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The measurement of the production of deuterons, tritons and 3He and their antiparticles in Pb-Pb collisions at √sNN = 5.02 TeV is presented in this article. The measurements are carried out at midrapidity (y|< 0.5) as a function of collision centrality using the ALICE detector. The pT-integrated yields, the coalescence parameters and the ratios to protons and antiprotons are reported and compared with nucleosynthesis models. The comparison of these results in different collision systems at different center-of-mass collision energies reveals a suppression of nucleus production in small systems. In the Statistical Hadronisation Model framework, this can be explained by a small correlation volume where the baryon number is conserved, as already shown in previous fluctuation analyses. However, a different size of the correlation volume is required to describe the proton yields in the same data sets. The coalescence model can describe this suppression by the fact that the wave functions of the nuclei are large and the fireball size starts to become comparable and even much smaller than the actual nucleus at low multiplicities.
We present the results of charged particle fluctuations measurements in Au+Au collisions at sqrt[sNN ]=130 GeV using the STAR detector. Dynamical fluctuations measurements are presented for inclusive charged particle multiplicities as well as for identified charged pions, kaons, and protons. The net charge dynamical fluctuations are found to be large and negative providing clear evidence that positive and negative charged particle production is correlated within the pseudorapidity range investigated. Correlations are smaller than expected based on model-dependent predictions for a resonance gas or a quark-gluon gas which undergoes fast hadronization and freeze-out. Qualitative agreement is found with comparable scaled p+p measurements and a heavy ion jet interaction generation model calculation based on independent particle collisions, although a small deviation from the 1/N scaling dependence expected from this model is observed.
We report the first observations of the first harmonic (directed flow, v1) and the fourth harmonic (v4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the BNL Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v2) generated at RHIC. From the correlation of v2 with v1 it is determined that v2 is positive, or in-plane. The integrated v4 is about a factor of 10 smaller than v2. For the sixth (v6) and eighth (v8) harmonics upper limits on the magnitudes are reported.
The transverse mass spectra and midrapidity yields for Xi s and Omega s are presented. For the 10% most central collisions, the Xi -bar+/h- ratio increases from the Super Proton Synchrotron to the Relativistic Heavy Ion Collider energies while the Xi -/h- stays approximately constant. A hydrodynamically inspired model fit to the Xi spectra, which assumes a thermalized source, seems to indicate that these multistrange particles experience a significant transverse flow effect, but are emitted when the system is hotter and the flow is smaller than values obtained from a combined fit to pi , K, p, and Lambda s.
The balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au+Au collisions at sqrt[sNN]=130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering. Widths in central collisions are smaller, consistent with trends predicted by models incorporating late hadronization.
Azimuthal anisotropy (v2) and two-particle angular correlations of high pT charged hadrons have been measured in Au+Au collisions at sqrt[sNN]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high pT partons. The monotonic rise of v2(pT) for pT<2 GeV/c is consistent with collective hydrodynamical flow calculations. At pT>3 GeV/c, a saturation of v2 is observed which persists up to pT=6 GeV/c.
Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
Data from the first physics run at the Relativistic Heavy-Ion Collider at Brookhaven National Laboratory, Au+Au collisions at sqrt[sNN]=130 GeV, have been analyzed by the STAR Collaboration using three-pion correlations with charged pions to study whether pions are emitted independently at freeze-out. We have made a high-statistics measurement of the three-pion correlation function and calculated the normalized three-particle correlator to obtain a quantitative measurement of the degree of chaoticity of the pion source. It is found that the degree of chaoticity seems to increase with increasing particle multiplicity.
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
Aims: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.
Methods and results: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies.
In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95–1.02) in group A, 0.98 (0.93–1.04) in group B, and 0.95 (0.89–1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07–1.23) in group A, 1.13 (1.05–1.22) in group B, and 1.12 (1.05–1.20) in group C.
Conclusions: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.
Background: Autism spectrum disorder (“autism”) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, but its potential as a neural stratification marker has not been widely examined. Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS (European Autism Interventions—A Multicentre Study for Developing New Medications) Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical control subjects as well as a replication dataset from ABIDE (Autism Brain Imaging Data Exchange) (513 individuals with autism, 691 neurotypical subjects) using a promising approach that moves beyond mean group comparisons. We derived gray matter voxelwise laterality values for each subject and modeled individual deviations from the normative pattern of brain laterality across age using normative modeling. Results: Individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language, motor, and visuospatial regions, associated with symptom severity. Language delay explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged, with individuals with autism with language delay showing more pronounced rightward deviations than individuals with autism without language delay. Conclusions: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism and indicate that atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
Background: Autism Spectrum Disorder (henceforth ‘autism’) is a highly heterogeneous neurodevelopmental condition with few effective treatments for core and associated features. To make progress we need to both identify and validate neural markers that help to parse heterogeneity to tailor therapies to specific neurobiological profiles. Atypical hemispheric lateralization is a stable feature across studies in autism, however its potential of lateralization as a neural stratification marker has not been widely examined.
