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Search Results: 1 - 10 of 395222 matches for " Peter C. G. Nijssen "
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A Case-Control Study of the Protective Effect of Alcohol, Coffee, and Cigarette Consumption on Parkinson Disease Risk: Time-Since-Cessation Modifies the Effect of Tobacco Smoking
Marianne van der Mark, Peter C. G. Nijssen, Jelle Vlaanderen, Anke Huss, Wim M. Mulleners, Antonetta M. G. Sas, Teus van Laar, Hans Kromhout, Roel Vermeulen
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095297
Abstract: The aim of this study was to investigate the possible reduced risk of Parkinson Disease (PD) due to coffee, alcohol, and/or cigarette consumption. In addition, we explored the potential effect modification by intensity, duration and time-since-cessation of smoking on the association between cumulative pack-years of cigarette smoking (total smoking) and PD risk. Data of a hospital based case-control study was used including 444 PD patients, diagnosed between 2006 and 2011, and 876 matched controls from 5 hospitals in the Netherlands. A novel modeling method was applied to derive unbiased estimates of the potential modifying effects of smoking intensity, duration, and time-since-cessation by conditioning on total exposure. We observed no reduced risk of PD by alcohol consumption and only a weak inverse association between coffee consumption and PD risk. However, a strong inverse association of total smoking with PD risk was observed (OR = 0.27 (95%CI: 0.18–0.42) for never smokers versus highest quartile of tobacco use). The observed protective effect of total smoking was significantly modified by time-since-cessation with a diminishing protective effect after cessation of smoking. No effect modification by intensity or duration of smoking was observed indicating that both intensity and duration have an equal contribution to the reduced PD risk. Understanding the dynamics of the protective effect of smoking on PD risk aids in understanding PD etiology and may contribute to strategies for prevention and treatment.
Readers as research detectives
Peter C G?tzsche
Trials , 2009, DOI: 10.1186/1745-6215-10-2
Abstract: We build on the scientific results of others when we choose treatments and plan new research. It is a challenge, however, how to do this most effectively and reliably, as flaws in research are common.Most users of the scientific literature read vastly more conclusions than they read abstracts, and vastly more abstracts than full papers. This approach is difficult to avoid, but it is a high-risk strategy. Although our intention might be to use conclusions and abstracts only as screening tests, helping us to identify those papers that merit a closer look, it is impossible to actively suppress what we have just "learnt" from a cursory reading. The human brain doesn't work that way, in fact, it is remarkably good at memorizing things we have been exposed to in a flash.Conclusions are the worst part of papers, and they are often tainted by wishful thinking, academic ambition, or the influence of money. Commercial pressures may explain, for example, why conclusions in randomised trials recommended the experimental drug as the drug of choice much more often if the trial was funded by for-profit organisations, even after adjustment for the effect size (odds ratio 5.3) [1].Abstracts may not be any better. A review of 520 randomly selected abstracts found that the first result in the abstract was statistically significant in 70% of the trials, 84% of cohort studies, and 84% of case-control studies [2]. Although many of these results were derived from subgroup or secondary analyses, or biased selection of results, they were presented without reservations in 98% of the trials. As true progress in therapeutics or in scientific knowledge is relatively rare, these results indicate that significant P-values in abstracts should generally be disbelieved.Because of the many problems in research papers, the task of reviewing research critically is important and has developed into a science of its own. But it took time to gain momentum. Gene Glass coined the term meta-analysis in 1976 [
Why we need easy access to all data from all clinical trials and how to accomplish it
Peter C G?tzsche
Trials , 2011, DOI: 10.1186/1745-6215-12-249
