Implications of subcutaneous or intravenous delivery of trastuzumab: further insight from patient interviews in the PrefHer study

BACKGROUND: The 2 Cohort randomised PrefHer trial examined the preferences of HER2+ve primary breast cancer patients for intravenous (IV) or subcutaneous (SC) delivery of trastuzumab via a Single Injectable Device (SID) or hand-held syringe (HHS). The novel approach and design of the study permitted an in-depth exploration of patients' experiences, the impact that different modes of delivery had on patients' well-being and implications for future management. METHODS: The preferences, experiences and general comments of patients in the PrefHer study were collected via specific semi-structured interview schedules. Exploratory analyses of data were conducted using standard methodology. The final question invited patients to make further comments, which were divided into 9 thematic categories - future delivery, compliments, time/convenience, practical considerations, pain/discomfort, study design, side-effects, psychological impact, and perceived efficacy. RESULTS: 267/467 (57%) patients made 396 additional comments, 7 were neutral, 305 positive and 86 negative. The three top categories generating the largest number of comments were compliments and gratitude about staff and being part of PrefHer (75/396; 19%), the potential future delivery of SC trastuzumab (73/396; 18%), and practical considerations about SC administration (60/396; 15%). CONCLUSIONS: Eliciting patient preferences about routes of administration of drugs via comprehensive interviews within a randomised cross-over trial yielded rich and important information. The few negative comments made demonstrated a need for proper staff training in SC administration Patients were grateful to have been part of the trial, and would have liked to continue with SC delivery. The possibility of home administration in the future also seemed acceptable. EUDRACT NUMBER: 2010-024099-25

Wind Climatology at 87 km above the Rocky Mountains at Bear Lake Observatory--Fabry-Perot Observations of OH

This paper presents the neutral -wind climatology at approximately 87-km 53 altitude from Utah State University\u27s Bear Lake Observatory (BLO). a mid-latitude site 54 situated in the middle of the Rocky Mountains. The winds were determined using a very 55 sensitive Fabry-Perot interferometer (FPI) observing the OH Me inel (6-2) PI (3) line al 56 843 nm. The climatology. determined from monthly averages of the nightly evolution of 57 the geographic meridional and zonal wind components over forty· five months, has three 58 distinct seasonal patterns: winter (November- February), summer (May-Jul y), and late 59 Slimmer (August and September). The background zonal wind is eastward the whole year 60 except March and April. The background meridional wind is northward in winter and 61 southward during the rest of the year. In late summer. the winds exhibit a very strong 62 semidiurnal tidal variation almost every night. In summer, they exhibit a similar tidal 63 variation on enough nights that a semi diurnal pattern appears in the climatology. In 64 winter. the nighHo·night variability is so great that little structure is evident in the 65 climatology . These winds are compared to those from other techniques or sites: ~l 66 observations from UARS. FPI observations from Michigan, and MF radar observations. 67 While generally agreeing in relative amplitudes and i.n phase. differences do exist. 68 especially the weak semidiurnal tide at BLO in winter and a greatly reduced {tide at spring 69 equinox compared to late summer. It is likely that these differences arise from the 2 70 topographical generation of gravity waves by winds flowing over the Rocky Mountains. 71 The tidal variations are also compared to results from the global-scale wave model 72 (GSWM): our semidiurnal amplitudes arc considerably bigger except in winter, and our 73 phases vary from showing very good agreement in July, fair agreement in April and 74 January, and disagreement in October. These large differences may be evidence that 11011 - 75 linear effects are more important than realized. The behavior of the background winds is 76 consistent with different populations of gravity waves reaching 87 km in summer and 77 winter. The behavior of the semidiurnal tidal variation is consistent\u27 with a strong 78 interaction between the tidal and gravity·wave wind fields, and is consistent with the 79 different summer and Winter gravity wave population s, and with a fall· spring asymmetry 80 characterized by much weaker gravity wave sources in late summer than near spring 81 equinox

Why are estimates of global isoprene emissions so similar (and why is this not so for monoterpenes)?

