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We examined the epidemiology of invasive meningococcal disease (IMD) in the Republic of Ireland (ROI) between epidemiological year (EY) 1996/1997 and EY2015/2016. Over the 20 EYs, 3707 cases were reported with annual incidence rates per 100 000 peaking at 11.6 in EY1999/2000, decreasing significantly to 1.5 in EY2015/2016. The highest disease burden was in infants and children <5, whereas adults aged ⩾65 years experienced the highest case fatality ratio (CFR) of 15.7% but over the study period the median annual CFR remained low (4.4%). Meningococcal serogroup B (menB) dominated (78%), followed by menC (17%), menW (1%) and menY (1%). The incidence of menC IMD declined significantly in all age groups after menC vaccine introduction in 2000. MenB incidence also declined over the 20 EYs with decreasing trends in all age groups under 65, including an almost 50% decrease in infants over the final four EYs. IMD incidence in the ROI has declined, partly attributable to menC vaccination success, coupled with a spontaneous decline in menB. However, recent gradual increases in non-menB IMD and the introduction of vaccines targeting menB demand continued detailed surveillance to accurately monitor trends and to assess vaccine impact.
Molecular characterization of pediatric low-grade glioma (pLGG) over the last decade has identified recurrent alterations, most commonly involving BRAF, and less frequently other pathways including MYB and MYBL1. Many of these molecular markers have been exploited clinically to aid in diagnosis and treatment decisions. However, their frequency and prognostic significance remain unknown. Further, a significant portion of cases do not have any of these alterations and what underlies these cases remains unknown. To address this we compiled a cohort of 562 patients diagnosed at SickKids from 1990-2017. We identified molecular alterations in 454 cases (81% of the cohort). The most frequent events were those involving BRAF; either as fusions (most commonly with KIAA1549 (30%)) or V600E mutations (17%) and NF-1 (22%). Less frequently, we identified recurrent FGFR1 fusions and mutations (3%), MYB/MYBL alterations (2%), H3F3AK27M (2%) or IDH1R132H (0.5%) mutations, as well as other novel rare events. Survival analysis revealed significantly better progression-free survival (PFS) and overall survival (OS) of KIAA1549-BRAF fused patients compared to BRAFV600E with 10-year OS 97.7% (95%, CI 95.5-100) and 83.9% (95%, CI 72.5-95.6), respectively. In addition to survival, molecular alterations predicted differences in response to conventional therapeutics; BRAF fused patients showed a 46% response-rate, versus only 14% in V600E patients. pLGGs harboring H3F3AK27M progressed early with median PFS of 11 months. In patients with MYB/MYBL1, FGFR1/FGFR2 alterations, we observed only one death (FGFR1N546K case). The work here represents the largest cohort of pLGGs with molecular profiling and their impact on the clinical behaviour of the disease.
Silicified beyrichiocopid and podocopid ostracods from limestone nodules derived from the middle part of the Ichinotani Formation within the Hida Gaien Terrane of central Honshu Island, Japan, are associated with fusulinid foraminifera that indicate strata of the middle Moscovian (Pennsylvanian, Carboniferous). This is a rare record of ostracods from the Palaeozoic of Japan and the first systematic description of ostracods from the Carboniferous of the Hida Gaien Terrane. The fauna comprises six ostracod species (two new) assigned to the genera Amphissites, Kirkbya, Bairdia, Aechmina and Healdia, and additional material of possible cavellinids. The numerical dominance of ornamented beyrichiocopids such as Kirkbya and Amphissites, along with smaller numbers of smooth podocopids such as Bairdia, indicates an ‘Eifelian mega-assemblage’ ecotype (sensu G. Becker), that is typical of mid Palaeozoic shallow marine, high-energy environments in a fore-reef ecosystem.
Approximately half of the variation in wellbeing measures overlaps with variation in personality traits. Studies of non-human primate pedigrees and human twins suggest that this is due to common genetic influences. We tested whether personality polygenic scores for the NEO Five-Factor Inventory (NEO-FFI) domains and for item response theory (IRT) derived extraversion and neuroticism scores predict variance in wellbeing measures. Polygenic scores were based on published genome-wide association (GWA) results in over 17,000 individuals for the NEO-FFI and in over 63,000 for the IRT extraversion and neuroticism traits. The NEO-FFI polygenic scores were used to predict life satisfaction in 7 cohorts, positive affect in 12 cohorts, and general wellbeing in 1 cohort (maximal N = 46,508). Meta-analysis of these results showed no significant association between NEO-FFI personality polygenic scores and the wellbeing measures. IRT extraversion and neuroticism polygenic scores were used to predict life satisfaction and positive affect in almost 37,000 individuals from UK Biobank. Significant positive associations (effect sizes <0.05%) were observed between the extraversion polygenic score and wellbeing measures, and a negative association was observed between the polygenic neuroticism score and life satisfaction. Furthermore, using GWA data, genetic correlations of -0.49 and -0.55 were estimated between neuroticism with life satisfaction and positive affect, respectively. The moderate genetic correlation between neuroticism and wellbeing is in line with twin research showing that genetic influences on wellbeing are also shared with other independent personality domains.
