| 1. |
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| 2. |
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| 3. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 4. |
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| 5. |
- Litter, M. I., et al.
(författare)
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Arsenic in Argentina : Occurrence, human health, legislation and determination
- 2019
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Ingår i: Science of the Total Environment. - : Elsevier B.V.. - 0048-9697 .- 1879-1026. ; 676, s. 756-766
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Tidskriftsartikel (refereegranskat)abstract
- An overview about the presence of arsenic (As) in groundwaters of Argentina, made by a transdisciplinary group of experts is presented. Aspects on As occurrence, effects of As on human health, regulations regarding the maximum allowable amount of As in drinking water as well as bottled water, and analytical techniques for As determination are presented. The most affected region in Argentina is the Chaco-Pampean plain, covering around 10 million km 2 , where approximately 88% of 86 groundwater samples collected in 2007 exceeded the World Health Organization (WHO) guideline value. In the Salí river basin, As concentrations ranged from 11.4 to 1660 μg/L, with 100% of the samples above the WHO guideline value. In the Argentine Altiplano (Puna) and Subandean valleys, 61% of 62 samples collected from surface and groundwaters exceeded the WHO limit. Thus, it can be estimated that, at present, the population at risk in Argentina reaches around four million people. Pathologies derived from the chronic consumption of As, the metabolism of As in the human body and the effects of the different As chemical forms, gathered under the name HACRE (hidroarsenicismo crónico regional endémico in Spanish, for chronic regional endemic hydroarsenicism) are described. Regarding the regulations, the 10 μg/L limit recommended by the WHO and the United States Environmental Protection Agency has been incorporated in the Argentine Food Code, but the application is still on hold. In addition, there is disparity regarding the maximal admitted values in several provinces. Considerations about the As concentrations in bottled water are also presented. A survey indicates that there are several Argentine laboratories with the suitable equipment for As determination at 10 μg/L, although 66% of them are concentrated in Buenos Aires City, and in the Santa Fe, Córdoba and Buenos Aires provinces. Conclusions and recommendations of this first part are provided.
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| 6. |
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| 7. |
- Mingardo, E, et al.
(författare)
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A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1203-
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Tidskriftsartikel (refereegranskat)abstract
- Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
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| 8. |
- Moayyeri, Alireza, et al.
(författare)
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Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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| 9. |
- Oei, Ling, et al.
(författare)
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A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus
- 2014
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Ingår i: Journal of Medical Genetics. - : BMJ Publishing Group. - 0022-2593 .- 1468-6244. ; 51:2, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk.AIM: To identify CNVs associated with osteoporotic bone fracture risk.METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies.RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p=8.69×10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p=0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk.CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.
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| 10. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 11. |
- Calbet, Albert, et al.
(författare)
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Future Climate Scenarios for a Coastal Productive Planktonic Food Web Resulting in Microplankton Phenology Changes and Decreased Trophic Transfer Efficiency
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:4, s. e94388-
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Tidskriftsartikel (refereegranskat)abstract
- We studied the effects of future climate change scenarios on plankton communities of a Norwegian fjord using a mesocosm approach. After the spring bloom, natural plankton were enclosed and treated in duplicates with inorganic nutrients elevated to pre-bloom conditions (N, P, Si; eutrophication), lowering of 0.4 pH units (acidification), and rising 3 degrees C temperature (warming). All nutrient-amended treatments resulted in phytoplankton blooms dominated by chain-forming diatoms, and reached 13-16 mu g chlorophyll (chl) a l(-1). In the control mesocosms, chl a remained below 1 mu g l(-1). Acidification and warming had contrasting effects on the phenology and bloom-dynamics of autotrophic and heterotrophic microplankton. Bacillariophyceae, prymnesiophyceae, cryptophyta, and Protoperidinium spp. peaked earlier at higher temperature and lower pH. Chlorophyta showed lower peak abundances with acidification, but higher peak abundances with increased temperature. The peak magnitude of autotrophic dinophyceae and ciliates was, on the other hand, lowered with combined warming and acidification. Over time, the plankton communities shifted from autotrophic phytoplankton blooms to a more heterotrophic system in all mesocosms, especially in the control unaltered mesocosms. The development of mass balance and proportion of heterotrophic/autotrophic biomass predict a shift towards a more autotrophic community and less-efficient food web transfer when temperature, nutrients and acidification are combined in a future climate-change scenario. We suggest that this result may be related to a lower food quality for microzooplankton under acidification and warming scenarios and to an increase of catabolic processes compared to anabolic ones at higher temperatures.
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| 12. |
- Garcia, J., et al.