International audienceEmissions of biogenic volatile organic compounds (BVOC) are a chief uncertainty in calculating the burdens of important atmospheric compounds like tropospheric ozone or secondary organic aerosol, reflecting either imperfect chemical oxidation mechanisms or unreliable emission estimates, or both. To provide a starting point for a more systematic discussion we review here global isoprene and monoterpene emission estimates to-date. We note a surprisingly small variation in the predictions of global isoprene emission rate that is in stark contrast with our lack of process understanding and the small number of observations for model parameterisation and evaluation. Most of the models are based on similar emission algorithms, using fixed values for the emission capacity of various plant functional types. In some studies these values are very similar, but they differ substantially in others. The models differ also broadly with regard to their representation of net primary productivity, method of biome coverage determination and climate data. Their similarities with regard to the global isoprene emission rate would suggest that the dominant parameters driving the ultimate global estimate, and thus the dominant determinant of model sensitivity, are the specific emission algorithm and isoprene emission capacity. Contrary to isoprene, monoterpene estimates show significantly larger model-to-model variation although variation in terms of leaf algorithm, emission capacities, the way of model upscaling, vegetation cover or climatology used in terpene models are comparable to those used for isoprene. From our summary of published studies there appears to be no evidence that the terrestrial modelling community has been any more successful in "resolving unknowns" in the mechanisms that control global isoprene emissions, compared to global monoterpene emissions. Rather, the proliferation of common parameterization schemes within a large variety of model platforms lends the illusion of convergence towards a common estimate of global isoprene emissions. This convergence might be used to provide optimism that the community has reached the "relief phase", the phase when sufficient process understanding and data for evaluation allows for models to converge, when applying a recently proposed concept. We argue that there is no basis for this apparent "relief" phase. Rather, we urge modellers to be bolder in their analysis to draw attention to the fact that terrestrial emissions, particularly in the area of biome-specific emission capacities, are unknown rather than uncertain

Hydration of a B-DNA Fragment in the Method of Atom-atom Correlation Functions with the Reference Interaction Site Model Approximation

We propose an efficient numerical algorithm for solving integral equations of the theory of liquids in the Reference Interaction Site Model (RISM) approximation for infinitely dilute solution of macromolecules with a large number of atoms. The algorithm is based on applying the nonstationary iterative methods for solving systems of linear algebraic equations. We calculate the solvent-solute atom-atom correlation functions for a fragment of the B-DNA duplex d(GGGGG).d(CCCCC) in infinitely dilute aqueous solution. The obtained results are compared with available experimental data and results from computer simulations.Comment: 9 pages, RevTeX, 9 pages of ps figures, accepted for publications in JC

Differential rates of perinatal maturation of human primary and nonprimary auditory cortex

Abstract Primary and nonprimary cerebral cortex mature along different timescales; however, the differences between the rates of maturation of primary and nonprimary cortex are unclear. Cortical maturation can be measured through changes in tissue microstructure detectable by diffusion magnetic resonance imaging (MRI). In this study, diffusion tensor imaging (DTI) was used to characterize the maturation of Heschl’s gyrus (HG), which contains both primary auditory cortex (pAC) and nonprimary auditory cortex (nAC), in 90 preterm infants between 26 and 42 weeks postmenstrual age (PMA). The preterm infants were in different acoustical environments during their hospitalization: 46 in open ward beds and 44 in single rooms. A control group consisted of 15 term-born infants. Diffusion parameters revealed that (1) changes in cortical microstructure that accompany cortical maturation had largely already occurred in pAC by 28 weeks PMA, and (2) rapid changes were taking place in nAC between 26 and 42 weeks PMA. At term equivalent PMA, diffusion parameters for auditory cortex were different between preterm infants and term control infants, reflecting either delayed maturation or injury. No effect of room type was observed. For the preterm group, disturbed maturation of nonprimary (but not primary) auditory cortex was associated with poorer language performance at age two years

