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Background: Challenges in predicting risk of recurrence for individual patients with meningioma limits appropriate selection of patients who may benefit from adjuvant radiation therapy to delay recurrence. Here, we aimed to develop and validate a combined clinicomolecular predictor of early recurrence for individual patients with meningiomas. Methods: A methylation-based predictor of 5-year recurrence-free-survival (RFS) was developed using DNA-methylation profiles from a training cohort of 228 patients. Model performance was compared to a standard-of-care histological-based model using three independent cohorts (N=54 ;N=140; N=64 patients). Subsequently, a nomogram that integrated the methylome-based predictor with prognostic clinical factors was developed and validated. Results: The methylome-based predictor of 5-year RFS performed favorably compared to a grade-based predictor when tested using the three validation cohorts (ΔAUC=0.10, 95%CI 0.03 – 0.018) and was independently associated with RFS on multivariable Cox regression analysis (HR=3.6, 95%CI 1.8–7.2, P<0.001). A nomogram combining the methylome-predictor with clinical factors demonstrated greater discrimination for recurrence than a nomogram using clinical factors alone (ΔAUC=0.25, 95%CI 0.22–0.27) and resulted in two risk groups with distinct recurrence patterns (HR=7.7, 95%CI 5.3–11.1, P<0.001) and clinical implications. Conclusions: Our validated models provide important novel prognostic information that could be used to individualize decisions regarding post-operative therapeutic interventions in meningioma.
Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia.
Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed.
Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: −0.63 (95% CI −1.10 to −0.16), p = 0.009, I2 = 77%], but not in the total, positive and general symptoms [SMD: −0.46 to −0.08 (95% CI −0.93 to 0.22), p = 0.06–0.60, I2 = 0–74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI −0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: −0.41 (95% CI −0.72 to −0.11), p = 0.008, I2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77–4.42), p < 0.00001, I2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76–2.37), p = 0.31, I2 = 0%] and adverse drug reactions between the two groups.
This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.
Supernova (SN) 1987A has provided a unique opportunity to study how SN ejecta evolve in 30 years time scale. We report our ALMA spectral observations of SN 1987A, taken in 2014, 2015 and 2016, with detections of CO, 28SiO, HCO+ and SO, with weaker lines of 29SiO.
We find a dip in the SiO line profiles, suggesting that the ejecta morphology is likely elongated. The difference of the CO and SiO line profiles is consistent with hydrodynamic simulations, which show that Rayleigh-Taylor instabilities causes mixing of gas, with heavier elements much more disturbed, making more elongated structure.
Using 28SiO and its isotopologues, Si isotope ratios were estimated for the first time in SN 1987A. The estimated ratios appear to be consistent with theoretical predictions of inefficient formation of neutron rich atoms at lower metallicity, such as observed in the Large Magellanic Cloud (about half a solar metallicity).
The deduced large HCO+ mass and small SiS mass, which are inconsistent to the predictions of chemical model, might be explained by some mixing of elements immediately after the explosion. The mixing might have made some hydrogen from the envelope to sink into carbon and oxygen-rich zone during early days after the explosion, enabling the formation of a substantial mass of HCO+. Oxygen atoms may penetrate into silicon and sulphur zone, suppressing formation of SiS.
Our ALMA observations open up a new window to investigate chemistry, dynamics and explosive-nucleosynthesis in supernovae.
To measure transmission frequencies and risk factors for household acquisition of community-associated and healthcare-associated (HA-) methicillin-resistant Staphylococcus aureus (MRSA).
Prospective cohort study from October 4, 2008, through December 3, 2012.
Seven acute care hospitals in or near Toronto, Canada.
Total of 99 MRSA-colonized or MRSA-infected case patients and 183 household contacts.
Baseline interviews were conducted, and surveillance cultures were collected monthly for 3 months from household members, pets, and 8 prespecified high-use environmental locations. Isolates underwent pulsed-field gel electrophoresis and staphylococcal cassette chromosome mec typing.
