The goal of early autism screening is earlier treatment. We pilot-tested a 12-week, low-intensity treatment with seven symptomatic infants ages 7–15 months. Parents mastered the intervention and ...maintained skills after treatment ended. Four comparison groups were matched from a study of infant siblings. The treated group of infants was significantly more symptomatic than most of the comparison groups at 9 months of age but was significantly less symptomatic than the two most affected groups between 18 and 36 months. At 36 months, the treated group had much lower rates of both ASD and DQs under 70 than a similarly symptomatic group who did not enroll in the treatment study. It appears feasible to identify and enroll symptomatic infants in parent-implemented intervention before 12 months, and the pilot study outcomes are promising, but testing the treatment’s efficacy awaits a randomized trial.
The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons
. The atmospheric concentration of ...trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s
. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased
. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown
. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.
The tumor suppressor p53, encoded by the TP53 gene, is recognized as the guardian of the human genome because it regulates many downstream genes to exercise its function in cell cycle and cell death. ...Recent studies have revealed that several microRNAs (miRNAs) are important components of the p53 tumor suppressor network with miR-125b and miR-504 directly targeting TP53. In this study, we use a screening method to identify that two miRNAs (miR-25 and miR-30d) directly target the 3'UTR of TP53 to downregulate p53 protein levels and reduce the expression of genes that are transcriptionally activated by p53. Correspondingly, both miR-25 and miR-30d adversely affect apoptotic cell death, cell cycle arrest and cellular senescence. Inhibition of either miR-25 or miR-30d expression increases endogenous p53 expression and elevates cellular apoptosis in several cell lines, including one from multiple myeloma that has little TP53 mutations. Thus, beyond miR-125b and miR-504, the human TP53 gene is negatively regulated by two more miRNAs: miR-25 and miR-30d.
Highlights • Vasopressin 1a receptor binding is diffuse and widespread in the titi monkey brain. • Oxytocin receptor binding is much more limited, with the densest binding in the hippocampus. • There ...is considerable interspecies variation in neuropeptide receptor expression in primates. • ALS-II-69 is a selective antagonist for the titi monkey oxytocin receptor. • SR49059 is a selective antagonist for the titi monkey vasopressin 1a receptor.
Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance remains largely ...unknown. Blood sequencing data from ~50,000 individuals reveal how mutation, genetic drift, and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis). We show that positive selection, not drift, is the major force shaping clonal hematopoiesis, provide bounds on the number of hematopoietic stem cells, and quantify the fitness advantages of key pathogenic variants, at single-nucleotide resolution, as well as the distribution of fitness effects (fitness landscape) within commonly mutated driver genes. These data are consistent with clonal hematopoiesis being driven by a continuing risk of mutations and clonal expansions that become increasingly detectable with age.
The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.
In ancestry-stratified models of 5962 European American (EA), ...2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves.
We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015≈0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5e-08 in the EA and ancestry-combined analysis, respectively Beta(se)=0.025(0.004);Beta(se)=0.021(0.003). No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects.
The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.
Inertial confinement fusion seeks to create burning plasma conditions in a spherical capsule implosion, which requires efficiently absorbing the driver energy in the capsule, transferring that energy ...into kinetic energy of the imploding DT fuel and then into internal energy of the fuel at stagnation. We report new implosions conducted on the National Ignition Facility (NIF) with several improvements on recent work Phys. Rev. Lett. 120, 245003 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.245003; Phys. Rev. E 102, 023210 (2020)PRESCM2470-004510.1103/PhysRevE.102.023210: larger capsules, thicker fuel layers to mitigate fuel-ablator mix, and new symmetry control via cross-beam energy transfer; at modest velocities, these experiments achieve record values for the implosion energetics figures of merit as well as fusion yield for a NIF experiment.
AimTo evaluate the association of dry eye disease (DED) with depression and anxiety.Patients and methodsWe conducted a systematic review and meta-analysis of studies that reported the prevalence, ...incidence and/or severity grading of depression and/or anxiety in DED patients and healthy controls. We searched MEDLINE, EMBASE, PsycINFO, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform for relevant studies.ResultsTwenty-two eligible studies consisted of 2 980 026 patients were analyzed. DED was associated with an increased prevalence of depression (summary odds ratio (OR)=2.92, 95% CI: 2.13-4.01, P<0.00001) and anxiety (OR=2.80, 95% CI: 2.61-3.02, P<0.00001). The depression score (standardized mean difference (SMD)=0.81, 95% CI: 0.48-1.15, P<0.00001) and anxiety score (SMD=0.37, 95% CI: 0.10-0.64, P=0.007) were higher in DED patients than in controls. Subgroup analyses revealed that the prevalence and severity of depression are greatest in primary Sjogren's syndrome patients. No study reported the incidence.ConclusionDepression and anxiety are more prevalent in DED patients than in controls. Among patients with DED, those suffering from primary Sjogren's syndrome have higher prevalence and severity of depression.
