Global navigation satellite system (GNSS) displacements at near‐source stations can be biased in both amplitude and phase due to fierce earthquake strike. We propose to inject inertial measurement ...unit (IMU)‐recorded ground motions into GNSS receivers to compensate their phase‐lock loops (PLLs) for seismic motion stress, aiming at keeping steady carrier‐phase tracking. We use a shake table to replay an acceleration record (0.5–2.0 g) from the 2008 Mw7.9 Wenchuan earthquake to test this IMU‐augmented PLL: It achieves a 1.9‐mm amplitude error (RMS) and an 8.0‐ms phase lag against the shake table's recordings, while the conventional PLL languishes to 6.0 mm and 56.5 ms, respectively. Moreover, the IMU‐augmented PLL enables a six‐degree‐of‐freedom integration among the GNSS and IMU data, where the displacement amplitude error and phase lag decline further to 0.9 mm and 3.5 ms, respectively. We believe that the IMU‐augmented GNSS receivers are ideal strong‐motion seismograph to capture trustworthy broadband displacements in the near fields.
Plain Language Summary
Understanding the origin and mechanism of destructive earthquakes is predicated on the faithful recordings of their induced ground displacements near the significantly deformed epicentral regions. Global navigation satellite system (GNSS) receivers have been recognized as the best tool to measure the large epicentral displacements. This is achieved within the GNSS receivers by continuously tracking the satellite carrier‐phase signals. However, GNSS receivers are likely to lose their fidelity in recording complete and accurate displacement waveforms in case of strong ground motions, since their carrier‐phase tracking becomes unstable when strained by such persistent and high dynamic stress. We hence developed an advanced GNSS receiver architecture where the dynamic stress suffered by the carrier‐phase tracking components is compensated for by an embedded inertial measurement unit consisting of one accelerometer and one gyroscope. In this case, the carrier‐phase signals can be tracked steadily by GNSS receivers, and the displacement accuracy can be improved from subcentimeter to millimeter level by about 70% when the ground accelerations reach up to twice the gravitational acceleration. We believe that this advanced GNSS receiver will be an excellent strong‐motion seismometer in recording displacements directly at a few millimeter resolution without missing or distorting any earthquake signals, even in case of fierce ground motions.
Key Points
A new GNSS receiver architecture is developed by embedding both accelerometer and gyroscope to capture fierce seismic displacements
GNSS displacement error and phase lag are both reduced by 70% and 85% to 2 mm and 8.0 ms, respectively, compared to conventional receivers
Six‐degree‐of‐freedom seismogeodesy is achieved with the displacement error and phase lag reduced further to 0.9 mm and 3.5 ms, respectively
Summary
Adult survivors of childhood acute lymphoblastic leukaemia (ALL) have a four‐fold excess risk of mortality from cardiovascular disease. This cardiovascular risk has not been fully ...characterized. ALL survivors n = 784, median age 31·7 years (18·9–59·1) in the St. Jude Lifetime Cohort Study underwent evaluation for cardiovascular risk and metabolic syndrome (MetS) according to National Cholesterol Education Program – Adult Treatment Panel III criteria. Comparisons were made to 777 age‐, sex‐, and race‐matched controls from the National Health and Nutrition Examination Survey (NHANES). MetS was identified in 259 survivors (33·6%) and associated with older age in 5‐year increments (relative risk RR 1·13, 95% confidence interval CI 1·06–1·19) and prior cranial radiotherapy (CRT) (with craniospinal radiation: RR 1·88, 95%CI 1·32–2·67; without: RR 1·67, 95%CI 1·26–2·23). Measures of obesity were highly prevalent among female survivors and CRT recipients. Compared to NHANES controls, ALL survivors had a higher risk of MetS (RR 1·43, 95%CI 1·22–1·69), hypertension (RR 2·43, 95%CI 2·06–2·86), low high‐density lipoprotein (RR 1·40, 95%CI 1·23–1·59), obesity (RR 1·47, 95%CI 1·29–1·68) and insulin resistance (1·64, 95%CI 1·44–1·86). This large study of clinically evaluated ALL survivors identified a high prevalence of MetS, obesity and cardiovascular risk, particularly in CRT recipients, underscoring the need for screening and aggressive reduction of modifiable risks.