(författare)
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Automatic detection of ST-T complex changes on the ECG using filtered RMS difference series: application to ambulatory ischemia monitoring
- 2000
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Ingår i: IEEE Transactions on Biomedical Engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 1558-2531 .- 0018-9294. ; 47:9, s. 1195-1201
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Tidskriftsartikel (refereegranskat)abstract
- A new detector is presented which finds changes in the repolarization phase (ST-T complex) of the cardiac cycle. It operates by applying a detection algorithm to the filtered root mean square (rms) series of differences between the beat segment (ST segment or ST-T complex) and an average pattern segment. The detector has been validated using the European ST-T database, which contains ST-T complex episodes manually annotated by cardiologists, resulting in sensitivity/positive predictivity of 85/86%, and 85/76%, for ST segment deviations and ST-T complex changes, respectively. The proposed detector has a performance similar to those which have a more complicated structure. The detector has the advantage of finding both ST segment deviations and entire ST-T complex changes thereby providing a wider characterization of the potential ischemic events. A post-processing stage, based on a cross-correlation analysis for the episodes in the rms series, is presented. With this stage subclinical events with repetitive pattern were found in around 20% of the recordings and improved the performance to 90/85%, and 89/76%, for ST segment and ST-T complex changes, respectively.
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| 13. |
- Garcia, J, et al.
(författare)
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Remote processing server for ECG-based clinical diagnosis support
- 2002
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Ingår i: IEEE Transactions on Information Technology in Biomedicine. - 1089-7771. ; 6:4, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present the development of a remote server that provides a user-friendly access to advanced electrocardiographic (ECG) signal processing techniques. The prototype supplies telemedicine facilities to doctors for clinical indexes remote computation to support diagnosis through the Internet. The user-friendly interface is based on the selection of the desired ECG signal processing tools on a Web browser window. The centralized structure of the system permits unique and user-independent update and management of the software and, therefore, is especially suitable for remote or rural regions to have access to the new ECG information techniques.
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| 14. |
- Garcia, J., et al.
(författare)
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Temporal evolution of traditional versus transformed ECG-based indexes in patients with induced myocardial ischemia
- 2000
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Ingår i: Journal of Electrocardiology. - 1532-8430. ; 33:1, s. 37-47
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Tidskriftsartikel (refereegranskat)abstract
- The time course of changes in the electrocardiogram as a result of myocardial ischemia induced during prolonged coronary angioplasty has been studied. We have analyzed the electrocardiogram evolution during the occlusion in terms of the Ischemic Changes Sensor, which is a parameter that describes the capacity of different indexes to detect induced changes. Traditional indexes at specific time locations (ST level, T wave amplitude and position, and durations of QT interval and QRS complex) and global indexes (based on the Karhunen-Loève transform as applied to the QRS complex, ST-T complex, ST segment and T wave) have been considered. The global indexes better detected ischemic changes than the traditional indexes. The most sensitive were the index for the ST-T complex (89%) in the Karhunen-Loève transform-derived group and for the ST level (61%) in the traditional group. Changes in the ventricular repolarization period usually appeared earlier (77% of patients) than changes in the depolarization period (23% of patients). A similar percentage of patients exhibited the earliest ischemic changes in the T wave (41%) and in the ST segment (36%). The evolution of the Ischemic Changes Sensor parameters showed that the majority (60%) of the total changes occurred during the first minute of occlusion. The results suggest that the use of global electrocardiogram indexes better reflect ischemic changes than do traditional indexes, such as the ST segment deviation.
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| 15. |
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| 16. |
- Litter, Marta I., et al.
(författare)
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Arsenic in Argentina : Technologies for arsenic removal from groundwater sources, investment costs and waste management practices
- 2019
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Ingår i: Science of the Total Environment. - : ELSEVIER. - 0048-9697 .- 1879-1026. ; 690, s. 778-789
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Tidskriftsartikel (refereegranskat)abstract
- An overview about the presence of arsenic (As) in groundwaters of Argentina, made by a transdisciplinary group of experts is presented. In this second part, the conventional and emerging technologies for As removal, management of wastes, and the initial investment costs of the proposed technologies, with emphasis on developments of local groups are described. Successful examples of real application of conventional and emerging technologies for As removal in waters for human consumption, for medium, small and rural and periurban communities are reported. In the country, the two most applied technologies for arsenic removal at a real scale are reverse osmosis and coagulation-adsorption-filtration processes using iron or aluminum salts or polyelectrolytes as coagulants. A decision tree to evaluate the possible technologies to be applied, based on the population size, the quality of the water and its intended use, is presented, including preliminary and indicative investment costs. Finally, a section discussing the treatment and final disposal of the liquid, semiliquid and solid wastes, generated by the application of the most used technologies, is included. Conclusions and recommendations, especially for isolated rural and periurban regions, have been added.
