| 1. |
- Adcox, K, et al.
(author)
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PHENIX detector overview
- 2003
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Journal article (peer-reviewed)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 2. |
- Nelson, G., et al.
(author)
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QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy
- 2021
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In: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 284:1, s. 56-73
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Journal article (peer-reviewed)abstract
- A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
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| 3. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 4. |
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| 5. |
- Dent, E., et al.
(author)
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Physical Frailty : ICFSR International Clinical Practice Guidelines for Identification and Management
- 2019
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In: The Journal of Nutrition, Health & Aging. - : SPRINGER FRANCE. - 1279-7707 .- 1760-4788. ; 23:9, s. 771-787
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Journal article (peer-reviewed)abstract
- Objective: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults.Methods: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care.Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation).Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.
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| 6. |
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| 7. |
- Kim, S. W., et al.
(author)
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Evaluations of NOx and highly reactive VOC emission inventories in Texas and their implications for ozone plume simulations during the Texas Air Quality Study 2006
- 2011
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:22, s. 11361-11386
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Journal article (peer-reviewed)abstract
- Satellite and aircraft observations made during the 2006 Texas Air Quality Study (TexAQS) detected strong urban, industrial and power plant plumes in Texas. We simulated these plumes using the Weather Research and Forecasting-Chemistry (WRF-Chem) model with input from the US EPA's 2005 National Emission Inventory (NEI-2005), in order to evaluate emissions of nitrogen oxides (NOx = NO + NO2) and volatile organic compounds (VOCs) in the cities of Houston and Dallas-FortWorth. We compared the model results with satellite retrievals of tropospheric nitrogen dioxide (NO2) columns and airborne in-situ observations of several trace gases including NOx and a number of VOCs. The model and satellite NO2 columns agree well for regions with large power plants and for urban areas that are dominated by mobile sources, such as Dallas. How-ever, in Houston, where significant mobile, industrial, and inport marine vessel sources contribute to NOx emissions, the model NO2 columns are approximately 50 %-70 % higher than the satellite columns. Similar conclusions are drawn from comparisons of the model results with the TexAQS 2006 aircraft observations in Dallas and Houston. For Dallas plumes, the model-simulated NO2 showed good agreement with the aircraft observations. In contrast, the model-simulated NO2 is similar to 60 % higher than the aircraft observations in the Houston plumes. Further analysis indicates that the NEI-2005 NOx emissions over the Houston Ship Channel area are overestimated while the urban Houston NOx emissions are reasonably represented. The comparisons of model and aircraft observations confirm that highly reactive VOC emissions originating from industrial sources in Houston are underestimated in NEI-2005. The update of VOC emissions based on Solar Occultation Flux measurements during the field campaign leads to improved model simulations of ethylene, propylene, and formaldehyde. Reducing NOx emissions in the Houston Ship Channel and increasing highly reactive VOC emissions from the point sources in Houston improve the model's capability of simulating ozone (O-3) plumes observed by the NOAA WP-3D aircraft, although the deficiencies in the model O-3 simulations indicate that many challenges remain for a full understanding of the O-3 formation mechanisms in Houston.
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| 8. |
- Adler, SS, et al.
(author)
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PHENIX on-line systems
- 2003
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 560-592
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Journal article (peer-reviewed)abstract
- The PHENIX On-Line system takes signals from the Front End Modules (FEM) on each detector subsystem for the purpose of generating events for physics analysis. Processing of event data begins when the Data Collection Modules (DCM) receive data via fiber-optic links from the FEMs. The DCMs format and zero suppress the data and generate data packets. These packets go to the Event Builders (EvB) that assemble the events in final form. The Level-1 trigger (LVL1) generates a decision for each beam crossing and eliminates uninteresting events. The FEMs carry out all detector processing of the data so that it is delivered to the DCMs using a standard format. The FEMs also provide buffering for LVL1 trigger processing and DCM data collection. This is carried out using an architecture that is pipelined and deadtimeless. All of this is controlled by the Master Timing System (MTS) that distributes the RHIC clocks. A Level-2 trigger (LVL2) gives additional discrimination. A description of the components and operation of the PHENIX On-Line system is given and the solution to a number of electronic infrastructure problems are discussed. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 9. |
- Parrish, D. D., et al.
