Background
Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice ...and policy.
Objective
To quantify the long‐term cognitive, motor, behavioural and academic performance of children born with different degrees of prematurity compared with term‐born children.
Search strategy
PubMed and Embase were searched from January 1980 to December 2016 without language restrictions.
Selection criteria
Observational studies that reported neurodevelopmental outcomes from 2 years of age in children born preterm compared with a term‐born cohort.
Data collection and analysis
We pooled individual estimates of standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals using a random effects model.
Main results
We included 74 studies (64 061 children). Preterm children had lower cognitive scores for FSIQ (SMD: −0.70; 95% CI: −0.73 to −0.66), PIQ (SMD: −0.67; 95% CI: −0.73 to −0.60) and VIQ (SMD: −0.53; 95% CI: −0.60 to −0.47). Lower scores for preterm children in motor skills, behaviour, reading, mathematics and spelling were observed at primary school age, and this persisted to secondary school age, except for mathematics. Gestational age at birth accounted for 38–48% of the observed IQ variance. ADHD was diagnosed twice as often in preterm children (OR: 1.6; 95% CI: 1.3–1.8), with a differential effect observed according to the severity of prematurity (I2 = 49.4%, P = 0.03).
Conclusions
Prematurity of any degree affects the cognitive performance of children born preterm. The poor neurodevelopment persists at various ages of follow up. Parents, educators, healthcare professionals and policy makers need to take into account the additional academic, emotional and behavioural needs of these children.
Tweetable
Adverse effect of preterm birth on a child's neurodevelopment persists up to adulthood.
Tweetable
Adverse effect of preterm birth on a child's neurodevelopment persists up to adulthood.
The habitability of the surface of any planet is determined by a complex evolution of its interior, surface, and atmosphere. The electromagnetic and particle radiation of stars drive thermal, ...chemical, and physical alteration of planetary atmospheres, including escape. Many known extrasolar planets experience vastly different stellar environments than those in our solar system: It is crucial to understand the broad range of processes that lead to atmospheric escape and evolution under a wide range of conditions if we are to assess the habitability of worlds around other stars. One problem encountered between the planetary and the astrophysics communities is a lack of common language for describing escape processes. Each community has customary approximations that may be questioned by the other, such as the hypothesis of H‐dominated thermosphere for astrophysicists or the Sun‐like nature of the stars for planetary scientists. Since exoplanets are becoming one of the main targets for the detection of life, a common set of definitions and hypotheses are required. We review the different escape mechanisms proposed for the evolution of planetary and exoplanetary atmospheres. We propose a common definition for the different escape mechanisms, and we show the important parameters to take into account when evaluating the escape at a planet in time. We show that the paradigm of the magnetic field as an atmospheric shield should be changed and that recent work on the history of Xenon in Earth's atmosphere gives an elegant explanation to its enrichment in heavier isotopes: the so‐called Xenon paradox.
Plain Language Summary
In addition to having the right surface temperature, a planet needs an atmosphere to keep surface liquid water stable. Although many planets have been found that may lie in the right temperature range, the existence of an atmosphere is not guaranteed. In particular, for planets that are kept warm by being close to dim stars, there are a number of ways that the star may remove a planetary atmosphere. These atmospheric escape processes depend on the behavior of the star as well as the nature of the planet, including the presence of a planetary magnetic field. Under certain conditions, a magnetic field can protect a planet's atmosphere from the loss due to the direct impact of the stellar wind, but it may actually enhance total atmospheric loss by connecting to the highly variable magnetic field of the stellar wind. These enhancements happen especially for planets close to dim stars. We review the complete range of atmospheric loss processes driven by interaction between a planet and a star to aid in the identification of planets that are both the correct temperature for liquid water and that have a chance of maintaining an atmosphere over long periods of time.
Key Points
The different escape processes at planets and exoplanets are reviewed along with their mathematical formulation
The major parameters for each escape processes are described; some escape processes negligible in the solar system may be major source at exoplanets, or for the early solar system
A magnetic field should not be a priori considered as a protection for the atmosphere
Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium-specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of ...vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 ClinicalTrials.gov.).
Abstract
The initiation mechanism of Earth’s plate tectonic cooling system remains uncertain. A growing consensus suggests that multi-plate tectonics was preceded by cooling through a single-plate ...lithosphere, but models for how this lithosphere was first broken into plates have not converged on a mechanism or a typical early plate scale. A commonality among prior efforts is the use of continuum mechanics approximations to evaluate this solid mechanics problem. Here we use 3D spherical shell models to demonstrate a self-organized fracture mechanism analogous to thermal expansion-driven lithospheric uplift, in which globe-spanning rifting occurs as a consequence of horizontal extension. Resultant fracture spacing is a function of lithospheric thickness and rheology, wherein geometrically-regular, polygonal-shaped tessellation is an energetically favored solution because it minimizes total crack length. Therefore, warming of the early lithosphere itself—as anticipated by previous studies—should lead to failure, propagating fractures, and the conditions necessary for the onset of multi-plate tectonics.
