Scientific perspectives on lunar exploration in Europe.

The Moon is a geological history book, preserving information about the history of the Solar System, including the formation and early evolution of the terrestrial planets and their bombardment histories, as well as providing insight into other fundamental Solar System processes. These topics form the basis for science "of the Moon", but the lunar surface is also a platform for science "on the Moon" and "from the Moon"-including astronomical observations, fundamental physics, and life science investigations. Recently, the Moon has become a destination for technology research and development-in particular for developing in situ resources, human exploration, and habitation, and for its potential use as a waypoint for the human exploration of Mars.

Impact Melt Facies in the Moon's Crisium Basin: Identifying, Characterizing, and Future Radiogenic Dating.

Both Earth and the Moon share a common history regarding the epoch of large basin formation, though only the lunar geologic record preserves any appreciable record of this Late Heavy Bombardment. The emergence of Earth's first life is approximately contemporaneous with the Late Heavy Bombardment; understanding the latter informs the environmental conditions of the former, which are likely necessary to constrain the mechanisms of abiogenesis. While the relative formation time of most of the Moon's large basins is known, the absolute timing is not.

Publication rates and reported results in a cohort of gene- and cell-based therapy trials.

We investigated publication rates and reported results for gene- and cell-based therapy trials. In a cohort of Institutional Review Board (IRB)-authorized trials during 2007-2017 in the Netherlands (n = 105), we examine publication rates and reported results in scientific papers and conference abstracts as well as associations with the occurrence of trial characteristics. The publication rate for scientific papers was 27% and 17% for conference abstracts (median survival time: 1050 days).

Causes of reporting bias: a theoretical framework.

Reporting of research findings is often selective. This threatens the validity of the published body of knowledge if the decision to report depends on the nature of the results. The evidence derived from studies on causes and mechanisms underlying selective reporting may help to avoid or reduce reporting bias.

Determinants of selective reporting: A taxonomy based on content analysis of a random selection of the literature.

Background: Selective reporting is wasteful, leads to bias in the published record and harms the credibility of science. Studies on potential determinants of selective reporting currently lack a shared taxonomy and a causal framework.

Objective: To develop a taxonomy of determinants of selective reporting in science.

Pharmacological vs. classical approaches in the design of first in man clinical drug trials.

Aims: The aims of the present study were to investigate the role of pharmacology in the design of first-in-man (FIM) trials in the Netherlands, and to evaluate the change in design approaches between 2007 and 2015.

Methods: All FIM drug trials approved by all Dutch Institutional Review Boards (IRBs) in 2007 and in 2015 were selected. The original trial protocols, investigator's brochures and investigational medicinal product dossiers were the data sources.

[Non-publication is common among phase 1, single-center, not prospectively registered, or early terminated clinical drug trials].

The objective of this study was to investigate the occurrence and determinants of non-publication of clinical drug trials in the Netherlands. All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followed-up from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination.

Primary endpoint discrepancies were found in one in ten clinical drug trials. Results of an inception cohort study.

Objective: To identify the occurrence and determinants of protocol-publication discrepancies in clinical drug trials.

Study Design And Setting: All published clinical drug trials reviewed by the Dutch institutional review boards in 2007 were analyzed. Discrepancies between trial protocols and publications were measured among key reporting aspects.

Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands.

Objectives: The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol.

Study Design And Setting: All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators.

Non-Publication Is Common among Phase 1, Single-Center, Not Prospectively Registered, or Early Terminated Clinical Drug Trials.

The objective of this study was to investigate the occurrence and determinants of non-publication of clinical drug trials in the Netherlands.All clinical drug trials reviewed by the 28 Institutional Review Boards (IRBs) in the Netherlands in 2007 were followed-up from approval to publication. Candidate determinants were the sponsor, phase, applicant, centers, therapeutic effect expected, type of trial, approval status of the drug(s), drug type, participant category, oncology or other disease area, prospective registration, and early termination.

Risk indicator taxonomy for supervision of clinical trials on medicinal products.

Aim: To facilitate a risk-based approach for the supervision of clinical trials on medicinal products, we identified and categorized indicators that may present an elevated safety and/or ethical risk for participants, and/or for data integrity. The indicators are relevant for all stakeholders including participants, regulatory bodies, health care inspectorates, sponsors and trial sites.

Methods: The sources of indicators included Medline (using the search terms risk-based/-triggered/-driven oversight/monitoring/inspection), relevant documents from websites of regulatory authorities in Europe, North America and Australia, and results of a brainstorm session organized for experts working in the field.

Occurrence and determinants of selective reporting of clinical drug trials: design of an inception cohort study.

Introduction: Responsible conduct of research implies that results of clinical trials should be completely and adequately reported. This article describes the design of a cohort study that aims to investigate the occurrence and the determinants of selective reporting in an inception cohort of all clinical drug trials that were reviewed by the Dutch Institutional Review Boards (IRBs) in 2007. It also describes the characteristics of the study cohort.

Screening Questions for Nonsteroidal Anti-inflammatory Drug Risk Knowledge.