Overall, of 183 household contacts 89 (49%) were MRSA colonized, with 56 (31%) detected at baseline. MRSA transmission from index case to contacts negative at baseline occurred in 27 (40%) of 68 followed-up households. Strains were identical within households. The transmission risk for HA-MRSA was 39% compared with 40% (P=.95) for community-associated MRSA. HA-MRSA index cases were more likely to be older and not practice infection control measures (P=.002–.03). Household acquisition risk factors included requiring assistance and sharing bath towels (P=.001–.03). Environmental contamination was identified in 78 (79%) of 99 households and was more common in HA-MRSA households.
Household transmission of community-associated and HA-MRSA strains was common and the difference in transmission risk was not statistically significant.
We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array’s performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.
Carbapenem-resistant Acinetobacter baumannii (CRAB) with diverse multilocus sequence typing emerged among our nursing home residents (6.5%) with a high background rate of MRSA (32.2%). Rectal swabs yielded a higher rate of CRAB detection than axillary or nasal swabs. Bed-bound status, use of adult diapers, and nasogastric tube were risk factors for CRAB colonization.
This paper describes the system architecture of a newly constructed radio telescope – the Boolardy engineering test array, which is a prototype of the Australian square kilometre array pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a six-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least nine dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.
Immunoglobulin G4 related disease is a rare condition. Cases involving the sinonasal region are exceptionally uncommon. This paper describes a case of immunoglobulin G4 related disease isolated solely to the nasal cavity.
Case report and literature review.
A 34-year-old man presented with painless, progressive bilateral nasal obstruction. Clinical examination and imaging findings demonstrated bilateral submucosal swelling of the anterior septum and right external nasal wall. Biopsy revealed immunoglobulin G4 related disease. The patient responded to oral corticosteroids initially, followed by long-term methotrexate.
To the best of our knowledge, this case represents the first report in the literature of immunoglobulin G4 related disease isolated solely to the nasal cavity.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.
On 2011 July 14, a transient X-ray source, Swift J1822.3–1606, was detected by Swift BAT via its burst activities. It was subsequently identified as a new magnetar upon the detection of a pulse period of 8.4 s. Using follow-up RXTE, Swift, and Chandra observations, we have determined a spin-down rate of Ṗ ~ 3 × 10−13, implying a dipole magnetic field of ~ 5 × 1013 G, second lowest among known magnetars, although our timing solution is contaminated by timing noise. The post-outburst flux evolution is well modelled by surface cooling resulting from heat injection in the outer crust, although we cannot rule out other models. We measure an absorption column density similar to that of the open cluster M17 at 10′ away, arguing for a comparable distance of ~1.6 kpc. If confirmed, this could be the nearest known magnetar.
This study aimed to determine whether patients with post-traumatic stress disorder (PTSD) show difficulty in recruitment of the regions of the frontal and parietal cortex implicated in top-down attentional control in the presence and absence of emotional distracters.
Unmedicated individuals with PTSD (n = 14), and age-, IQ- and gender-matched individuals exposed to trauma (n = 15) and healthy controls (n = 19) were tested on the affective number Stroop task. In addition, blood oxygen level-dependent responses, as measured via functional magnetic resonance imaging, were recorded.
Patients with PTSD showed disrupted recruitment of lateral regions of the superior and inferior frontal cortex as well as the parietal cortex in the presence of negative distracters. Trauma-comparison individuals showed indications of a heightened ability to recruit fronto-parietal regions implicated in top-down attentional control across distracter conditions.
These results are consistent with suggestions that emotional responsiveness can interfere with the recruitment of regions implicated in top-down attentional control; the heightened emotional responding of patients with PTSD may lead to the heightened interference in the recruitment of these regions.
Nanoscale superlattice-like (SLL) dielectric was employed to reduce the power consumption of the Phase-change random access memory (PCRAM) cells. In this study, we have simulated and found that the cells with the SLL dielectric have a higher peak temperature compared to that of the cells with the SiO2 dielectric after constant pulse activation, due to the interface scattering mechanism. Scaling of the SLL dielectric has resulted in higher peak temperatures, which can be even higher after material/structural modifications. Furthermore, the SLL dielectric has good material properties that enable the cells to have high endurance. This shows the effectiveness of the SLL dielectric for advanced memory applications.