Abstract: Calls for data sharing have mostly been restricted to publicly-funded research, but I argue that the distinction between publicly-funded and industry-funded research is an artificial and irrelevant one, as the interests of the patients must override commercial interests.I also argue why it is a moral imperative to render all results from all trials involving humans, also healthy volunteers, publicly available. Respect for trial participants who often run a personal and unknown risk by participating in trials requires that they - and therefore also the society at large that they represent - be seen as the ultimate owners of trial data.Data sharing would lead to tremendous benefits for patients, progress in science, and rational use of healthcare resources based on evidence we can trust. The harmful consequences are minor compared to the benefits. It has been amply documented that the current situation, with selective reporting of favorable research and biased data analyses being the norm rather than the exception, is harmful to patients and has led to the death of tens of thousands of patients that could have been avoided.National and supranational legislation is needed to make data sharing happen as guidelines and other voluntary agreements do not work. I propose the contents of such legislation and of appropriate sanctions to hold accountable those who refuse to share their data.International calls for registering all trials involving humans and for sharing the results - and sometimes also the raw data and the trial protocols - have increased in recent years. Calls for such data sharing have mostly been restricted to publicly-funded research, but I argue here that the distinction between publicly-funded and industry-funded research is an artificial and irrelevant one, as the interests of the patients must override commercial interests. The main focus of this paper is therefore drug trials.I also argue why data sharing would lead to tremendous benefits for patients,
Deep Inspiration Breath Hold Reduces Dose to the Left Ventricle and Proximal Left Anterior Descending Artery during Radiotherapy for Left-Sided Breast Cancers  [PDF]
Lesley A. Jarvis, Peter G. Maxim, Kathleen C. Horst
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.325087
Abstract: The purpose of this study was to analyze motion of the left anterior descending coronary artery (LAD) and left ventricle during normal breathing and deep inspiration breath hold (DIBH). This is a dosimetric study utilizing free-breathing and static DIBH scans from eleven patients treated with radiotherapy for breast cancer. The anterior-posterior displacement along the length of the LAD was measured in each respiratory phase. Standard treatment plans targeting the whole breast without treatment of the internal mammary lymph nodes were generated and dose to the LAD and LV calculated. Non-uniform movement of the LAD during respiratory maneuvers with the proximal third exhibiting the greatest displacement was observed. In DIBH compared to end-expiration (EP), the mean posterior displacement of the proximal 1/3 of the LAD was 8.99 mm, the middle 1/3 of the artery was 6.37 mm, and the distal 1/3 was 3.27 mm. In end-inspiration (IP) compared to end-expiration the mean posterior displacements of the proximal 1/3 of the LAD was 2.08 mm, the middle 1/3 of the artery was 0.91 mm, and the distal 1/3 was 0.97 mm. Mean doses to the LAD using tangential treatment fields and a prescribed dose of 50.4 Gy were 11.32 Gy in EP, 8.98 Gy in IP, and 3.50 Gy in DIBH. Mean doses to the LV were 2.38 Gy in EP, 2.31 Gy in IP, and 1.24 Gy in DIBH. In conclusion, inspiration and especially DIBH, cause a displacement of the origin and proximal 2/3 of the LAD away from the chest wall, resulting in sparing of the most critical segment of the artery during tangential radiotherapy.
Analysis of regulation of pentose utilisation in Aspergillus niger reveals evolutionary adaptations in Eurotiales
E. Battaglia,L. Visser,A. Nijssen,G.J. van Veluw
Studies in Mycology , 2011,
Abstract: Aspergilli are commonly found in soil and on decaying plant material. D-xylose and L-arabinose are highly abundant components of plant biomass. They are released from polysaccharides by fungi using a set of extracellular enzymes and subsequently converted intracellularly through the pentose catabolic pathway (PCP).In this study, the L-arabinose responsive transcriptional activator (AraR) is identified in Aspergillus niger and was shown to control the L-arabinose catabolic pathway as well as expression of genes encoding extracellular L-arabinose releasing enzymes. AraR interacts with the D-xylose-responsive transcriptional activator XlnR in the regulation of the pentose catabolic pathway, but not with respect to release of L-arabinose and D-xylose.AraR was only identified in the Eurotiales, more specifically in the family Trichocomaceae and appears to have originated from a gene duplication event (from XlnR) after this order or family split from the other filamentous ascomycetes. XlnR is present in all filamentous ascomycetes with the exception of members of the Onygenales. Since the Onygenales and Eurotiales are both part of the subclass Eurotiomycetidae, this indicates that strong adaptation of the regulation of pentose utilisation has occurred at this evolutionary node. In Eurotiales a unique two-component regulatory system for pentose release and metabolism has evolved, while the regulatory system was lost in the Onygenales. The observed evolutionary changes (in Eurotiomycetidae) mainly affect the regulatory system as in contrast, homologues for most genes of the L-arabinose/D-xylose catabolic pathway are present in all the filamentous fungi, irrespective of the presence of XlnR and/or AraR.
