Explore the vast range of titles available.

The addition of cyclo-oxygenase-2 (COX-2) inhibitors and prolonged constant infusion (PCI) of gemcitabine to treatment for advanced non-small-cell lung cancer (NSCLC) might improve treatment efficacy. We aimed to assess whether the addition of rofecoxib or PCI gemcitabine could improve overall survival compared with first-line treatment with cisplatin plus gemcitabine given by standard infusion. Patients with stage IV or IIIb (with supraclavicular nodes or pleural effusion) NSCLC who were under 70 years of age and who had performance status 0 or 1 were eligible for this multicentre, prospective, open-label, randomised phase III trial with 2×2 factorial design. Patients were randomly assigned to one of four treatment groups: group A, gemcitabine 1200 mg/m 2 in a 30-min intravenous infusion on days 1 and 8 and intravenous cisplatin 80 mg/m 2 on day 1, every 21 days for six cycles; group B, the same treatments as group A plus oral rofecoxib 50 mg/day until disease progression; group C, intravenous PCI gemcitabine 1200 mg/m 2 in a 120-min infusion on days 1 and 8 and intravenous cisplatin 80 mg/m 2 on day 1, every 21 days for six cycles; group D, the same drugs as group C plus oral rofecoxib 50 mg/day until disease progression. The primary endpoint was overall survival; secondary endpoints were progression-free survival, response rate, quality of life, and toxicity. Analyses were intention-to-treat. This trial is registered on the clinical trials site of the US National Institutes of Health website http://clinicaltrials.gov/ct/show/NCT00385606. Between Jan 30, 2003, and May 3, 2005, 400 patients were enrolled. Median age was 60 years (range 29–71). PCI gemcitabine did not improve overall survival (median 47 weeks [95% CI 40–55] vs 44 [36–52], with standard gemcitabine infusion, hazard ratio (HR) of death 0·93 [0·74–1·17], p=0·41), progression-free survival, nor any other secondary endpoint. Vomiting and fatigue were significantly worse with PCI gemcitabine. The two rofecoxib groups were closed early (on Oct 1, 2004) due to withdrawal of the drug because of safety issues. With intention-to-treat statistical analyses limited to 240 patients (ie, those randomised before July 1, 2004) who had at least 3 months of treatment, rofecoxib did not prolong overall survival (median 44 weeks [CI 36–55] vs 44 [40–54] without rofecoxib, and HR of death 1·00 [0·75–1·34], p=0·85), or progression-free survival, but did improve response rate (41% vs 26%, p=0·02), global quality of life, physical, emotional and role functioning, fatigue, and sleeping. Rofecoxib significantly increased the incidence of diarrhoea and decreased constipation, fatigue, fever, weight loss, and pain, and analgesic consumption. Severe cardiac ischaemia was more frequent with rofecoxib than without; however, the difference was not statistically significant in the primary analysis (p=0·06) and became significant when patients who were randomised between July 1, 2004, and Sept 30, 2004, were included in the analysis (p=0·03). Neither PCI gemcitabine nor rofecoxib prolonged survival in the patients in this study. Rofecoxib improved response rate and several quality-of-life items, including pain-related items and global quality of life. Further studies with less cardiotoxic COX-2 inhibitors are needed in NSCLC.

Flood risk maps for the built environment can be obtained by integrating geo-spatial information on hazard, vulnerability and exposure. They provide precious support for strategic urban planning and decision-making. These maps, generated in a probabilistic framework, can consider various sources of uncertainty in the flood risk assessment such as the occurrence of extreme flooding events, future land use and land cover, characteristics of the buildings, and exposure to flooding. This paper investigates how these maps can be used in complicated urban context such as developing countries, where engineers are forced to work with scarce or little data. Specifically, a detailed investigation on the city of Addis Ababa, Ethiopia, has been conducted. Although the city of Addis Ababa is undergoing extensive formal housing development, it is most likely that the informal settlements will continue to constitute a significant portion of urban housing landscape in the years to come. Recent research findings and field work from a large project (FP7-CLUVA) are employed in order to provide a quantified basis for decision-making between alternative adaptation strategies for informal buildings in Addis Ababa. Risk maps, obtained by up-scaling more accurate risk assessment results at neighborhood level, are adopted for risk zoning of the urban residential texture within the city. This provides risk-based criteria for both identifying suitable flood adaptation strategies and prioritizing between viable risk mitigation measures.

