| 1. |
- Armbrecht, Gabriele, et al.
(författare)
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Degenerative inter-vertebral disc disease osteochondrosis intervertebralis in Europe : Prevalence, geographic variation and radiological correlates in men and women aged 50 and over
- 2017
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Ingår i: Rheumatology. - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 56:7, s. 1189-1199
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To assess the prevalences across Europe of radiological indices of degenerative inter-vertebral disc disease (DDD); and to quantify their associations with, age, sex, physical anthropometry, areal BMD (aBMD) and change in aBMD with time. Methods. In the population-based European Prospective Osteoporosis Study, 27 age-stratified samples of men and women from across the continent aged 50+ years had standardized lateral radiographs of the lumbar and thoracic spine to evaluate the severity of DDD, using the Kellgren-Lawrence (KL) scale. Measurements of anterior, mid-body and posterior vertebral heights on all assessed vertebrae from T4 to L4 were used to generate indices of end-plate curvature. Results. Images from 10 132 participants (56% female, mean age 63.9 years) passed quality checks. Overall, 47% of men and women had DDD grade 3 or more in the lumbar spine and 36% in both thoracic and lumbar spine. Risk ratios for DDD grades 3 and 4, adjusted for age and anthropometric determinants, varied across a three-fold range between centres, yet prevalences were highly correlated in men and women. DDD was associated with flattened, non-ovoid inter-vertebral disc spaces. KL grade 4 and loss of inter-vertebral disc space were associated with higher spine aBMD. Conclusion. KL grades 3 and 4 are often used clinically to categorize radiological DDD. Highly variable European prevalences of radiologically defined DDD grades 3+ along with the large effects of age may have growing and geographically unequal health and economic impacts as the population ages. These data encourage further studies of potential genetic and environmental causes.
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| 2. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 3. |
- Menkveld, Albert J., et al.
(författare)
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Nonstandard Errors
- 2024
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Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
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Tidskriftsartikel (refereegranskat)abstract
- In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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| 4. |
- Lewin, Harris A., et al.
(författare)
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The Earth BioGenome Project 2020 : Starting the clock
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Fang, Jun, et al.
(författare)
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Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele.
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| 6. |
- Haissaguerre, Michel, et al.
(författare)
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Localized sources maintaining atrial fibrillation organized by prior ablation
- 2006
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 113, s. 616-625
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Tidskriftsartikel (refereegranskat)abstract
- Background— Endocardial mapping of localized sources drivingatrial fibrillation (AF) in humans has not been reported.Methods and Results— Fifty patients with AF organizedby prior pulmonary vein and linear ablation were studied. AFwas considered organized if mapping during AF showed irregularbut discrete atrial complexes exhibiting consistent activationsequences for >75% of the time using a 20-pole catheter with5 radiating spines covering 3.5-cm diameter or sequential conventionalmapping. A site or region centrifugally activating the remainingatrial tissue defined a source. During AF with a cycle lengthof 211±32 ms, activation mapping identified 1 to 3 sourcesat the origin of atrial wavefronts in 38 patients (76%) predominantlyin the left atrium, including the coronary sinus region. Electrogramsat the earliest area varied from discrete centrifugal activationto an activity spanning 75% to 100% of the cycle length in 42%of cases, the latter indicating complex local conduction ora reentrant circuit. A gradient of cycle length (>20 ms)to the surrounding atrium was observed in 28%. Local radiofrequencyablation prolonged AF cycle length by 28±22 ms and eitherterminated AF or changed activation sequence to another organizedrhythm. In 4 patients, the driving source was isolated, surroundedby the atrium in sinus rhythm, and still firing at high frequency(228±31 ms) either permanently or in bursts.Conclusions— AF associated with consistent atrial activationsequences after prior ablation emanates mostly from localizedsources that can be mapped and ablated. Some sources harborelectrograms suggesting the presence of localized reentry.
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| 7. |
- Haïssaguerre, Michel, et al.
(författare)
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Sudden cardiac arrest associated with early repolarization
- 2008
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 358:19, s. 2016-2023
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest.METHODS: We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS-ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects.RESULTS: Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (+/-SD) follow-up of 61+/-50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008).CONCLUSIONS: Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.
