Electronic structure of the Au/benzene-1,4-dithiol/Au transport interface: Effects of chemical bonding

We present results of electronic structure calculations for well-relaxed Au/benzene-1,4-dithiol/Au molecular contacts, based on density functional theory and the generalized gradient approximation. Electronic states in the vicinity of the Fermi energy are mainly of Au 5d and S 3p symmetry, whereas contributions of C 2p states are very small. Hybridization between C 2p orbitals within the benzene substructure is strongly suppressed due to S-C bonding. In agreement with experimental findings, this corresponds to a significantly reduced conductance of the molecular contact.Comment: 7 pages, 5 figures, accepted by Chemical Physics Letter

Electronic Patient Reporting of Adverse Events and Quality of Life: A Prospective Feasibility Study in General Oncology

PURPOSE: Adverse event (AE) reporting is essential in clinical trials. Clinician interpretation can result in under-reporting; therefore, the value of patient self-reporting has been recognized. The National Cancer Institute has developed a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for direct patient AE reporting. A nonrandomized prospective cohort feasibility study aimed to explore the compliance and acceptability of an electronic (Internet or telephone) system for collecting patient self-reported AEs and quality of life (QOL). METHODS: Oncology patients undergoing treatment (chemotherapy, targeted agents, hormone therapy, radiotherapy, and/or surgery) at 2 hospitals were sent automated weekly reminders to complete PRO-CTCAE once a week and QOL (for a maximum of 12 weeks). Patients had to speak/understand English and have access to the Internet or a touch-tone telephone. Primary outcome was compliance (proportion of expected questionnaires), and recruitment rate, attrition, and patient/staff feedback were also explored. RESULTS: Of 520 patients, 249 consented (47.9%)—mean age was 62 years, 51% were male, and 70% were married—and 230 remained on the study at week 12. PRO-CTCAE was completed at 2,301 (74.9%) of 3,074 timepoints and QOL at 749 (79.1%) of 947 timepoints. Individual weekly/once every 4 weeks compliance reduced over time but was more than 60% throughout. Of 230 patients, 106 (46.1%) completed 13 or more PRO-CTCAE, and 136 (59.1%) of 230 patients completed 4 QOL questionnaires. Most were completed on the Internet (82.3%; mean age, 60.8 years), which was quicker, but older patients preferred the telephone option (mean age, 70.0 years). Positive feedback was received from patients and staff. CONCLUSION: Self-reporting of AEs and QOL using an electronic home-based system is feasible and acceptable. Implementation of this approach in cancer clinical trials may improve the precision and accuracy of AE reporting

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

Origin of pyroxenites in the oceanic mantle and their implications on the reactive percolation of depleted melts

Pyroxenites are diffuse in fertile mantle peridotites and considered an important component in the mantle source of oceanic basalts. They are rarely documented in abyssal and ophiolitic peridotites representing residual mantle after melt generation, and few studies defining their origin are to date available. We present a field-based microstructural and geochemical investigation of the pyroxenite layers associated with depleted peridotites from the Mt. Maggiore ophiolitic body (Corsica, France). Field and petrographic evidence indicate that pyroxenite formation preceded the melt\u2013rock interaction history that affected this mantle sector during Jurassic exhumation, namely (1) spinel-facies reactive porous flow leading to partial dissolution of the pyroxenites, and (2) plagioclase-facies melt impregnation leading to [plagioclase + orthopyroxene] interstitial crystallization. Pyroxenes show major element compositions similar to abyssal pyroxenites from slow-spreading ridges, indicative of magmatic segregation at pressures higher than 7 kbar. Both the parental melts of pyroxenites and the melts involved in the subsequent percolation were characterized by Na2O-poor, LREE-depleted compositions, consistent with unaggregated melt increments. This implies that they represent the continuous evolution of similarly depleted melts leading to different processes (pyroxenite segregation and later melt\u2013rock interaction) during their upward migration. To support the genetic relation and the continuity between the formation of pyroxenites and the subsequent melt\u2013rock interaction history, we modeled all the documented processes in sequence, i.e.: (1) formation of single-melt increments after 6% mantle decompressional fractional melting; (2) high-pressure segregation of pyroxenites; (3) spinel-facies reactive porous flow, (4) plagioclase-facies melt impregnation. The early fractionation of pyroxenites leads to a decrease in pyroxene saturation that is necessary for the subsequent reactive porous flow process, without any significant change in the melt REE composition

Overcoming barriers to integrating patient-reported outcomes in clinical practice and electronic health records

There is burgeoning interest in integrating electronic patient-reported outcomes (PROs) into the workflow of routine cancer care. In general, this involves offering patients an interface for self-reporting their symptoms, distress, physical functioning, and other clinically oriented information through online or telephone systems, with this information conveyed to clinicians through real-time alerts and longitudinal graphic reports