(author)
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Primary and secondary sources of formaldehyde in urban atmospheres: Houston Texas region
- 2012
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:7, s. 3273-3288
-
Journal article (peer-reviewed)abstract
- We evaluate the rates of secondary production and primary emission of formaldehyde (CH2O) from petrochemical industrial facilities and on-road vehicles in the Houston Texas region. This evaluation is based upon ambient measurements collected during field studies in 2000, 2006 and 2009. The predominant CH2O source (92 +/- 4% of total) is secondary production formed during the atmospheric oxidation of highly reactive volatile organic compounds (HRVOCs) emitted from the petrochemical facilities. Smaller contributions are primary emissions from these facilities (4 +/- 2%), and secondary production (similar to 3%) and primary emissions (similar to 1%) from vehicles. The primary emissions from both sectors are well quantified by current emission inventories. Since secondary production dominates, control efforts directed at primary CH2O emissions cannot address the large majority of CH2O sources in the Houston area, although there may still be a role for such efforts. Ongoing efforts to control alkene emissions from the petrochemical facilities, as well as volatile organic compound emissions from the motor vehicle fleet, will effectively reduce the CH2O concentrations in the Houston region. We do not address other emission sectors, such as off-road mobile sources or secondary formation from biogenic hydrocarbons. Previous analyses based on correlations between ambient concentrations of CH2O and various marker species have suggested much larger primary emissions of CH2O, but those results neglect confounding effects of dilution and loss processes, and do not demonstrate the causes of the observed correlations. Similar problems must be suspected in any source apportionment analysis of secondary species based upon correlations of ambient concentrations of pollutants.
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| 10. |
- De Gouw, J. A., et al.
(author)
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Airborne Measurements of Ethene from Industrial Sources Using Laser Photo-Acoustic Spectroscopy
- 2009
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In: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 43:7, s. 2437-2442
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Journal article (peer-reviewed)abstract
- A laser photoacoustic spectroscopy (LPAS) instrument was developed and used for aircraft measurements of ethene from industrial sources near Houston, Texas. The instrument provided 20 s measurements with a detection limit of less than 0.7 ppbv. Data from this instrument and from the GC-FID analysis of air samples collected in flight agreed within 15% on average. Ethene fluxes from the Mt. Belvieu chemical complex to the northeast of Houston were quantified during 10 different flights. The average flux was 520 +/- 140 kg h(-1) in agreement with independent results from solar occultation flux (SOF) measurements, and roughly an order of magnitude higher than regulatory emission inventories indicate. This study shows that ethene emissions are routinely at levels that qualify as emission upsets, which need to be reported to regional air quality managers.
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| 11. |
- Kaucka, M., et al.
(author)
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Altered developmental programs and oriented cell divisions lead to bulky bones during salamander limb regeneration
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Journal article (peer-reviewed)abstract
- There are major differences in duration and scale at which limb development and regeneration proceed, raising the question to what extent regeneration is a recapitulation of development. We address this by analyzing skeletal elements using a combination of micro-CT imaging, molecular profiling and clonal cell tracing. We find that, in contrast to development, regenerative skeletal growth is accomplished based entirely on cartilage expansion prior to ossification, not limiting the transversal cartilage expansion and resulting in bulkier skeletal parts. The oriented extension of salamander cartilage and bone appear similar to the development of basicranial synchondroses in mammals, as we found no evidence for cartilage stem cell niches or growth plate-like structures during neither development nor regeneration. Both regenerative and developmental ossification in salamanders start from the cortical bone and proceeds inwards, showing the diversity of schemes for the synchrony of cortical and endochondral ossification among vertebrates. Normal limb development relies on synchronized formation of cartilage and bone. Here, the authors show that in salamander limb regeneration these processes are decoupled: ossification occurs after the final size of regenerating cartilage is reached, allowing fast regeneration and leading to bulky bones.
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| 12. |
- Nissenbaum, J, et al.
