Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

Neoadjuvant chemotherapy and trastuzumab versus neoadjuvant chemotherapy followed by post-operative trastuzumab for patients with HER2-positive breast cancer

Neoadjuvant chemotherapy plus trastuzumab (NCT) increases the rate of pathological complete response (pCR) and event-free survival (EFS) compared to neoadjuvant chemotherapy (NC) alone in women with HER2 positive breast cancer (BC). pCR in this setting is associated with improved EFS. Whether NCT preferentially improves EFS in comparison to NC followed by adjuvant trastuzumab initiated postoperatively (NCAT) has not been addressed. Using clinical data from women with HER2 positive BC treated at 7 European institutions between 2007 and 2010 we sought to investigate the impact on breast cancer outcomes of concomitant (NCT) versus sequential (NCAT) treatment in HER2 positive early BC. The unadjusted hazard ratio (HR) for event free survival with NCT compared with NCAT was 0.63 (95% CI 0.37–1.08; p = 0.091). Multivariable analysis revealed that treatment group, tumour size and ER status were significantly associated with EFS from diagnosis. In the whole group NCT was associated with a reduced risk of an event relative to NCAT, an effect that was confined to ER negative (HR: 0.25; 95% CI, 0.10–0.62; p = 0.003) as opposed to ER positive tumours (HR: 1.07; 95% CI, 0.46–2.52; p = 0.869). HER2 positive/ER negative BC treated with NC gain greatest survival benefit when trastuzumab is administered in both the neoadjuvant and adjuvant period rather than in the adjuvant period alone. These data support the early introduction of targeted combination therapy in HER2 positive/ER negative BC

The role of coping strategies in quality of life of adolescents with asthma

This study aimed to determine which coping strategies are associated with better quality of life (QOL) in adolescents with asthma. Furthermore, because coping can mediate the effects of health stressors on QOL, this study also examined the indirect effect of asthma severity on QOL via coping. Between January and May 2003, 553 Dutch adolescents with asthma (aged 12–6 years) completed questionnaires assessing coping strategies, symptom severity, overall QOL and positive QOL domain (positive effects of asthma domain). The relations between symptom severity, coping strategies and QOL were tested with structural equation modelling (SEM). Symptom severity affected overall and positive QOL, both directly and indirectly via coping. The coping strategies restricted lifestyle and worrying about asthma were associated with poorer overall QOL. The use of the coping strategies restricted lifestyle, positive reappraisal, and information seeking was related to increased scores on the positive QOL domain, whereas hiding asthma was related to lower scores on the positive QOL domain

The ELFIN mission

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E 1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.Published versio

Phylogenetic Signal and Bias in Paleontology

An unprecedented amount of evidence now illuminates the phylogeny of living mammals and birds on the Tree of Life. We use this tree to measure phylogenetic value of data typically used in paleontology (bones and teeth) from six datasets derived from five published studies. We ask three interrelated questions: 1) Can these data adequately reconstruct known parts of the Tree of Life? 2) Is accuracy generally similar for studies using morphology, or do some morphological datasets perform better than others? 3) Does the loss of non-fossilizable data cause taxa to occur in misleadingly basal positions? Adding morphology to DNA datasets usually increases congruence of resulting topologies to the well corroborated tree, but this varies among morphological datasets. Extant taxa with a high proportion of missing morphological characters can greatly reduce phylogenetic resolution when analyzed together with fossils. Attempts to ameliorate this by deleting extant taxa missing morphology are prone to decreased accuracy due to long-branch artefacts. We find no evidence that fossilization causes extinct taxa to incorrectly appear at or near topologically basal branches. Morphology comprises the evidence held in common by living taxa and fossils, and phylogenetic analysis of fossils greatly benefits from inclusion of molecular and morphological data sampled for living taxa, whatever methods are used for phylogeny estimation

Convergence vs. Specialization in the Ear Region of Moles Mammalia

We investigated if and how the inner ear region undergoes similar adaptations in small, fossorial, insectivoran grade mammals, and found a variety of inner ear phenotypes. In our sample, afrotherian moles Chrysochloridae and the marsupial Notoryctes differ from most other burrowing mammals in their relatively short radii of semicircular canal curvature; chrysochlorids and fossorial talpids share a relatively long interampullar width. Chrysochlorids are unique in showing a highly coiled cochlea with nearly four turns. Extensive cochlear coiling may reflect their greater ecological dependence on low frequency auditory cues compared to talpids, tenrecids, and the marsupial Notoryctes. Correspondingly, the lack of such extensive coiling in the inner ear of other fossorial species may indicate a greater reliance on other senses to enable their fossorial lifestyle, such as tactile sensation from vibrissae and Eimer s organs. The reliance of chrysochlorids on sound is evident in the high degree of coiling and in the diversity of its mallear types, and may help explain the lack of any semiaquatic members of that group. The simplest mallear types among chrysochlorids are not present in the basal most members of that clade, but all extant chrysochlorids investigated to date exhibit extensive cochlear coiling. The chrysochlorid ear region thus exhibits mosaic evolution; our data suggest that extensive coiling evolved in chrysochlorids prior to and independently of diversification in middle ear ossicle size and shape. J. Morphol. 276 900 914, 2015. VC 2015 Wiley Periodicals, In

Handbook of Game Theory with Economic Applications

In this article, we consider how important developments in game theory have contributed to the theory of industrial organization. Our goal is not to survey the theory of industrial organization; rather, we consider the contribution of game theory through a careful discussion of a small number of topics within the industrial organization field. We also identify some points in which developments in the theory of industrial organization have contributed to game theory. The topics that we consider are: commitment in two-stage games and the associated theories of strategic-trade policy and entry deterrence; asymmetric-information games and the associated theories of limit pricing and predation; repeated games with public moves and the associated theory of collusion in markets with public demand fluctuations; mixed-strategy equilibria and purification theory and the associated theory of sales; and repeated games with imperfect monitoring and the associated theory of collusion and price wars. We conclude with a general assessment concerning the contribution of game theory to industrial organization.