To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL).
Survivors of childhood ALL treated at St ...Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion.
Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk RR, 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment.
This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature.
Summary Background Therapy for ependymoma includes aggressive surgical intervention and radiotherapy administered by use of methods that keep the risk of side-effects to a minimum. We extended this ...treatment approach to include children under the age of 3 years with the aim of improving tumour control. Methods Between July 11, 1997, and Nov 18, 2007, 153 paediatric patients (median age 2·9 years range 0·9–22·9 months) with localised ependymoma were treated. 85 patients had anaplastic ependymoma; the tumours of 122 were located in the infratentorial region, and 35 had received previous chemotherapy. Patients received conformal radiotherapy after definitive surgery (125 patients had undergone gross total, 17 near total, and 11 subtotal resection). Doses of 59·4 Gy (n=131) or 54·0 Gy (n=22) were prescribed to a 10 mm margin around the target volume. Disease control, patterns of failure, and complications were recorded for patients followed over 10 years. Overall survival, event-free survival (EFS), cumulative incidence of local recurrences, and cumulative incidence of distant recurrences were assessed. Variables considered included tumour grade, tumour location, ethnic origin, sex, age when undergoing conformal radiotherapy, total radiotherapy dose, number of surgical procedures, surgery extent, and preradiotherapy chemotherapy. Findings After a median follow-up of 5·3 years (range 0·4–10·4), 23 patients had died and tumour progression noted in 36, including local (n=14), distant (n=15), and combined failure (n=7). 7-year local control, EFS, and overall survival were 87·3% (95% CI 77·5–97·1), 69·1% (56·9–81·3), and 81·0% (71·0–91·0), respectively. The cumulative incidences of local and distant failure were 16·3% (9·6–23·0) and 11·5% (5·9–17·1), respectively. In the 107 patients treated with immediate postoperative conformal radiotherapy (without delay or chemotherapy), 7-year local control, EFS, and overall survival were 88·7% (77·9–99·5), 76·9% (63·4–90·4), and 85·0% (74·2–95·8), respectively; the cumulative incidence of local and distant failure were 12·6% (5·1–20·1), and 8·6% (2·8–14·3), respectively. The incidence of secondary malignant brain tumour at 7 years was 2·3% (0–5·6) and brainstem necrosis 1·6% (0–4·0). Overall survival was affected by tumour grade (anaplastic vs differentiated: HR 3·98 95% CI 1·51–10·48; p=0·0052), extent of resection (gross total vs near total or subtotal: 0·16 0·07–0·37; p<0·0001), and ethnic origin (non-white vs white: 3·0 1·21–7·44; p=0·018). EFS was affected by tumour grade (anaplastic vs differentiated: 2·52 1·27–5·01; p=0·008), extent of resection (gross total vs near total or subtotal: 0·20 0·11–0·39; p<0·0001), and sex (male vs female: 2·19 1·03–4·66; p=0·042). Local failure was affected by extent of resection (gross total vs near total or subtotal: 0·16 0·067–0·38; p<0·0001), sex (male vs female: 3·85 1·10–13·52; p=0·035), and age (<3 years vs ≥3 years: 3·25 1·30–8·16; p=0·012). Distant recurrence was only affected by tumour grade (anaplastic vs differentiated: 4·1 1·2–14·0; p=0·017). Interpretation Treatment of ependymoma should include surgery with the aim of gross-total resection and conformal, high-dose, postoperative irradiation. Future trials might consider treatment stratification based on sex and age. Funding American Cancer Society and American Lebanese Syrian Associated Charities (ALSAC).