(author)
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Susceptibility to chronic pain following nerve injury is genetically affected by CACNG2
- 2010
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In: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 20:9, s. 1180-1190
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Journal article (peer-reviewed)abstract
- Chronic neuropathic pain is affected by specifics of the precipitating neural pathology, psychosocial factors, and by genetic predisposition. Little is known about the identity of predisposing genes. Using an integrative approach, we discovered that CACNG2 significantly affects susceptibility to chronic pain following nerve injury. CACNG2 encodes for stargazin, a protein intimately involved in the trafficking of glutamatergic AMPA receptors. The protein might also be a Ca2+ channel subunit. CACNG2 has previously been implicated in epilepsy. Initially, using two fine-mapping strategies in a mouse model (recombinant progeny testing [RPT] and recombinant inbred segregation test [RIST]), we mapped a pain-related quantitative trait locus (QTL) (Pain1) into a 4.2-Mb interval on chromosome 15. This interval includes 155 genes. Subsequently, bioinformatics and whole-genome microarray expression analysis were used to narrow the list of candidates and ultimately to pinpoint Cacng2 as a likely candidate. Analysis of stargazer mice, a Cacng2 hypomorphic mutant, provided electrophysiological and behavioral evidence for the gene's functional role in pain processing. Finally, we showed that human CACNG2 polymorphisms are associated with chronic pain in a cohort of cancer patients who underwent breast surgery. Our findings provide novel information on the genetic basis of neuropathic pain and new insights into pain physiology that may ultimately enable better treatments.
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| 13. |
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| 19. |
- Dong, Yiran, et al.
(author)
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Physiology, Metabolism, and Fossilization of Hot-Spring Filamentous Microbial Mats
- 2019
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In: Astrobiology. - : MARY ANN LIEBERT, INC. - 1531-1074 .- 1557-8070. ; 19:12
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Journal article (peer-reviewed)abstract
- The evolutionarily ancient Aquificales bacterium Sulfurihydrogenibium spp. dominates filamentous microbial mat communities in shallow, fast-flowing, and dysoxic hot-spring drainage systems around the world. In the present study, field observations of these fettuccini-like microbial mats at Mammoth Hot Springs in Yellowstone National Park are integrated with geology, geochemistry, hydrology, microscopy, and multi-omic molecular biology analyses. Strategic sampling of living filamentous mats along with the hot-spring CaCO3 (travertine) in which they are actively being entombed and fossilized has permitted the first direct linkage of Sulfurihydrogenibium spp. physiology and metabolism with the formation of distinct travertine streamer microbial biomarkers. Results indicate that, during chemoautotrophy and CO2 carbon fixation, the 87-98% Sulfurihydrogenibium-dominated mats utilize chaperons to facilitate enzyme stability and function. High-abundance transcripts and proteins for type IV pili and extracellular polymeric substances (EPSs) are consistent with their strong mucus-rich filaments tens of centimeters long that withstand hydrodynamic shear as they become encrusted by more than 5mm of travertine per day. Their primary energy source is the oxidation of reduced sulfur (e.g., sulfide, sulfur, or thiosulfate) and the simultaneous uptake of extremely low concentrations of dissolved O-2 facilitated by bd-type cytochromes. The formation of elevated travertine ridges permits the Sulfurihydrogenibium-dominated mats to create a shallow platform from which to access low levels of dissolved oxygen at the virtual exclusion of other microorganisms. These ridged travertine streamer microbial biomarkers are well preserved and create a robust fossil record of microbial physiological and metabolic activities in modern and ancient hot-spring ecosystems.
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| 20. |
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| 22. |
- Fried, S, et al.
(author)
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Outpatients' perspectives on problems and needs related to female genital mutilation/cutting: a qualitative study from somaliland
- 2013
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In: Obstetrics and gynecology international. - : Hindawi Limited. - 1687-9589 .- 1687-9597. ; 2013, s. 165893-
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Journal article (peer-reviewed)abstract
- Aim. To explore female outpatients’ perspectives on problems related to female genital mutilation/cutting (FGM/C) and their views on information, care, and counseling.Setting. An FGM/C support center at a maternity clinic in Hargeisa, Somaliland.Methods. A qualitative, descriptive study, using content analysis of seven semistructured interviews with female outpatients.Results. All participants had been ignorant of the etiology of their FGM/C-related complications and hesitant to seek care. All had undergone infibulation but did not wish the same for their daughters. In recent years they had learnt through religious leaders and media campaigns that infibulation was unapproved by Islam. A less severe FGM/C type, “Sunna,” was more accepted; however, few could define what “Sunna” meant. Condemning and ridiculing attitudes against uncircumcised women prevailed in their community.Conclusions. New ideas and concepts related to FGM/C enter the common discourse in the Somali society while traditional norms and values still prevail. Religion was shown to have a strong impact on FGM/C practices and beliefs. Interventions aiming to raise awareness of health consequences of all types of FGM/C, as well as where to seek care for complications, are needed in Somaliland. Involvement of religious leaders in anti-FGM/C programs is essential.
