318 research outputs found

    Intermittent dislocation flow in viscoplastic deformation

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    The viscoplastic deformation (creep) of crystalline materials under constant stress involves the motion of a large number of interacting dislocations. Analytical methods and sophisticated `dislocation-dynamics' simulations have proved very effective in the study of dislocation patterning, and have led to macroscopic constitutive laws of plastic deformation. Yet, a statistical analysis of the dynamics of an assembly of interacting dislocations has not hitherto been performed. Here we report acoustic emission measurements on stressed ice single crystals, the results of which indicate that dislocations move in a scale-free intermittent fashion. This result is confirmed by numerical simulations of a model of interacting dislocations that successfully reproduces the main features of the experiment. We find that dislocations generate a slowly evolving configuration landscape which coexists with rapid collective rearrangements. These rearrangements involve a comparatively small fraction of the dislocations and lead to an intermittent behavior of the net plastic response. This basic dynamical picture appears to be a generic feature in the deformation of many other materials. Moreover, it should provide a framework for discussing fundamental aspects of plasticity, that goes beyond standard mean-field approaches that see plastic deformation as a smooth laminar flow

    Predicting Kindergarteners' End-Of-Year Spelling Ability Based On Their Reading, Alphabetic, Vocabulary, And Phonological Awareness Skills, As Well As Prior Literacy Experiences

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    This study examined the role of home literacy, parental education, and demographic factors in addition to conventional literacy skills at the beginning and end of kindergarten in predicting end-of-kindergarten spelling achievement. The study involved 9 schools and 29 classrooms serving an economically and ethnically diverse population (N = 288). Students spelled three types of words: sight words, decodable real words, and decodable pseudowords; spellings were scored to allow partial credit for invented spelling. Results from a three-step hierarchical regression indicated the variables accounted for 66% of the variance in spelling scores, with the single strongest spring predictor being a 1-minute letter-sound fluency test. Implications for instruction and for identifying students at risk for spelling and reading difficulties are discussed

    Pharmacokinetics and safety of panobacumab: specific adjunctive immunotherapy in critical patients with nosocomial Pseudomonas aeruginosa O11 pneumonia

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    Objectives Nosocomial Pseudomonas aeruginosa pneumonia remains a major concern in critically ill patients. We explored the potential impact of microorganism-targeted adjunctive immunotherapy in such patients. Patients and methods This multicentre, open pilot Phase 2a clinical trial (NCT00851435) prospectively evaluated the safety, pharmacokinetics and potential efficacy of three doses of 1.2 mg/kg panobacumab, a fully human monoclonal anti-lipopolysaccharide IgM, given every 72 h in 18 patients developing nosocomial P. aeruginosa (serotype O11) pneumonia. Results Seventeen out of 18 patients were included in the pharmacokinetic analysis. In 13 patients receiving three doses, the maximal concentration after the third infusion was 33.9 ± 8.0 μg/mL, total area under the serum concentration-time curve was 5397 ± 1993 μg h/mL and elimination half-life was 102.3 ± 47.8 h. Panobacumab was well tolerated, induced no immunogenicity and was detected in respiratory samples. In contrast to Acute Physiology and Chronic Health Evaluation II (APACHE II) prediction, all 13 patients receiving three doses survived, with a mean clinical resolution in 9.0 ± 2.7 days. Two patients suffered a recurrence at days 17 and 20. Conclusions These data suggest that panobacumab is safe, with a pharmacokinetic profile similar to that in healthy volunteers. It was associated with high clinical cure and survival rates in patients developing nosocomial P. aeruginosa O11 pneumonia. We concluded that these promising results warrant further trial

    Multicenter Evaluation of a Novel Surveillance Paradigm for Complications of Mechanical Ventilation

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    Ventilator-associated pneumonia (VAP) surveillance is time consuming, subjective, inaccurate, and inconsistently predicts outcomes. Shifting surveillance from pneumonia in particular to complications in general might circumvent the VAP definition's subjectivity and inaccuracy, facilitate electronic assessment, make interfacility comparisons more meaningful, and encourage broader prevention strategies. We therefore evaluated a novel surveillance paradigm for ventilator-associated complications (VAC) defined by sustained increases in patients' ventilator settings after a period of stable or decreasing support.We assessed 600 mechanically ventilated medical and surgical patients from three hospitals. Each hospital contributed 100 randomly selected patients ventilated 2-7 days and 100 patients ventilated >7 days. All patients were independently assessed for VAP and for VAC. We compared incidence-density, duration of mechanical ventilation, intensive care and hospital lengths of stay, hospital mortality, and time required for surveillance for VAP and for VAC. A subset of patients with VAP and VAC were independently reviewed by a physician to determine possible etiology.Of 597 evaluable patients, 9.3% had VAP (8.8 per 1,000 ventilator days) and 23% had VAC (21.2 per 1,000 ventilator days). Compared to matched controls, both VAP and VAC prolonged days to extubation (5.8, 95% CI 4.2-8.0 and 6.0, 95% CI 5.1-7.1 respectively), days to intensive care discharge (5.7, 95% CI 4.2-7.7 and 5.0, 95% CI 4.1-5.9), and days to hospital discharge (4.7, 95% CI 2.6-7.5 and 3.0, 95% CI 2.1-4.0). VAC was associated with increased mortality (OR 2.0, 95% CI 1.3-3.2) but VAP was not (OR 1.1, 95% CI 0.5-2.4). VAC assessment was faster (mean 1.8 versus 39 minutes per patient). Both VAP and VAC events were predominantly attributable to pneumonia, pulmonary edema, ARDS, and atelectasis.Screening ventilator settings for VAC captures a similar set of complications to traditional VAP surveillance but is faster, more objective, and a superior predictor of outcomes

    Krüppel-Like Factor 6 Expression Changes during Trophoblast Syncytialization and Transactivates ßhCG and PSG Placental Genes

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    BACKGROUND: Krüppel-like factor-6 (KLF6) is a widely expressed member of the Sp1/KLF family of transcriptional regulators involved in differentiation, cell cycle control and proliferation in several cell systems. Even though the highest expression level of KLF6 has been detected in human and mice placenta, its function in trophoblast physiology is still unknown. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we explored KLF6 expression and sub-cellular distribution in human trophoblast cells differentiating into the syncytial pathway, and its role in the regulation of genes associated with placental development and pregnancy maintenance. Confocal immunofluorescence microscopy demonstrated that KLF6 is expressed throughout human cytotrophoblast differentiation showing no evident modifications in its nuclear and cytoplasmic localization pattern. KLF6 transcript and protein peaked early during the syncytialization process as determined by qRT-PCR and western blot assays. Overexpression of KLF6 in trophoblast-derived JEG-3 cells showed a preferential nuclear signal correlating with enhanced expression of human β-chorionic gonadotropin (βhCG) and pregnancy-specific glycoprotein (PSG) genes. Moreover, KLF6 transactivated βhCG5, PSG5 and PSG3 gene promoters. Deletion of KLF6 Zn-finger DNA binding domain or mutation of the consensus KLF6 binding site abolished transactivation of the PSG5 promoter. CONCLUSIONS/SIGNIFICANCE: Results are consistent with KLF6 playing a role as transcriptional regulator of relevant genes for placental differentiation and physiology such as βhCG and PSG, in agreement with an early and transient increase of KLF6 expression during trophoblast syncytialization
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