18 research outputs found
Left Ventricular Endocardial Pacing Techniques as an Alternative for Ineffective Cardiac Resynchronization Therapy and the Role of Acute Hemodynamic Evaluation
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Solve-RD: systematic pan-European data sharing and collaborative analysis to solve rare diseases.
For the first time in Europe hundreds of rare disease (RD) experts team up to actively share and jointly analyse existing patient's data. Solve-RD is a Horizon 2020-supported EU flagship project bringing together >300 clinicians, scientists, and patient representatives of 51 sites from 15 countries. Solve-RD is built upon a core group of four European Reference Networks (ERNs; ERN-ITHACA, ERN-RND, ERN-Euro NMD, ERN-GENTURIS) which annually see more than 270,000 RD patients with respective pathologies. The main ambition is to solve unsolved rare diseases for which a molecular cause is not yet known. This is achieved through an innovative clinical research environment that introduces novel ways to organise expertise and data. Two major approaches are being pursued (i) massive data re-analysis of >19,000 unsolved rare disease patients and (ii) novel combined -omics approaches. The minimum requirement to be eligible for the analysis activities is an inconclusive exome that can be shared with controlled access. The first preliminary data re-analysis has already diagnosed 255 cases form 8393 exomes/genome datasets. This unprecedented degree of collaboration focused on sharing of data and expertise shall identify many new disease genes and enable diagnosis of many so far undiagnosed patients from all over Europe
Twist exome capture allows for lower average sequence coverage in clinical exome sequencing
Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques
Solving patients with rare diseases through programmatic reanalysis of genome-phenome data.
Funder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health); doi: https://doi.org/10.13039/100011272; Grant(s): 305444, 305444Funder: Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness); doi: https://doi.org/10.13039/501100003329Funder: Generalitat de Catalunya (Government of Catalonia); doi: https://doi.org/10.13039/501100002809Funder: EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj); doi: https://doi.org/10.13039/501100008530Funder: Instituto Nacional de Bioinformática ELIXIR Implementation Studies Centro de Excelencia Severo OchoaFunder: EC | EC Seventh Framework Programm | FP7 Health (FP7-HEALTH - Specific Programme "Cooperation": Health)Reanalysis of inconclusive exome/genome sequencing data increases the diagnosis yield of patients with rare diseases. However, the cost and efforts required for reanalysis prevent its routine implementation in research and clinical environments. The Solve-RD project aims to reveal the molecular causes underlying undiagnosed rare diseases. One of the goals is to implement innovative approaches to reanalyse the exomes and genomes from thousands of well-studied undiagnosed cases. The raw genomic data is submitted to Solve-RD through the RD-Connect Genome-Phenome Analysis Platform (GPAP) together with standardised phenotypic and pedigree data. We have developed a programmatic workflow to reanalyse genome-phenome data. It uses the RD-Connect GPAP's Application Programming Interface (API) and relies on the big-data technologies upon which the system is built. We have applied the workflow to prioritise rare known pathogenic variants from 4411 undiagnosed cases. The queries returned an average of 1.45 variants per case, which first were evaluated in bulk by a panel of disease experts and afterwards specifically by the submitter of each case. A total of 120 index cases (21.2% of prioritised cases, 2.7% of all exome/genome-negative samples) have already been solved, with others being under investigation. The implementation of solutions as the one described here provide the technical framework to enable periodic case-level data re-evaluation in clinical settings, as recommended by the American College of Medical Genetics
New-generation atrial antitachycardia pacing (Reactive ATP) is associated with reduced risk of persistent or permanent atrial fibrillation in patients with bradycardia: Results from the MINERVA randomized multicenter international trial
BACKGROUND Atrial fibrillation (AF) is a frequent comorbidity in
patients with pacemaker and is a recognized cause of mortality,
morbidity, and quality-of-life impairment. The international MINimizE
Right Ventricular pacing to prevent Atrial fibrillation and heart
failure trial established that atrial preventive pacing and atrial
antitachycardia pacing (DDDRP) in combination with managed ventricular
pacing (MVP) reduce permanent AF occurrence in comparison with standard
dual-chamber pacing (DDDR).
