Moving on up: Second-Line Agents as Initial Treatment for Newly-Diagnosed Patients with Chronic Phase CML

The treatment of chronic myelogenous leukemia (CML) was revolutionized by the development of imatinib mesylate, a small molecule inhibitor of several protein tyrosine kinases, including the ABL1 protein tyrosine kinase. The current second generation of FDA-approved ABL tyrosine kinase inhibitors, dasatinib and nilotinib, are more potent inhibitors of BCR-ABL1 kinase in vitro. Originally approved for the treatment of patients who were refractory to or intolerant of imatinib, dasatinib and nilotinib are now also FDA approved in the first-line setting. The choice of tyrosine kinase inhibitor (ie, standard or high dose imatinib, dasatinib, nilotinib) to use for initial therapy in chronic-phase CML (CML-CP) will not always be obvious. Therapy selection will depend on both clinical and molecular factors, which we will discuss in this review

Development of biomass fast proximate analysis by thermogravimetric scale

[EN] EN norms set the methods for determining the ash and volatile content in biomass. These establish the use of a muffle to heat the samples at temperatures of 550 degrees C and 900 degrees C respectively, with a minimum analysis time of 4 h as standard method. The objective of this work was to reduce significantly the analysis times, making very short heating periods using a thermogravimetric scale (TGA), and to apply an equation to the residual weight to obtain the weight of ash, volatiles and fixed carbon in biomass samples. We analyzed the factors: the temperature ramp, atmosphere and airflow in the determination. In this work new validated methods were developed with an analysis time of 10-20 min. (C) 2018 Elsevier Ltd. All rights reserved.This research work has been carried out inside the cooperation framework funded by the ADSIDEO program of the Centro de Cooperacion al Desarrollo (CCD) of Universidad Politecnica de Valencia (Spain), in collaboration with the Centro de Estudios de la Biomasa (CEB), Universidad Estatal de Bolivar, Guaranda, Ecuador.Velázquez Martí, B.; Gaibor-Chavez, J.; Niño-Ruiz, Z.; Cortes-Rojas, E. (2018). Development of biomass fast proximate analysis by thermogravimetric scale. Renewable Energy. 126:954-959. https://doi.org/10.1016/j.renene.2018.04.021S95495912

Sensitivity analysis in optimized parametric curve fitting

Purpose – Curve fitting from unordered noisy point samples is needed for surface reconstruction in many applications -- In the literature, several approaches have been proposed to solve this problem -- However, previous works lack formal characterization of the curve fitting problem and assessment on the effect of several parameters (i.e. scalars that remain constant in the optimization problem), such as control points number (m), curve degree (b), knot vector composition (U), norm degree (k), and point sample size (r) on the optimized curve reconstruction measured by a penalty function (f) -- The paper aims to discuss these issues -- Design/methodology/approach - A numerical sensitivity analysis of the effect of m, b, k and r on f and a characterization of the fitting procedure from the mathematical viewpoint are performed -- Also, the spectral (frequency) analysis of the derivative of the angle of the fitted curve with respect to u as a means to detect spurious curls and peaks is explored -- Findings - It is more effective to find optimum values for m than k or b in order to obtain good results because the topological faithfulness of the resulting curve strongly depends on m -- Furthermore, when an exaggerate number of control points is used the resulting curve presents spurious curls and peaks -- The authors were able to detect the presence of such spurious features with spectral analysis -- Also, the authors found that the method for curve fitting is robust to significant decimation of the point sample -- Research limitations/implications - The authors have addressed important voids of previous works in this field -- The authors determined, among the curve fitting parameters m, b and k, which of them influenced the most the results and how -- Also, the authors performed a characterization of the curve fitting problem from the optimization perspective -- And finally, the authors devised a method to detect spurious features in the fitting curve -- Practical implications – This paper provides a methodology to select the important tuning parameters in a formal manner -- Originality/value - Up to the best of the knowledge, no previous work has been conducted in the formal mathematical evaluation of the sensitivity of the goodness of the curve fit with respect to different possible tuning parameters (curve degree, number of control points, norm degree, etc.