We report a 9-year-old girl with 3 Mb interstitial deletion of chromosome 15q24 identified by oligonucleotide array comparative hybridization. She is of Chinese ancestry and shared some typical features of previously reported 15q24 deletion cases such as mild dysmorphism with developmental and speech delay. She also had mild hearing loss that was reported in one other case. We compared all 19 cases that are identified from array-CGH. The deletion occurred within an 8.3 Mb region from 15q23 to 15q24.3. The minimum overlapping deleted region is less than 0.5 Mb from 72.3 Mb to 72.7 Mb. The functions of the nine annotated genes within the region and how they might contribute to the microdeletion phenotype are discussed.
The present study assessed the relationship between breakfast frequency and measures of obesity in Hong Kong Chinese children aged 9–18 years. A total of 11 570 children (50 % boys) underwent anthropometric measurements and completed a simple self-administered dietary behaviour questionnaire. Their parents completed a questionnaire providing demographic information. Breakfast frequency was assessed by a single question, ‘How many days over the past week did you have breakfast?’ Children were categorised into three groups: skippers (ate breakfast 0–2 times/week); semi-skippers (ate breakfast 3–4 times/week); non-skippers (ate breakfast 5–7 times/week), to assess all associated characteristics. Of the 3644 primary and 7926 secondary school students, 8 % (8·7 % of boys and 6·9 % of girls) and 14 % (14 % of boys and 15 % of girls), respectively, were breakfast skippers. The prevalence of obesity among breakfast skippers, semi-skippers and non-skippers was, respectively, 9·8, 10·6 and 3·8 % (P < 0·001) for primary school students and 3·9, 3·1 and 2·4 % (P < 0·001) for secondary school students. The 12 % of Hong Kong children aged 9–18 years who skipped breakfast had higher BMI, BMI z-scores and percentage of body fat (PBF) than their counterparts. The dose effects of breakfast frequency (unstandardised regression coefficient, P < 0·001) on BMI and PBF were, respectively, − 0·125 kg/m2 and − 0·219 % for boys and − 0·165 kg/m2 and − 0·353 % for girls, adjusting for physical activity per additional breakfast meal per week. Further study is recommended to elucidate whether regular breakfast consumption may have a role in the prevention of childhood obesity.
A review is given on insulators (oxides and nitrides) which have been deposited on GaN to form metal-insulator (oxides and nitrides)-semiconductor (MOS or MIS) diodes with a low interfacial density of states (Dit). These insulators include AlN, SiO2, Si3N4, SiO2/Ga2O3, and Ga2O3(Gd2O3). Techniques for depositing these insulators and methods for cleaning GaN surfaces prior to the insulator deposition are discussed. Recent progress on GaN MOSFET's (with SiO2/Ga2O3, and Ga2O3(Gd2O3) as gate dielectrics) and MISFET's (with AlN as a gate dielectric) is also reviewed. When exposed to room air, GaN surface is not as robust as previously thought. Therefore, preparation of a clean GaN surface for deposition of oxides and nitrides is necessary to achieve a low Dit. By heating GaN samples in UHV to clean the surfaces followed by deposition of Ga2O3(Gd2O3) and SiO2, we have achieved a low Dit with negligible hysteretic loops in the capacitance-voltage curves
Results are presented for 850°C oxygen annealing experiments (up to 62 hr) on the 2122 (Tl:Ca:Ba:Cu) oxide phase, with and without intermediate grinding. Samples were characterized by powder X-ray diffraction and a.c. magnetic susceptibility. The 2122 phase appears to be thermodynamically stable in oxygen under conditions of both extensive grinding, and, annealing of long duration. However, onset Tc's vary from 71 K to 109 K for apparently single-phase 2122 samples with nearly identical X-ray powder patterns, depending upon the heat treatment.
Spectra of the oxygen K-edge extended x-ray absorption fine structure (EXAFS) of the superconducting compound Y-Ba-Cu-O were obtained by measuring the total electron yield as a function of incident x-ray energy at temperatures between 77K and 300K. This technique affords a convenient way for probing the local environment around the oxygen atoms and soft modes in the lattice.