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"CONSOLIDATION"
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Consolidation analyses of soils
When stresses are applied to saturated soil, deformation will occur as water in voids is squeezed out. Consolidation Analyses of Soils focuses on the consolidation of fully saturated soils. The book follows a classic approach by beginning with one-dimensional constitutive relations of soils and one-dimensional consolidation. It then moves on to analytical solutions to several one-dimensional consolidation problems and one-dimensional finite strain consolidation. The authors also present a finite element method for consolidation analysis of one-dimensional problems, analytical solutions to consolidation of soil with vertical drains, and a finite difference method for consolidation analysis of one-dimensional problems. Simplified methods for consolidation analysis of soils exhibiting creep are introduced and applied to different cases. Three-dimensional consolidation equations and solutions of typical three-dimensional consolidation problems are covered, as well as simplified finite element consolidation analysis of soils with vertical drain and finite element method for three-dimensional consolidation problems. The book is unique in that it covers both classic solutions and state-of-the-art work in consolidation analyses of soils. Authors Jian-Hua Yin is Chair Professor of Soil Mechanics in the Department of Civil and Environmental Engineering at The Hong Kong Polytechnic University. Guofu Zhu is a Professor in the Department of Engineering Structures and Mechanics at Wuhan University of Technology, China.
Book
«ATHENIS AREOPAGI ANTIQUITATIS EXEMPLAR ...» (VITR., 2, 1, 5), «ET APP REHENSUM AD ARIOP AGUM DUXERUNT» (AT 17, 19-34). RAFF AELLO, IL DE ARCHITECTURA, GLI ACTA APOSTOLORUM E L'ARAZZO DELLA PREDICA DI SAN PAOLO AD ATENE
Il saggio prende le mosse da un passo del De architectura in cui Vitruvio tratta delle antiche coperture in terra e paglia ram mentando l'Areopago di Atene (Vitr. 2, 1, 5) per poi dirigersi verso l'arazzo vaticano, eseguito dalla bottega di Pieter van Aelst da un cartone di Raffaello, raffigurante la Predica di San Paolo ad Atene (Atti degli Apostoli, 17, 19-34). Del soggetto dell'arazzo si suggerisce una nuova interpretazione. Le fonti greche (mai sinora utilizzate) e romane, da Isocrate a Demostene, da Eschilo a Pausania, da Valerio Massimo ad Arator, accertano l'identità del luogo raffigurato
Journal Article
Locus coeruleus and dopaminergic consolidation of everyday memory
The retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine-hydroxylase-expressing (TH
+
) neurons in the ventral tegmental area. Here we report that neuronal firing in the locus coeruleus is especially sensitive to environmental novelty, locus coeruleus TH
+
neurons project more profusely than ventral tegmental area TH
+
neurons to the hippocampus, optogenetic activation of locus coeruleus TH
+
neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by ventral tegmental area inactivation. Surprisingly, two effects of locus coeruleus TH
+
photoactivation are sensitive to hippocampal D
1
/D
5
receptor blockade and resistant to adrenoceptor blockade: memory enhancement and long-lasting potentiation of synaptic transmission in CA1
ex vivo
. Thus, locus coeruleus TH
+
neurons can mediate post-encoding memory enhancement in a manner consistent with possible co-release of dopamine in the hippocampus.
Projections from the locus coeruleus, an area typically defined by noradrenergic signalling, to the hippocampus drive novelty-based memory enhancement through possible co-release of dopamine.
Memory consolidation in the locus coeruleus
Memory retention can be enhanced when something novel or categorically relevant occurs shortly before or after the time of memory encoding, as in 'flashbulb memory'. Dopamine-based mechanisms originating in the ventral tegmental area have been implicated in the phenomenon. These authors suggest that projections from the locus coeruleus—typically defined by noradrenergic signalling—to the hippocampus drive this novelty-based memory enhancement through the possible local release of dopamine.
Journal Article
Intelligent M & A : navigating the mergers and acquisitions minefield
\"Intelligent M & A is the first book that looks at the full process of a merger or acquisition to identify where business intelligence can improve those odds of a favorable outcome. Using techniques developed by governmental intelligence services and honed by savvy business leaders over the two huge merger waves of the past decade, this book uses a wide range of actual case studies, quotations, and anecdotes to demonstrate how to build success into every phase of the deal. Not just large global corporate mergers, but also small company acquisitions, public sector mergers, and private deals are discussed.\"--Jacket.
Book
Arsenic trioxide replacing or reducing chemotherapy in consolidation therapy for acute promyelocytic leukemia (APL2012 trial)
As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).