We have analyzed a sample of 1150 type ab, and 550 type c RR Lyrae stars found in 24 of 94 bulge fields of the MACHO database. These fields cover a range in Galactocentric distances from 0.3 to 1.6 kpc. In combination with the data on the outer bulge fields of Alard (1997) and Wesselink (1987), here we present the surface density distribution of bulge RR Lyrae between 0.3 and 3 kpc.
We discuss GHRS spectra of single and binary late-type stars and describe in detail the spectra of α TrA and of ζ Aurigae obtained at ten orbital phases. The wind properties of α TrA are derived using a complete redistribution radiative transfer code, and we describe the properties of a new code, PRISMA, that we are building to fit line profiles using partial redistribution in a spherically-symmetric geometry. The ζ Aur spectra show that the mass loss process is variable on the timescale of several months, the wind density structure does not repeat from orbit to orbit, and the wind ionization structure is complex.
The MACHO microlensing experiment's time-sampled photometry database contains blue and red lightcurves for nearly 9 million stars in the central bar region of the Large Magellanic Cloud (LMC). We have identified known LMC Planetary Nebulae (PN) in the database and find one, Jacoby 5, to be variable. We additionally present data on the “parent populations” of LMC PN, and discuss the star formation history of the LMC bar.
A review of the properties of Type II Cepheids and RV Tauri stars in the Magellanic Clouds is presented. In the behaviour of their light and colour curves, the RV Tauri stars appear to be a direct extension of the Type II Cepheids to longer periods. A single P – L – C relationship describes both the Type II Cepheids and RV Tauri stars in the LMC. The derived high intrinsic magnitudes for the RV Tauri variables supports the proposition that these objects are luminous stars evolving off the AGB. Preliminary analysis of the long time-series MACHO photometry indicates one star (MACHO*05:37:45.0–69:54:16) has an obvious ‘period-quadrupled’ periodicity, which is supporting evidence for a period-doubling bifurcation transition to chaotic pulsations.
We present the first results of the analysis of 22 Blazhko stars. We find: 1) Blazhko RRab stars that are nearly pure amplitude modulators; 2) Blazhko RRab stars that have both amplitude and phase modulation; 3) A Blazhko RRab star that has an abrupt period change; 4) Proof of the Blazhko effect in RRc stars. Our data show the character of the amplitude and phase modulations of the light curves over the Blazhko cycles far better than has been previously possible.
We present the preliminary results of a frequency analysis of 1457 fundamental mode RR Lyrae (RR0) stars in the Large Magellanic Cloud (LMC) from MACHO Project photometry. We find the same classes of pulsational behavior as were found in our earlier survey of first overtone RR Lyrae (RR1) stars. Variables whose prewhitened power spectra contain one or two peaks close to the main frequency component in the original power spectra are commonly known as Blazhko-type variables. The present analysis shows the overall frequency of Blazhko-type stars in the total RR0 population analysed to date to be ≈ 10%. This is lower than the often cited Galactic field/globular rate of 20-30% (Szeidl, 1988).
The incidence rate of Blazhko-type variability in the LMC appears to be about three times higher in RR0 stars than in RR1 stars. This puts important constraints on possible models of the Blazhko effect.
We present the first massive frequency analysis of the 1200 first overtone RR Lyrae stars in the Large Magellanic Cloud observed in the first 4.3 yr of the MACHO project. Besides the many new double-mode variables, we also discovered stars with closely spaced frequencies. These variables are most probably nonradial pulsators.
The Cosmic Background Explorer, launched November 18, 1989, has nearly completed its first full mapping of the sky with all three of its instruments: a Far Infrared Absolute Spectrophotometer (FIRAS) covering 0.1 to 10 mm, a set of Differential Microwave Radiometers (DMR) operating at 3.3, 5.7, and 9.6 mm, and a Diffuse Infrared Background Experiment (DIRBE) spanning 1 to 300 µm in ten bands. A preliminary map of the sky derived from DIRBE data is presented. Initial cosmological implications include: a limit on the Comptonization y parameter of 10−3, on the chemical potential μ parameter of 10−2, a strong limit on the existence of a hot smooth intergalactic medium, and a confirmation that the dipole anisotropy has the spectrum expected from a Doppler shift of a blackbody. There are no significant anisotropies in the microwave sky detected, other than from our own galaxy and a cosθ dipole anisotropy whose amplitude and direction agree with previous data. At shorter wavelengths, the sky spectrum and anisotropies are dominated by emission from ‘local’ sources of emission within our Galaxy and Solar System. Preliminary comparison of IRAS and DIRBE sky brightnesses toward the ecliptic poles shows the IRAS values to be significantly higher than found by DIRBE at 100 μm. We suggest the presence of gain and zero-point errors in the IRAS total brightness data. The spacecraft, instrument designs, and data reduction methods are described.