Objective: The aim of this study was to evaluate screening questions for estimating nonsteroidal anti-inflammatory drug (NSAID) risk knowledge.

Methods: Cross-sectional data from a telephone interview of NSAID users 50 years or older from 39 physician practices in Alabama were used. Patient-reported awareness of prescription NSAID risk and health literacy were the independent variables, and a cumulative index score of objectively tested knowledge of 4 prominent NSAID risks was the dependent variable.

Evidence of recent thrust faulting on the Moon revealed by the Lunar Reconnaissance Orbiter Camera.

Lunar Reconnaissance Orbiter Camera images reveal previously undetected lobate thrust-fault scarps and associated meter-scale secondary tectonic landforms that include narrow extensional troughs or graben, splay faults, and multiple low-relief terraces. Lobate scarps are among the youngest landforms on the Moon, based on their generally crisp appearance, lack of superposed large-diameter impact craters, and the existence of crosscut small-diameter impact craters. Identification of previously known scarps was limited to high-resolution Apollo Panoramic Camera images confined to the equatorial zone.

Effects of piroxicam on prostaglandin E2 levels in rectal mucosa of adenomatous polyp patients: a randomized phase IIb trial.

Prostaglandin E2 (PGE2) has served as a surrogate end point biomarker in colorectal tumor progression. Colonic mucosa PGE2 levels of patients with colorectal adenomas or carcinomas have been shown to be higher than in control subjects. Our dose-finding study on piroxicam, a nonsteroidal anti-inflammatory drug with chemopreventive effects in preclinical colon carcinoma models, suggested that 7.

Physical activity, body mass index, and prostaglandin E2 levels in rectal mucosa.

Background: Evidence suggests a relationship between prostaglandin levels in colonic mucosa and risk of colon cancer. Physical inactivity and a higher body mass index (BMI; weight in kilograms divided by [height in meters]2) have been consistently shown to increase risk of this cancer. We investigated whether higher levels of leisure-time physical activity or a lower BMI was associated with lower concentrations of prostaglandin E2 (PGE2) in rectal mucosa.

Assembly of cytochrome-c oxidase in cultured human cells.

The assembly of cytochrome-c oxidase was studied in human cells cultured in the presence of inhibitors of mitochondrial or cytosolic protein synthesis. Mitochondrial fractions were resolved using two-dimensional PAGE (blue native PAGE and tricine/SDS/PAGE) and subsequent western blots were developed with monoclonal antibodies against specific subunits of cytochrome-c oxidase. Proteins were also visualized using metabolic labeling followed by two-dimensional electrophoresis and fluorography.

Familial mitochondrial DNA depletion in liver: haplotype analysis of candidate genes.

Two sons and one daughter of healthy consanguineous parents presented with fatal hepatic failure in association with severe depletion of mitochondrial (mt)DNA in liver; a third son is healthy. Other published cases of mtDNA depletion concern single members of a family, which excludes the use of haplotype analysis. In the family presented here, the inheritance of the genes for mitochondrial transcription factor A (mtTFA), nuclear respiratory factor 1 (NRF-1), mitochondrial single-stranded DNA-binding protein (mtSSBP), and endonuclease G (EndoG) was studied using microsatellite markers linked to these genes.

Preferential amplification and phenotypic selection in a population of deleted and wild-type mitochondrial DNA in cultured cells.

In order to study the still poorly understood dynamics of mitochondrial gene segregation, we attempted to alter the percentage of deleted mtDNA (del-mtDNA) over wild-type mtDNA in cell-culture by manipulating respiratory chain capacity. For this purpose, we used a cell-line harbouring a 6-kb mtDNA-deletion which normally was present in 70% of the molecules. The results show that in the presence of low concentrations of doxycycline (DC), an inhibitor of mitochondrial protein synthesis, the average percentage of del-mtDNA in culture steadily declined.

Sulindac sulfone inhibits azoxymethane-induced colon carcinogenesis in rats without reducing prostaglandin levels.

Nonsteroidal anti-inflammatory drugs (NSAIDs), such as sulindac, have cancer chemopreventive properties by a mechanism that has been suggested to involve cyclooxygenase inhibition and reduction of prostaglandin (PGE2) levels in the target tissue. To test this hypothesis, we studied the effect of dietary sulindac sulfone (500-2000 ppm), a metabolite of sulindac reported to lack cyclooxygenase inhibitory activity, on tumor formation and PGE2 levels in the azoxymethane model of colon carcinogenesis. Rats treated with sulindac at 400 ppm and piroxicam at 150 ppm were used as positive controls.

Cerebellar hypoplasia in respiratory chain dysfunction.

Disruption of early or late fetal brain development resulting in structural abnormalities may be associated with inborn errors of mitochondrial metabolism. It is common in patients with deficiency of pyruvate dehydrogenase activity and it has sporadically been described in patients with dysfunction of the tricarboxylic acid cycle. Mitochondrial respiratory chain disorders are not commonly known to interfere with early brain development.