Molecular chaperones are key components of the cellular proteostasis network whose role includes the suppression of the formation and proliferation of pathogenic aggregates associated with neurodegenerative diseases. The molecular principles that allow chaperones to recognize misfolded and aggregated proteins remain, however, incompletely understood. To address this challenge, here we probe the thermodynamics and kinetics of the interactions between chaperones and protein aggregates under native solution conditions using a microfluidic platform. We focus on the binding between amyloid fibrils of α-synuclein, associated with Parkinson’s disease, to the small heat-shock protein αB-crystallin, a chaperone widely involved in the cellular stress response. We find that αB-crystallin binds to α-synuclein fibrils with high nanomolar affinity and that the binding is driven by entropy rather than enthalpy. Measurements of the change in heat capacity indicate significant entropic gain originates from the disassembly of the oligomeric chaperones that function as an entropic buffer system. These results shed light on the functional roles of chaperone oligomerization and show that chaperones are stored as inactive complexes which are capable of releasing active subunits to target aberrant misfolded species.

Purpose This study aims to couple two codes, one able to perform icing simulations and another one capable to simulate the performance of an electrothermal anti-icing system in an integrated fashion. Design/methodology/approach The classical tool chain of icing simulation (aerodynamics, water catch and impact, mass and energy surface balance) is coupled to the thermal analysis through the surface substrate and the ice thickness. In the present approach, the ice protection simulation is not decoupled from the ice accretion simulation, but a single computational workflow is considered. Findings A fast approach to simulate advanced anti-icing systems is found in this study. Originality/value This study shows the validation of present procedure against literature data, both experimental and numerical.

We consider polyconvex functionals of the Calculus of Variations defined on maps from the three-dimensional Euclidean space into itself. Counterexamples show that minimizers need not to be bounded. We find conditions on the structure of the functional, which force minimizers to be locally bounded.

Let us consider continuous minimizers$ u : \\bar \\Omega \\subset \\mathbb{R}^n \\to \\mathbb{R}^n $of $ \\mathcal{F}(v) = \\int_{\\Omega} [|Dv|^p \\, + \\, |{\\rm det}\\,Dv|^r] dx, $ with$ p > 1 $and$ r > 0 $ ; then it is known that every component$ u^\\alpha $of$ u = (u^1, ..., u^n) $enjoys maximum principle: the set of interior points$ x $ , for which the value$ u^\\alpha(x) $is greater than the supremum on the boundary, has null measure, that is,$ \\mathcal{L}^n(\\{ x \\in \\Omega: u^\\alpha (x) > \\sup_{\\partial \\Omega} u^\\alpha \\}) = 0 $ . If we change the structure of the functional, it might happen that the maximum principle fails, as in the case $ \\mathcal{F}(v) = \\int_{\\Omega}[\\max\\{(|Dv|^p - 1); 0 \\} \\, + \\, |{\\rm det}\\,Dv|^r] dx, $ with$ p > 1 $and$ r > 0 $ . Indeed, for a suitable boundary value, the set of the interior points$ x $ , for which the value$ u^\\alpha(x) $is greater than the supremum on the boundary, has a positive measure, that is$ \\mathcal{L}^n(\\{ x \\in \\Omega: u^\\alpha (x) > \\sup_{\\partial \\Omega} u^\\alpha \\}) > 0 $ . In this paper we show that the measure of the image of these bad points is zero, that is$ \\mathcal{L}^n(u(\\{ x \\in \\Omega: u^\\alpha (x) > \\sup_{\\partial \\Omega} u^\\alpha \\})) = 0 $ , provided$ p > n $ . This is a particular case of a more general theorem.

The need for a specific risk score system for infective endocarditis (IE) surgery has been previously claimed. In a single-center pilot study, preliminary to future multicentric development and validation, bivariate and multivariate (logistic regression) analysis of early postoperative mortality predictors in 440 native valve IE patients were performed. Mathematical procedures assigned scores to the independent predictors emerged (AUC of the ROC curve: 0.88). Overall mortality was 9.1%. Six predictors were identified and assigned scores, including age (5–13 points), renal failure (5), NYHA class IV (9), critical preoperative state (11), lack of preoperative attainment of blood culture negativity (5), perivalvular involvement (5). Four risk classes were drawn ranging from “very low risk” (≤5 points, mean predicted mortality 1%), and to “very high risk” (≥20 points, 43% mortality). IE-specific risk stratification models are both needed, as disease-specific factors (e.g., cultures, abscess), beside the generic ones (e.g., age, renal impairment) affect mortality, and feasible.

In the present manuscript we give a structure condition that allows for energy approximation in the vectorial case and we provide two examples, enjoying such a condition.

We prove “fractional” higher differentiability for the gradient of minimizers of anisotropic integral functionals, if the growth exponents are no too far apart. This allows us to give an estimate for the Hausdorff dimension of the singular set of the minimizers.