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Träfflista för sökning "WFRF:(Burger Christian) "

Sökning: WFRF:(Burger Christian)

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1.
  • Breznau, Nate, et al. (författare)
  • Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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2.
  • Cantù, Claudio, et al. (författare)
  • Mutations in Bcl9 and Pygo genes cause congenital heart defects by tissue-specific perturbation of Wnt/beta-catenin signaling
  • 2018
  • Ingår i: Genes & Development. - : COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. - 0890-9369 .- 1549-5477. ; 32:21-22, s. 1443-1458
  • Tidskriftsartikel (refereegranskat)abstract
    • Bcl9 and Pygopus (Pygo) are obligate Wnt/beta-catenin cofactors in Drosophila, yet their contribution to Wnt signaling during vertebrate development remains unresolved. Combining zebrafish and mouse genetics, we document a conserved, beta-catenin-associated function for BCL9 and Pygo proteins during vertebrate heart development. Disrupting the beta-catenin-BCL9-Pygo complex results in a broadly maintained canonical Wnt response yet perturbs heart development and proper expression of key cardiac regulators. Our work highlights BCL9 and Pygo as selective beta-catenin cofactors in a subset of canonical Wnt responses during vertebrate development. Moreover, our results implicate alterations in BCL9 and BCL9L in human congenital heart defects.
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3.
  • Broushaki, Farnaz, et al. (författare)
  • Early Neolithic genomes from the eastern Fertile Crescent.
  • 2016
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 353:6298
  • Tidskriftsartikel (refereegranskat)abstract
    • We sequenced Early Neolithic genomes from the Zagros region of Iran (eastern Fertile Crescent), where some of the earliest evidence for farming is found, and identify a previously uncharacterized population that is neither ancestral to the first European farmers nor has contributed substantially to the ancestry of modern Europeans. These people are estimated to have separated from Early Neolithic farmers in Anatolia some 46,000 to 77,000 years ago and show affinities to modern-day Pakistani and Afghan populations, but particularly to Iranian Zoroastrians. We conclude that multiple, genetically differentiated hunter-gatherer populations adopted farming in southwestern Asia, that components of pre-Neolithic population structure were preserved as farming spread into neighboring regions, and that the Zagros region was the cradle of eastward expansion.
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4.
  • Burger, Gregor, et al. (författare)
  • Designing and implementing a multi-core capable integrated urban drainage modelling Toolkit : Lessons from CityDrain3
  • 2016
  • Ingår i: Advances in Engineering Software. - : Elsevier BV. - 0965-9978 .- 1873-5339. ; 100, s. 277-289
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrated urban drainage modelling combines different aspects of the urban water system into a common framework. With increasing pressures of a changing climate, urban growth and economic constraints, the need for wider spread integration is necessary in the interest of a sustainable future. Greater complexity results in greater computational burden but modelling packages will, likewise, need to be flexible enough to allow incorporation of new algorithms. With advancements in modern information technology, a parallel implementation of such a modelling toolkit is mandatory while still leaving its users the flexibility of extensions. The design and implementation of the integrated modelling framework CityDrain3 shows that it is possible to write research code that is high-performance and extensible by many research projects. Three use case scenarios are presented to showcase the application of CityDrain3. The performance advantage of parallelization (up to 40 times compared to its predecessor) and the scalability of the framework are also demonstrated.
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5.