We examined the development of coral reef science and the policies, institutions, and governance frameworks for management of coral reefs in China in order to highlight the wicked problem of ...preserving reefs while simultaneously promoting human development and nation building. China and other sovereign states in the region are experiencing unprecedented economic expansion, rapid population growth, mass migration, widespread coastal development, and loss of habitat. We analyzed a large, fragmented literature on the condition of coral reefs in China and the disputed territories of the South China Sea. We found that coral abundance has declined by at least 80% over the past 30 years on coastal fringing reefs along the Chinese mainland and adjoining Hainan Island. On offshore atolls and archipelagos claimed by 6 countries in the South China Sea, coral cover has declined from an average of >60% to around 20% within the past 10-15 years. Climate change has affected these reefs far less than coastal development, pollution, overfishing, and destructive fishing practices. Ironically, these widespread declines in the condition of reefs are unfolding as China's research and reef-management capacity are rapidly expanding. Before the loss of corals becomes irreversible, governance of China's coastal reefs could be improved by increasing public awareness of declining ecosystem services, by providing financial support for training of reef scientists and managers, by improving monitoring of coral reef dynamics and condition to better inform policy development, and by enforcing existing regulations that could protect coral reefs. In the South China Sea, changes in policy and legal frameworks, refinement of governance structures, and cooperation among neighboring countries are urgently needed to develop cooperative management of contested offshore reefs. Examinamos el desarrollo de la ciencia sobre arrecifes de coral y los marcos de referencia de políticas, instituciones y gobernanza para el manejo de arrecifes de coral en China para resaltar el problema malvado de la preservación de arrecifes al mismo tiempo que se promueve el desarrollo humano y nacional. China y otros estados soberanos en la región están experimentando una expansión económica, un crecimiento poblacional acelerado, migración masiva, desarrollo costero extensivo y pérdida de hábitat sin precedentes. Analizamos literatura, extensa y fragmentada, sobre la condición de los arrecifes de coral en China y en los territorios en disputa en el Mar de la China Meridional. Encontramos que la abundancia de coral ha declinado en por lo menos 80% durante los últimos 30 años en los arrecifes costeros a lo largo de la China continental y en la Isla Hainan adyacente. En los atolones y archipiélagos reclamadas por 6 países en el Mar de la China Meridional, la cobertura de coral ha declinado en un promedio de >60% a cerca de 20% en los últimos 10-15 años. El cambio climático ha afectado a estos arrecifes mucho menos que el desarrollo costero, la contaminación, la sobrepesca y las prácticas pesqueras destructivas. Irónicamente, estas declinaciones extensivas en la condición de los arrecifes se están revelando al mismo tiempo que se está expandiendo rápidamente la capacidad china de investigación y manejo de arrecifes. Antes que la pérdida de arrecifes sea irreversible, la gobernanza de los arrecifes costeros debe ser mejorada mediante el incremento de la conciencia pública sobre la declinación de los servicios del ecosistema, proporcionando soporte financiero para la capacitación de científicos y manejadores de arrecifes, mejorando el monitoreo de la dinámica y condición de los arrecifes de coral para obtener información para el desarrollo de políticas y aplicando la regulación existente que puede proteger a los arrecifes de coral. En el Mar de la China Meridional, se requiere urgentemente de cambios en los marcos políticos y legales, refinamiento de las estructuras de gobernanza y cooperación entre los países vecinos para desarrollar manejo colaborativo de los arrecifes en disputa.
An unambiguous determination of the three-dimensional structure of nanoparticles is challenging. Electron tomography requires a series of images taken for many different specimen orientations. This ...approach is ideal for stable and stationary structures. But ultrasmall nanoparticles are intrinsically structurally unstable and may interact with the incident electron beam, constraining the electron beam density that can be used and the duration of the observation. Here we use aberration-corrected scanning transmission electron microscopy, coupled with simple imaging simulation, to determine with atomic resolution the size, three-dimensional shape, orientation and atomic arrangement of size-selected gold nanoclusters that are preformed in the gas phase and soft-landed on an amorphous carbon substrate. The structures of gold nanoclusters containing 309±6 atoms can be identified with either Ino-decahedral, cuboctahedral or icosahedral geometries. Comparison with theoretical modelling of the system suggests that the structures are consistent with energetic considerations. The discovery that nanoscale gold particles function as active and selective catalysts for a variety of important chemical reactions has provoked much research interest in recent years. We believe that the detailed structure information we provide will help to unravel the role of these nanoclusters in size- and structure-specific catalytic reactions. We note that the technique will be of use in investigations of other supported ultrasmall metal cluster systems.
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