The Contribution of dα-Tocopherol and dγ-Tocopherol to the Antioxidant Capacity of Several Edible Plant Oils  [PDF]
Garry G. Duthie, Peter T. Gardner, Philip C. Morrice, Donald B. McPhail
Natural Science (NS) , 2016, DOI: 10.4236/ns.2016.82005
Abstract: Many oils from plants are important components of our food chain and maintaining their oxidative stability (OS) is economically and nutritionally important. OS is dependent in part on antioxidant capacity (AC) arising from the electron donating ability of endogenous compounds in the oils. Attention has focused on the contribution to AC of phenolic compounds in oils as many have bioactivities in vitro. However, the relevance of such phenolics to healthy nutrition remains unclear. In contrast, many plant-derived oils also contain tocopherol homologs, which as vitamin E are dietary-essential, lipid-soluble antioxidants. We have determined the AC of twelve “off the shelf” edible oils by assessing their ability to quench galvinoxyl, a stable free radical species. The stochiometric reactivity of vitamin E with galvinoxyl indicates that the combined dα-tocopherol and dγ-tocopherol homologs contribute between 20% (olive) and 85% (soya) to AC depending on type of oil. Tocopherols are important contributors to the AC of several vegetable oils. Breeding and photo mixotrophic programmes to enhance content in edible oil crops of this important vitamin may have a positive impact not only on oil stability during storage but also in contributing to provision of optimum dietary intakes for health.
Pathological Outcomes in Kidney and Brain in Male Fischer Rats Given Dietary Ochratoxin A, Commencing at One Year of Age
Peter G. Mantle,Christopher C. Nolan
Toxins , 2010, DOI: 10.3390/toxins2051100
Abstract: Malignant renal carcinoma, manifest in morbid ageing rats, is the striking component of an otherwise silent response after about nine months of exposure to ochratoxin A in the first year of life (daily intake ~100–250 μg/kg body weight). Reasons for the long latency are unclear, as is whether there would be a similar carcinogenic response if toxin exposure started at one year of age. Therefore, 24 male Fischer rats were given 100 μg ochratoxin A as a daily dietary contaminant for 35 weeks from age 50 weeks. Plasma ochratoxin A concentration reached a maximum value of ~8 μg/mL within one month of starting the toxin regimen. No renal carcinomas occurred. Four renal adenomas, two of which were only microscopic, were found among the six rats surviving for 110 weeks. The findings raise new questions about a difference between young adults and mature adults in sensitivity of male rats to the ochratoxin A-induced DNA damage necessary for renal carcinogenesis. A pilot histological study of perfuse-fixed brains of the toxin-treated rats showed no gross abnormalities, correlating with the consistent absence of behavioral or neurological disorders from chronic ochratoxin A exposure regimens in the range 100–250 μg/kg/day during the second half of life. Reasoned questioning concerning ochratoxin A as a neurotoxic mycotoxin is made.
Dangerous for ferrets: lethal for humans?
