Crossover from self-defocusing to discrete trapping in nonlinear waveguide arrays

We predict a sharp crossover from nonlinear self-defocusing to discrete self-trapping of a narrow Gaussian beam with the increase of the refractive index contrast in a periodic photonic lattice. We demonstrate experimentally nonlinear discrete localization of light with defocusing nonlinearity by single site excitation in LiNbO$_3$ waveguide arrays.Comment: 6 pages, 4 figure

European LeukemiaNet 2017 risk stratification for acute myeloid leukemia: validation in a risk-adapted protocol

Risk stratification; Acute myeloid leukemiaEstratificació del risc; Leucèmia mieloide agudaEstratificación de riesgo; Leucemia mieloide agudaThe 2017 European LeukemiaNet (ELN 2017) guidelines for the diagnosis and management of acute myeloid leukemia (AML) have become fundamental guidelines to assess the prognosis and postremission therapy of patients. However, they have been retrospectively validated in few studies with patients included in different treatment protocols. We analyzed 861 patients included in the Cooperativo Para el Estudio y Tratamiento de las Leucemias Agudas y Mielodisplasias-12 risk-adapted protocol, which indicates cytarabine-based consolidation for patients allocated to the ELN 2017 favorable-risk group, whereas it recommends allogeneic stem cell transplantation (alloSCT) as a postremission strategy for the ELN 2017 intermediate- and adverse-risk groups. We retrospectively classified patients according to the ELN 2017, with 327 (48%), 109 (16%), and 245 (36%) patients allocated to the favorable-, intermediate-, and adverse-risk group, respectively. The 2- and 5-year overall survival (OS) rates were 77% and 70% for favorable-risk patients, 52% and 46% for intermediate-risk patients, and 33% and 23% for adverse-risk patients, respectively. Furthermore, we identified a subgroup of patients within the adverse group (inv(3)/t(3;3), complex karyotype, and/or TP53 mutation/17p abnormality) with a particularly poor outcome, with a 2-year OS of 15%. Our study validates the ELN 2017 risk stratification in a large cohort of patients treated with an ELN-2017 risk-adapted protocol based on alloSCT after remission for nonfavorable ELN subgroups and identifies a genetic subset with a very poor outcome that warrants investigation of novel strategies.This study was supported (in part) by Fondo de Investigaciones Sanitarias/Instituto de Salud Carlos III (ISCIII) grants PI16/01027, PI19/1476, and PI20/01621; Health Research and Innovation Strategic Plan (PERIS) grant SLT002/16/00433 and research group support SGR 1395 and SGR 1655 from Generalitat de Catalunya; resident award “Emili Letang” 2019 (Hospital Clínic de Barcelona); and “Beca de Investigación FEHH 2019” (Fundación Española de Hematologia y Hemoterapia)

Observation of surface gap solitons in semi-infinite waveguide arrays

We report on the first observation of surface gap solitons, recently predicted to exist at the interface between uniform and periodic dielectric media with defocusing nonlinearity [Ya.V. Kartashov et al., Phys. Rev. Lett. 96, 073901 (2006). We demonstrate strong self-trapping at the edge of a LiNbO_3 waveguide array and the formation of staggered surface solitons with propagation constant inside the first photonic band gap. We study the crossover between linear repulsion and nonlinear attraction at the surface, revealing the mechanism of nonlinearity-mediated stabilization of the surface gap modes.Comment: 4 pages, 5 figure