OBJECTIVE We aimed to determine the role of new-generation atrial
antitachycardia pacing (Reactive ATP) in preventing AF disease
progression.
METHODS Patients with dual-chamber pacemaker and with previous atrial
tachyarrhythmias were randomly assigned to DDDR (n = 385 (3310)), MVP (n
= 398 (34%)), or DDDRP+MVP (n = 383 (33%)) group. The incidence of
permanent AF, as defined by the study investigator, or persistent AF,
defined as >= 7 consecutive days with AF, was estimated using the
Kaplan-Meier method, while its association with patients’
characteristics was evaluated via multivariable Cox regression.
RESULTS At 2 years, the incidence of permanent or persistent AF was 26%
(95% confidence interval [CI] 22%-31%) in the DDDR group, 25%
(95% CI 21%-30%) in the MVP group, and 15% (95% CI 12%-20%) in
the DDDRP+MVP group (P < .001 vs DDDR; P = .002 vs MVP). Generalized
estimating equation-adjusted Reactive ATP efficacy was 44.4% (95% CI
41.3%-47.6%). Multivariate modeling identified high Reactive ATP
efficacy (> 44.4%) as a significant predictor of reduced permanent or
persistent AF risk (hazard ratio 0.32; 95% CI 0.13-0.781; P = .012) and
episodes’ characteristics, such as long atrial arrhythmia cycle length,
regularity, and the number of rhythm transitions, as predictors of high
ATP efficacy.
CONCLUSION In patients with bradycardia, DDDRP+MVP delays AF disease
progression, with Reactive ATP efficacy being an independent predictor
of permanent or persistent AF reduction
Non-adherence to Anti-TNF Therapy is Associated with Illness Perceptions and Clinical Outcomes in Outpatients with Inflammatory Bowel Disease: Results from a Prospective Multicentre Study
Non-adherence to anti-tumour necrosis factor [TNF] agents in patients with inflammatory bowel disease [IBD] is a serious problem. In this study, we assessed risk factors for non-adherence and examined the association between adherence to anti-TNF agents and loss of response [LOR]. In this multicentre, 12-month observational study, outpatients with IBD were included. Demographic and clinical characteristics were recorded. Adherence was measured with the Modified Morisky Adherence Scale-8 [MMAS-8] and 12-month pharmacy refills [medication possession ratio, MPR]. Risk factors included demographic and clinical characteristics, medication beliefs, and illness perceptions. Cox regression analysis was performed to determine the association between MPR and LOR to anti-TNF, IBD-related surgery or hospitalisation, dose intensification, or discontinuation of anti-TNF. In total, 128 patients were included [67 infliximab, 61 adalimumab], mean age 37 ( ± standard deviation [SD] 14) years, 71 [56%] female. Median disease duration was 8 (interquartile range [IQR] 4-14) years. Clinical disease activity was present in 41/128 [32%] patients, 36/127 [28%] patients had an MMAS-8 < 6 ['low adherence'], and 25/99 [25%] patients had an MPR < 80% [non-adherence]. Risk factors for non-adherence included adalimumab use (odds ratio [OR] 10.1, 95% confidence interval [CI] 2.62-40.00), stronger emotional response [OR 1.16, 95% CI 1.02-1.31], and shorter timeline perception, i.e. short perceived illness duration [OR 0.60, 95% CI 0.38-0.96]. Adherence is linearly and negatively [OR 0.14, 95% CI 0.03-0.63] associated with LOR. Non-adherence to anti-TNF agents is strongly associated with LOR to anti-TNF agents, adalimumab use, and illness perceptions. The latter may provide an important target for interventions aimed at improving adherence and health outcome
Non-adherence to Anti-TNF Therapy is Associated with Illness Perceptions and Clinical Outcomes in Outpatients with Inflammatory Bowel Disease: Results from a Prospective Multicentre Study
Non-adherence to anti-TNF therapy is associated with illness perceptions and clinical outcomes in outpatients with inflammatory bowel disease : results from a prospective multicentre study