Patient-Reported Outcomes for Tolerability Assessment in Phase i Cancer Clinical Trials

Patient-reported outcomes (PROs) have historically been used in clinical trials to assess symptoms or quality of life in pivotal (late phase) or postmarketing trials. More recently, interest has risen to use PROs to elicit information about symptomatic adverse events directly from patients, for example, nausea or peripheral sensory neuropathy associated with investigational treatments

Visual Assessment of the Impact of Agricultural Management Practices on Soil Quality

The intensification of agricultural practices to increase food and feed outputs is a pressing challenge causing deterioration of soil quality and soil functions. Such a challenge demands provision of empirical evidence to provide context-sensitive guidance on agricultural management practices (AMPs) that may enhance soil quality. The objectives of this study are to identify the most promising AMPs (and their combinations) applied by farmers with the most positive effects on soil quality and to evaluate the sensitivity of the soil quality indicators to the applied AMPs. The effect of selected AMPs on soil quality was assessed using a visual soil assessment tool in a total of 138 pairs of plots spread across 14 study site areas in Europe and China covering representative pedo-climatic zones. The inventory and scoring of soil quality were conducted together with landowners. Results show that 104 pairs show a positive effect of AMPs on soil quality. Higher effects of the AMPs were observed in lower fertile soils (i.e., Podzols and Calcisols) as opposed to higher fertile soils (i.e., Luvisols and Fluvisols). For the single use applications, the AMPs with positive effects were crop rotation; manuring, composting, and no-tillage; followed by organic agriculture and residue maintenance. Cluster analysis showed that the most promising combinations of AMPs with the most positive effects on soil quality are composed of crop rotation, mulching, and min-till. The agreement between scientific skills and empirical knowledge in the field identified by the farmers confirm our findings and ensures their applicability

First-principles calculation on the transport properties of molecular wires between Au clusters under equilibrium

Based on the matrix Green's function method combined with hybrid tight-binding / density functional theory, we calculate the conductances of a series of gold-dithiol molecule-gold junctions including benzenedithiol (BDT), benzenedimethanethiol (BDMT), hexanedithiol (HDT), octanedithiol (ODT) and decanedithiol (DDT). An atomically-contacted extended molecule model is used in our calculation. As an important procedure, we determine the position of the Fermi level by the energy reference according to the results from ultraviolet photoelectron spectroscopy (UPS) experiments. After considering the experimental uncertainty in UPS measurement, the calculated results of molecular conductances near the Fermi level qualitatively agree with the experimental values measured by Tao et. al. [{\it Science} 301, 1221 (2003); {\it J. Am. Chem. Soc.} 125, 16164 (2003); {\it Nano. Lett.} 4, 267 (2004).]Comment: 12 pages,8 figure

Symptom Monitoring in Pediatric Oncology Using Patient-Reported Outcomes: Why, How, and Where Next

Symptom monitoring using patient-reported outcomes (PROs) is not common in pediatric oncology, despite interest from stakeholders—including patients, families, clinicians, and regulatory organizations—and proven clinical benefit in adult oncology. This article examines the foundational data for patient-reported symptom reporting in this population and posits the next investigative steps toward the implementation of patient-reported symptom monitoring in the care and research of pediatric oncology patients. The reasoning behind, and feasibility of, monitoring symptoms in pediatric oncology patients using PRO measures are discussed, as well as specific tools that have been developed to track symptoms in this population, including innovative electronic self-reporting platforms built to engage children in the symptom reporting process. Aspects of engaging both patients and clinicians in the symptom self-report process are reviewed, as are the experiences of “early adopters” of this process in pediatric oncology and across pediatrics. It is clear that there are key issues that remain regarding the use of PROs for symptom monitoring, including selection of specific outcomes to monitor, how to resolve discrepant reports, and determination of benefit. The next steps for investigation of these issues are discussed. Unanswered questions notwithstanding, work should continue to make patient-reported symptom monitoring an established, evidence-based part of routine and research practice in pediatric oncology

Surrogate End Points and Patient-Reported Outcomes for Novel Oncology Drugs Approved between 2011 and 2017

The US Food and Drug Administration (FDA) may approve drugs based on surrogate end points that reasonably predict that a drug provides clinical benefit. If approved via the accelerated approval pathway, the FDA may require postmarketing studies to confirm the perceived clinical benefit. Assessment of patient-reported outcomes (PROs), defined as any report on a patient’s health that comes directly from the patient, can also play a key role in understanding benefits and tolerability of oncology drugs. We sought to examine the use of surrogate end points for overall survival (OS) in new oncology drug approvals, to evaluate the use of PROs in trials supporting approvals, and to determine whether oncology drugs initially approved without evidence of OS or PRO benefits demonstrated improvements in either measure postapproval