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

Revision in the first steps of the biosynthesis of the red antibiotic prodigiosin: use of a synthetic thioester to validate a new intermediate.

Funder: Frances and Augustus Newman FoundationFunder: Emmanuel College, University of CambridgeFunder: Cambridge Commonwealth TrustA biosynthetic pathway for the red-antibiotic, prodigiosin, was proposed over a decade ago but not all the suggested intermediates could be detected experimentally. Here we show that a thioester that was not originally included in the pathway is an intermediate. In addition, the enzyme PigE was originally described as a transaminase but we present evidence that it also catalyses the reduction of the thioester intermediate to its aldehyde substrate

Effects of a vitamin B<SUB>12</SUB> deficiency on liver enzymes in the rat

This article does not have an abstract

The properties of fully flexible Lennard-Jones chains in the solid phase: Wertheim theory and simulation

NpT ensemble Monte Carlo simulations were performed for fully flexible Lennard-Jones chains in the solid phase. The bond length between monomers within the chains is fixed to $L=\sigma$ and the molecule is free to adopt any configuration. The solid structure of fully flexible chains is obtained by randomly locating the bonds of the chain within a face centered cubic close packed arrangement of atoms. For fully flexible chains it is believed that the stable solid phase is disordered. Such a solid is considered in this work. Computer simulations were performed for chains with $m=3, 4$ and 5 monomer units, and results were obtained for the equation of state and internal energy of the chains. An extension of Wertheim's TPT1 to the solid phase of Lennard-Jones chains (C.Vega, F.J.Blas and A.Galindo, J.Chem.Phys.,{\bf 116},7645,2002) has been proposed recently. The simulation results of this work provide a check on the performance of this theory. It is found that Wertheim's TPT1 successfully predicts the equation of state and internal energies of fully flexible LJ chains in the solid phase. Finally, a rigid LJ chain in a linear configuration has been considered. Computer simulations were also performed for the rigid chain in an ordered solid structure. It is found that fully flexible and linear rigid chains present quite different equations of state and different thermodynamic properties in the solid phase.Comment: PrEprint of the paper published in Molecular Physics volume 101, pp. 2241-2255 (2003

Far-Infrared Blocked Impurity Band Detector Development

DRS Sensors & Targeting Systems, supported by detector materials supplier Lawrence Semiconductor Research Laboratory, is developing far-infrared detectors jointly with NASA Langley under the Far-IR Detector Technology Advancement Partnership (FIDTAP). The detectors are intended for spectral characterization of the Earth's energy budget from space. During the first year of this effort we have designed, fabricated, and evaluated pilot Blocked Impurity Band (BIB) detectors in both silicon and germanium, utilizing pre-existing customized detector materials and photolithographic masks. A second-year effort has prepared improved silicon materials, fabricated custom photolithographic masks for detector process, and begun detector processing. We report the characterization results from the pilot detectors and other progress

Polarized Secretory Trafficking Directs Cargo for Asymmetric Dendrite Growth and Morphogenesis

SummaryProper growth of dendrites is critical to the formation of neuronal circuits, but the cellular machinery that directs the addition of membrane components to generate dendritic architecture remains obscure. Here, we demonstrate that post-Golgi membrane trafficking is polarized toward longer dendrites of hippocampal pyramidal neurons in vitro and toward apical dendrites in vivo. Small Golgi outposts partition selectively into longer dendrites and are excluded from axons. In dendrites, Golgi outposts concentrate at branchpoints where they engage in post-Golgi trafficking. Within the cell body, the Golgi apparatus orients toward the longest dendrite, and this Golgi polarity precedes asymmetric dendrite growth. Manipulations that selectively block post-Golgi trafficking halt dendrite growth in developing neurons and cause a shrinkage of dendrites in mature pyramidal neurons. Further, disruption of Golgi polarity produces neurons with symmetric dendritic arbors lacking a single longest principal dendrite. These results define a novel polarized organization of neuronal secretory trafficking and demonstrate a mechanistic link between directed membrane trafficking and asymmetric dendrite growth

Light Curves of the Neutron Star Merger GW170817/SSS17a: Implications for R-Process Nucleosynthesis