We report the detection of ammonia (NH
) on Pluto's surface in spectral images obtained with the New Horizons spacecraft that show absorption bands at 1.65 and 2.2 μm. The ammonia signature is ...spatially coincident with a region of past extensional tectonic activity (Virgil Fossae) where the presence of H
O ice is prominent. Ammonia in liquid water profoundly depresses the freezing point of the mixture. Ammoniated ices are believed to be geologically short lived when irradiated with ultraviolet photons or charged particles. Thus, the presence of NH
on a planetary surface is indicative of a relatively recent deposition or possibly through exposure by some geological process. In the present case, the areal distribution is more suggestive of cryovolcanic emplacement, however, adding to the evidence for ongoing geological activity on Pluto and the possible presence of liquid water at depth today.
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer lacking specific biomarkers that can be correlated to disease onset, promotion and progression. To assess whether tumor cell ...electrophysiology may serve as a marker for PDAC tumorigenicity, we use multi-frequency impedance cytometry at high throughput (∼350 cells/s) to measure the electrical phenotype of single PDAC tumor cells from xenografts, which are derived from primary pancreatic tumors versus those from liver metastases of different patients. A novel phase contrast metric based on variations in the high and low frequency impedance phase responses that is related to electrophysiology of the cell interior is found to be systematically altered as a function of tumorigenicity. PDAC cells of higher tumorigenicity exhibited lowered interior conductivity and enhanced permittivity, which is validated by the dielectrophoresis on the respective cell types. Using genetic analysis, we suggest the role of dysregulated Na+ transport and removal of Ca2+ ions from the cytoplasm on key oncogenic KRAS-driven processes that may be responsible for lowering of the interior cell conductivity. We envision that impedance cytometry can serve as a tool to quantify phenotypic heterogeneity for rapidly stratifying tumorigenicity. It can also aid in protocols for dielectrophoretic isolation of cells with a particular phenotype for prognostic studies on patient survival and to tailor therapy selection to specific patients.
Display omitted
•High-throughput (∼350 cells/s) impedance cytometry to measure ∼10,000 cells/sample.•Samples of patient-derived pancreatic tumor xenografts of varying tumorigenicity.•Impedance phase due to electrophysiology of cell interior varies with tumorigenicity.•Lowered interior conductivity and enhanced permittivity for cells of higher tumorigenicity.•Validated based on level of positive dielectrophoresis and its crossover frequency.
Improving maternal health has been a primary goal of international health agencies for many years, with the aim of reducing maternal and child deaths and improving access to antenatal care (ANC) ...services, particularly in low-and-middle-income countries (LMICs). Health interventions with these aims have received more attention from a clinical effectiveness perspective than for cost impact and economic efficiency.
We collected data on resource use and costs as part of a large, multi-country study assessing the use of routine antenatal screening ultrasound (US) with the aim of considering the implications for economic efficiency. We assessed typical antenatal outpatient and hospital-based (facility) care for pregnant women, in general, with selective complication-related data collection in women participating in a large maternal health registry and clinical trial in five LMICs. We estimated average costs from a facility/health system perspective for outpatient and inpatient services. We converted all country-level currency cost estimates to 2015 United States dollars (USD). We compared average costs across countries for ANC visits, deliveries, higher-risk pregnancies, and complications, and conducted sensitivity analyses.
Our study included sites in five countries representing different regions. Overall, the relative cost of individual ANC and delivery-related healthcare use was consistent among countries, generally corresponding to country-specific income levels. ANC outpatient visit cost estimates per patient among countries ranged from 15 to 30 USD, based on average counts for visits with and without US. Estimates for antenatal screening US visits were more costly than non-US visits. Costs associated with higher-risk pregnancies were influenced by rates of hospital delivery by cesarean section (mean per person delivery cost estimate range: 25-65 USD).
Despite substantial differences among countries in infrastructures and health system capacity, there were similarities in resource allocation, delivery location, and country-level challenges. Overall, there was no clear suggestion that adding antenatal screening US would result in either major cost savings or major cost increases. However, antenatal screening US would have higher training and maintenance costs. Given the lack of clinical effectiveness evidence and greater resource constraints of LMICs, it is unlikely that introducing antenatal screening US would be economically efficient in these settings--on the demand side (i.e., patients) or supply side (i.e., healthcare providers).
Trial number: NCT01990625 (First posted: November 21, 2013 on https://clinicaltrials.gov ).
Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night ...vision, but knowledge of its efficacy in humans is limited.
We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings.
Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG.
Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).
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