Two dimensional smoothing via an optimised Whittaker smoother

Background In many applications where moderate to large datasets are used, plotting relationships between pairs of variables can be problematic. A large number of observations will produce a scatter-plot which is difficult to investigate due to a high concentration of points on a simple graph. In this article we review the Whittaker smoother for enhancing scatter-plots and smoothing data in two dimensions. To optimise the behaviour of the smoother an algorithm is introduced, which is easy to programme and computationally efficient. Results The methods are illustrated using a simple dataset and simulations in two dimensions. Additionally, a noisy mammography is analysed. When smoothing scatterplots the Whittaker smoother is a valuable tool that produces enhanced images that are not distorted by the large number of points. The methods is also useful for sharpening patterns or removing noise in distorted images. Conclusion The Whittaker smoother can be a valuable tool in producing better visualisations of big data or filter distorted images. The suggested optimisation method is easy to programme and can be applied with low computational cost

Gene therapy for carcinoma of the breast: Genetic ablation strategies

The gene therapy strategy of mutation compensation is designed to rectify the molecular lesions that are etiologic for neoplastic transformation. For dominant oncogenes, such approaches involve the functional knockout of the dysregulated cellular control pathways provoked by the overexpressed oncoprotein. On this basis, molecular interventions may be targeted to the transcriptional level of expression, via antisense or ribozymes, or post-transcriptionally, via intracellular single chain antibodies (intrabodies). For carcinoma of the breast, these approaches have been applied in the context of the disease linked oncogenes erbB-2 and cyclin D(1), as well as the estrogen receptor. Neoplastic revision accomplished in modal systems has rationalized human trials on this basis

Aktuelle Praxis und Perspektiven beim CRO Oversight - Umfrage unter den Mitgliedern des Verbandes Forschender Arzneimittelhersteller (vfa)

In recent years, the number and scope of outsourced activities in the pharmaceutical industry have increased heavily. In addition, also the type of outsourcing has changed significantly in that time. This raises the question of whether and how sponsors retain the capability to select and to control the contract research organizations (CROs) involved and what expertise still has to be present in the development department as well as other relevant departments to ensure adequate oversight, also in line with the expectations of regulators and health authorities. In order to answer these questions, a survey was conducted among the German vfa member companies. The survey describes the latest developments and experiences in outsourcing by 18 German vfa member companies. It concentrates on measures how to implement Quality Assurance (QA) when performing outsourced clinical studies.This study shows that the majority of companies apply a full-outsourcing, preferred-provider model of clinical trial services, with the clinical research department playing the major role in this process. A large amount of guiding documents, processes and tools are used to ensure an adequate oversight of the services performed by the CRO(s).Finally the guiding principles for all oversight processes should be transparent communication, a clearly established expectation for quality, a precise definition of accountability and responsibility while avoiding silo mentality, and a comprehensive documentation of the oversight's evidence. For globally acting and outsourcing sponsors, oversight processes need to be aligned with regards to local and global perspectives. This survey shows that the current implementation of oversight processes in the participating companies covers all relevant areas to ensure highest quality and integrity of the data produced by the outsourced clinical trial.In den letzten Jahren haben sich sowohl die Anzahl als auch der Umfang der ausgelagerten Tätigkeiten in der pharmazeutischen Industrie stark erhöht. Darüber hinaus hat sich auch die Art des Outsourcings in dieser Zeit verändert.Dies wirft die Frage auf, ob und wie die Sponsoren die Fähigkeit, geeignete CROs auszuwählen und zu überprüfen, beibehalten und welches Know-how noch in den Forschungs-, Entwicklungs- und anderen Abteilungen vorhanden sein muss, um eine angemessene Aufsicht zu gewährleisten, wie sie auch vom Gesetzgeber und den Überwachungsbehörden erwartet wird. Um diese Fragen zu beantworten, wurde eine Umfrage unter den deutschen vfa-Mitgliedsunternehmen durchgeführt. Die Studie beschreibt die neuesten Entwicklungen und Erfahrungen im Outsourcing von 18 deutschen Vfa-Mitgliedsunternehmen. Es werden Maßnahmen zur Umsetzung von Quality Assurance (QA) beschrieben, die bei der Auslagerung von klinischen Studien angewendet werden sollten.Diese Studie zeigt, dass die Mehrheit der Unternehmen ein Full-Outsourcing-Modell mit bevorzugten Anbietern ("Preferred Provider") im Bereich der klinischen Studien anwendet; dabei spielt die Abteilung "Klinische Forschung" die Hauptrolle in diesem Prozess. Eine große Menge von Guidelines, Prozessen und Werkzeugen werden verwendet, um eine angemessene Aufsicht über die Leistungen von den CROs zu gewährleisten.Schließlich sollten die Leitprinzipien für alle Oversight-Prozesse folgende Punkte umfassen: transparente Kommunikation, klar festgelegte Erwartung hinsichtlich der Qualität, genaue Definition der Verantwortlichkeiten ohne Silodenken, sowie eine umfassende Dokumentation der Oversight-Tätigkeiten. Für global agierende Sponsoren sollten die Oversight-Prozesse in Bezug auf lokale und globale Perspektiven abgestimmt sein.Diese Studie zeigt, dass die aktuelle Implementierung der Oversight-Prozesse in den beteiligten Unternehmen alle relevanten Bereiche abdeckt, um höchste Qualität und Integrität der durch die ausgelagerten klinischen Studien generierten Daten zu gewährleisten

Early Life Triclocarban Exposure During Lactation Affects Neonate Rat Survival

Triclocarban (3,4,4′-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation only (cross-fostering) to determine the susceptible windows of exposure for developmental consequences. Reduced offspring survival occurred when offspring were exposed to TCC at concentrations of 0.2% w/w and 0.5% w/w during lactation, in which only 13% of offspring raised by 0.2% w/w TCC dams survived beyond weaning and no offspring raised by 0.5% w/w TCC dams survived to this period. In utero exposure status had no effect on survival, as all pups nursed by control dams survived regardless of their in utero exposure status. Microscopic evaluation of dam mammary tissue revealed involution to be a secondary outcome of TCC exposure rather than a primary effect of compound administration. The average concentration of TCC in the milk was almost 4 times that of the corresponding maternal serum levels. The results demonstrate that gestational TCC exposure does not affect the ability of dams to carry offspring to term but TCC exposure during lactation has adverse consequences on the survival of offspring although the mechanism of reduced survival is currently unknown. This information highlights the importance of evaluating the safety of TCC application in personal care products and the impacts during early life exposure