Fowler-Nordheim-like local injection of photoelectrons from a silicon tip

Tunneling between a photo-excited p-type silicon tip and a gold surface is studied as a function of tip bias, tip/sample distance and light intensity. In order to extend the range of application of future spin injection experiments, the measurements are carried out under nitrogen gas at room temperature. It is found that while tunneling of valence band electrons is described by a standard process between the semiconductor valence band and the metal, the tunneling of photoelectrons obeys a Fowler-Nordheim-like process directly from the conduction band. In the latter case, the bias dependence of the photocurrent as a function of distance is in agreement with theoretical predictions which include image charge effects. Quantitative analysis of the bias dependence of the dark and photocurrent spectra gives reasonable values for the distance, and for the tip and metal work functions. For small distances image charge effects induce a vanishing of the barrier and the bias dependence of the photocurrent is exponential. In common with many works on field emission, fluctuations in the tunneling currents are observed. These are mainly attributed to changes in the prefactor for the tunneling photocurrent, which we suggest is caused by an electric-field-induced modification of the thickness of the natural oxide layer covering the tip apex.Comment: 12 pages, 11 figures. Submitted to Phys. Rev.

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

Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia

BACKGROUND: Little is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics. METHODS: Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI). Single nucleotide polymorphism (SNP) analysis of genes in the glucocorticoid pathway was also performed. RESULTS: Nine prepubertal subjects aged 8.1 ± 2.3 years completed the study. Mean ACTH, androstenedione, and 17-hydroxyprogesterone (17-OHP) values were lower following the DEX arm of the study than after subjects received HC (p ≤ 0.016) or PDN (p ≤ 0.002). 17-OHP was also lower after HC than PDN (p < 0.001). There was no difference in IGF-1, GH, or change in BMI. SNP analysis revealed significant associations between hormone concentrations, pharmacokinetic parameters, and variants in several glucocorticoid pathway genes (ABCB1, NR3C1, IP013, GLCCI1). CONCLUSIONS: DEX resulted in marked adrenal suppression suggesting that its potency relative to hydrocortisone and prednisone was underestimated. SNPs conferred significant differences in responses between subjects. Although preliminary, these pilot data suggest that incorporating pharmacogenetics has the potential to eventually lead to targeted therapy in children with CAH

Foodways in transition: food plants, diet and local perceptions of change in a Costa Rican Ngäbe community

Background Indigenous populations are undergoing rapid ethnobiological, nutritional and socioeconomic transitions while being increasingly integrated into modernizing societies. To better understand the dynamics of these transitions, this article aims to characterize the cultural domain of food plants and analyze its relation with current day diets, and the local perceptions of changes given amongst the Ngäbe people of Southern Conte-Burica, Costa Rica, as production of food plants by its residents is hypothesized to be drastically in recession with an decreased local production in the area and new conservation and development paradigms being implemented. Methods Extensive freelisting, interviews and workshops were used to collect the data from 72 participants on their knowledge of food plants, their current dietary practices and their perceptions of change in local foodways, while cultural domain analysis, descriptive statistical analyses and development of fundamental explanatory themes were employed to analyze the data. Results Results show a food plants domain composed of 140 species, of which 85 % grow in the area, with a medium level of cultural consensus, and some age-based variation. Although many plants still grow in the area, in many key species a decrease on local production–even abandonment–was found, with much reduced cultivation areas. Yet, the domain appears to be largely theoretical, with little evidence of use; and the diet today is predominantly dependent on foods bought from the store (more than 50 % of basic ingredients), many of which were not salient or not even recognized as ‘food plants’ in freelists exercises. While changes in the importance of food plants were largely deemed a result of changes in cultural preferences for store bought processed food stuffs and changing values associated with farming and being food self-sufficient, Ngäbe were also aware of how changing household livelihood activities, and the subsequent loss of knowledge and use of food plants, were in fact being driven by changes in social and political policies, despite increases in forest cover and biodiversity. Conclusions Ngäbe foodways are changing in different and somewhat disconnected ways: knowledge of food plants is varied, reflecting most relevant changes in dietary practices such as lower cultivation areas and greater dependence on food from stores by all families. We attribute dietary shifts to socioeconomic and political changes in recent decades, in particular to a reduction of local production of food, new economic structures and agents related to the State and globalization

Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC

PMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Exercise load monitoring: integrated approaches to advance the individualisation of exercise oncology

Whether slowing disease progression or combatting the ills of advancing age, the extensive utility of exercise training has contributed to the outright declaration by the American College of Sports Medicine that ‘exercise is medicine’. Consistent with general framework of adaptation, the advantages of exercise training are indiscriminate—benefitting even the most susceptible clinical populations. Still, the benefit of exercise training presupposes healthy adaptation wherein progressive overload matches sufficient recovery. Indeed, a difference exists between healthy adaptation and non-functional over-reaching (ie, when internal/external load exceeds recovery capacity)—a difference that may be blurred by cancer treatment and/or comorbidity. Recent advances in smartwatches make them ideally suited to non-invasively monitor the physiological stresses to exercise training. Resolving whether individuals are successfully adapting to exercise training via load monitoring bears clinical and practical relevance. While behaviour-change research aims to identify positive constructs of exercise adherence, further attention is needed to uncover how to optimise exercise prescription among cancer populations. Herein, we briefly discuss the constituents of exercise load monitoring, present examples of internal and external load and consider how such practices can be applied to cancer populations

Effect of Biodiversity Changes in Disease Risk: Exploring Disease Emergence in a Plant-Virus System

The effect of biodiversity on the ability of parasites to infect their host and cause disease (i.e. disease risk) is a major question in pathology, which is central to understand the emergence of infectious diseases, and to develop strategies for their management. Two hypotheses, which can be considered as extremes of a continuum, relate biodiversity to disease risk: One states that biodiversity is positively correlated with disease risk (Amplification Effect), and the second predicts a negative correlation between biodiversity and disease risk (Dilution Effect). Which of them applies better to different host-parasite systems is still a source of debate, due to limited experimental or empirical data. This is especially the case for viral diseases of plants. To address this subject, we have monitored for three years the prevalence of several viruses, and virus-associated symptoms, in populations of wild pepper (chiltepin) under different levels of human management. For each population, we also measured the habitat species diversity, host plant genetic diversity and host plant density. Results indicate that disease and infection risk increased with the level of human management, which was associated with decreased species diversity and host genetic diversity, and with increased host plant density. Importantly, species diversity of the habitat was the primary predictor of disease risk for wild chiltepin populations. This changed in managed populations where host genetic diversity was the primary predictor. Host density was generally a poorer predictor of disease and infection risk. These results support the dilution effect hypothesis, and underline the relevance of different ecological factors in determining disease/infection risk in host plant populations under different levels of anthropic influence. These results are relevant for managing plant diseases and for establishing conservation policies for endangered plant species

Lethal effect of high concentrations of Parecoxib and Flunixin meglumine on the in vitro culture of bovine embryos

Abstract Since cyclooxygenase (COX) inhibitors have been pointed out as potential treatments to increase pregnancy rates after embryo transfer, the present experiment aimed to evaluate the effects of flunixin meglumine (FM) and parecoxib (P), a COX-1 and 2 or COX-2 specific inhibitor, respectively, on the development of bovine embryos until the hatched blastocyst stage. In vitro produced bovine embryos were cultured in media with different concentrations of FM (0.14; 1.4; 14; 140 or 1400 µg/ml) or P (0.09; 0.9; 9; 90 or 900 µg/ml) and the production rates were evaluated. Concentrations of FM ≤14 µg/ml and P ≤90 µg/ml did not impair embryo development, although compiled data from non-lethal FM concentrations (≤14 µg/ml) indicated a toxic effect enough to decrease the hatching rate of blastocysts. Concentrations of FM at 140 and 1400 µg/ml and P at 900 µg/ml were lethal as no cleavage was detected on presumptive zygotes