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| 17. |
- Liu, Ching-Ti, et al.
(författare)
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Assessment of gene-by-sex interaction effect on bone mineral density
- 2012
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 27:10, s. 2051-2064
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Tidskriftsartikel (refereegranskat)abstract
- Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however, the extent to which genes explain these sex differences is unclear. To identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p?
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| 18. |
- Martinez, J P, et al.
(författare)
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Accuracy of QT Measurement in the EASI-derived 12-lead ECG
- 2006
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Ingår i: Conference proceedings (IEEE Engineering in Medicine and Biology Society. Conf.). - 1557-170X. ; 1, s. 3986-3989
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Konferensbidrag (refereegranskat)abstract
- The purpose of this study is to assess QT interval measurements from the EASI 12-lead ECG as compared to the standard 12-lead ECG. The QT interval was automatically measured in simultaneously recorded standard and EASI 12- lead ECGs, using a validated wavelet-based delineator. The agreement between the two sets of measurements was quantified both on a lead-by-lead basis and a multilead basis. The results show an acceptable agreement between QT measurements in the two lead systems, with correlation coefficients (CC) 0.91-0.98 depending on the lead. Standard deviations range from 9.2 ms to 26.4 ms depending on the selected lead. In a few patients large inter-system differences were found, mainly due to different T wave morphologies. Using a multilead delineation, QT intervals were considerably more stable than single-lead measurements and resulted in a much better agreement between the two lead systems (CC: 0.98, QT difference: 1.1 ms ± 9.8 ms). Thus, EASI-derived 12- lead ECG may be used for reliable QT monitoring when the multilead delineation approach is adopted.
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| 19. |
- Olmedo, Miguel Iglesias, et al.
(författare)
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Chirp investigation in EMLs towards frequency shift keying modulation
- 2014
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Ingår i: Asia Communications and Photonics Conference 2014. - Washington, D.C. : OSA.
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Konferensbidrag (refereegranskat)abstract
- This paper presents a chirp modeling and experimental results that support our vision of enabling frequency shift keying (FSK) exploiting the chirp effect in externally modulated lasers (EMLs).
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| 20. |
- Olmos, S, et al.
(författare)
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Block adaptive filters with deterministic reference inputs for event-related signals: BLMS and BRLS
- 2002
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Ingår i: IEEE Transactions on Signal Processing. - : Institute of Electrical and Electronics Engineers (IEEE). - 1053-587X. ; 50:5, s. 1102-1112
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive estimation of the linear coefficient vector in truncated expansions is considered for the purpose of modeling noisy, recurrent signals. Two different criteria are studied for block-wise processing of the signal: the mean square error (MSE) and the least squares (LS) error. The block LMS (BLMS) algorithm, being the solution of the steepest descent strategy for minimizing the MSE, is shown to be steady-state unbiased and with a lower variance than the LMS algorithm. It is demonstrated that BLMS is equivalent to an exponential averager in the subspace spanned by the truncated set of basis functions. The block recursive least squares (BRLS) solution is shown to be equivalent to the BLMS algorithm with a decreasing step size. The BRLS is unbiased at any occurrence number of the signal and has the same steady-state variance as the BLMS but with a lower variance at the transient stage. The estimation methods can be interpreted in terms of linear, time-variant filtering. The performance of the methods is studied on an ECG signal, and the results show that the performance of the block algorithms is superior to that of the LMS algorithm. In addition, measurements with clinical interest are found to be more robustly estimated in noisy signals.
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| 21. |
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| 22. |
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| 23. |
- Scott, Robert A., et al.
(författare)
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A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease
- 2016
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 8:341
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.
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| 24. |
- Van der Poel, Henk G., et al.
