The Mayo Clinic Manuscript Series Relative to the Discussion, Dissemination, and Operationalization of the Food and Drug Administration Guidance on Patient-Reported Outcomes

AbstractPatient-reported outcomes (PROs) have become increasingly prevalent in clinical research and practice. On February 2, 2006, the Food and Drug Administration (FDA) released a draft guidance document with respect to incorporating PROs into clinical research endeavors which include FDA involvement. Researchers at the Mayo Clinic worked with FDA personnel and experts from academia, industry, clinical research, and clinical practice to facilitate discussion, dissemination, and operationalization of the FDA guidance document. This article introduces a manuscript series that resulted from this collective effort. Basic terms are definedand a précis of each article in the manuscript series is given. The ultimate conclusion to be drawn from this series is that, while the goals of assessing and analyzing PRO elements of clinical practice and research are challenging, there now exists a scientific foundation that makes achieving these goals feasible and the results credible. This is vitally important because after all, at the heart of all healthcare endeavors is the patient

Patient reported symptoms associated with quality of life during chemo- or immunotherapy for bladder cancer patients with advanced disease

Background: Bladder cancer (BC) patients with advanced disease have poor outcomes. The use of patient-reported outcomes (PROs) could lead to improvements in symptom management and hence quality of life (QoL). The aim of this study is to report correlations between selected PROs and QoL and thus to present symptoms that influence QoL. Identification of these symptoms during treatment can lead to earlier symptom management and thus secure improvements in QoL. Methods: BC patients in chemo- or immunotherapy for locally advanced or metastatic disease reported weekly PROs for the duration of their treatment. The PROs included EORTC QLQ-C30 and QLQ-BLM30 and 45 selected PRO-CTCAE items. Spearman's correlation analysis was performed for all PRO-CTCAE items and QLQ-C30 global QoL and subdomains. Results: In this study, 78 BC patients reported 724 questionnaires. Spearman's analysis showed significant correlations between almost all PRO-CTCAE items and the expected domain of QoL. The PRO-CTCAE items with the strongest correlations with QoL were anxiety (F, frequency item) and emotional function (rs = −0.603, P '.0001), concentration (S, severity item) and cognitive function (rs = −0.704, P '.0001), discouraged (F) and emotional function (rs = −0.659, P '.0001), fatigue (S) and role function (rs = −0.659, P '.0001) and sad (F) and emotional function (rs = −0.711, P '.0001). The weakest correlations were found for the PRO-CTCAE items urinary frequency, incontinence and urge, all with variations in the direction and significance of the correlations. Conclusions: This study delivers information on which PROs may influence QoL for patients in clinical trials or daily clinic. Psychological issues have a strong impact on QoL and should be dealt with during treatment to secure the best possible QoL for BC patients

741phealth related quality of life hrqol in patients with early stage pancreatic cancer espc receiving adjuvant or neoadjuvant chemotherapy a nac a systematic literature review slr

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Lichtspectrum bij stuur- en groeilicht in Freesia: Indicatief praktijkonderzoek naar de effecten van stuurlicht met LED lampen en groeilicht met plasmalampen

Wageningen UR glastuinbouw heeft samen met Penning Freesia en Pronk Consultancy in 2012 onderzoek gedaan naar de teeltkundige toepassingsmogelijkheden van LED- en zwavelplasmalampen in de teelt van. Met LED onderzoeksmodules is dagverlenging gerealiseerd van 10 uur bij een laag lichtniveau van 4 μmol/m 2 /s. Met zwavelplasmalampen is groeilicht gegeven ter vervanging van SON-T lampen. Rood licht heeft een toename van het cumulatief geoogst gewicht gegeven van 7% in Albatros tot 20% in Red Beauty. Verrood licht had een positief effect op het takgewicht van de hoofdtak. In beide rassen was de lengte onder zwavelplasma lampen korter en in Red Beauty was de lengte onder stuurlicht van alle kleuren ook iets korter dan onder SON-T. Er is in deze proef geen extra stimulering van de groei waargenomen door belichten met 35 μmol/m 2 /s Ecoplasma zwavelplasmalampen ten opzichte van SON-T. Het onderzoek is mogelijk gemaakt door financiering door het Productschap Tuinbouw en uitgevoerd onder begeleiding van de BCO en de landelijke commissie Freesia van LTO Groeiservice