BACKGROUND AND AIMS: Non-adherence to anti-tumor necrosis factor (TNF) agents in patients with inflammatory bowel disease (IBD) is a serious problem. In this study, we assessed risk factors for non-adherence and examined the association between adherence to anti-TNF agents and loss of response (LOR). METHODS: In this multicentre, 12-month observational study, outpatients with IBD were included. Demographic and clinical characteristics were recorded. Adherence was measured with the Modified Morisky Adherence Scale-8 (MMAS-8) and 12-month pharmacy refills (medication possession ratio, MPR). Risk factors included demographic and clinical characteristics, medication beliefs and illness perceptions. Cox regression analysis was performed to determine the association between MPR and LOR to anti-TNF, IBD-related surgery or hospitalization, dose intensification or discontinuation of anti-TNF. RESULTS: In total, 128 patients were included (67 infliximab, 61 adalimumab), mean age 37 (±SD 14) years, 71 (56%) females. Median disease duration was 8 (IQR 4-14) years. Clinical disease activity was present in 41/128 (32%) patients, 36/127 (28%) patients had a MMAS-8 <6 ("low adherence") and 25/99 (25%) patients had a MPR<80% (non-adherence). Risk factors for non-adherence included adalimumab use (OR 10.1, 95%CI 2.62-40.00), stronger emotional response (OR 1.16, 95%CI 1.02-1.31) and shorter timeline perception, i.e. short perceived illness duration (OR 0.60, 95%CI 0.38-0.96). Adherence is linearly and negatively (OR 0.14, 95%CI 0.03-0.63) associated with LOR. CONCLUSION: Non-adherence to anti-TNF agents is strongly associated with LOR to anti-TNF agents, adalimumab use and illness perceptions. The latter may provide an important target for interventions aimed at improving adherence and health outcomes
Non-adherence to anti-TNF therapy is associated with illness perceptions and clinical outcomes in outpatients with inflammatory bowel disease : results from a prospective multicentre study
BACKGROUND AND AIMS: Non-adherence to anti-tumor necrosis factor (TNF) agents in patients with inflammatory bowel disease (IBD) is a serious problem. In this study, we assessed risk factors for non-adherence and examined the association between adherence to anti-TNF agents and loss of response (LOR). METHODS: In this multicentre, 12-month observational study, outpatients with IBD were included. Demographic and clinical characteristics were recorded. Adherence was measured with the Modified Morisky Adherence Scale-8 (MMAS-8) and 12-month pharmacy refills (medication possession ratio, MPR). Risk factors included demographic and clinical characteristics, medication beliefs and illness perceptions. Cox regression analysis was performed to determine the association between MPR and LOR to anti-TNF, IBD-related surgery or hospitalization, dose intensification or discontinuation of anti-TNF. RESULTS: In total, 128 patients were included (67 infliximab, 61 adalimumab), mean age 37 (±SD 14) years, 71 (56%) females. Median disease duration was 8 (IQR 4-14) years. Clinical disease activity was present in 41/128 (32%) patients, 36/127 (28%) patients had a MMAS-8 <6 ("low adherence") and 25/99 (25%) patients had a MPR<80% (non-adherence). Risk factors for non-adherence included adalimumab use (OR 10.1, 95%CI 2.62-40.00), stronger emotional response (OR 1.16, 95%CI 1.02-1.31) and shorter timeline perception, i.e. short perceived illness duration (OR 0.60, 95%CI 0.38-0.96). Adherence is linearly and negatively (OR 0.14, 95%CI 0.03-0.63) associated with LOR. CONCLUSION: Non-adherence to anti-TNF agents is strongly associated with LOR to anti-TNF agents, adalimumab use and illness perceptions. The latter may provide an important target for interventions aimed at improving adherence and health outcomes