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Epigenetic modifications, such as DNA methylation, are enzymatically regulated processes that directly impact gene expression patterns. In early life, they are central to developmental programming and have also been implicated in regulating inflammatory responses. Research into the role of epigenetics in neonatal health is limited, but there is a growing body of literature related to the role of DNA methylation patterns and diseases of prematurity, such as the intestinal disease necrotizing enterocolitis (NEC). NEC is a severe intestinal inflammatory disease, but the key factors that precede disease development remain to be determined. This knowledge gap has led to a failure to design effective targeted therapies and identify specific biomarkers of disease. Recent literature has identified altered DNA methylation patterns in the stool and intestinal tissue of neonates with NEC. These findings provide the foundation for a new avenue in NEC research. In this review, we will provide a general overview of DNA methylation and then specifically discuss the recent literature related to methylation patterns in neonates with NEC. We will also discuss how DNA methylation is used as a biomarker for other disease states and how, with further research, methylation patterns may serve as potential biomarkers for NEC.
While paediatric arteriovenous malformations (AVMs) often require aggressive therapeutic intervention due to their high bleeding incidence, choosing a course of treatment for deep and eloquent areas and asymptomatic cases is difficult. Sequelae are a concern in children, as they survive for longer after treatment. The authors have long recommended and implemented staged Gamma Knife radiosurgery (GKRS) in their treatment guidelines to maximise therapeutic effects.
Methods:
Fifty-eight paediatric patients with AVM and ≤15 years old who underwent GKRS under general anesthesia from 2002 to 2020 were followed up for an average of 81·5 months. Obliteration dynamics and clinical outcomes were analysed.
Results:
The mean patient age was 10·5 years. The mean nidus volume was 6·6 cm3, the complete occlusion rate was 69%, the annual post-irradiation bleeding rate was 2·19% and nine (16%) cases had transient radiation-induced changes. One (1·7%) patient had sequela, and three (5·1%) developed encapsulated hematomas and cysts. Additionally, the 3- and 5-year cumulative occlusion rates were 39·0% and 53·3%, respectively. Multivariate analysis showed significantly higher occlusion rates in patients ≤12 years old and with a nidus volume of ≤4 cm3.
Conclusions:
GKRS is a useful treatment for paediatric AVM; however, its use poses some challenges.
The ALMA twenty-six arcmin2 survey of GOODS-S at one millimeter (ASAGAO) is a deep (1σ ∼ 61μJy/beam) and wide area (26 arcmin2) survey on a contiguous field at 1.2 mm. By combining with archival data, we obtained a deeper map in the same region (1σ ∼ 30μJy/beam−1, synthesized beam size 0.59″ × 0.53″), providing the largest sample of sources (25 sources at 5σ, 45 sources at 4.5σ) among ALMA blank-field surveys. The median redshift of the 4.5σ sources is 2.4. The number counts shows that 52% of the extragalactic background light at 1.2 mm is resolved into discrete sources. We create IR luminosity functions (LFs) at z = 1–3, and constrain the faintest luminosity of the LF at 2 < z < 3. The LFs are consistent with previous results based on other ALMA and SCUBA-2 observations, which suggests a positive luminosity evolution and negative density evolution.
Alumina-pillared fluorine micas were prepared from synthetic highly layer-charged expandable fluorine mica and polyhydroxoaluminium solutions under different solution loadings (Al mmol in solutions per 1.0 g mica) in order to clarify the effects of solution loading on thermal durability and microporous properties. The intercalated Al content of the pillared micas increased with increased solution loading. The intercalated Al content (i.e. the pillar density) of the pillared micas influenced both the thermal durability and specific surface areas of the pillared micas. The pillared micas obtained from the high solution loadings showed better thermal durability than those obtained from the low solution loadings. Through micropore formation upon heating, the pillared micas exhibit cation exchangeability due to the liberation of residual Na+ ions from steric hindrance in the interlayer pillaring space. The amount of the exchangeable ions depends on the heating temperature of the pillared micas.
In order to evaluate the long-term behaviour of the engineered barriers in geological disposal sites for transuranic element-bearing (TRU) waste, an evaluation by numerical analysis is required. Although chemical and hydraulic/mechanical analyses have been conducted independently until now, essentially both type of phenomena occur simultaneously and produce synergistic effects. Therefore, we focused attention on the buffer (bentonite) engineered barrier and conducted a study of which involved incorporating hydraulic/mechanical phenomena into the chemical analysis of bentonite alteration. The simulations employed weakly-coupled chemical and hydraulic/mechanical effects to study the behaviour in one dimension.