The primary objective of this study was to examine whether children with low-grade glioma (LGG) or craniopharyngioma had impaired learning and memory after conformal radiation therapy (CRT). A ...secondary objective was to determine whether children who received chemotherapy before CRT, a treatment often used to delay radiation therapy in younger children with LGG, received any protective benefit with respect to learning.
Learning and memory in 57 children with LGG and 44 children with craniopharyngioma were assessed with the California Verbal Learning Test-Children's Version and the Visual-Auditory Learning tests. Learning measures were administered before CRT, 6 months later, and then yearly for a total of 5 years.
No decline in learning scores after CRT was observed when patients were grouped by diagnosis. For children with LGG, chemotherapy before CRT did not provide a protective effect on learning. Multiple regression analyses, which accounted for age and tumor volume and location, found that children treated with chemotherapy before CRT were at greater risk of decline on learning measures than those treated with CRT alone. Variables predictive of learning and memory decline included hydrocephalus, shunt insertion, younger age at time of treatment, female gender, and pre-CRT chemotherapy.
This study did not reveal any impairment or decline in learning after CRT in overall aggregate learning scores. However, several important variables were found to have a significant effect on neurocognitive outcome. Specifically, chemotherapy before CRT was predictive of worse outcome on verbal learning in LGG patients. In addition, hydrocephalus and shunt insertion in craniopharyngioma were found to be predictive of worse neurocognitive outcome, suggesting a more aggressive natural history for those patients.
Neurocognitive impairment in survivors of childhood cancer may be associated with direct neurotoxicity, as well as indirect effects of systemic health complications. We evaluated associations among ...treatment exposures, chronic health conditions, and neurocognitive outcomes in adult survivors of childhood cancer.
Participants included 5507 adult survivors of childhood cancer (47.1% male; mean SD age = 31.8 7.6 years at evaluation; 23.1 4.5 years postdiagnosis) in the Childhood Cancer Survivor Study who completed a self-report measure of neurocognitive function. Cardiac, pulmonary, and endocrine chronic health conditions were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Structural equation modeling was used to examine a priori hypothesized causal pathways among cancer treatment, subsequent chronic health conditions, and neurocognitive outcomes. Multivariable models were used to estimate relative risk for associations of treatments and chronic conditions on neurocognitive function. All statistical tests were two-sided.
One-third of survivors with a grade 2 or higher chronic condition reported impairments in task efficiency and memory. In addition to direct effects of cranial radiation, path analyses and multivariable models demonstrated direct effects of cardiopulmonary (β = 0.10, P = .002; relative risk RR = 1.27, 95% confidence interval CI = 1.12 to 1.44) and endocrine (β = 0.07, P = .04; RR = 1.14, 95% CI = 1.02 to 1.28) conditions on impaired task efficiency. We identified similar effects of cardiopulmonary condition on memory (P = .01) and emotional regulation (P = .01). Thoracic radiation was associated with impaired task efficiency (P = .01) and emotional regulation (P = .01) through endocrine morbidity.
Non-neurotoxic exposures, such as thoracic radiation, can adversely impact survivors' neurocognitive function through chronic conditions. Management of chronic diseases may mitigate neurocognitive outcomes among aging survivors of childhood cancer.
Macromolecules containing N-diazeniumdiolates of secondary amines are proposed scaffolds for controlled nitrogen oxide (NO) release medical applications. Preparation of these compounds often involves ...converting primary amine groups to secondary amine groups through N-alkylation. However, N-alkylation results in not only secondary amines but tertiary amines as well. Only N-diazeniumdiolates of secondary amines are suitable for controlled NO release; therefore, the yield of secondary amines is crucial to the total NO load of the carrier. In this paper, 1H NMR spectroscopy was used to estimate the rate constants for formation of secondary amine (k 1) and tertiary amine (k 2) for alkylation reagents such as propylene oxide (PO), methyl acrylate (MA), and acrylonitrile (ACN). At room temperature, the ratio of k 2/k 1 for the three reactions was found to be around 0.50, 0.026, and 0.0072.
