Risk of Invasive Fungal Infections in Patients with Chronic Lymphocytic Leukemia treated with Bruton Tyrosine Kinase Inhibitors – A Case-Control Propensity Score Matched Analysis

Background: Prior reports have suggested a possible increase in the frequency of invasive fungal infections (IFIs) with use of a Bruton tyrosine kinase inhibitors (BTKi) for treatment of chronic lymphoid malignancies such as chronic lymphocytic leukemia (CLL), but precise estimates are lacking. We aim to characterize the prevalence of IFIs among patients with CLL, for whom BTKi are now the first line recommended therapy. Methods: We queried TriNetX, a global research network database, to identify adult patients with CLL using the ICD-10 codes (C91.1) and laboratory results. We performed a case-control propensity score-matched analysis to determine IFIs events by BTKi use. We adjusted for age, sex, ethnicity, and clinical risk factors associated with an increased risk of IFIs. Results: Among 5,358 matched patients with CLL, we found an incidence of 4.6% of IFIs in patients on a BTKi vs. 3.5% among patients with CLL not on a BTKi at five years. Approximately 1% of patients with CLL developed an IFI while on a BTKi within this period. Our adjusted IFI event analysis found an elevated rate of Pneumocytis jirovecii pneumonia (PJP) (0.5% vs. 0.3%, p = 0.02) and invasive candidiasis (3.5% vs 2.7%, p = 0.012) with the use of a BTKi. The number needed to harm for patients taking a BTKi was 120 and 358 for invasive candidiasis and PJP, respectively. Conclusions: We found an adjusted elevated rate of PJP and invasive candidiasis with BTKi use. The rates are however low with a high number needed to harm. Additional studies stratifying other IFIs with specific BTKi are required to identify at-risk patients and preventive, cost-effective interventions

CARACTERIZACIÓN SISMOTECTÓNICA REGIONAL PRELIMINAR DE UN SECTOR DEL PIEDEMONTE LLANERO COLOMBIANO: CORREDOR SAN JUAN DE ARAMA – CUMARAL,META

  With the regional tectonic scenario determination carried out with remote sensors, secondary information and field observations, be determined that the faults related to the Eastern Frontal Fault System - EFFS, obeys to a geometry of shortcut planes with maximum longitudes of 30 km, these represent thrust faults that limit to the Andean basement with the South American plate. Also with the support of the historical seismicity and instrumental seismicity registration of the RSNC for the period 1993 - 2001, low seismic activity was determined between 3º and 4º N, and moderate seismic activity to the south of this latitude. This sector of EFFS is composed by listric fault type with low dip angle toward depth under compression stress regime and it seismicity obeys to stress release of these planes in the contact area where the basements converge. The maximum magnitude estimated is M ≥ 6,0 with 5 - 30 km depth hypocenters. However the low previous seismological information and few studies in these faults yet hinder the realization of earthquake prediction in probabilistic sense for these.   Key Words: Andean Eastern Cordillera Foothill, Eastern Frontal Fault System, Geotectonics, Seismicity, Seismotectonics    Con la determinación del escenario tectónico regional realizado con sensores remotos, información secundaria y observaciones de campo, se ha encontrado que las fallas relacionadas al Sistema de Fallas de la Falla Frontal de la Cordillera Oriental   - SFFFCO, obedecen a una geometría de planos muy seccionados con longitudes máximas de 30 km que representan fallas de cabalgamiento que limitan al basamento Andino con la placa suramericana. Con el apoyo de la sismicidad histórica y del registro instrumental de la RSNC para el período 1993 - 2001, se determinó igualmente poca actividad sísmica entre los 3º y 4º N, y una actividad moderada al sur de esta latitud. Este sector del SFFFCO se caracteriza por presentar planos de tipo lístrico bajo régimen compresivo cuyo buzamiento decrece en ángulo hacía profundidad y la sismicidad obedece a la liberación de esfuerzos de estos planos en la zona de contacto donde convergen los basamentos. La magnitud máxima posible esperada es M ≥ 6,0, con hipocentros que oscilan entre 5 y 30 km Sin embargo la baja información sismológica y los pocos estudios realizados en estas fallas todavía impiden realizar la estimación en el sentido probabilístico de los periodos intersísmicos en estas.   Palabras Clave: Piedemonte Llanero colombiano, Sistema de Fallas de la Falla Frontal de de la Cordillera Oriental, Geotectónica,  Sismicidad, Sismotectónica.     &nbsp

CARACTERIZACIÓN SISMOTECTÓNICA REGIONAL PRELIMINAR DE UN SECTOR DEL PIEDEMONTE LLANERO COLOMBIANO: CORREDOR SAN JUAN DE ARAMA – CUMARAL,META