The results showed that the dissolution of the montmorillonite is suppressed in the buffer section nearest the cement material. Moreover, in order to achieve a fully coupled analysis in future, the present study also identifies issues that need to be resolved.
Amphibole in the Larvik alkaline plutonic complex in the Oslo rift, Norway, has Ti-rich compositions from edenite through pargasite to kaersutite, and has a large H+ deficiency (0.7–1.1 atoms per formula unit: a.p.f.u.) with a large oxy component in the amphibole OH– site (O2– = 2 – (OH + F + Cl) = 0.2–0.9 a.p.f.u.), similar to the mantle-derived kaersutites. Their compositions reveal a characteristically low Fe3+/(Fe3++Fe2+) ratio (<0.23) and a high F concentration (0.3–0.9 a.p.f.u.). Correlation with the Fe3+ ratio caused by Fe2+ + OH– = Fe3+ + O2– + 1/2H2 substitution is negligible, which is supported by H and O isotope compositions. A possible substitution, [6]Al3+ + OH– = [6]Ti4+ + O2– may be operative for Larvik kaersutites when the O2–/Ti is 1.0. A relatively larger O2–/Ti ratio (1.2—2.0) suggests an another kaersutite substitution mechanism, [6]R2+ + 2OH– = [6]Ti4+ + 2O2–, where [6]R2+ = Fe2+ + Mg + Mn. These effects might result in the limited O2–/Ti ratio value from 1.0 to 2.0.
A negative correlation between Ti and F, suggesting F incorporation into kaersutite may diminish the O2–/Ti ratio, not only due to the occupation of this non-oxy species in the O3 site, but also due to F—Ti avoidance. Composition-dependent H and O isotope variations (δD = –106 to –71% and δ18O = 4.6–5.2%) suggest equilibrium in the closed-system magma with differentiation. The mineral chemistry of Larvik oxy-kaersutitic amphibole could reflect the crystallization in a closed-system magma during rifting with passive crustal thinning at the Oslo palaeorift.
We initiated a long-term and highly frequent monitoring project toward 442 methanol masers at 6.7 GHz (Dec >−30 deg) using the Hitachi 32-m radio telescope in December 2012. The observations have been carried out daily, monitoring a spectrum of each source with intervals of 9–10 days. In September 2015, the number of the target sources and intervals were redesigned into 143 and 4–5 days, respectively. This monitoring provides us complete information on how many sources show periodic flux variations in high-mass star-forming regions, which have been detected in 20 sources with periods of 29.5–668 days so far (e.g., Goedhart et al. 2004). We have already obtained new detections of periodic flux variations in 31 methanol sources with periods of 22–409 days. These periodic flux variations must be a unique tool to investigate high-mass protostars themselves and their circumstellar structure on a very tiny spatial scale of 0.1–1 au.
Insufficient nutrition during the perinatal period causes structural alterations in humans and experimental animals, leading to increased vulnerability to diseases in later life. Japanese quail, Coturnix japonica, in which partial (8–10%) egg white was withdrawn (EwW) from eggs before incubation had lower birth weights than controls (CTs). EwW birds also had reduced hatching rates, smaller glomeruli and lower embryo weight. In EwW embryos, the surface condensate area containing mesenchymal cells was larger, suggesting that delayed but active nephrogenesis takes place. In mature EwW quail, the number of glomeruli in the cortical region (mm2) was significantly lower (CT 34.7±1.4, EwW 21.0±1.2); capillary loops showed focal ballooning, and mesangial areas were distinctly expanded. Immunoreactive cell junction proteins, N-cadherin and podocin, and slit diaphragms were clearly seen. With aging, the mesangial area and glomerular size continued to increase and were significantly larger in EwW quail, suggesting compensatory hypertrophy. Furthermore, apoptosis measured by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling analysis was higher in EwWs than in CTs on embryonic day 15 and postnatal day 4 (D4). Similarly, plasma glucocorticoid (corticosterone) was higher (P<0.01) on D4 in EwW quail. These results suggest that although nephrogenic activity is high in low-nutrition quail during the perinatal period, delayed development and increased apoptosis may result in a lower number of mature nephrons. Damaged or incompletely mature mesangium may trigger glomerular injury, leading in later life to nephrosclerosis. The present study shows that birds serve as a model for ‘fetal programming,’ which appears to have evolved phylogenetically early.