Methods: In order to dissect heterogeneity in lateralization in autism, we used the large EU-AIMS Longitudinal European Autism Project dataset comprising 352 individuals with autism and 233 neurotypical (NT) controls as well as a replication dataset from ABIDE (513 autism, 691 NT) using a promising approach that moves beyond mean-group comparisons. We derived grey matter voxelwise laterality values for each subject and modelled individual deviations from the normative pattern of brain laterality across age using normative modeling.
Results: Results showed that individuals with autism had highly individualized patterns of both extreme right- and leftward deviations, particularly in language-, motor- and visuospatial regions, associated with symptom severity. Language delay (LD) explained most variance in extreme rightward patterns, whereas core autism symptom severity explained most variance in extreme leftward patterns. Follow-up analyses showed that a stepwise pattern emerged with individuals with autism with LD showing more pronounced rightward deviations than autism individuals without LD.
Conclusion: Our analyses corroborate the need for novel (dimensional) approaches to delineate the heterogeneous neuroanatomy in autism, and indicate atypical lateralization may constitute a neurophenotype for clinically meaningful stratification in autism.
White matter abnormalities across different epilepsy syndromes in adults: an ENIGMA Epilepsy study
(2019)
The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analyzed from 1,069 non-epileptic controls and 1,249 patients: temporal lobe epilepsy with hippocampal sclerosis (N=599), temporal lobe epilepsy with normal MRI (N=275), genetic generalized epilepsy (N=182) and nonlesional extratemporal epilepsy (N=193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fiber tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at p<0.001). Across “all epilepsies” lower fractional anisotropy was observed in most fiber tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. Less robust effects were seen with mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Those with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced differences in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and in mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of microstructural abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibers in a large multicentre study of epilepsy. Overall, epilepsy patients showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding new insights into pathological substrates that may be used to guide future therapeutic and genetic studies.
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Aims: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.
Methods and results: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.
Conclusion: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.
The first evidence of spin alignment of vector mesons (K*0 and ϕ) in heavy-ion collisions at the Large Hadron Collider (LHC) is reported. The spin density matrix element ρ00 is measured at midrapidity (|y|< 0.5) in Pb-Pb collisions at a center-of-mass energy (√sNN) of 2.76 TeV
with the ALICE detector. ρ00 values are found to be less than 1/3 (1/3 implies no spin alignment) at low transverse momentum (pT<2 GeV/c) for K*0 and ϕ at a level of 3σ and 2σ, respectively. No significant spin alignment is observed for the K0S meson (spin = 0) in Pb-Pb collisions and for the vector mesons in pp collisions. The measured spin alignment is unexpectedly large but qualitatively consistent with the expectation from models which attribute it to a polarization of quarks in the presence of angular momentum in heavy-ion collisions and a subsequent hadronization by the process of recombination.
The transverse momentum (pT) differential yields of (anti-)3He and (anti-)3H measured in p-Pb collisions at sNN−−−√ = 5.02 TeV with ALICE at the Large Hadron Collider (LHC) are presented. The ratios of the pT-integrated yields of (anti-)3He and (anti-)3H to the proton yields are reported, as well as the pT dependence of the coalescence parameters B3 for (anti-)3He and (anti-)3H. For (anti-)3He, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of 4He¯ is determined.
Scattering studies with low-energy kaon-proton femtoscopy in proton-proton collisions at the LHC
(2020)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Scattering studies with low-energy kaon-proton femtoscopy in
proton–proton collisions at the LHC
(2019)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to several models. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Scattering studies with low-energy kaon-proton femtoscopy in proton–proton collisions at the LHC
(2020)
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p–Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection.
Measurements of the elliptic flow coefficient relative to the collision plane defined by the spectator neutrons v2{ΨSP} in collisions of Pb ions at center-of-mass energy per nucleon–nucleon pair sNN=2.76 TeV and Xe ions at sNN=5.44 TeV are reported. The results are presented for charged particles produced at midrapidity as a function of centrality and transverse momentum for the 5–70% and 0.2–6 GeV/c ranges, respectively. The ratio between v2{ΨSP} and the elliptic flow coefficient relative to the participant plane v2{4}, estimated using four-particle correlations, deviates by up to 20% from unity depending on centrality. This observation differs strongly from the magnitude of the corresponding eccentricity ratios predicted by the TRENTo and the elliptic power models of initial state fluctuations that are tuned to describe the participant plane anisotropies. The differences can be interpreted as a decorrelation of the neutron spectator plane and the reaction plane because of fragmentation of the remnants from the colliding nuclei, which points to an incompleteness of current models describing the initial state fluctuations. A significant transverse momentum dependence of the ratio v2{ΨSP}/v2{4} is observed in all but the most central collisions, which may help to understand whether momentum anisotropies at low and intermediate transverse momentum have a common origin in initial state fluctuations. The ratios of v2{ΨSP} and v2{4} to the corresponding initial state eccentricities for Xe–Xe and Pb–Pb collisions at similar initial entropy density show a difference of (7.0±0.9)% with an additional variation of +1.8% when including RHIC data in the TRENTo parameter extraction. These observations provide new experimental constraints for viscous effects in the hydrodynamic modeling of the expanding quark–gluon plasma produced in heavy-ion collisions at the LHC.
