Patient-derived iPSCs show premature neural differentiation and neuron type-specific phenotypes relevant to neurodevelopment.

Ras/MAPK pathway signaling is a major participant in neurodevelopment, and evidence suggests that BRAF, a key Ras signal mediator, influences human behavior. We studied the role of the mutation BRAFQ257R, the most common cause of cardiofaciocutaneous syndrome (CFC), in an induced pluripotent stem cell (iPSC)-derived model of human neurodevelopment. In iPSC-derived neuronal cultures from CFC subjects, we observed decreased p-AKT and p-ERK1/2 compared to controls, as well as a depleted neural progenitor pool and rapid neuronal maturation. Pharmacological PI3K/AKT pathway manipulation recapitulated cellular phenotypes in control cells and attenuated them in CFC cells. CFC cultures displayed altered cellular subtype ratios and increased intrinsic excitability. Moreover, in CFC cells, Ras/MAPK pathway activation and morphological abnormalities exhibited cell subtype-specific differences. Our results highlight the importance of exploring specific cellular subtypes and of using iPSC models to reveal relevant human-specific neurodevelopmental events

Trends and projections in sexually transmitted infections in people aged 45 years and older in England: analysis of national surveillance data.

AimsWe describe the epidemiology of sexually transmitted infections (STIs) and HIV in people aged ⩾45 years in England and provide future projections about the burden of STIs in this age group.MethodsAnalysis of national surveillance data in England from 2014 to 2019 for chlamydia, gonorrhoea, herpes, syphilis, anogenital warts and HIV was carried out. Time trends were assessed by the Poisson regression and reported using incidence rate ratios (IRRs). Two scenarios were modelled to predict the number of new STI diagnoses and associated costs in 2040.ResultsIn 2019, there were 37,692 new STI diagnoses in people ⩾45 years in England. Between 2014 and 2019, there was a significant increase in the rate of new STI diagnoses in men (IRR = 1.05, p = .05) and those aged 45-64 years (IRR = 1.04, p = .05). Absolute numbers of new STI diagnoses in men who have sex with men increased by 76% between 2014 and 2019 (IRR = 1.15, p p ConclusionSTI rates in England are increasing in people aged ⩾45 years. The population is ageing and older people will contribute an increasing burden to STI costs if this trend continues. The reasons for this trend are not fully understood and further longitudinal epidemiological research is needed. Sexual health promotion campaigns and healthcare interventions targeted at older people should be prioritised

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

Carbon uptake by mature Amazon forests has mitigated Amazon nations' carbon emissions

BACKGROUND: Several independent lines of evidence suggest that Amazon forests have provided a significant carbon sink service, and also that the Amazon carbon sink in intact, mature forests may now be threatened as a result of different processes. There has however been no work done to quantify non-land-use-change forest carbon fluxes on a national basis within Amazonia, or to place these national fluxes and their possible changes in the context of the major anthropogenic carbon fluxes in the region. Here we present a first attempt to interpret results from ground-based monitoring of mature forest carbon fluxes in a biogeographically, politically, and temporally differentiated way. Specifically, using results from a large long-term network of forest plots, we estimate the Amazon biomass carbon balance over the last three decades for the different regions and nine nations of Amazonia, and evaluate the magnitude and trajectory of these differentiated balances in relation to major national anthropogenic carbon emissions. RESULTS: The sink of carbon into mature forests has been remarkably geographically ubiquitous across Amazonia, being substantial and persistent in each of the five biogeographic regions within Amazonia. Between 1980 and 2010, it has more than mitigated the fossil fuel emissions of every single national economy, except that of Venezuela. For most nations (Bolivia, Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname) the sink has probably additionally mitigated all anthropogenic carbon emissions due to Amazon deforestation and other land use change. While the sink has weakened in some regions since 2000, our analysis suggests that Amazon nations which are able to conserve large areas of natural and semi-natural landscape still contribute globally-significant carbon sequestration. CONCLUSIONS: Mature forests across all of Amazonia have contributed significantly to mitigating climate change for decades. Yet Amazon nations have not directly benefited from providing this global scale ecosystem service. We suggest that better monitoring and reporting of the carbon fluxes within mature forests, and understanding the drivers of changes in their balance, must become national, as well as international, priorities

Generating EQ-5D-3L health utility scores from the Edinburgh Postnatal Depression Scale: a perinatal mapping study

Background: Perinatal depression (PND) describes depression experienced by parents during pregnancy or in the first year after a baby is born. The EQ-5D instrument (a generic measure of health status) is not often collected in perinatal research, however disease-specific measures, such as the Edinburgh Postnatal Depression Scale (EPDS) are widely used. Mapping can be used to estimate generic health utility index values from disease-specific measures like the EPDS. Objective: To develop a mapping algorithm to estimate EQ-5D utility index values from the EPDS. Methods: Patient-level data from the BaBY PaNDA study (English observational cohort study) provided 1068 observations with paired EPDS and EQ-5D (3-level version; EQ-5D-3L) responses. We compared the performance of six alternative regression model types, each with four specifications of covariates (EPDS score and age: base, squared, and cubed). Model performance (ability to predict utility values) was assessed by ranking mean error, mean absolute error, and root mean square error. Algorithm performance in 3 external datasets was also evaluated. Results: There was moderate correlation between EPDS score and utility values (coefficient: – 0.42). The best performing model type was a two-part model, followed by ordinary least squared. Inclusion of squared and cubed covariates improved model performance. Based on graphs of observed and predicted utility values, the algorithm performed better when utility was above 0.6. Conclusions: This direct mapping algorithm allows the estimation of health utility values from EPDS scores. The algorithm has good external validity but is likely to perform better in samples with higher health status