(författare)
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Sentinel node biopsy for prostate cancer : Report from a consensus panel meeting
- 2017
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Ingår i: BJU International. - : Wiley. - 1464-4096. ; 120:2, s. 204-211
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the evidence and knowledge gaps in sentinel node biopsy (SNB) in prostate cancer through a consensus panel of experts. Methods: A two-round Delphi survey among experts was followed by a consensus panel meeting of 16 experts in February 2016. Agreement voting was performed using the research and development project/University of California, Los Angeles Appropriateness Methodology on 150 statements in nine domains. The disagreement index based on the interpercentile range, adjusted for symmetry score, was used to assess consensus and non-consensus among panel members. Results: Consensus was obtained on 91 of 150 statements (61%). The main outcomes were: (1) the results from an extended lymph node dissection (eLND) are still considered the 'gold standard', and sentinel node (SN) detection should be combined with eLND, at least in patients with intermediate- and high-risk prostate cancer; (2) the role of SN detection in low-risk prostate cancer is unclear; and (3) future studies should contain oncological endpoints as number of positive nodes outside the eLND template, false-negative and false-positive SN procedures, and recurrence-free survival. A high rate of consensus was obtained regarding outcome measures of future clinical trials on SNB (89%). Consensus on tracer technology was only obtained in 47% of statements, reflecting a need for further research and standardization in this area. The low-level evidence in the available literature and the composition of mainly SNB users in the panel constitute the major limitations of the study. Conclusions: Consensus on a majority of elementary statements on SN detection in prostate cancer was obtained.; therefore, the results from this consensus report will provide a basis for the design of further studies in the field. A group of experts identified evidence and knowledge gaps on SN detection in prostate cancer and its application in daily practice. Information from the consensus statements can be used to direct further studies.
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| 25. |
- Wit, Esther M K, et al.
(författare)
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Sentinel Node Procedure in Prostate Cancer : A Systematic Review to Assess Diagnostic Accuracy
- 2017
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Ingår i: European Urology. - : Elsevier BV. - 0302-2838. ; 71:4, s. 596-605
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Forskningsöversikt (refereegranskat)abstract
- Context: Extended pelvic lymph node dissection (ePLND) is the gold standard for detecting lymph node (LN) metastases in prostate cancer (PCa). The benefit of sentinel node biopsy (SNB), which is the first draining LN as assessed by imaging of locally injected tracers, remains controversial. Objective: To assess the diagnostic accuracy of SNB in PCa. Evidence acquisition: A systematic literature search of Medline, Embase, and the Cochrane Library (1999-2016) was undertaken using PRISMA guidelines. All studies of SNB in men with PCa using PLND as reference standard were included. The primary outcomes were the nondiagnostic rate (NDR), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false positive (FP) and false negative (FN) rates. Relevant sensitivity analyses based on SN definitions, ePLND as reference standard, and disease risk were undertaken, including a risk of bias (RoB) assessment. Evidence synthesis: Of 373 articles identified, 21 studies recruiting a total of 2509 patients were eligible for inclusion. Median cumulative percentage (interquartile range) results were 4.1% (1.5-10.7%) for NDR, 95.2% (81.8-100%) for sensitivity, 100% (95.0-100%) for specificity, 100% (87.0-100%) for PPV, 98.0% (94.3-100%) for NPV, 0% (0-5.0%) for the FP rate, and 4.8% (0-18.2%) for the FN rate. The findings did not change significantly on sensitivity analyses. Most studies (17/22) had low RoB for index test and reference standard domains. Conclusions: SNB appears to have diagnostic accuracy comparable to ePLND, with high sensitivity, specificity, PPV and NPV, and a low FN rate. With a low FP rate (rate of detecting positive nodes outside the ePLND template), SNB may not have any additional diagnostic value over and above ePLND, although SNB appears to increase nodal yield by increasing the number of affected nodes when combined with ePLND. Thus, in high-risk disease it may be prudent to combine ePLND with SNB. Patient summary: This literature review showed a high diagnostic accuracy for sentinel node biopsy in detecting positive lymph nodes in prostate cancer, but further studies are needed to explore the effect of sentinel node biopsy on complications and oncologic outcome. The accuracy of sentinel node biopsy (SNB) in detecting positive lymph nodes in prostate cancer appears to have diagnostic accuracy comparable to that of extended pelvic lymph node dissection (ePLND). However, SNB may not have any additional diagnostic value over and above ePLND.
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| 26. |
- Åström, Mattias, et al.
(författare)
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Wavelet-based event detection in implantable cardiac rhythm management devices
- 2006
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Ingår i: IEEE Transactions on Biomedical Engineering. - 1558-2531. ; 53:3, s. 478-484
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a novel event detector for implantable devices. The algorithm is based on a signal model which describes an event as a linear combination of basis functions. The linear combination involves two fundamental electrogram waveforms represented at different time scales. An efficient, low-complexity detector is developed using the dyadic wavelet transform with integer filter coefficients, and a generalized likelihood ratio test. The results show that reliable detection is obtained at an intermediate signal-to-noise ratio (SNR = 25 dB) for various common noise sources. In terms of probabilities of missed events and false alarms, an over-all performance of 0.7% and 0.1%, respectively, was achieved on electrograms corrupted by the different noise types at an intermediate SNR.
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