Prognostic impact of DNMT3A mutation in acute myeloid leukemia with mutated NPM1

Prognostic impact; Mutation; Acute myeloid leukemiaImpacte pronòstic; Mutació; Leucèmia mieloide agudaImpacto pronóstico; Mutación; Leucemia mieloide agudaThe negative prognostic impact of internal tandem duplication of FLT3 (FLT3-ITD) in patients with acute myeloid leukemia with mutated NPM1 (AML-NPM1) is restricted to those with a higher FLT3-ITD allelic ratio (FLT3high; ≥0.5) and considered negligible in those with a wild-type (FLT3WT)/low ITD ratio (FLT3low). Because the comutation of DNMT3A (DNMT3Amut) has been suggested to negatively influence prognosis in AML-NPM1, we analyzed the impact of DNMT3Amut in FLT3-ITD subsets (absent, low, and high ratios). A total of 164 patients diagnosed with AML-NPM1 included in 2 consecutive CETLAM protocols and with DNMT3A and FLT3 status available were studied. Overall, DNMT3Amut status did not have a prognostic impact, with comparable overall survival (P = .2). Prognostic stratification established by FLT3-ITD (FLT3WT = FLT3low > FLT3high) was independent of DNMT3Amut status. Measurable residual disease (MRD) based on NPM1 quantitative polymerase chain reaction was available for 94 patients. DNMT3Amut was associated with a higher number of mutated NPM1 transcripts after induction (P = .012) and first consolidation (C1; P < .001). All DNMT3Amut patients were MRD+ after C1 (P < .001) and exhibited significant MRD persistence after C2 and C3 (MRD+ vs MRD−; P = .027 and P = .001, respectively). Finally, DNMT3Amut patients exhibited a trend toward greater risk of molecular relapse (P = .054). In conclusion, DNMT3Amut did not modify the overall prognosis exerted by FLT3-ITD in AML-NPM1 despite delayed MRD clearance, possibly because of MRD-driven preemptive intervention.This work was supported in part by the Biomedical Research Institute (IIB Sant-Pau) and the José Carreras Leukemia Research Institute as well as grants from the Catalan Government (PERIS SLT002/16/0043 and AGAUR 2017 SGR 139) and the Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Spain (PI17/01246, PI20/01621 and CM20/00061)

Using nutritional geometry to define the fundamental macronutrient niche of the widespread invasive ant <i>Monomorium pharaonis</i>

The emerging field of nutritional geometry (NG) provides powerful new approaches to test whether and how organisms prioritize specific nutritional blends when consuming chemically complex foods. NG approaches can thus help move beyond food-level estimates of diet breadth to predict invasive success, for instance by revealing narrow nutritional niches if broad diets are actually composed of nutritionally similar foods. We used two NG paradigms to provide different, but complementary insights into nutrient regulation strategies and test a hypothesis of extreme nutritional generalism in colony propagules of the globally distributed invasive ant Monomorium pharaonis. First, in two dimensions (protein:carbohydrates; P:C), M. pharaonis colonies consistently defended a slightly carbohydrate-biased intake target, while using a generalist equal-distance strategy of collectively overharvesting both protein and carbohydrates to reach this target when confined to imbalanced P:C diets. Second, a recently developed right-angled mixture triangle method enabled us to define the fundamental niche breadth in three dimensions (protein:carbohydrates:lipid, P:C:L). We found that colonies navigated the P:C:L landscape, in part, to mediate a tradeoff between worker survival (maximized on high-carbohydrate diets) and brood production (maximized on high-protein diets). Colonies further appeared unable to avoid this tradeoff by consuming extra lipids when the other nutrients were limiting. Colonies also did not rely on nutrient regulation inside their nests, as they did not hoard or scatter fractions of harvested diets to adjust the nutritional blends they consumed. These complementary NG approaches highlight that even the most successful invasive species with broad fundamental macronutrient niches must navigate complex multidimensional nutritional landscapes to acquire limiting macronutrients and overcome developmental constraints as small propagules

Dielectrophoresis of micro/nano particles using curved microelectrodes

Dielectrophoresis, the induced motion of polarisable particles in non-homogenous electric field, has been proven as a versatile mechanism to transport, immobilise, sort and characterise micro/nano scale particle in microfluidic platforms. The performance of dielectrophoretic (DEP) systems depend on two parameters: the configuration of microelectrodes designed to produce the DEP force and the operating strategies devised to employ this force in such processes. This work summarises the unique features of curved microelectrodes for the DEP manipulation of target particles in microfluidic systems. The curved microelectrodes demonstrate exceptional capabilities including (i) creating strong electric fields over a large portion of their structure, (ii) minimising electro-thermal vortices and undesired disturbances at their tips, (iii) covering the entire width of the microchannel influencing all passing particles, and (iv) providing a large trapping area at their entrance region, as evidenced by extensive numerical and experimental analyses. These microelectrodes have been successfully applied for a variety of engineering and biomedical applications including (i) sorting and trapping model polystyrene particles based on their dimensions, (ii) patterning carbon nanotubes to trap low-conductive particles, (iii) sorting live and dead cells based on their dielectric properties, (iv) real-time analysis of drug-induced cell death, and (v) interfacing tumour cells with environmental scanning electron microscopy to study their morphological properties. The DEP systems based on curved microelectrodes have a great potential to be integrated with the future lab-on-a-chip systems.<br /