  With the regional tectonic scenario determination carried out with remote sensors, secondary information and field observations, be determined that the faults related to the Eastern Frontal Fault System - EFFS, obeys to a geometry of shortcut planes with maximum longitudes of 30 km, these represent thrust faults that limit to the Andean basement with the South American plate. Also with the support of the historical seismicity and instrumental seismicity registration of the RSNC for the period 1993 - 2001, low seismic activity was determined between 3º and 4º N, and moderate seismic activity to the south of this latitude. This sector of EFFS is composed by listric fault type with low dip angle toward depth under compression stress regime and it seismicity obeys to stress release of these planes in the contact area where the basements converge. The maximum magnitude estimated is M ≥ 6,0 with 5 - 30 km depth hypocenters. However the low previous seismological information and few studies in these faults yet hinder the realization of earthquake prediction in probabilistic sense for these.   Key Words: Andean Eastern Cordillera Foothill, Eastern Frontal Fault System, Geotectonics, Seismicity, Seismotectonics    Con la determinación del escenario tectónico regional realizado con sensores remotos, información secundaria y observaciones de campo, se ha encontrado que las fallas relacionadas al Sistema de Fallas de la Falla Frontal de la Cordillera Oriental   - SFFFCO, obedecen a una geometría de planos muy seccionados con longitudes máximas de 30 km que representan fallas de cabalgamiento que limitan al basamento Andino con la placa suramericana. Con el apoyo de la sismicidad histórica y del registro instrumental de la RSNC para el período 1993 - 2001, se determinó igualmente poca actividad sísmica entre los 3º y 4º N, y una actividad moderada al sur de esta latitud. Este sector del SFFFCO se caracteriza por presentar planos de tipo lístrico bajo régimen compresivo cuyo buzamiento decrece en ángulo hacía profundidad y la sismicidad obedece a la liberación de esfuerzos de estos planos en la zona de contacto donde convergen los basamentos. La magnitud máxima posible esperada es M ≥ 6,0, con hipocentros que oscilan entre 5 y 30 km Sin embargo la baja información sismológica y los pocos estudios realizados en estas fallas todavía impiden realizar la estimación en el sentido probabilístico de los periodos intersísmicos en estas.   Palabras Clave: Piedemonte Llanero colombiano, Sistema de Fallas de la Falla Frontal de de la Cordillera Oriental, Geotectónica,  Sismicidad, Sismotectónica.     &nbsp

The genomic basis of the plant island syndrome in Darwin’s giant daisies

The repeated, rapid and often pronounced patterns of evolutionary divergence observed in insular plants, or the ‘plant island syndrome’, include changes in leaf phenotypes, growth, as well as the acquisition of a perennial lifestyle. Here, we sequence and describe the genome of the critically endangered, Galápagos-endemic species Scalesia atractyloides Arnot., obtaining a chromosome-resolved, 3.2-Gbp assembly containing 43,093 candidate gene models. Using a combination of fossil transposable elements, k-mer spectra analyses and orthologue assignment, we identify the two ancestral genomes, and date their divergence and the polyploidization event, concluding that the ancestor of all extant Scalesia species was an allotetraploid. There are a comparable number of genes and transposable elements across the two subgenomes, and while their synteny has been mostly conserved, we find multiple inversions that may have facilitated adaptation. We identify clear signatures of selection across genes associated with vascular development, growth, adaptation to salinity and flowering time, thus finding compelling evidence for a genomic basis of the island syndrome in one of Darwin’s giant daisies

A constructive study of the module structure of rings of partial differential operators

The purpose of this paper is to develop constructive versions of Stafford's theorems on the module structure of Weyl algebras A n (k) (i.e., the rings of partial differential operators with polynomial coefficients) over a base field k of characteristic zero. More generally, based on results of Stafford and Coutinho-Holland, we develop constructive versions of Stafford's theorems for very simple domains D. The algorithmization is based on the fact that certain inhomogeneous quadratic equations admit solutions in a very simple domain. We show how to explicitly compute a unimodular element of a finitely generated left D-module of rank at least two. This result is used to constructively decompose any finitely generated left D-module into a direct sum of a free left D-module and a left D-module of rank at most one. If the latter is torsion-free, then we explicitly show that it is isomorphic to a left ideal of D which can be generated by two elements. Then, we give an algorithm which reduces the number of generators of a finitely presented left D-module with module of relations of rank at least two. In particular, any finitely generated torsion left D-module can be generated by two elements and is the homomorphic image of a projective ideal whose construction is explicitly given. Moreover, a non-torsion but non-free left D-module of rank r can be generated by r+1 elements but no fewer. These results are implemented in the Stafford package for D=A n (k) and their system-theoretical interpretations are given within a D-module approach. Finally, we prove that the above results also hold for the ring of ordinary differential operators with either formal power series or locally convergent power series coefficients and, using a result of Caro-Levcovitz, also for the ring of partial differential operators with coefficients in the field of fractions of the ring of formal power series or of the ring of locally convergent power series. © 2014 Springer Science+Business Media

