Fault-Tolerant Computing: An Overview

Coordinated Science Laboratory was formerly known as Control Systems LaboratoryNASA / NAG-1-613Semiconductor Research Corporation / 90-DP-109Joint Services Electronics Program / N00014-90-J-127

Steroid hormone-related polymorphisms associate with the development of bone erosions in rheumatoid arthritis and help to predict disease progression: Results from the REPAIR consortium

Here, we assessed whether 41 SNPs within steroid hormone genes associated with erosive disease. The most relevant finding was the rheumatoid factor (RF)-specific effect of the CYP1B1, CYP2C9, ESR2, FcγR3A, and SHBG SNPs to modulate the risk of bone erosions (P = 0.004, 0.0007, 0.0002, 0.013 and 0.015) that was confirmed through meta-analysis of our data with those from the DREAM registry (P = 0.000081, 0.0022, 0.00074, 0.0067 and 0.0087, respectively). Mechanistically, we also found a gender-specific correlation of the CYP2C9rs1799853T/T genotype with serum vitamin D3 levels (P = 0.00085) and a modest effect on IL1β levels after stimulation of PBMCs or blood with LPS and PHA (P = 0.0057 and P = 0.0058). An overall haplotype analysis also showed an association of 3 ESR1 haplotypes with a reduced risk of erosive arthritis (P = 0.009, P = 0.002, and P = 0.002). Furthermore, we observed that the ESR2, ESR1 and FcγR3A SNPs influenced the immune response after stimulation of PBMCs or macrophages with LPS or Pam3Cys (P = 0.002, 0.0008, 0.0011 and 1.97•10−7). Finally, we found that a model built with steroid hormone-related SNPs significantly improved the prediction of erosive disease in seropositive patients (PRF+ = 2.46•10−8) whereas no prediction was detected in seronegative patients (PRF− = 0.36). Although the predictive ability of the model was substantially lower in the replication population (PRF+ = 0.014), we could confirm that CYP1B1 and CYP2C9 SNPs help to predict erosive disease in seropositive patients. These results are the first to suggest a RF-specific association of steroid hormone-related polymorphisms with erosive disease

Bone Mineral Density in Adult Survivors of Pediatric Differentiated Thyroid Carcinoma:A Longitudinal Follow-Up Study

Background: Survivors of pediatric differentiated thyroid carcinoma (DTC) receive thyrotropin-suppressive therapy to minimize disease recurrence. However, knowledge about long-term effects of subclinical hyperthyroidism on bone mineral density (BMD) in pediatric DTC survivors is scarce, as is the information regarding long-term consequences of permanent hypoparathyroidism on BMD. We evaluated BMD in pediatric DTC survivors and investigated if BMD was affected by subclinical hyperthyroidism and/or permanent hypoparathyroidism during long-term follow-up. Methods: In this nationwide longitudinal study, we determined BMD in the lumbar spine and femur by dual energy X-ray absorptiometry in 65 pediatric DTC survivors. Measurements were repeated after minimal 5 years of follow-up in 46 pediatric DTC survivors. BMD results were evaluated according to the recommendations of the International Society for Clinical Densitometry (ISCD) and WHO. At both visits, we determined biochemical parameters and markers of bone resorption (C-terminal telopeptide of type I collagen [β-CTX]) and formation (N-propeptide of type I collagen [PINP] and osteocalcin). Results: First and second BMD measurements were done after a median follow-up of 17.0 (interquartile range [IQR] 8.0-25.0) and 23.5 (IQR 14.0-30.0) years after diagnosis, respectively. Median age at diagnosis was 15 years (IQR 13.0-17.0). Twenty-nine percent of the survivors had subclinical hyperthyroidism. In most survivors, BMD T-and Z-scores were within the reference range during both BMD evaluations. However, after 23.5 years of follow-up, a low BMD was found in 13.0%. In the 13 survivors with permanent hypoparathyroidism, BMD values did not differ after 5 years of follow-up compared with baseline values or in comparison with the 33 survivors without permanent hypoparathyroidism. During follow-up, turnover markers β-CTX and PINP remained stable. Conclusions: This longitudinal study of pediatric DTC survivors demonstrated normal and stable median lumbar spine and femur BMD values after a median time of 17 and 23.5 years after diagnosis. However, compared with controls, a lower BMD was still found in 13.0% after prolonged follow-up despite intensive follow-up. Based on the studied follow-up period, these data do not provide convincing evidence in support of standard monitoring of bone mass among DTC survivors, but may be restricted to individual cases at low frequency. Trial Registration: This follow-up study was registered in The Netherlands Trial Register under no. NL3280 (www.trialregister.nl/trial/3280)