Distinctive patterns of growth rings in increment cores from old-growth Douglas-fir (Pseudotsuga menziesii) stands identify A.D. 1800 as a more precise date for the eruption of tephra layer T by Mount St. Helens, Washington. Layer T was previously inferred to date to about A.D. 1802. Growth patterns also establish A.D. 1480 as the date of eruption of the earlier layer Wn, previously estimated as dating to about A.D. 1500. The timing of radial tree growth places a small limitation on the seasonal resolution of these new tree-ring dates.
With few exceptions, today's tidal trees near Washington's Pacific coast postdate an earthquake that lowered the region by 1 m or more. The earthquake, which occurred in A.D. 1700, is the most recent to have ruptured much of the plate boundary at this central part of the Cascadia subduction zone. Because of the coseismic subsidence, lowland forests became tidal flats where thousands of trees died. Most of the trees killed were Sitka spruce (Picea sitchensis). In the centuries since the earthquake, tidal deposits have built new land that has been colonized by new Sitka spruce. All but several tens of the region's tidal spruce consequently postdate 1700, as shown by counts of annual rings in 121 of the largest spruce in tidal forests at Copalis River, Grays Harbor, and Willapa Bay. Forests began to return to each of these estuaries in the early 1700s and spread seaward in the late 1700s and 1800s. Annual rings in the oldest of the trees thus record a large fraction of the earthquake-recurrence interval that began with the 1700 earthquake.
During the past 8 centuries, light rings (LRs) have occasionally formed in black spruce (Picea mariana) at treeline near Bush Lake, northern Quebec (L. Filion, S. Payette, L. Gauthier, and Y. Boutin, 1986, Quaternary Research 26, 272-279; A. Delwaide, L. Filion, and S. Fayette, 1991, Canadian Journal of Forest Research 21, 1828-1832). New analyses of climate data compiled during the period of overlapping tree-ring and instrumental records show that years of LR formation at Bush Lake have unusually cool May, June, August, and September temperatures. The analyses also show that August-September temperatures strongly correlate with May-July temperatures. Thus, late spring and entire growing-season temperatures influence LR formation at subarctic treeline. LRs formed in at least 5% of the trees at Bush Lake when May-September mean temperatures at Inukjuak fell below 4.2°C and August-September mean temperatures fell below 6.7°C. These threshold temperature/LR relationships can be used to infer limiting summer temperatures during the period preceding instrumental records. For example, the LR record suggests that May-September temperatures at northern Quebec treeline dropped below 4.2°C in A.D. 1601 after a major volcanic eruption of unknown source. Visual assessments of LR occurrence provide a new approach for extracting quantitative paleoclimatic information from tree rings.
Public stigma alters attitudes towards people with mental illness, and is a particular concern for young people since most mental health problems occur in adolescence and young adulthood. However, little is known about the long-term effects of repeated filmed social contact (FSC) on reducing mental health-related stigma among young adults in the general population, compared with self-instructional Internet search (INS) and control interventions.
Methods.
This study is a parallel-group randomised controlled trial over 12 months conducted in Tokyo, Japan. A total of 259 university students (male n = 150, mean age = 20.0 years, s.d. = 1.2) were recruited from 20 colleges and universities between November 2013 and July 2014, without being provided information about the mental health-related survey or trial. Participants were assigned to one of three groups before completion of the baseline survey (FSC/INS/control = 89/83/87). The FSC group received a computer-based 30-min social contact film with general mental health education and five follow-up web-based FSCs at 2-month intervals. The INS group undertook a 30-min search for mental health-related information with five follow-up web-based reminders for self-instructional searches at 2-month intervals. The control group played PC games and had no follow-up intervention. The main outcome measures were the future (intended behaviour) domain of the Reported and Intended Behaviour Scale at 12 months after the intervention. Analysis was conducted in September 2015.
Results.
At the 12-month follow-up, 218 participants completed the survey (84.1%, 75:70:73). The FSC group showed the greatest change at the 12-month follow-up (FSC: mean change 2.11 [95% CI 1.49, 2.73], INS: 1.04 [0.29, 1.80], control: 0.71 [0.09, 1.33]; FSC v. INS p = 0.037, FSC v. controls p = 0.004). No adverse events were reported during the follow-up period.
