression was used to examine the association between intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-3,4,8-dimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and prostate cancer. RESULTS: Men in the highest quartiles of PhIP, MeIQx, and DiMeIQx intake, respectively, had no increased risk of prostate cancer compared with men in the lowest quartiles (HR = 0.89, 95% CI 0.66-1.22 [PhIP]; 1.06, 0.77-1.45 [MeIQx]; 0.98, 0.72-1.34 [DiMeIQx]). There were no associations between HCA intake and advanced prostate cancer or between high consumption of strongly browned meat and prostate cancer. DISCUSSION: Our data do not support the hypothesis that HCA intake as consumed in a regular diet is a risk factor for prostate cancer

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

Minimization of phonon-tunneling dissipation in mechanical resonators

Micro- and nanoscale mechanical resonators have recently emerged as ubiquitous devices for use in advanced technological applications, for example in mobile communications and inertial sensors, and as novel tools for fundamental scientific endeavors. Their performance is in many cases limited by the deleterious effects of mechanical damping. Here, we report a significant advancement towards understanding and controlling support-induced losses in generic mechanical resonators. We begin by introducing an efficient numerical solver, based on the "phonon-tunneling" approach, capable of predicting the design-limited damping of high-quality mechanical resonators. Further, through careful device engineering, we isolate support-induced losses and perform the first rigorous experimental test of the strong geometric dependence of this loss mechanism. Our results are in excellent agreement with theory, demonstrating the predictive power of our approach. In combination with recent progress on complementary dissipation mechanisms, our phonon-tunneling solver represents a major step towards accurate prediction of the mechanical quality factor.Comment: 12 pages, 4 figure

Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.Peer reviewedFinal Published versio