Primula vulgaris (primrose) genome assembly, annotation and gene expression, with comparative genomics on the heterostyly supergene

Primula vulgaris (primrose) exhibits heterostyly: plants produce self-incompatible pin- or thrum-form flowers, with anthers and stigma at reciprocal heights. Darwin concluded that this arrangement promotes insect-mediated cross-pollination; later studies revealed control by a cluster of genes, or supergene, known as the S (Style length) locus. The P. vulgaris S locus is absent from pin plants and hemizygous in thrum plants (thrum-specific); mutation of S locus genes produces self-fertile homostyle flowers with anthers and stigma at equal heights. Here, we present a 411 Mb P. vulgaris genome assembly of a homozygous inbred long homostyle, representing ~87% of the genome. We annotate over 24,000 P. vulgaris genes, and reveal more genes up-regulated in thrum than pin flowers. We show reduced genomic read coverage across the S locus in other Primula species, including P. veris, where we define the conserved structure and expression of the S locus genes in thrum. Further analysis reveals the S locus has elevated repeat content (64%) compared to the wider genome (37%). Our studies suggest conservation of S locus genetic architecture in Primula, and provide a platform for identification and evolutionary analysis of the S locus and downstream targets that regulate heterostyly in diverse heterostylous species

Search for supersymmetry in events with four or more leptons in √s =13 TeV pp collisions with ATLAS

Results from a search for supersymmetry in events with four or more charged leptons (electrons, muons and taus) are presented. The analysis uses a data sample corresponding to 36.1 fb −1 of proton-proton collisions delivered by the Large Hadron Collider at s √ =13 TeV and recorded by the ATLAS detector. Four-lepton signal regions with up to two hadronically decaying taus are designed to target a range of supersymmetric scenarios that can be either enriched in or depleted of events involving the production and decay of a Z boson. Data yields are consistent with Standard Model expectations and results are used to set upper limits on the event yields from processes beyond the Standard Model. Exclusion limits are set at the 95% confidence level in simplified models of General Gauge Mediated supersymmetry, where higgsino masses are excluded up to 295 GeV. In R -parity-violating simplified models with decays of the lightest supersymmetric particle to charged leptons, lower limits of 1.46 TeV, 1.06 TeV, and 2.25 TeV are placed on wino, slepton and gluino masses, respectively

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Search for the direct production of charginos and neutralinos in final states with tau leptons in √s=13 TeV collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with at least two hadronically decaying tau leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of 36.1 fb−1, recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13TeV.Nosignificant deviation from the expected Standard Model background is observed. Limits are derived in scenarios of ˜χ+1 ˜χ−1 pair production and of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 production in simplified models where the neutralinos and charginos decay solely via intermediate left-handed staus and tau sneutrinos, and the mass of the ˜ τL state is set to be halfway between the masses of the ˜χ±1 and the ˜χ01. Chargino masses up to 630 GeV are excluded at 95% confidence level in the scenario of direct production of ˜χ+1 ˜χ−1 for a massless ˜χ01. Common ˜χ±1 and ˜χ02 masses up to 760 GeV are excluded in the case of production of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 assuming a massless ˜χ01. Exclusion limits for additional benchmark scenarios with large and small mass-splitting between the ˜χ±1 and the ˜χ01 are also studied by varying the ˜ τL mass between the masses of the ˜χ±1 and the ˜χ01

Performance of missing transverse momentum reconstruction with the ATLAS detector using proton–proton collisions at √s = 13 TeV

The performance of the missing transverse momentum (EmissT) reconstruction with the ATLAS detector is evaluated using data collected in proton–proton collisions at the LHC at a centre-of-mass energy of 13 TeV in 2015. To reconstruct EmissT, fully calibrated electrons, muons, photons, hadronically decaying τ -leptons, and jets reconstructed from calorimeter energy deposits and charged-particle tracks are used. These are combined with the soft hadronic activity measured by reconstructed charged-particle tracks not associated with the hard objects. Possible double counting of contributions from reconstructed charged-particle tracks from the inner detector, energy deposits in the calorimeter, and reconstructed muons from the muon spectrometer is avoided by applying a signal ambiguity resolution procedure which rejects already used signals when combining the various EmissT contributions. The individual terms as well as the overall reconstructed EmissT are evaluated with various performance metrics for scale (linearity), resolution, and sensitivity to the data-taking conditions. The method developed to determine the systematic uncertainties of the EmissT scale and resolution is discussed. Results are shown based on the full 2015 data sample corresponding to an integrated luminosity of 3.2 fb−1