Effective linear damping and stiffness coefficients of nonlinear systems for design spectrum based analysis

A stochastic approach for obtaining reliable estimates of the peak response of nonlinear systems to excitations specified via a design seismic spectrum is proposed. This is achieved in an efficient manner without resorting to numerical integration of the governing nonlinear equations of motion. First, a numerical scheme is utilized to derive a power spectrum which is compatible in a stochastic sense with a given design spectrum. This power spectrum is then treated as the excitation spectrum to determine effective damping and stiffness coefficients corresponding to an equivalent linear system (ELS) via a statistical linearization scheme. Further, the obtained coefficients are used in conjunction with the (linear) design spectrum to estimate the peak response of the original nonlinear systems. The cases of systems with piecewise linear stiffness nonlinearity, along with bilinear hysteretic systems are considered. The seismic severity is specified by the elastic design spectrum prescribed by the European aseismic code provisions (EC8). Monte Carlo simulations pertaining to an ensemble of nonstationary EC8 design spectrum compatible accelerograms are conducted to confirm that the average peak response of the nonlinear systems compare reasonably well with that of the ELS, within the known level of accuracy furnished by the statistical linearization method. In this manner, the proposed approach yields ELS which can replace the original nonlinear systems in carrying out computationally efficient analyses in the initial stages of the aseismic design of structures under severe seismic excitations specified in terms of a design spectrum

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

"It's a can of worms": understanding primary care practitioners' behaviours in relation to HPV using the Theoretical Domains Framework

Background: The relationship between infection with high-risk human papillomavirus (HPV) and cervical cancer is transforming cervical cancer prevention. HPV tests and vaccinations have recently become available. In Ireland, as elsewhere, primary care practitioners play a key role in prevention. ATHENS (A Trial of HPV Education and Support) aims to develop a theorybased intervention to support primary care practitioners in their HPV-related practice. This study, the first step in the intervention development process, aimed to: identify HPV-related clinical behaviours that the intervention will target; clarify general practitioners’ (GPs’) and practice nurses’ roles and responsibilities; and determine factors that potentially influence clinical behaviour. A secondary objective was to informally assess the utility of the Theoretical Domains Framework (TDF) in understanding clinical behaviours in an area with an evolving evidence-base. Methods: In-depth semi-structured telephone interviews were conducted with GPs and practice nurses. The topic guide, which contained open questions and HPV-related clinical scenarios, was developed through literature review and clinical experience. Interview transcripts were content-analysed using the TDF as the coding framework. Results: 19 GPs and 14 practice nurses were interviewed. The major HPV-related clinical behaviours were: initiating a discussion about HPV infection with female patients; offering/recommending HPV vaccination to appropriate patients; and answering patients’ questions about HPV testing. While the responsibility for taking smears was considered a female role, both male and female practitioners dealt with HPV-related issues. All 12 theoretical domains arose in relation to HPV infection; the domains judged to be most important were: knowledge, emotion, social influences, beliefs about capabilities and beliefs about consequences. Eleven domains emerged in relation to HPV vaccination, with beliefs about consequences, social influences, knowledge and environmental context and resources judged to be the most important. Nine domains were relevant to HPV testing, with knowledge and beliefs about capabilities judged to be the most important. Conclusions: The findings confirm the need for an intervention to support primary care practitioners around HPV and suggest it should target a range of theoretical domains. The TDF proved valuable in analysing qualitative data collected using a topic guide not specifically designed to capture TDF domains and understanding clinical behaviours in an area with an evolving evidence-base

Teaching of Energy Issues: A debate proposal for a GLobal Reorientation

The growing awareness of serious difficulties in the learning of energy issues has produced a great deal of research, most of which is focused on specific conceptual aspects. In our opinion, the difficulties pointed out in the literature are interrelated and connected to other aspects (conceptual as well as procedural and axiological), which are not sufficiently taken into account in previous research. This paper aims to carry out a global analysis in order to avoid the more limited approaches that deal only with individual aspects. From this global analysis we have outlined 24 propositions that are put forward for debate to lay the foundations for a profound reorientation of the teaching of energy topics in upper high school courses, in order to facilitate a better scientific understanding of these topics, avoid many students' misconceptions and enhance awareness of the current situation of planetary emergency

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Crime, bandits, and community: how public panic shaped the social control of territory in the Ottoman Empire