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| 8. |
- Jais, Pierre, et al.
(författare)
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Stepwise catheter ablation of chronic atrial fibrillation : Importance of descrete anatomic sites for termination
- 2006
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Ingår i: Journal of Cardiovascular Electrophysiology. - : Wiley. - 1540-8167 .- 1045-3873. ; 17:Suppl 3, s. 28-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic atrial fibrillation (CAF) can be acutely terminated using a combination of approaches targeting thoracic veins, left atrial areas showing rapid/heterogeneous electrical activity, and by linear ablation. This observational study emphasizes the crucial role for conventional endocardial mapping to identify discrete anatomical sites, ablation of which is indispensable for the achievement of atrial fibrillation (AF) termination. Methods: Eighty consecutive patients with CAF underwent catheter ablation using the stepwise approach. Pulmonary vein isolation and roof-line ablation were performed as the initial two steps in all patients. In the presence of locally rapid or heterogeneous activity, ablation was then performed at all sites within the left atrium and coronary sinus (CS) region with the endpoint of local organization or slowing. If AF persisted, the mitral isthmus was targeted. Patients in whom AF terminated during one of these five ablation steps were differentiated from those in whom AF was terminated by radiofrequency ablation at a single discrete anatomic site within 1 minute. Electrograms at discrete anatomic sites of termination were classified according to morphology. Results: Termination of AF was achieved in 69 (86%) patients by ablation alone. In 50 patients (72%), this occurred while following the predetermined ablation schema. In the remaining 19 patients (28%), ablation targeting a discrete site (preferentially located at the CS, the base of left atrial appendage, and the interatrial septum) terminated AF. Such sites were identified by (1) continuous electrical activity and fractionation and (2) bursts of short cycle activity (130–160 msec), centrifugal activation or local activation gradients, indicating sources perpetuating AF. Conclusion: In 28% of patients with termination of CAF, the final successful ablation site is anatomically discrete and displays electrophysiological characteristics that can be effectively identified by point and activation mapping. Failure to identify these sites may significantly reduce the likelihood of termination of CAF by catheter ablation.
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| 9. |
- Matsuo, Seiichiro, et al.
(författare)
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Clinical Predictors of Termination and Clinical Outcome of Catheter Ablation for Persistent Atrial Fibrillation
- 2009
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 54:9, s. 788-795
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study evaluated the role of pre-procedural clinical variables to predict procedural and clinical outcomes of catheter ablation in patients with long-lasting persistent atrial fibrillation (AF). Background Catheter ablation of persistent AF remains a challenging task. Methods Catheter ablation was performed in 90 patients (76 men, age 57 +/- 11 years) with long-lasting persistent AF. The history of AF, echocardiographic parameters, presence of structural heart disease, and surface electrocardiogram (ECG) AF cycle length (CL) were assessed before ablation and analyzed with respect to procedural termination and clinical outcome. Mean follow-up was 28 +/- 4 months. Results Persistent AF was terminated in 76 of 90 patients (84%) by ablation. The duration of continuous AF was shorter (p < 0.0001), the surface ECG AFCL was longer (p < 0.0001), and the left atrium was smaller (p < 0.01) in patients in whom AF was terminated by catheter ablation. The surface ECG AFCL was the only independent predictor of AF termination (p < 0.01). Maintenance of sinus rhythm was associated with a shorter duration of continuous AF (p < 0.0001), a longer surface ECG AFCL (p < 0.001), and a smaller left atrium (p < 0.05) compared with those with recurrent arrhythmia. In multivariate analysis, the surface ECG AFCL and the AF duration predicted clinical success of persistent AF ablation (p < 0.01 and p < 0.05, respectively). Conclusions The surface ECG AFCL is a clinically useful pre-ablation tool for predicting patients in whom sinus rhythm can be restored by catheter ablation. The duration of continuous AF and the surface ECG AFCL are predictive of maintenance of sinus rhythm. (J Am Coll Cardiol 2009; 54: 788-95) (C) 2009 by the American College of Cardiology Foundation
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| 10. |
- 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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