Transfer RNA-derived small RNAs in the cancer transcriptome

The cellular lifetime includes stages such as differentiation, proliferation, division, senescence and apoptosis.These stages are driven by a strictly ordered process of transcription dynamics. Molecular disruption to RNA polymerase assembly, chromatin remodelling and transcription factor binding through to RNA editing, splicing, post-transcriptional regulation and ribosome scanning can result in significant costs arising from genome instability. Cancer development is one example of when such disruption takes place. RNA silencing is a term used to describe the effects of post-transcriptional gene silencing mediated by a diverse set of small RNA molecules. Small RNAs are crucial for regulating gene expression and microguarding genome integrity.RNA silencing studies predominantly focus on small RNAs such as microRNAs, short-interfering RNAs and piwi-interacting RNAs. We describe an emerging renewal of inter-est in a‘larger’small RNA, the transfer RNA (tRNA).Precisely generated tRNA-derived small RNAs, named tRNA halves (tiRNAs) and tRNA fragments (tRFs), have been reported to be abundant with dysregulation associated with cancer. Transfection of tiRNAs inhibits protein translation by displacing eukaryotic initiation factors from messenger RNA (mRNA) and inaugurating stress granule formation.Knockdown of an overexpressed tRF inhibits cancer cell proliferation. Recovery of lacking tRFs prevents cancer metastasis. The dual oncogenic and tumour-suppressive role is typical of functional small RNAs. We review recent reports on tiRNA and tRF discovery and biogenesis, identification and analysis from next-generation sequencing data and a mechanistic animal study to demonstrate their physiological role in cancer biology. We propose tRNA-derived small RNA-mediated RNA silencing is an innate defence mechanism to prevent oncogenic translation. We expect that cancer cells are percipient to their ablated control of transcription and attempt to prevent loss of genome control through RNA silencing

Neutrino Mass and μ→e+γ\mu \rightarrow e + \gamma from a Mini-Seesaw

The recently proposed "mini-seesaw mechanism" combines naturally suppressed Dirac and Majorana masses to achieve light Standard Model neutrinos via a low-scale seesaw. A key feature of this approach is the presence of multiple light (order GeV) sterile-neutrinos that mix with the Standard Model. In this work we study the bounds on these light sterile-neutrinos from processes like \mu ---> e + \gamma, invisible Z-decays, and neutrinoless double beta-decay. We show that viable parameter space exists and that, interestingly, key observables can lie just below current experimental sensitivities. In particular, a motivated region of parameter space predicts a value of BR(\mu ---> e + \gamma) within the range to be probed by MEG.Comment: 1+26 pages, 7 figures. v2 JHEP version (typo's fixed, minor change to presentation, results unchanged

Local Search Algorithms for Portfolio Selection: Search Space and Correlation Analysis

Modern Portfolio Theory dates back from the fifties, and quantitative approaches to solve optimization problems stemming from this field have been proposed ever since. We propose a metaheuristic approach for the Portfolio Selection Problem that combines local search and Quadratic Programming, and we compare our approach with an exact solver. Search space and correlation analysis are performed to analyse the algorithm's performance, showing that metaheuristics can be efficiently used to determine optimal portfolio allocation

Investigating a Hybrid Metaheuristic For Job Shop Rescheduling

Previous research has shown that artificial immune systems can be used to produce robust schedules in a manufacturing environment. The main goal is to develop building blocks (antibodies) of partial schedules that can be used to construct backup solutions (antigens) when disturbances occur during production. The building blocks are created based upon underpinning ideas from artificial immune systems and evolved using a genetic algorithm (Phase I). Each partial schedule (antibody) is assigned a fitness value and the best partial schedules are selected to be converted into complete schedules (antigens). We further investigate whether simulated annealing and the great deluge algorithm can improve the results when hybridised with our artificial immune system (Phase II). We use ten fixed solutions as our target and measure how well we cover these specific scenarios