Variability in concentrations of potentially toxic elements in urban parks from six European cities

Use of a harmonised sampling regime has allowed comparison of concentrations of copper, chromium, nickel, lead and zinc in six urban parks located in different European cities differing markedly in their climate and industrial history. Wide concentrations ranges were found for copper, lead and zinc at most sites, but for chromium and nickel a wide range was only seen in the Italian park, where levels were also considerably greater than in other soils. As might be expected, the soils from older cities with a legacy of heavy manufacturing industry (Glasgow, Torino) were richest in potentially toxic elements (PTEs); soils from Ljubljana, Sevilla and Uppsala had intermediate metal contents, and soils from the most recently established park, in the least industrialised city (Aveiro), displayed lowest concentrations. When principal component analysis was applied to the data, associations were revealed between pH and organic carbon content; and between all five PTEs. When pH and organic carbon content were excluded from the PCA, a distinction became clear between copper, lead and zinc (the "urban" metals) on the one hand, and chromium and nickel on the other. Similar results were obtained for the surface (0-10 cm depth) and sub-surface (10-20 cm depth) samples. Comparisons with target or limit concentrations were limited by the existence of different legislation in different countries and the fact that few guidelines deal specifically with public-access urban soils intended for recreational use

Estimation of the real population and its impact on the utilisation of healthcare services in Mediterranean resort regions: an ecological study

BACKGROUND: The demographic structure has a significant influence on the use of healthcare services, as does the size of the population denominators. Very few studies have been published on methods for estimating the real population such as tourist resorts. The lack of information about these problems means there is a corresponding lack of information about the behaviour of populational denominators (the floating population or tourist load) and the effect of this on the use of healthcare services. The objectives of the study were: a) To determine the Municipal Solid Waste (MSW) ratio, per person per day, among populations of known size; b) to estimate, by means of this ratio, the real population in an area where tourist numbers are very significant; and c) to determine the impact on the utilisation of hospital emergency healthcare services of the registered population, in comparison to the non-resident population, in two areas where tourist numbers are very significant. METHODS: An ecological study design was employed. We analysed the Healthcare Districts of the Costa del Sol and the island of Menorca. Both are Spanish territories in the Mediterranean region. RESULTS: In the two areas analysed, the correlation coefficient between the MSW ratio and admissions to hospital emergency departments exceeded 0.9, with p < 0.001. On the basis of MSW generation ratios, obtained for a control zone and also measured in neighbouring countries, we estimated the real population. For the summer months, when tourist activity is greatest and demand for emergency healthcare at hospitals is highest, this value was found to be double that of the registered population. CONCLUSION: The MSW indicator, which is both ecological and indirect, can be used to estimate the real population in areas where population levels vary significantly during the year. This parameter is of interest in planning and dimensioning the provision of healthcare services

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Robotic Wireless Sensor Networks

In this chapter, we present a literature survey of an emerging, cutting-edge, and multi-disciplinary field of research at the intersection of Robotics and Wireless Sensor Networks (WSN) which we refer to as Robotic Wireless Sensor Networks (RWSN). We define a RWSN as an autonomous networked multi-robot system that aims to achieve certain sensing goals while meeting and maintaining certain communication performance requirements, through cooperative control, learning and adaptation. While both of the component areas, i.e., Robotics and WSN, are very well-known and well-explored, there exist a whole set of new opportunities and research directions at the intersection of these two fields which are relatively or even completely unexplored. One such example would be the use of a set of robotic routers to set up a temporary communication path between a sender and a receiver that uses the controlled mobility to the advantage of packet routing. We find that there exist only a limited number of articles to be directly categorized as RWSN related works whereas there exist a range of articles in the robotics and the WSN literature that are also relevant to this new field of research. To connect the dots, we first identify the core problems and research trends related to RWSN such as connectivity, localization, routing, and robust flow of information. Next, we classify the existing research on RWSN as well as the relevant state-of-the-arts from robotics and WSN community according to the problems and trends identified in the first step. Lastly, we analyze what is missing in the existing literature, and identify topics that require more research attention in the future

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

FUNDING. Instituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation.BACKGROUND. Persistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure. METHODS. The characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq). RESULTS. PCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs. CONCLUSIONS. These results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.Instituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127, PI22/01796)Gilead Fellowships (GLD22/00147)NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHEBill and Melinda Gates Foundatio

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers.

BACKGROUNDPersistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure.METHODSThe characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using next-generation sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq).RESULTSPCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONSThese results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.FUNDINGInstituto de Salud Carlos III (FI17/00186, FI19/00083, MV20/00057, PI18/01532, PI19/01127 and PI22/01796), Gilead Fellowships (GLD22/00147). NIH grants AI155171, AI116228, AI078799, HL134539, DA047034, MH134823, amfAR ARCHE and the Bill and Melinda Gates Foundation

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13