Objective To calculate a reliable estimate of the population prevalence of Down syndrome in the US. Study design The annual number of births of infants with Down syndrome were estimated by applying ...published birth prevalence rates of Down syndrome by maternal age to US data from the Centers for Disease Control and Prevention for the years for which births by maternal age were available (1940-2008). Death certificate data for persons with Down syndrome were available for the years 1968-2007. We estimated the number of people with Down syndrome on January 1, 2008, using a life table approach based on proportions of deaths by age. Monte Carlo sampling was used to create 90% uncertainty intervals (UIs) for our estimates. Results We estimated the January 1, 2008, population prevalence of Down syndrome as approximately 250 700 (90% UI, 185 900-321 700) based on proportions of deaths by age from the most recent 2 years (2006-2007) of death certificate data. This estimate corresponds to a prevalence of 8.27 people with Down syndrome per 10 000 population (90% UI, 6.14-10.62). Conclusion Our estimate of Down syndrome prevalence is roughly 25%-40% lower than estimates based solely on current birth prevalence. The results presented here can be considered a starting point for facilitating policy and services planning for persons with Down syndrome.
Nasal high-flow therapy is an alternative to nasal continuous positive airway pressure (CPAP) as a means of respiratory support for newborn infants. The efficacy of high-flow therapy in nontertiary ...special care nurseries is unknown.
We performed a multicenter, randomized, noninferiority trial involving newborn infants (<24 hours of age; gestational age, ≥31 weeks) in special care nurseries in Australia. Newborn infants with respiratory distress and a birth weight of at least 1200 g were assigned to treatment with either high-flow therapy or CPAP. The primary outcome was treatment failure within 72 hours after randomization. Infants in whom high-flow therapy failed could receive CPAP. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome, with a noninferiority margin of 10 percentage points.
A total of 754 infants (mean gestational age, 36.9 weeks, and mean birth weight, 2909 g) were included in the primary intention-to-treat analysis. Treatment failure occurred in 78 of 381 infants (20.5%) in the high-flow group and in 38 of 373 infants (10.2%) in the CPAP group (risk difference, 10.3 percentage points; 95% confidence interval CI, 5.2 to 15.4). In a secondary per-protocol analysis, treatment failure occurred in 49 of 339 infants (14.5%) in the high-flow group and in 27 of 338 infants (8.0%) in the CPAP group (risk difference, 6.5 percentage points; 95% CI, 1.7 to 11.2). The incidences of mechanical ventilation, transfer to a tertiary neonatal intensive care unit, and adverse events did not differ significantly between the groups.
Nasal high-flow therapy was not shown to be noninferior to CPAP and resulted in a significantly higher incidence of treatment failure than CPAP when used in nontertiary special care nurseries as early respiratory support for newborn infants with respiratory distress. (Funded by the Australian National Health and Medical Research Council and Monash University; HUNTER Australian and New Zealand Clinical Trials Registry number, ACTRN12614001203640.).
Summary
Background
Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the ...patterns of usage are incompletely defined.
Objectives
To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic‐naïve and non‐naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR).
Methods
The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time–trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined.
Results
In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic‐naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic.
Conclusions
More than one‐third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real‐world observational studies.
What's already known about this topic?
Published evidence concerning the utilization patterns of biologic therapies for psoriasis, including dosing, switching, discontinuation and restarts is limited to biologic‐naïve patients.
Furthermore, the ability to determine the patterns of concomitant use of conventional systemic therapies with biologic therapies is confined to a few small‐scale studies.
What does this study add?
Based on a cohort of 2980 patients receiving biologic therapies for psoriasis, 33·7% of patients experienced treatment modifications during their first year of treatment.
There were no significant differences between biologic‐naïve and non‐naïve patients in the proportions of patients who switched, discontinued or restarted therapy.
Conventional systemic therapies, particularly methotrexate, were commonly used concurrently with biologics.
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The nucleus of the Jupiter-family comet 19P/Borrelly was closely observed by the Miniature Integrated Camera and Spectrometer aboard the Deep Space 1 spacecraft on 22 September 2001. The ...8-kilometer-long body is highly variegated on a scale of 200 meters, exhibiting large albedo variations (0.01 to 0.03) and complex geologic relationships. Short-wavelength infrared spectra (1.3 to 2.6 micrometers) show a slope toward the red and a hot, dry surface (≤345 kelvin, with no trace of water ice or hydrated minerals), consistent with ∼10% or less of the surface actively sublimating. Borrelly's coma exhibits two types of dust features: fans and highly collimated jets. At encounter, the near-nucleus coma was dominated by a prominent dust jet that resolved into at least three smaller jets emanating from a broad basin in the middle of the nucleus. Because the major dust jet remained fixed in orientation, it is evidently aligned near the rotation axis of the nucleus.
To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and ...114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
•Time-averaged small world measures in fMRI do not yield consistent results.•Entropy of small world dynamics is a robust predictor of levels of awareness.•Network dynamics have predictive power ...beyond functional connectivity dynamics.•Subcortical dynamics have more predictive power than cortical dynamics.•Participation coefficient dynamics are independently predictive in the cerebellum.