Protocol for the development of core set of domains of the core outcome set for patients with congenital melanocytic naevi (OCOMEN project)

Background: Having large congenital melanocytic naevi (CMN) is associated with a psychosocial burden on patients and their parents because of its remarkable appearance and the extra care it may require. Large CMN also pose an increased risk of malignant melanoma or neurocutaneous melanosis. There is a lack of international consensus on what important outcome domains to measure in relation to treatment. This makes it difficult to compare options, to properly inform patients and their parents, and to set up treatment policy for CMN. Therefore, we aim to develop a core outcome set (COS), i.e. the minimum set of outcomes that are recommended to be measured and reported in all clinical trials of a specific health condition. This COS can be used in the follow-up of CMN patients with or without treatment, in clinical research and practice. Methods: In the Outcomes for Congenital Melanocytic Nevi (OCOMEN) projects, we follow the recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) initiative and the Cochrane Skin Core Outcomes Set Initiative (CS-COUSIN). This project entails the following: (i) a systematic review to identify the previous reported outcomes in literature; (ii) focus groups with national and international patients and parents to identify patient-important outcomes; (iii) classification of outcomes into outcome domains; (iv) e-Delphi surveys in which stakeholders (patients/parents and professionals) can rate the importance of domains and outcomes; and (v) an online consensus meeting to finalize the core outcome domains of the COS. Results: The results will be disseminated by means of publication in a leading journal and presentations in international meetings or conferences. We engage international experts in CMN, both patients and professionals, to ensure the international utility and applicability of the COS

Gestational jet lag predisposes to later-life skeletal and cardiac disease

cardiovascular disease, and cancer. In the present study, we investigated later life adverse health effects triggered by repeated jet lag during gestation. Pregnant mice were subjected to a regular light-dark cycle (CTRL) or to a repeated delay (DEL) or advance (ADV) jet lag protocol. Both DEL and ADV offspring showed reduced weight gain. ADV offspring had an increased circadian period, and an altered response to a jet lag was observed in both DEL and ADV offspring. Analysis of the bones of adult male ADV offspring revealed reduced cortical bone mass and strength. Strikingly, analysis of the heart identified structural abnormalities and impaired heart function. Finally, DNA methylation analysis revealed hypermethylation of miR17-92 cluster and differential methylation within circadian clock genes, which correlated with altered gene expression. We show that developmental CRD affects the circadian system and predisposes to non-communicable disease in adult life

Sub-arcsecond imaging with the International LOFAR Telescope I. Foundational calibration strategy and pipeline

The International LOFAR Telescope is an interferometer with stations spread across Europe. With baselines of up to ~2000 km, LOFAR has the unique capability of achieving sub-arcsecond resolution at frequencies below 200 MHz. However, it is technically and logistically challenging to process LOFAR data at this resolution. To date only a handful of publications have exploited this capability. Here we present a calibration strategy that builds on previous high-resolution work with LOFAR. It is implemented in a pipeline using mostly dedicated LOFAR software tools and the same processing framework as the LOFAR Two-metre Sky Survey (LoTSS). We give an overview of the calibration strategy and discuss the special challenges inherent to enacting high-resolution imaging with LOFAR, and describe the pipeline, which is publicly available, in detail. We demonstrate the calibration strategy by using the pipeline on P205+55, a typical LoTSS pointing with an 8 h observation and 13 international stations. We perform in-field delay calibration, solution referencing to other calibrators in the field, self-calibration of these calibrators, and imaging of example directions of interest in the field. We find that for this specific field and these ionospheric conditions, dispersive delay solutions can be transferred between calibrators up to ~1.5° away, while phase solution transferral works well over ~1°. We also demonstrate a check of the astrometry and flux density scale with the in-field delay calibrator source. Imaging in 17 directions, we find the restoring beam is typically ~0.3′′ ×0.2′′ although this varies slightly over the entire 5 deg2 field of view. We find we can achieve ~80–300 μJy bm−1 image rms noise, which is dependent on the distance from the phase centre; typical values are ~90 μJy bm−1 for the 8 h observation with 48 MHz of bandwidth. Seventy percent of processed sources are detected, and from this we estimate that we should be able to image roughly 900 sources per LoTSS pointing. This equates to ~ 3 million sources in the northern sky, which LoTSS will entirely cover in the next several years. Future optimisation of the calibration strategy for efficient post-processing of LoTSS at high resolution makes this estimate a lower limit