This study explores the role of crime, bandits, and public panic in in the nineteenth century Ottoman society by using archival documents and employing a comparative perspective. In addition to the social bandit concept of Eric Hobsbawm, there is an introduction of two new banditry forms in this study—opportunist bandits and imagined bandits. The comparison of different bandit forms clarifies that social bandits and opportunist bandits aggravated public panic and produced imagined bandits. Hence, public panic and the dissent of local people unveiled through rumors about the imagined bandits. The exploration of different forms of bandits in the Ottoman Empire is a response to the vexed issue concerning the challenges in the social control of territories in a multiethnic and multi-religious empire. This study provides new conceptual tools to rethink about the spatial dimensions in the emergence of bandits. This article shows that spatial factors in the social control of territory can be influenced by the reaction of local people from bottom-to-top and, in doing so, can determine the response of state authority. The present study, therefore, unveils the power relationship in the social control of territory whether it is manifested by physical force or public panic.N/

Beneficial effect of Mentha suaveolens essential oil in the treatment of vaginal candidiasis assessed by real-time monitoring of infection

<p>Abstract</p> <p>Background</p> <p>Vaginal candidiasis is a frequent and common distressing disease affecting up to 75% of the women of fertile age; most of these women have recurrent episodes. Essential oils from aromatic plants have been shown to have antimicrobial and antifungal activities. This study was aimed at assessing the anti-fungal activity of essential oil from <it>Mentha suaveolens </it>(EOMS) in an experimental infection of vaginal candidiasis.</p> <p>Methods</p> <p>The <it>in vitro </it>and <it>in vivo </it>activity of EOMS was assessed. The <it>in vitro </it>activity was evaluated under standard CLSI methods, and the <it>in vivo </it>analysis was carried out by exploiting a novel, non-invasive model of vaginal candidiasis in mice based on an <it>in vivo </it>imaging technique.</p> <p>Differences between essential oil treated and saline treated mice were evaluated by the non-parametric Mann-Whitney U-test. Viable count data from a time kill assay and yeast and hyphae survival test were compared using the Student's t-test (two-tailed).</p> <p>Results</p> <p>Our main findings were: i) EOMS shows potent candidastatic and candidacidal activity in an <it>in vitro </it>experimental system; ii) EOMS gives a degree of protection against vaginal candidiasis in an <it>in vivo </it>experimental system.</p> <p>Conclusions</p> <p>This study shows for the first time that the essential oil of a Moroccan plant <it>Mentha suaveolens </it>is candidastatic and candidacidal <it>in vitro</it>, and has a degree of anticandidal activity in a model of vaginal infection, as demonstrated in an <it>in vivo </it>monitoring imaging system. We conclude that our findings lay the ground for further, more extensive investigations to identify the active EOMS component(s), promising in the therapeutically problematic setting of chronic vaginal candidiasis in humans.</p

Sentinel lymph node biopsy as guidance for radical trachelectomy in young patients with early stage cervical cancer

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to assess the feasibility and accuracy of sentinel lymph nodes (SLNs) detection using 99mTc phytate in predicting pelvic lymph nodes status for radical abdominal trachelectomy (RAT) in patients with early stage cervical cancer.</p> <p>Methods</p> <p>Sixty-eight women with stage IA2-IB1 cervical cancer and scheduled to undergo fertility-sparing surgery enrolled in this study. 99mTc-labeled phytate was injected before surgery. Intraoperatively, SLNs were identified, excised, and submitted to fast frozen section. Systematic bilateral pelvic lymphadenectomy and/or para-aortic lymph node dissection was performed. Then RAT was performed in patients with negative SLNs. All nodes were sent for routine pathological examination and immunostained with anti-cytokeratin antibody to detect micrometastases. Outcomes of follow up and fertility were observed.</p> <p>Results</p> <p>SLNs were identified in 64 of 68 patients (94.1%). Of these, SLNs of 8 patients (11.8%) were positive on frozen sections and proved to be metastasis by final pathologic examination. The sensitivity, accuracy, and false negative rates were 100%, 100%, and 0%, respectively. All 60 patients with negative SLN underwent RAT successfully. Two relapses occurred and no one died of tumor progression during follow-up. Five of the 15 patients with procreative desire conceived 8 pregnancies (3 term delivery, 2 premature birth, 1 spontaneous abortion, and 2 were still in the duration of pregnancy) after surgery.</p> <p>Conclusions</p> <p>The identification of SLN using 99mTc-labeled phytate is accurate and safe to assess pelvic nodes status in patients with early cervical cancer. SLNs biopsy guided RAT is feasible for patients who desire to have fertility preservation.</p