Dynamic visual evoked response

Dynamic visual evoked respons

Pre-operative serum vascular endothelial growth factor can select patients for adjuvant treatment after curative resection in colorectal cancer

We aim to determine the clinical usefulness of pre-operative serum vascular endothelial growth factor (VEGF) as a predictor of outcome in patients undergoing curative resection for colorectal cancer. Serum VEGF was assayed by quantitative ELISA in 81 patients prior to curative resection for node-negative (n = 53) and node-positive (n = 28) disease. Median follow-up for patients without cancer death was 27 months (range 21–37). Pre-operative serum VEGF was significantly higher in patients who went on to develop metastases than those who did not (median, 713 pg ml–1 vs. 314 pg ml–1, P < 0.0001). Using multivariate Cox regression analysis, pre-operative serum VEGF was the most important prognostic factor independent of nodal status and adjuvant chemotherapy, and was superior to nodal status in predicting outcome (P < 0.00001). At 575 pg ml–1, pre-operative serum VEGF was 64% sensitive and 89% specific in predicting the development of metastases in curative resections, with a positive predictive value of 73% and a negative predictive value of 85%. Pre-operative serum VEGF is a powerful predictor of outcome following curative surgery for colorectal cancer. These data support the measurement of pre-operative serum VEGF as a method for selecting patients who require adjuvant therapy. © 2000 Cancer Research Campaign http://www.bjcancer.co

Using sonic anemometer temperature to measure sensible heat flux in strong winds

Sonic anemometers simultaneously measure the turbulent fluctuations of vertical wind (&lt;i&gt;w&lt;/i&gt;') and sonic temperature (&lt;i&gt;T&lt;/i&gt;&lt;sub&gt;s&lt;/sub&gt;'), and are commonly used to measure sensible heat flux (&lt;i&gt;H&lt;/i&gt;). Our study examines 30-min heat fluxes measured with a Campbell Scientific CSAT3 sonic anemometer above a subalpine forest. We compared &lt;i&gt;H&lt;/i&gt; calculated with &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;s&lt;/sub&gt; to &lt;i&gt;H&lt;/i&gt; calculated with a co-located thermocouple and found that, for horizontal wind speed (&lt;i&gt;U&lt;/i&gt;) less than 8 m s&lt;sup&gt;−1&lt;/sup&gt;, the agreement was around ±30 W m&lt;sup&gt;−2&lt;/sup&gt;. However, for &lt;i&gt;U&lt;/i&gt; &amp;asymp; 8 m s&lt;sup&gt;−1&lt;/sup&gt;, the CSAT &lt;i&gt;H&lt;/i&gt; had a generally positive deviation from &lt;i&gt;H&lt;/i&gt; calculated with the thermocouple, reaching a maximum difference of ≈250 W m&lt;sup&gt;−2&lt;/sup&gt; at &lt;i&gt;U&lt;/i&gt; ≈ 18 m s&lt;sup&gt;−1&lt;/sup&gt;. With version 4 of the CSAT firmware, we found significant underestimation of the speed of sound and thus &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;s&lt;/sub&gt; in high winds (due to a delayed detection of the sonic pulse), which resulted in the large CSAT heat flux errors. Although this &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;s&lt;/sub&gt; error is qualitatively similar to the well-known fundamental correction for the crosswind component, it is quantitatively different and directly related to the firmware estimation of the pulse arrival time. For a CSAT running version 3 of the firmware, there does not appear to be a significant underestimation of &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;s&lt;/sub&gt;; however, a &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;s&lt;/sub&gt; error similar to that of version 4 may occur if the CSAT is sufficiently out of calibration. An empirical correction to the CSAT heat flux that is consistent with our conceptual understanding of the &lt;i&gt;T&lt;/i&gt;&lt;sub&gt;s&lt;/sub&gt; error is presented. Within a broader context, the surface energy balance is used to evaluate the heat flux measurements, and the usefulness of side-by-side instrument comparisons is discussed