Diffraction-managed solitons and nonlinear beam diffusion in modulated arrays of optical waveguides

We study propagation of light in nonlinear diffraction-managed photonic lattices created with arrays of periodically-curved coupled optical waveguides which were fabricated using femtosecond laser writing in silica glass, and titanium indiffusion in LiNbO3 crystals. We identify different regimes of the nonlinear propagation of light beams depending on the input power, and present the first experimental observation of diffraction-managed solitons, which are formed as a result of the interplay between the engineered beam diffraction and nonlinear self-focusing or defocusing. We observe that in self-collimating structures where linear diffraction is suppressed, a novel regime of nonlinear beam diffusion takes place at the intermediate powers before the lattice soliton is formed at higher powers

Management-dependent effects of pollinator functional diversity on apple pollination services: A response–effect trait approach

Data available via the Dryad Digital Repository https://doi.org/10.5061/dryad.63xsj3v39 (Roquer-Beni et al., 2021).Functional traits mediate the response of communities to disturbances (response traits) and their contribution to ecosystem functions (effect traits). To predict how anthropogenic disturbances influence ecosystem services requires a dual approach including both trait concepts. Here, we used a response–effect trait conceptual framework to understand how local and landscape features affect pollinator functional diversity and pollination services in apple orchards. We worked in 110 apple orchards across four European regions. Orchards differed in management practices. Low-intensity (LI) orchards were certified organic or followed close-to-organic practices. High-intensity (HI) orchards followed integrated pest management practices. Within each management type, orchards encompassed a range of local (flower diversity, agri-environmental structures) and landscape features (orchard and pollinator-friendly habitat cover). We measured pollinator visitation rates and calculated trait composition metrics based on 10 pollinator traits. We used initial fruit set as a measure of pollination service. Some pollinator traits (body size and hairiness) were negatively related to orchard cover and positively affected by pollinator-friendly habitat cover. Bee functional diversity was lower in HI orchards and decreased with increased landscape orchard cover. Pollination service was not associated with any particular trait but increased with pollinator trait diversity in LI orchards. As a result, LI orchards with high pollinator trait diversity reached levels of pollination service similar to those of HI orchards. Synthesis and applications. Pollinator functional diversity enables pollinator communities to respond to agricultural intensification and to increase pollination function. Our results show that efforts to promote biodiversity provide greater returns in low-intensity than in high-intensity orchards. The fact that low-intensity orchards with high pollinator functional diversity reach levels of pollination services similar to those of high-intensity orchards provides a compelling argument for the conversion of high-intensity into low-intensity farms.This research (EcoFruit project) was funded through the 2013–2014 BiodivERsA/FACCE-JPI joint call (2014-74), Spanish MinECo (PCIN-2014-145-C02), German BMBF (PT-DLR/BMBF, 01LC1403) and Swedish Research Council Formas (2014-1784) by Formas (2013-934 to M.T.), Stiftelsen Lantbruksforskning (H1256150 to M.P.), INIA (RTA2013-00039-C03-00 to G.A. and M.M.), MinECo/FEDER (CGL2015-68963-C2-2-R to D.G.), FI-AGAUR (to L.R.-B.) and MinECo (RYC-2015-18448 to X.A.)

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients : Protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)

Altres ajuts: The BEATLE study is a non-commercial, investigator-driven clinical trial funded by the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005; RD16/0016/0010) The Spanish Clinical Research Network (SCReN) provides clinical trial data monitoring and oversees pharmacovigilance (PT17/0017/0010).Background: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN. Methods: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied. Discussion: Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes. Trial registration: European Clinical Trials Database: EudraCT 2018-001476-37. ClinicalTrials.gov, ID: NCT04233996