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| 23. |
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| 24. |
- Isman, E, et al.
(author)
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Midwives' Experiences in Providing Care and Counselling to Women with Female Genital Mutilation (FGM) Related Problems
- 2013
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In: Obstetrics and gynecology international. - : Hindawi Limited. - 1687-9589 .- 1687-9597. ; 2013, s. 785148-
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Journal article (peer-reviewed)abstract
- Aim. The aim of this study was to elucidate midwives experiences in providing care and counselling to women with FGM related problems.Setting. The study was conducted at a maternity clinic in Hargeisa, Somaliland.Method. A qualitative, inductive study were performed with eight midwives living in Somaliland. The interviews had semi-structured questions. Content analysis was used for the analysis.Findings. The main findings of the present study were how midwives are challenged by culture and religion when providing FGM counselling. The most prominent challenge is the perception that FGM is an important part of the culture and from this point of view the midwives work is apprehended as interfering and subverting the Somali culture. Having personal experience of FGM emerged as a benefit when counselling women.Conclusion. There is a contradiction between the professional actions of performing FGM despite a personal belief against FGM. Midwives as a professional group could be important agents of change and further research is needed about the midwives role in this process.
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| 25. |
- Kameneva, P, et al.
(author)
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Serotonin limits generation of chromaffin cells during adrenal organ development
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 2901-
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Journal article (peer-reviewed)abstract
- Adrenal glands are the major organs releasing catecholamines and regulating our stress response. The mechanisms balancing generation of adrenergic chromaffin cells and protecting against neuroblastoma tumors are still enigmatic. Here we revealed that serotonin (5HT) controls the numbers of chromaffin cells by acting upon their immediate progenitor “bridge” cells via 5-hydroxytryptamine receptor 3A (HTR3A), and the aggressive HTR3Ahigh human neuroblastoma cell lines reduce proliferation in response to HTR3A-specific agonists. In embryos (in vivo), the physiological increase of 5HT caused a prolongation of the cell cycle in “bridge” progenitors leading to a smaller chromaffin population and changing the balance of hormones and behavioral patterns in adulthood. These behavioral effects and smaller adrenals were mirrored in the progeny of pregnant female mice subjected to experimental stress, suggesting a maternal-fetal link that controls developmental adaptations. Finally, these results corresponded to a size-distribution of adrenals found in wild rodents with different coping strategies.
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| 26. |
- Krivanek, J, et al.
(author)
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Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4816-
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Journal article (peer-reviewed)abstract
- Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.
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| 27. |
- Newton, P. T., et al.
(author)
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A radical switch in clonality reveals a stem cell niche in the epiphyseal growth plate
- 2019
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 567:7747
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Journal article (peer-reviewed)abstract
- Longitudinal bone growth in children is sustained by growth plates, narrow discs of cartilage that provide a continuous supply of chondrocytes for endochondral ossification(1). However, it remains unknown how this supply is maintained throughout childhood growth. Chondroprogenitors in the resting zone are thought to be gradually consumed as they supply cells for longitudinal growth(1,2), but this model has never been proved. Here, using clonal genetic tracing with multicolour reporters and functional perturbations, we demonstrate that longitudinal growth during the fetal and neonatal periods involves depletion of chondroprogenitors, whereas later in life, coinciding with the formation of the secondary ossification centre, chondroprogenitors acquire the capacity for self-renewal, resulting in the formation of large, stable monoclonal columns of chondrocytes. Simultaneously, chondroprogenitors begin to express stem cell markers and undergo symmetric cell division. Regulation of the pool of self-renewing progenitors involves the hedgehog and mammalian target of rapamycin complex 1 (mTORC1) signalling pathways. Our findings indicate that a stem cell niche develops postnatally in the epiphyseal growth plate, which provides a continuous supply of chondrocytes over a prolonged period.