  • Burger, Ronelle, et al. (författare)
  • Use of simulated patients to assess hypertension case management at public healthcare facilities in South Africa
  • 2020
  • Ingår i: Journal of Hypertension. - 1473-5598. ; 38:2, s. 362-367
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Our study aims to evaluate hypertensive case management in South Africa's public health sector using simulated patients.METHOD: Our study describes interactions between hypertensive simulated patients and primary healthcare workers at 39 public sector healthcare facilities in two metropolitan centres in the Eastern and Western Cape Provinces of South Africa. Our analysis focus on 97 interactions where our eight simulated patients tested within range for stage 1 hypertension, that is with SBP 140-159 mmHg and/or DBP 90-99 mmHg. For this subset, we describe how healthcare workers communicated the outcome of the blood pressure test, and whether they follow government guidelines on risk assessment and lifestyle advice.RESULTS: Healthcare workers highlighted the risks associated with hypertension in one out of three cases and stressed the importance of regular monitoring of blood pressure in less than half of cases. Hypertensive patients received advice on all six lifestyle risk factors in 8% of cases. 39% of patients received no lifestyle advice at all. In one out of four cases, hypertensive patients left the facility without a hypertension diagnosis and with no prospect of a follow-up visit.CONCLUSION: Simulated patients can assess the quality of hypertension case management, yielding granular and comprehensive information that can help mobilize resources to improve care. The management of hypertension patients in South African public healthcare facilities is critically insufficient. Given that hypertension is responsible for a rising share of deaths in South Africa and many of these deaths are preventable, urgent intervention is needed.
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6.
  • Carlsson, Thomas, et al. (författare)
  • Reversal of dyskinesias in an animal model of Parkinson's disease by continuous L-DOPA delivery using rAAV vectors.
  • 2005
  • Ingår i: Brain. - : Oxford University Press (OUP). - 1460-2156. ; 128:3, s. 559-569
  • Tidskriftsartikel (refereegranskat)abstract
    • Dyskinesias are a major complication of long-term l-3,4-dihydroxyphenylalanine (L-DOPA) treatment in Parkinson's disease, and are believed to result from the intermittent and pulsatile supply of L-DOPA. Daily injections of L-DOPA can prime similar abnormal involuntary movements of the limb, orolingual and axial muscles in rats rendered parkinsonian by destruction of the nigrostriatal dopamine (DA) neurons. In this study we used 33 rats with severe nigrostriatal dopamine depletion and showed that in vivo gene transfer of the DA-synthetic enzymes tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1) using recombinant adeno-associated virus vectors can provide a constant source of DOPA production locally in the striatum, at a level that is effective in reducing L-DOPA-induced dyskinesias by >85%, and reverse lesion-induced motor impairments. Furthermore, the abnormal expression of DeltaFosB, prodynorphin and preproenkephalin mRNA within the striatal projection neurons normally seen in dyskinetic animals was completely reversed by TH-GCH1 gene transfer. These findings form a strong basis for replacing, or supplementing, conventional systemic L-DOPA therapy by continuous intrastriatal DOPA using in vivo gene transfer in the treatment of patients with advanced Parkinson's disease.
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7.
  • Christian, Carmen S, et al. (författare)
  • Measuring Quality Gaps in TB Screening in South Africa Using Standardised Patient Analysis
  • 2018
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 15:4
  • Tidskriftsartikel (refereegranskat)abstract
    • This is the first multi-district Standardised Patient (SP) study in South Africa. It measures the quality of TB screening at primary healthcare (PHC) facilities. We hypothesise that TB screening protocols and best practices are poorly adhered to at the PHC level. The SP method allows researchers to observe how healthcare providers identify, test and advise presumptive TB patients, and whether this aligns with clinical protocols and best practice. The study was conducted at PHC facilities in two provinces and 143 interactions at 39 facilities were analysed. Only 43% of interactions resulted in SPs receiving a TB sputum test and being offered an HIV test. TB sputum tests were conducted routinely (84%) while HIV tests were offered less frequently (47%). Nurses frequently neglected to ask SPs whether their household contacts had confirmed TB (54%). Antibiotics were prescribed without taking temperatures in 8% of cases. The importance of returning to the facility to receive TB test results was only explained in 28%. The SP method has highlighted gaps in clinical practice, signalling missed opportunities. Early detection of sub-optimal TB care is instrumental in decreasing TB-related morbidity and mortality. The findings provide the rationale for further quality improvement work in TB management.
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8.