Conclusions.
FSC was more successful in reducing stigma at 12 months after intervention than INS or control interventions. FSC could be used to reduce stigma in educational lectures and anti-stigma campaigns targeted at young people.
Study registration.
This study is registered at UMIN-CTR (No. UMIN000012239).
Little is known about the economic benefits of cognitive remediation and supported employment (CR + SE). The present study aimed to investigate the cost-effectiveness of CR + SE compared with traditional vocational services (TVS).
Method
Individuals with mental illness and low cognitive function were recruited at six sites in Japan. A total of 111 participants were randomly allocated to the CR + SE group or the TVS group. Clinical and vocational outcomes were assessed at baseline and 12-month follow-up. Service utilization data were collected monthly. The data on outcomes and costs were combined to examine cost-effectiveness.
Results
The data were obtained from a total of 92 participants. The CR + SE group resulted in better vocational and clinical outcomes (employment rate, 62.2%; work tenures, 78.6 days; cognitive improvement, 0.5) than the TVS group (19.1%, 24.9 days and 0.2). There was no significant difference in mean total costs between the groups (CR + SE group: $9823, s.d. = $6372, TVS group: $11 063, s.d. = $11 263) with and without adjustment for covariates. However, mean cost for medical services in the CR + SE group was significantly lower than that in the TVS group after adjusting covariates (Β = −$3979, 95% confidence interval −$7816 to −$143, p = 0.042). Cost-effectiveness acceptability curves for vocational outcomes illustrated the high probabilities (approximately 70%) of the CR + SE group being more cost-effective than TVS when society is not willing to pay additional costs.
Conclusions
CR + SE appears to be a cost-effective option for people with mental illness who have low cognitive functioning when compared with TVS.
Pregnancy and calving are elements indispensable for dairy production, but the daily milk yield of cows decline as pregnancy progresses, especially during the late stages. Therefore, the effect of stage of pregnancy on daily milk yield must be clarified to accurately estimate the breeding values and lifetime productivity of cows. To improve the genetic evaluation model for daily milk yield and determine the effect of the timing of pregnancy on productivity, we used a test-day model to assess the effects of stage of pregnancy on variance component estimates, daily milk yields and 305-day milk yield during the first three lactations of Holstein cows. Data were 10 646 333 test-day records for the first lactation; 8 222 661 records for the second; and 5 513 039 records for the third. The data were analyzed within each lactation by using three single-trait random regression animal models: one model that did not account for the stage of pregnancy effect and two models that did. The effect of stage of pregnancy on test-day milk yield was included in the model by applying a regression on days pregnant or fitting a separate lactation curve for each days open (days from calving to pregnancy) class (eight levels). Stage of pregnancy did not affect the heritability estimates of daily milk yield, although the additive genetic and permanent environmental variances in late lactation were decreased by accounting for the stage of pregnancy effect. The effects of days pregnant on daily milk yield during late lactation were larger in the second and third lactations than in the first lactation. The rates of reduction of the 305-day milk yield of cows that conceived fewer than 90 days after the second or third calving were significantly (P<0.05) greater than that after the first calving. Therefore, we conclude that differences between the negative effects of early pregnancy in the first, compared with later, lactations should be included when determining the optimal number of days open to maximize lifetime productivity in dairy cows.
We have conducted 1.1 mm ALMA observations of a contiguous 105” × 50” or 1.5 arcmin2 window in the SXDF-UDS-CANDELS. We achieved a 5σ sensitivity of 0.28 mJy, giving a flat sensus of dusty star-forming galaxies with LIR ~6×1011L⊙ (if Tdust=40K) up to z ~ 10 thanks to the negative K-correction at this wavelength. We detected 5 brightest sources (S/N>6) and 18 low-significant sources (5>S/N>4; they may contain spurious detections, though). One of the 5 brightest ALMA sources (S1.1mm = 0.84 ± 0.09 mJy) is extremely faint in the WFC3 and VLT/HAWK-I images, demonstrating that a contiguous ALMA imaging survey uncovers a faint dust-obscured population invisible in the deep optical/near-infrared surveys. We find a possible [CII]-line emitter at z=5.955 or a low-z CO emitting galaxy within the field, allowing us to constrain the [CII] and/or CO luminosity functions across the history of the universe.