Journal Article
The value killers: how mergers and acquisitions cost companies billions - and how to prevent it
In a business climate marked by escalating global competition and industry disruption, successful mergers and acquisitions are increasingly vital to the growth and profitability of many corporations. If history is any guide, 60 to 70 per cent of new mergers will fail - and will destroy shareholder value. To date, analyses of the M&A failure rate tend to focus on individual causes - e.g., culture clashes, valuation methods, or CEO overconfidence - rather than examining the problem holistically. The Value Killers is the first book based on a holistic analysis of successful and unsuccessful transactions. Based on research, interviews with top executives, and case studies, this book identifies the key causes of failures and successes and offers prescriptions to increase the odds that future transactions will deliver all the anticipated synergies. The Value Killers offers practical advice in the form of 5 Golden Rules. These rules will help managers and boards to ensure that target companies are properly valued; potential synergies and risks are identified in advance; checks and balances are installed to make sure that the pros and cons of the transaction are rationally and objectively evaluated; mechanisms are created that will trigger termination of bad deals; and obstacles to successful post-merger integrations are assessed (and solutions developed) before the deal closes. Each chapter includes questions for executives considering future M&As to allow them to see whether they are on the right track or not.
Book
Augmented post-remission therapy for a minimal residual disease-defined high-risk subgroup of children and young people with clinical standard-risk and intermediate-risk acute lymphoblastic leukaemia (UKALL 2003): a randomised controlled trial
No randomised study has shown whether stratification of treatment by minimal residual disease (MRD) response improves outcome in children and young people with acute lymphoblastic leukaemia (ALL). We assessed whether children and young people with clinical standard and intermediate-risk ALL who have persistent MRD at the end of induction therapy benefit from augmented post-remission therapy.
Between Oct 1, 2003, and June 30, 2011, we enrolled eligible patients aged 1–24 years and initially categorised them into clinical standard-risk, intermediate-risk, and high-risk groups on the basis of a combination of National Cancer Institute criteria, cytogenetics, and early morphological response to induction therapy. Clinical standard-risk and intermediate-risk patients with MRD of 0·01% or higher at day 29 of induction (MRD high risk) were randomly assigned (1:1) to standard therapy (treatment regimens A and B) or augmented post-remission therapy (regimen C). Compared with standard therapy, the augmented treatment regimen (regimen C) included an additional eight doses of pegylated asparaginase, 18 doses of vincristine, and escalated-dose intravenous methotrexate without folinic acid rescue during interim maintenance courses. Computer randomisation was used for treatment allocation and was balanced for sex, age (<10 years vs ≥10 years), and white blood cell count at diagnosis (<50 × 109/L vs ≥50 × 109/L) by minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcomes were event-free survival and overall survival. Analyses were by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07355119.
533 MRD high-risk patients were randomly assigned to receive standard (n=266) or augmented (n=267) post-remission therapy. After a median follow-up of 70 months (IQR 52–91), 5-year event-free survival was better in the augmented treatment group (89·6% [95% CI 85·9–93·3]) than in the standard group (82·8% [78·1–87·5]; odds ratio [OR] 0·61 [95% CI 0·39–0·98], p=0·04). Overall survival at 5 years was numerically, but not significantly, higher in the augmented treatment group (92·9% [95% CI 89·8–96·0]) than in the standard therapy group (88·9% [85·0–92·8]; OR 0·67 [95% CI 0·38–1·17], p=0·16). More adverse events occurred in the augmented treatment group than in the standard group (asparaginase-related hypersensitivity in 18 [6·7%] in the augmented group vs two [0·8%] in the standard group and asparaginase-related pancreatitis in eight [3·0%] vs one [0·4%]; intravenous methotrexate-related mucositis in 11 [4·1%] vs three [1·1%] and methotrexate-related stomatitis in 48 [18·0%] vs 12 [4·5%]).
Our findings suggest that children and young people with acute lymphoblastic leukaemia and 0·01% or more MRD at the end of remission induction therapy could benefit from augmented post-remission therapy. However, the asparaginase and intravenous methotrexate used in the augmented treatment regimen is associated with more adverse events than is the standard post-remission treatment regimen.
Medical Research Council and Leukaemia and Lymphoma Research.
Journal Article
Optogenetic reactivation of memory ensembles in the retrosplenial cortex induces systems consolidation
The neural circuits underlying memory change over prolonged periods after learning, in a process known as systems consolidation. Postlearning spontaneous reactivation of memory-related neural ensembles is thought to mediate this process, although a causal link has not been established. Here we test this hypothesis in mice by using optogenetics to selectively reactivate neural ensembles representing a contextual fear memory (sometimes referred to as engram neurons). High-frequency stimulation of these ensembles in the retrosplenial cortex 1 day after learning produced a recent memory with features normally observed in consolidated remote memories, including higher engagement of neocortical areas during retrieval, contextual generalization, and decreased hippocampal dependence. Moreover, this effect was only present if memory ensembles were reactivated during sleep or light anesthesia. These results provide direct support for postlearning memory ensemble reactivation as a mechanism of systems consolidation, and show that this process can be accelerated by ensemble reactivation in an unconscious state.
Journal Article