  • Hompashe, Dumisani MacDonald, et al. (författare)
  • The nurse did not even greet me' : How informed versus non-informed patients evaluate health systems responsiveness in South Africa
  • 2021
  • Ingår i: BMJ Global Health. - : BMJ. - 2059-7908. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Universal Health Coverage is not only about access to health services but also about access to high-quality care, since poor experiences may deter patients from accessing care. Evidence shows that quality of care drives health outcomes, yet little is known about non-clinical dimensions of care, and patients' experience thereof relative to satisfaction with visits. This paper investigates the role of non-clinical dimensions of care in patient satisfaction.METHODS: Our study describes the interactions of informed and non-informed patients with primary healthcare workers at 39 public healthcare facilities in two metropolitan centres in two South African provinces. Our analysis included 1357 interactions using standardised patients (for informed patients) and patients' exit interviews (for non-informed patients). The data were combined for three types of visits: contraception, hypertension and tuberculosis. We describe how satisfaction with care was related to patients' experiences of non-clinical dimensions.RESULTS: We show that when real patients (RPs) reported being satisfied (vs dissatisfied) with a visit, it was associated with a 30% increase in the probability that a patient is greeted at the facilities. Likewise, when the RPs reported being satisfied (vs dissatisfied) with the visit, it was correlated with a 15% increase in the prospect that patients are pleased with healthcare workers' explanations of health conditions.CONCLUSION: Informed patients are better equipped to assess health-systems responsiveness in healthcare provision. Insights into responsiveness could guide broader efforts aimed at targeted education and empowerment of primary healthcare users to strengthen health systems and shape expectations for appropriate care and conduct.
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9.
  • Kirik, Deniz, et al. (författare)
  • Reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of L-dopa using rAAV-mediated gene transfer.
  • 2002
  • Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 99:7, s. 4708-4713
  • Tidskriftsartikel (refereegranskat)abstract
    • Intrastriatal delivery of the tyrosine hydroxylase gene by viral vectors is being explored as a tool for local delivery of L-dopa in animals with lesions of the nigrostriatal pathway. The functional effects reported using this approach have been disappointing, probably because the striatal L-dopa levels attained have been too low. In the present study, we have defined a critical threshold level of L-dopa, 1.5 pmol/mg of tissue, that has to be reached to induce any significant functional effects. Using new generation high-titer recombinant adeno-associated virus vectors, we show that levels of striatal L-dopa production exceeding this threshold can be obtained provided that tyrosine hydroxylase is coexpressed with the cofactor synthetic enzyme, GTP-cyclohydrolase-1. After striatal transduction with this combination of vectors, substantial functional improvement in both drug-induced and spontaneous behavior was observed in rats with either complete or partial 6-hydroxydopamine lesions of the nigrostriatal pathway. However, complete reversal of motor deficits occurred only in animals in which part of the striatal dopamine innervation was left intact. Spared nigrostriatal fibers thus may convert L-dopa to dopamine and store and release dopamine in a more physiologically relevant manner in the denervated striatum to mediate better striatal output-dependent motor function. We conclude that intrastriatal L-dopa delivery may be a viable strategy for treatment and control of adverse side effects associated with oral L-dopa therapy such as on-off fluctuations and drug-induced dyskinesias in patients with Parkinson's disease.
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10.
  • Lacy, Michael, et al. (författare)
  • Cell-specific and divergent roles of the CD40L-CD40 axis in atherosclerotic vascular disease
  • 2021
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition of the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on the cell-cell interactions involved, we sought to investigate the function of the most relevant CD40L-expressing cell types in atherosclerosis: T cells and platelets. Atherosclerosis-prone mice with a CD40L-deficiency in CD4+ T cells display impaired Th1 polarization, as reflected by reduced interferon-γ production, and smaller atherosclerotic plaques containing fewer T-cells, smaller necrotic cores, an increased number of smooth muscle cells and thicker fibrous caps. Mice with a corresponding CD40-deficiency in CD11c+ dendritic cells phenocopy these findings, suggesting that the T cell-dendritic cell CD40L-CD40 axis is crucial in atherogenesis. Accordingly, sCD40L/sCD40 and interferon-γ concentrations in carotid plaques and plasma are positively correlated in patients with cerebrovascular disease. Platelet-specific deficiency of CD40L does not affect atherogenesis but ameliorates atherothrombosis. Our results establish divergent and cell-specific roles of CD40L-CD40 in atherosclerosis, which has implications for therapeutic strategies targeting this pathway.
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