Small world topologies are thought to provide a valuable insight into human brain organisation and consciousness. However, functional magnetic resonance imaging studies in consciousness have not yielded consistent results. Given the importance of dynamics for both consciousness and cognition, here we investigate how the diversity of small world dynamics (quantified by sample entropy; dSW-E11dSW-E= dynamic small world entropy) scales with decreasing levels of awareness (i.e., sedation and disorders of consciousness). Paying particular attention to result reproducibility, we show that dSW-E is a consistent predictor of levels of awareness even when controlling for the underlying functional connectivity dynamics. We find that dSW-E of subcortical, and cortical areas are predictive, with the former showing higher and more robust effect sizes across analyses. We find that the network dynamics of intermodular communication in the cerebellum also have unique predictive power for levels of awareness. Consequently, we propose that the dynamic reorganisation of the functional information architecture, in particular of the subcortex, is a characteristic that emerges with awareness and has explanatory power beyond that of the complexity of dynamic functional connectivity.
A molecular phylogeny and a review of family-group classification are presented for 137 species (ca. 125 genera) of the insect family Cicadidae, the true cicadas, plus two species of hairy cicadas ...(Tettigarctidae) and two outgroup species from Cercopidae. Five genes, two of them mitochondrial, comprise the 4992 base-pair molecular dataset. Maximum-likelihood and Bayesian phylogenetic results are shown, including analyses to address potential base composition bias. Tettigarcta is confirmed as the sister-clade of the Cicadidae and support is found for three subfamilies identified in an earlier morphological cladistic analysis. A set of paraphyletic deep-level clades formed by African genera are together named as Tettigomyiinae n. stat. Taxonomic reassignments of genera and tribes are made where morphological examination confirms incorrect placements suggested by the molecular tree, and 11 new tribes are defined (Arenopsaltriini n. tribe, Durangonini n. tribe, Katoini n. tribe, Lacetasini n. tribe, Macrotristriini n. tribe, Malagasiini n. tribe, Nelcyndanini n. tribe, Pagiphorini n. tribe, Pictilini n. tribe, Psaltodini n. tribe, and Selymbriini n. tribe). Tribe Tacuini n. syn. is synonymized with Cryptotympanini, and Tryellina n. syn. is synonymized with an expanded Tribe Lamotialnini. Tribe Hyantiini n. syn. is synonymized with Fidicinini. Tribe Sinosenini is transferred to Cicadinae from Cicadettinae, Cicadatrini is moved to Cicadettinae from Cicadinae, and Ydiellini and Tettigomyiini are transferred to Tettigomyiinae n. stat from Cicadettinae. While the subfamily Cicadinae, historically defined by the presence of timbal covers, is weakly supported in the molecular tree, high taxonomic rank is not supported for several earlier clades based on unique morphology associated with sound production.
Genomic sequencing is no longer a novelty, but gene function annotation remains a key challenge in modern biology. A variety of functional genomics experimental techniques are available, from classic ...methods such as affinity precipitation to advanced high-throughput techniques such as gene expression microarrays. In the future, more disparate methods will be developed, further increasing the need for integrated computational analysis of data generated by these studies. We address this problem with Magic (Multisource Association of Genes by Integration of Clusters), a general framework that uses formal Bayesian reasoning to integrate heterogeneous types of high-throughput biological data (such as large-scale two-hybrid screens and multiple microarray analyses) for accurate gene function prediction. The system formally incorporates expert knowledge about relative accuracies of data sources to combine them within a normative framework. Magic provides a belief level with its output that allows the user to vary the stringency of predictions. We applied Magic to Saccharomyces cerevisiae genetic and physical interactions, microarray, and transcription factor binding sites data and assessed the biological relevance of gene groupings using Gene Ontology annotations produced by the Saccaromyces Genome Database. We found that by creating functional groupings based on heterogeneous data types, Magic improved accuracy of the groupings compared with microarray analysis alone. We describe several of the biological gene groupings identified.
The Juno Microwave Radiometer (MWR) is a six-frequency scientific instrument designed and built to investigate the deep atmosphere of Jupiter. It is one of a suite of instruments on NASA’s New ...Frontiers Mission Juno launched to Jupiter on August 5, 2011. The focus of this paper is the description of the scientific objectives of the MWR investigation along with the experimental design, observational approach, and calibration that will achieve these objectives, based on the Juno mission plan up to Jupiter orbit insertion on July 4, 2016. With frequencies distributed approximately by octave from 600 MHz to 22 GHz, the MWR will sample the atmospheric thermal radiation from depths extending from the ammonia cloud region at around 1 bar to pressure levels as deep as 1000 bars. The primary scientific objectives of the MWR investigation are to determine the presently unknown dynamical properties of Jupiter’s subcloud atmosphere and to determine the global abundance of oxygen and nitrogen, present in the atmosphere as water and ammonia deep below their respective cloud decks. The MWR experiment is designed to measure both the thermal radiation from Jupiter and its emission-angle dependence at each frequency relative to the atmospheric local normal with high accuracy. The antennas at the four highest frequencies (21.9, 10.0, 5.2, and 2.6 GHz) have ∼12° beamwidths and will achieve a spatial resolution approaching 600 km near perijove. The antennas at the lowest frequencies (0.6 and 1.25 GHz) are constrained by physical size limitations and have 20° beamwidths, enabling a spatial resolution of as high as 1000 km to be obtained. The MWR will obtain Jupiter’s brightness temperature and its emission-angle dependence at each point along the subspacecraft track, over angles up to 60° from the normal over most latitudes, during at least six perijove passes after orbit insertion. The emission-angle dependence will be obtained for all frequencies to an accuracy of better than one part in
10
3
, sufficient to detect small variations in atmospheric temperature and absorber concentration profiles that distinguish dynamical and compositional properties of the deep Jovian atmosphere.
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