Long-term survivors of childhood cancer are at risk for fatigue, sleep problems, and neurocognitive impairment, although the association between these outcomes has not been previously examined.
...Outcomes were evaluated in 1426 survivors from the Childhood Cancer Survivor Study using a validated Neurocognitive Questionnaire. Relative risks for neurocognitive impairment were calculated using demographic and treatment factors, and survivors' report on the Functional Assessment of Chronic Illness Therapy-Fatigue, the Short Form-36 Vitality Scale, the Pittsburgh Sleep Quality Index, and the Epworth Sleepiness Scale.
Neurocognitive impairment was identified in >20% of survivors, using sibling-based norms for comparison. Multivariate logistic regression models revealed that fatigue (risk ratio RR, 1.34; 95% confidence interval CI, 1.13-1.59), daytime sleepiness (RR, 1.68; 95% CI, 1.55-1.83), poor sleep quality (RR, 1.23; 95% CI, 1.01-1.49), and decreased vitality (RR, 1.75; 95% CI 1.33-2.30) were all associated with impaired task efficiency. Likewise, fatigue (RR, 1.77; 95% CI, 1.23-2.55), sleepiness (RR, 1.38; 95% CI, 1.14-1.67), and decreased vitality (RR, 3.08; 95% CI, 1.98-4.79) were predictive of emotional regulation problems. Diminished organization was associated with increased sleepiness (RR, 1.80; 95% CI, 1.31-2.48) and decreased vitality (RR, 1.90; 95% CI, 1.37-2.63). Impaired memory was associated with poor sleep quality (RR, 1.45; 95% CI, 1.19-1.76), increased sleepiness (RR, 2.05; 95% CI, 1.63-2.58), and decreased vitality (RR, 2.01; 95% CI, 1.42-2.86). The impact of fatigue, sleepiness, sleep quality, and vitality on neurocognitive outcomes was independent of the effects of cranial radiation therapy, steroids and antimetabolite chemotherapy, sex, and current age.
Neurocognitive function in long-term survivors of childhood cancer appears particularly vulnerable to the effects of fatigue and sleep disruption. These findings suggest sleep hygiene should be emphasized among survivors, as it may provide an additional mechanism for intervention to improve neurocognitive outcomes.
Pseudomonas aeruginosa (P. aeruginosa) is a known bacterium that produces biofilms and causes severe infection. Furthermore, P. aeruginosa biofilms are extremely difficult to eradicate, leading to ...the development of chronic and antibiotic-resistant infections. Our previous study showed that a cathelicidin-related antimicrobial peptide (CRAMP) inhibits the formation of P. aeruginosa biofilms and markedly reduces the biomass of preformed biofilms, while the mechanism of eradicating bacterial biofilms remains elusive. Therefore, in this study, the potential mechanism by which CRAMP eradicates P. aeruginosa biofilms was investigated through an integrative analysis of transcriptomic, proteomic, and metabolomic data. The omics data revealed CRAMP functioned against P. aeruginosa biofilms by different pathways, including the Pseudomonas quinolone signal (PQS) system, cyclic dimeric guanosine monophosphate (c-di-GMP) signalling pathway, and synthesis pathways of exopolysaccharides and rhamnolipid. Moreover, a total of 2914 differential transcripts, 785 differential proteins, and 280 differential metabolites were identified. A series of phenotypic validation tests demonstrated that CRAMP reduced the c-di-GMP level with a decrease in exopolysaccharides, especially alginate, in P. aeruginosa PAO1 biofilm cells, improved bacterial flagellar motility, and increased the rhamnolipid content, contributing to the dispersion of biofilms. Our study provides new insight into the development of CRAMP as a potentially effective antibiofilm dispersant.
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