Peter C Doherty, Paul G Thomas
BMC Biology , 2012, DOI: 10.1186/1741-7007-10-10
Abstract: The Fouchier experiment was the talk of the Malta meeting, though not because of safety concerns. Influenza virologists had been debating for years whether these HPAI H5N1 viruses could ever change in a way that would allow them to transmit readily between human beings. Informed opinion was strongly divided. We all knew that, given exposure to what has been assumed to be a large virus dose from an infected bird, people can develop severe H5N1 disease, with a very high death rate (345 fatalities out of 584 cases since 2003) [3]. A few instances where family members may have been secondarily infected are on record, while two recent cases with no known history of avian contact have been reported from China. We are not there yet, but what these ferret adaptation studies suggest (though by no means prove) is that a 'human' H5N1 pandemic virus may indeed emerge from nature.The issue of safety blew up much later when it came to publishing the Fouchier et al. findings. Should these genetic changes be 'out there' for all to see? Might that information be used by sophisticated bioterrorists? The furor about whether these ferret adaptation studies should ever have been done and, if so, whether the results should be openly published came as something of a surprise to us. Though some medical epidemiologists did raise the issue of risk, the resurrection of the catastrophic 1918 H1N1 virus by Jeff Taubengerger, Johan Hultin et al. more than a decade back met with general acclaim as an undoubted scientific achievement. The 1918 virus killed around 50 million people but nobody, so far as we recall, objected when (from 1999) segments of the virus sequence started to appear in the journals. Was the difference that there was, at that time, more trust in those who work in high security government laboratories? Then, much of the 1918 sequence was published before 9/11, 2001. The world has changed.Of course, citizens, commentators, funding agencies and national governments have every righ
Recommendations by Cochrane Review Groups for assessment of the risk of bias in studies
Andreas Lundh, Peter C G?tzsche
BMC Medical Research Methodology , 2008, DOI: 10.1186/1471-2288-8-22
Abstract: We examined the instructions to authors of the 50 Cochrane Review Groups that focus on clinical interventions for recommendations on methodological quality assessment of studies.Forty-one of the review groups (82%) recommended quality assessment using components and nine using a scale. All groups recommending components recommended to assess concealment of allocation, compared to only two of the groups recommending scales (P < 0.0001). Thirty-five groups (70%) recommended assessment of sequence generation and 21 groups (42%) recommended assessment of intention-to-treat analysis. Only 28 groups (56%) had specific recommendations for using the quality assessment of studies analytically in reviews, with sensitivity analysis, quality as an inclusion threshold and subgroup analysis being the most commonly recommended methods. The scales recommended had problems in the individual items and some of the groups recommending components recommended items not related to bias in their quality assessment.We found that recommendations by some groups were not based on empirical evidence and many groups had no recommendations on how to use the quality assessment in reviews. We suggest that all Cochrane Review Groups refer to the Cochrane Handbook for Systematic Reviews of Interventions, which is evidence-based, in their instructions to authors and that their own guidelines are kept to a minimum and describe only how methodological topics that are specific to their fields should be handled.The strength of systematic reviews of randomized trials and observational studies, as opposed to narrative reviews and expert opinion, is the application of systematic strategies to reduce bias. Since the conclusion may become unreliable if the data are flawed, this involves an assessment of the internal validity of the included studies [1]. The term methodological quality is often used instead of internal validity, but as quality may address issues that are not related to bias, it would be prefera
Instructional Strategies of Distance Education Instructors in China
Victor C. X. Wang,Peter G. Kreysa
Journal of Educators Online , 2006,
Abstract: This study investigated the teaching strategies of distance education instructors at the major universities in Beijing and Shanghai, China in the summer of 2005. The study utilized Conti’s 1983 and 2004 Principles of Adult Learning Scale (PALS) and researcher-designed open-ended questions to determine the teaching strategies of Chinese distance education instructors. Data were collected from 40 distance education instructors at the major universities to determine the extent to which the Western democratic form of distance education was employed. The study’s results show that although Chinese distance education instructors teach their courses in the Western educational manner, to some extent; they nevertheless oppose the Western collaborative mode of instruction and, instead, feature the teacher-directed form of instruction.
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