On 2017 August 17, gravitational waves were detected from a binary neutron star merger, GW170817, along with a coincident short gamma-ray burst, GRB170817A. An optical transient source, Swope Supernova Survey 17a (SSS17a), was subsequently identified as the counterpart of this event. We present ultraviolet, optical and infrared light curves of SSS17a extending from 10.9 hours to 18 days post-merger. We constrain the radioactively-powered transient resulting from the ejection of neutron-rich material. The fast rise of the light curves, subsequent decay, and rapid color evolution are consistent with multiple ejecta components of differing lanthanide abundance. The late-time light curve indicates that SSS17a produced at least ~0.05 solar masses of heavy elements, demonstrating that neutron star mergers play a role in r-process nucleosynthesis in the Universe.Comment: Accepted to Scienc

Cancer mortality in IBM Endicott plant workers, 1969–2001: an update on a NY production plant

<p>Abstract</p> <p>Background</p> <p>In response to concerns expressed by workers at a public meeting, we analyzed the mortality experience of workers who were employed at the IBM plant in Endicott, New York and died between 1969–2001. An epidemiologic feasibility assessment indicated potential worker exposure to several known and suspected carcinogens at this plant.</p> <p>Methods</p> <p>We used the mortality and work history files produced under a court order and used in a previous mortality analysis. Using publicly available data for the state of New York as a standard of comparison, we conducted proportional cancer mortality (PCMR) analysis.</p> <p>Results</p> <p>The results showed significantly increased mortality due to melanoma (PCMR = 367; 95% CI: 119, 856) and lymphoma (PCMR = 220; 95% CI: 101, 419) in males and modestly increased mortality due to kidney cancer (PCMR = 165; 95% CI: 45, 421) and brain cancer (PCMR = 190; 95% CI: 52, 485) in males and breast cancer (PCMR = 126; 95% CI: 34, 321) in females.</p> <p>Conclusion</p> <p>These results are similar to results from a previous IBM mortality study and support the need for a full cohort mortality analysis such as the one being planned by the National Institute for Occupational Safety and Health.</p

Drought supersedes warming in determining volatile and tissue defenses of piñon pine (Pinus edulis)

Trees are suffering mortality across the globe as a result of drought, warming, and biotic attacks. The combined effects of warming and drought on in situ tree chemical defenses against herbivory have not been studied to date. To address this, we transplanted mature pinon pine trees-a well-studied species that has undergone extensive drought and herbivore-related mortality-within their native woodland habitat and also to a hotter-drier habitat and measured monoterpene emissions and concentrations across the growing season. We hypothesized that greater needle temperatures in the hotter-drier site would increase monoterpene emission rates and consequently lower needle monoterpene concentrations, and that this temperature effect would dominate the seasonal pattern of monoterpene concentrations regardless of drought. In support of our hypothesis, needle monoterpene concentrations were lower across all seasons in trees transplanted to the hotter-drier site. Contrary to our hypothesis, basal emission rates (emission rates normalized to 30 degrees C and a radiative flux of 1000 mu mol m(-2) s(-1)) did not differ between sites. This is because an increase in emissions at the hotter-drier site from a 1.5 degrees C average temperature increase was offset by decreased emissions from greater plant water stress. High emission rates were frequently observed during June, which were not related to plant physiological or environmental factors but did not occur below pre-dawn leaf water potentials of -2 MPa, the approximate zero carbon assimilation point in pinon pine. Emission rates were also not under environmental or plant physiological control when pre-dawn leaf water potential was less than -2 MPa. Our results suggest that drought may override the effects of temperature on monoterpene emissions and tissue concentrations, and that the influence of drought may occur through metabolic processes sensitive to the overall needle carbon balance.National Science Foundation, Division of Atmospheric and Geospace Sciences [0919189]; USDA National Institute of Food and Agriculture Hatch project [MONB00389, 228396]; National Science Foundation, Division of Integrative Organismal Systems [1755346]; National Science Foundation Division of Environmental Biology [1552976]; Department of the Energy National Institute for Climate Change Research (Western Region) [DE-FCO2-O6ER64159]; National Science Foundation Macrosystems Biology [EF-1340624, EF-1550756]; Critical Zone Observatories [EAR-1331408]; DIRENet [DEB-0443526]; Biosphere 2 through the Philecology Foundation (Fort Worth, TX); US Environmental Protection Agency (STAR Fellowship Assistance Agreement) [FP-91717801-0]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]