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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.
Stocks that hedge sustained market downturns should have low expected returns, but they do not. We use ex ante firm characteristics and covariances to construct a tradable safe minus risky (SMR) portfolio that hedges market downturns out of sample. Although downturns (peaks to troughs in market index levels at the business-cycle frequency) predict significant declines in gross domestic product growth, SMR has significant positive average returns and 4-factor alphas (both around 0.8% per month). Risk-based models do not explain SMR’s returns, but mispricing does. Risky stocks are overpriced when sentiment is high, resulting in subsequent returns of -0.9% per month.
In this prospective study, we monitored 4 epidemiologically important pathogens (EIPs): methicillin-resistane Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), Clostridium difficile, and multidrug-resistant (MDR) Acinetobacter to assess the effectiveness of 3 enhanced disinfection strategies for terminal room disinfection against standard practice. Our data demonstrated that a decrease in room contamination with EIPs of 94% was associated with a 35% decrease in subsequent patient colonization and/or infection.
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.
Background: Depression and anxiety are the two most frequently studied emotional outcomes of stroke. However, few previous studies have been carried out at a population level or beyond 6 months post stroke. The aim of this study was to describe depression and anxiety across the first year following incident ischemic stroke (IS), and identify predictive factors in a population-based study.
Method: The Hospital Anxiety Depression Scale (HADS) was administered at baseline (within 2 weeks of onset), and again at 1-month, 6-months and 12-months after IS in a sample (N = 365) drawn from a population-based study.
Results: Over 75% of those assessed experienced depression or anxiety symptoms below cut-offs for probable disorder across the year post stroke. Moderate to severe symptoms for anxiety were approximately twice as likely (range 4.1%–10.6%) as compared to depression (range 2.5%–5.0%) at each assessment. The greatest improvement in anxiety occurred within the first month post stroke. In contrast, the greatest reduction in depression occurred between 1- to 6-months post stroke.
Conclusions: Anxiety symptoms in the moderate to severe range were twice as common as depression, and improved over the first month post stroke, whilst depression symptoms persisted for up to 6 months, indicating a need to target these two issues at different points in the recovery process.
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.
Background: Neuropsychological deficits occur in over half of the stroke survivors and are associated with the reduced functioning and a decline in quality of life. However, the trajectory of recovery and predictors of neuropsychological outcomes over the first year post stroke are poorly understood.
Method: Neuropsychological performance, assessed using the CNS-Vital signs, was examined at 1 month, 6 months and 12 months after ischaemic stroke (IS) in a sample drawn from a population-based study (N = 198).
Results: While mean scores across neuropsychological domains at each time-point fell in the average range, one in five individuals produced very low-range scores for verbal memory, attention and psychomotor speed. Significant improvements were seen for executive functioning, psychomotor speed and cognitive flexibility within 6 months post stroke, but no gains were noted from 6 to 12 months. Stroke-related neurological deficits and depression at baseline significantly contributed to the prediction of neuropsychological function at 12 month follow-up.
Conclusions: In a significant minority of IS survivors, focal deficits are evident in psychomotor speed, verbal memory, executive functions and attention. Significant improvements in these domains were only evident in the first 6 months post stroke. Initial stroke-related neurological deficits and concurrent depression may be the best predictors of later cognitive functioning.
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.
Objectives: Evaluate the association between pediatric sleep-disordered breathing (SDB) and executive functioning. Methods: We searched multiple electronic databases for peer-reviewed journal articles related to pediatric SDB and executive functioning. We included studies that assessed SDB via polysomnography, included objective or questionnaire measures of executive function, and had an age-matched control group. Fourteen articles met inclusion criteria with a total sample of 1697 children ages 5 to 17 years (M=9.81 years; SD=0.34). We calculated an overall effect size for each of the five executive domains (vigilance, inhibition, working memory, shifting, and generativity) as well as effect sizes according to SDB severity: mild, moderate, severe. We also calculated effect sizes separately for objective and subjective questionnaires of executive functioning. Results: We found a medium effect size (−0.427) for just one of five executive function domains on objective neuropsychological measures (generativity). In contrast, effect sizes on all three executive domains measured via questionnaire data were significant, with effect sizes ranging from medium (−0.64) to large (−1.06). We found no difference between executive domains by severity of SDB. Conclusions: This meta-analysis of executive function separated into five domains in pediatric SDB suggested lower performance in generativity on objective neuropsychological measures. There were no differences associated with SDB severity. Questionnaire data suggested dysfunction across the three executive domains measured (inhibition, working memory, shifting). Overall, limited evidence suggested poorer performance in executive function in children with SDB according to objective testing, and subjective ratings of executive function suggested additional worsened performance. (JINS, 2016, 22, 839–850)
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)
We present the first statistical analysis of the exoplanet frequency using planets found by a microlensing survey rather than follow-up observations. We present an analysis of 2007-2012 MOA (Microlensing Observations in Astrophysics) survey data to derive the planet frequency as a function of the planet/star mass ratio, q and separation, s, relative to the Einstein radius. Our sample includes 1472 microlensing events, including 22 planetary events and 1 ambiguous event with possible planetary and stellar binary solutions. The detection efficiency is calculated for each event and we employ a Bayesian analysis to deal with the ambiguous event. A broken power law model is used to fit the mass ratio function and we find a break and likely peak at q ~1.0−4.
Introduced accidentally from South America, deeproot sedge is rapidly expanding in a variety of habitats throughout the southeastern United States. Of particular concern is its rapid expansion, naturalization, and formation of monocultures in Texas coastal prairie, one of the most imperiled temperate ecoregions in North America. The objective of this research was to examine how deeproot sedge responds to prescribed fire, to the herbicide imazapic, and to treatment combinations of both. Combinations of prescribed fire and imazapic treatments and imazapic-only treatments effectively reduced deeproot sedge cover and frequency. However, plots exposed to dormant season fires (with no imazapic) had greater deeproot sedge cover after burn treatments were applied, indicating that coastal prairie management using only dormant season prescribed fire will not work toward reduction or management of this exotic invasive species. Although deeproot sedge cover was often reduced in fire–imazapic treatment combinations, it was still present in treatment plots. Moreover, desirable functional plant groups (i.e., native bunchgrasses) did not respond positively to the fire–imazapic treatments, but in some instances, woody plant coverage increased. Repeated, long-term approaches using integrated and coordinated efforts with multiple treatment options will be necessary to restore community structure to desired compositional levels. Such integrated approaches should be effective in reducing deeproot sedge frequency, cover, and extent to more manageable levels throughout its introduced geographic range.