Major depressive disorder (MDD) is moderately heritable, however genome-wide association studies (GWAS) for MDD, as well as for related continuous outcomes, have not shown consistent results. Attempts to elucidate the genetic basis of MDD may be hindered by heterogeneity in diagnosis. The Center for Epidemiological Studies Depression (CES-D) scale provides a widely used tool for measuring depressive symptoms clustered in four different domains which can be combined together into a total score but also can be analysed as separate symptom domains.
We performed a meta-analysis of GWAS of the CES-D symptom clusters. We recruited 12 cohorts with the 20- or 10-item CES-D scale (32 528 persons).
One single nucleotide polymorphism (SNP), rs713224, located near the brain-expressed melatonin receptor (MTNR1A) gene, was associated with the somatic complaints domain of depression symptoms, with borderline genome-wide significance (pdiscovery = 3.82 × 10−8). The SNP was analysed in an additional five cohorts comprising the replication sample (6813 persons). However, the association was not consistent among the replication sample (pdiscovery+replication = 1.10 × 10−6) with evidence of heterogeneity.
Despite the effort to harmonize the phenotypes across cohorts and participants, our study is still underpowered to detect consistent association for depression, even by means of symptom classification. On the contrary, the SNP-based heritability and co-heritability estimation results suggest that a very minor part of the variation could be captured by GWAS, explaining the reason of sparse findings.
Objectives: Clinical neuroscience is increasingly turning to imaging the human brain for answers to a range of questions and challenges. To date, the majority of studies have focused on the neural basis of current psychiatric symptoms, which can facilitate the identification of neurobiological markers for diagnosis. However, the increasing availability and feasibility of using imaging modalities, such as diffusion imaging and resting-state fMRI, enable longitudinal mapping of brain development. This shift in the field is opening the possibility of identifying predictive markers of risk or prognosis, and also represents a critical missing element for efforts to promote personalized or individualized medicine in psychiatry (i.e., stratified psychiatry). Methods: The present work provides a selective review of potentially high-yield populations for longitudinal examination with MRI, based upon our understanding of risk from epidemiologic studies and initial MRI findings. Results: Our discussion is organized into three topic areas: (1) practical considerations for establishing temporal precedence in psychiatric research; (2) readiness of the field for conducting longitudinal MRI, particularly for neurodevelopmental questions; and (3) illustrations of high-yield populations and time windows for examination that can be used to rapidly generate meaningful and useful data. Particular emphasis is placed on the implementation of time-appropriate, developmentally informed longitudinal designs, capable of facilitating the identification of biomarkers predictive of risk and prognosis. Conclusions: Strategic longitudinal examination of the brain at-risk has the potential to bring the concepts of early intervention and prevention to psychiatry. (JINS, 2016, 22, 164–179)
A fourth season of work was carried out in the Spring of 1984. The centrepiece of the programme was the investigation of the well-preserved farm in the Wadi el-Amud (Lamout). The main farm buildings were excavated, faunal and botanical samples were collected systematically from within and between them, the field systems and sluices were examined in detail and investigations begun on the geomorphological and hydrological context. This report presents the basic description of the archaeological data resulting from excavation and survey; a second report will present the results of the various laboratory studies which were generated by the field work.
Diverse strain types of methicillin-resistant Staphylococcus aureus (MRSA) cause infections in community settings worldwide. To examine heterogeneity of spread within households and to identify common risk factors for household transmission across settings, primary data from studies conducted in New York (USA), Breda (The Netherlands), and Melbourne (Australia) were pooled. Following MRSA infection of the index patient, household members completed questionnaires and provided nasal swabs. Swabs positive for S. aureus were genotyped by spa sequencing. Poisson regression with robust error variance was used to estimate prevalence odds ratios for transmission of the clinical isolate to non-index household members. Great diversity of strain types existed across studies. Despite differences between studies, the index patient being colonized with the clinical isolate at the home visit (P < 0·01) and the percent of household members aged <18 years (P < 0·01) were independently associated with transmission. Targeted decolonization strategies could be used across geographical settings to limit household MRSA transmission.