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| 28. |
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| 29. |
- Settele, Josef, et al.
(author)
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Rice ecosystem services in South-east Asia
- 2018
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In: Paddy and Water Environment. - : Springer. - 1611-2490 .- 1611-2504. ; 16:2, s. 211-224
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Journal article (other academic/artistic)
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| 30. |
- Torchia, Jonathon, et al.
(author)
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Molecular subgroups of atypical teratoid rhabdoid tumours in children : an integrated genomic and clinicopathological analysis
- 2015
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In: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 16:5, s. 569-582
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Journal article (peer-reviewed)abstract
- Background Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort of patients with atypical teratoid rhabdoid tumours to find out the molecular basis for clinical heterogeneity in these tumours. Methods We obtained 259 rhabdoid tumours from 37 international institutions and assessed transcriptional profiles in 43 primary tumours and copy number profiles in 38 primary tumours to discover molecular subgroups of atypical teratoid rhabdoid tumours. We used gene and pathway enrichment analyses to discover group-specific molecular markers and did immunohistochemical analyses on 125 primary tumours to evaluate clinicopathological significance of molecular subgroup and ASCL1-NOTCH signalling. Findings Transcriptional analyses identified two atypical teratoid rhabdoid tumour subgroups with differential enrichment of genetic pathways, and distinct clinicopathological and survival features. Expression of ASCL1, a regulator of NOTCH signalling, correlated with supratentorial location (p=0.004) and superior 5-year overall survival (35%, 95% CI 13-57, and 20%, 6-34, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.033) in 70 patients who received multimodal treatment. ASCL1 expression also correlated with superior 5-year overall survival (34%, 7-61, and 9%, 0-21, for ASCL1-positive and ASCL1-negative tumours, respectively; p=0.001) in 39 patients who received only chemotherapy without radiation. Cox hazard ratios for overall survival in patients with differential ASCL1 enrichment treated with chemotherapy with or without radiation were 2.02 (95% CI 1.04-3.85; p=0.038) and 3.98 (1.71-9.26; p=0.001). Integrated analyses of molecular subgroupings with clinical prognostic factors showed three distinct clinical risk groups of tumours with different therapeutic outcomes. Interpretation An integration of clinical risk factors and tumour molecular groups can be used to identify patients who are likely to have improved long-term radiation-free survival and might help therapeutic stratification of patients with atypical teratoid rhabdoid tumours.
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| 31. |
- Uhlmann, Eric, L., et al.
(author)
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Subjective Evidence Evaluation Survey For Multi-Analyst Studies
- 2024
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Other publication (other academic/artistic)abstract
- Multi-analyst studies explore how well an empirical claim withstands plausible alternative analyses of the same data set by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g., effect size) provided by each analysis team. Although informative about the range of plausible effects in a data set, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item Subjective Evidence Evaluation Survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous multi-analyst study.
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| 49. |
- Fried, D., et al.
(author)
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Complexity of Canadian traveler problem variants
- 2013
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In: Theoretical Computer Science. - : Elsevier BV. - 0304-3975 .- 1879-2294. ; 487, s. 1-16
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Journal article (peer-reviewed)abstract
- The Canadian traveler problem (CTP) is the problem of traversing a given graph, where some of the edges may be blocked-a state which is revealed only upon reaching an incident vertex. Originally stated by Papadimitriou and Yannakakis (1991) [1], the adversarial version of the CTP was shown to be PSPACE-complete, with the stochastic version shown to be in PSPACE and #P-hard. We show that the stochastic CTP is also PSPACE-complete: initially proving PSPACE-hardness for the dependent version of the stochastic CTP, and proceeding with gadgets that allow us to extend the proof to the independent case. Since for disjoint-path graphs, the CTP can be solved in polynomial time, we examine the complexity of the more general remote-sensing CTP, and show that it is NP-hard even for disjoint-path graphs.
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