Modeling the Subsurface Structure of Sunspots

While sunspots are easily observed at the solar surface, determining their subsurface structure is not trivial. There are two main hypotheses for the subsurface structure of sunspots: the monolithic model and the cluster model. Local helioseismology is the only means by which we can investigate subphotospheric structure. However, as current linear inversion techniques do not yet allow helioseismology to probe the internal structure with sufficient confidence to distinguish between the monolith and cluster models, the development of physically realistic sunspot models are a priority for helioseismologists. This is because they are not only important indicators of the variety of physical effects that may influence helioseismic inferences in active regions, but they also enable detailed assessments of the validity of helioseismic interpretations through numerical forward modeling. In this paper, we provide a critical review of the existing sunspot models and an overview of numerical methods employed to model wave propagation through model sunspots. We then carry out an helioseismic analysis of the sunspot in Active Region 9787 and address the serious inconsistencies uncovered by \citeauthor{gizonetal2009}~(\citeyear{gizonetal2009,gizonetal2009a}). We find that this sunspot is most probably associated with a shallow, positive wave-speed perturbation (unlike the traditional two-layer model) and that travel-time measurements are consistent with a horizontal outflow in the surrounding moat.Comment: 73 pages, 19 figures, accepted by Solar Physic

Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm{NN}}} = 2.76 TeV

The inclusive transverse momentum ($p_{\rm T}$) distributions of primary charged particles are measured in the pseudo-rapidity range $|\eta|<0.8$ as a function of event centrality in Pb-Pb collisions at $\sqrt{s_{\rm{NN}}}=2.76$ TeV with ALICE at the LHC. The data are presented in the $p_{\rm T}$ range $0.15<p_{\rm T}<50$ GeV/$c$ for nine centrality intervals from 70-80% to 0-5%. The Pb-Pb spectra are presented in terms of the nuclear modification factor $R_{\rm{AA}}$ using a pp reference spectrum measured at the same collision energy. We observe that the suppression of high-$p_{\rm T}$ particles strongly depends on event centrality. In central collisions (0-5%) the yield is most suppressed with $R_{\rm{AA}}\approx0.13$ at $p_{\rm T}=6$-7 GeV/$c$. Above $p_{\rm T}=7$ GeV/$c$, there is a significant rise in the nuclear modification factor, which reaches $R_{\rm{AA}} \approx0.4$ for $p_{\rm T}>30$ GeV/$c$. In peripheral collisions (70-80%), the suppression is weaker with $R_{\rm{AA}} \approx 0.7$ almost independently of $p_{\rm T}$. The measured nuclear modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/284

Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}=2.76 TeV

The elliptic, $v_2$, triangular, $v_3$, and quadrangular, $v_4$, azimuthal anisotropic flow coefficients are measured for unidentified charged particles, pions and (anti-)protons in Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV with the ALICE detector at the Large Hadron Collider. Results obtained with the event plane and four-particle cumulant methods are reported for the pseudo-rapidity range $|\eta|<0.8$ at different collision centralities and as a function of transverse momentum, $p_{\rm T}$, out to $p_{\rm T}=20$ GeV/$c$. The observed non-zero elliptic and triangular flow depends only weakly on transverse momentum for $p_{\rm T}>8$ GeV/$c$. The small $p_{\rm T}$ dependence of the difference between elliptic flow results obtained from the event plane and four-particle cumulant methods suggests a common origin of flow fluctuations up to $p_{\rm T}=8$ GeV/$c$. The magnitude of the (anti-)proton elliptic and triangular flow is larger than that of pions out to at least $p_{\rm T}=8$ GeV/$c$ indicating that the particle type dependence persists out to high $p_{\rm T}$.Comment: 16 pages, 5 captioned figures, authors from page 11, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186

Measurement of charm production at central rapidity in proton-proton collisions at s=2.76\sqrt{s} = 2.76 TeV

The $p_{\rm T}$-differential production cross sections of the prompt (B feed-down subtracted) charmed mesons D$^0$, D$^+$, and D$^{*+}$ in the rapidity range $|y|<0.5$, and for transverse momentum $1< p_{\rm T} <12$ GeV/$c$, were measured in proton-proton collisions at $\sqrt{s} = 2.76$ TeV with the ALICE detector at the Large Hadron Collider. The analysis exploited the hadronic decays D$^0 \rightarrow$K$\pi$, D$^+ \rightarrow$K$\pi\pi$, D$^{*+} \rightarrow$D$^0\pi$, and their charge conjugates, and was performed on a $L_{\rm int} = 1.1$ nb$^{-1}$ event sample collected in 2011 with a minimum-bias trigger. The total charm production cross section at $\sqrt{s} = 2.76$ TeV and at 7 TeV was evaluated by extrapolating to the full phase space the $p_{\rm T}$-differential production cross sections at $\sqrt{s} = 2.76$ TeV and our previous measurements at $\sqrt{s} = 7$ TeV. The results were compared to existing measurements and to perturbative-QCD calculations. The fraction of cdbar D mesons produced in a vector state was also determined.Comment: 20 pages, 5 captioned figures, 4 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/307

Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The yield of charged particles associated with high-$p_{\rm T}$ trigger particles ($8 < p_{\rm T} < 15$ GeV/$c$) is measured with the ALICE detector in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV relative to proton-proton collisions at the same energy. The conditional per-trigger yields are extracted from the narrow jet-like correlation peaks in azimuthal di-hadron correlations. In the 5% most central collisions, we observe that the yield of associated charged particles with transverse momenta $p_{\rm T}> 3$ GeV/$c$ on the away-side drops to about 60% of that observed in pp collisions, while on the near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/350