The production yields of non-prompt Ds+ mesons, namely Ds+ mesons from beauty-hadron decays, were measured for the first time as a function of the transverse momentum (pT) at midrapidity (|y|<0.5) in central and semi-central Pb−Pb collisions at a centre-of-mass energy per nucleon pair sNN−−−√=5.02 TeV with the ALICE experiment at the LHC. The Ds+ mesons and their charge conjugates were reconstructed from the hadronic decay channel Ds+→ϕπ+, with ϕ→K−K+, in the 4<pT<36 GeV/c and 2<pT<24 GeV/c intervals for the 0−10% and 30−50% centrality classes, respectively. The measured yields of non-prompt Ds+ mesons are compared to those of prompt Ds+ and non-prompt D0 mesons by calculating the ratios of the production yields in Pb−Pb collisions and the nuclear modification factor RAA. The ratio between the RAA of non-prompt Ds+ and prompt Ds+ mesons, and that between the RAA of non-prompt Ds+ and non-prompt D0 mesons in central Pb−Pb collisions are found to be on average higher than unity in the 4<pT<12 GeV/c interval with a statistical significance of about 1.6σ and 1.7σ, respectively. The measured RAA ratios are compared with the predictions of theoretical models of heavy-quark transport in a hydrodynamically expanding QGP that incorporate hadronisation via quark recombination.
This letter reports measurements which characterize the underlying event associated with hard scatterings at mid-pseudorapidity (|η|<0.8) in pp, p−Pb and Pb−Pb collisions at centre-of-mass energy per nucleon pair, sNN−−−√=5.02 TeV. The measurements are performed with ALICE at the LHC. Different multiplicity classes are defined based on the event activity measured at forward rapidities. The hard scatterings are identified by the leading particle defined as the charged particle with the largest transverse momentum (pT) in the collision and having 8<pT<15 GeV/c. The pT spectra of associated particles (0.5≤pT<6 GeV/c) are measured in different azimuthal regions defined with respect to the leading particle direction: toward, transverse, and away. The associated charged particle yields in the transverse region are subtracted from those of the away and toward regions. The remaining jet-like yields are reported as a function of the multiplicity measured in the transverse region. The measurements show a suppression of the jet-like yield in the away region and an enhancement of high-pT associated particles in the toward region in central Pb−Pb collisions, as compared to minimum-bias pp collisions. These observations are consistent with previous measurements that used two-particle correlations, and with an interpretation in terms of parton energy loss in a high-density quark gluon plasma. These yield modifications vanish in peripheral Pb−Pb collisions and are not observed in either high-multiplicity pp or p−Pb collisions.
The study of the azimuthal anisotropy of inclusive muons produced in p–Pb collisions at √sNN=8.16 TeV, using the ALICE detector at the LHC is reported. The measurement of the second-order Fourier coefficient of the particle azimuthal distribution, v2, is performed as a function of transverse momentum pT in the 0–20% high-multiplicity interval at both forward (2.03<yCMS<3.53) and backward (−4.46<yCMS<−2.96) rapidities over a wide pT range, 0.5<pT<10 GeV/c, in which a dominant contribution of muons from heavy-flavour hadron decays is expected at pT>2 GeV/c. The v2 coefficient of inclusive muons is extracted using two different techniques, namely two-particle cumulants, used for the first time for heavy-flavour measurements, and forward–central two-particle correlations. Both techniques give compatible results. A positive v2 is measured at both forward and backward rapidities with a significance larger than 4.7σ and 7.6σ, respectively, in the interval 2<pT<6 GeV/c. Comparisons with previous measurements in p–Pb collisions at √sNN=5.02 TeV, and with AMPT and CGC-based theoretical calculations are discussed. The findings impose new constraints on the theoretical interpretations of the origin of the collective behaviour in small collision systems.
An excess of J/ψ yield at very low transverse momentum (pT<0.3 GeV/c), originating from coherent photoproduction, is observed in peripheral and semicentral hadronic Pb–Pb collisions at a center-of-mass energy per nucleon pair of sNN=5.02 TeV. The measurement is performed with the ALICE detector via the dimuon decay channel at forward rapidity (2.5<y<4). The nuclear modification factor at very low pT and the coherent photoproduction cross section are measured as a function of centrality down to the 10% most central collisions. These results extend the previous study at sNN=2.76 TeV, confirming the clear excess over hadronic production in the pT range 0−0.3 GeV/c and the centrality range 70–90%, and establishing an excess with a significance greater than 5σ also in the 50–70% and 30–50% centrality ranges. The results are compared with earlier measurements at sNN=2.76 TeV and with different theoretical predictions aiming at describing how coherent photoproduction occurs in hadronic interactions with nuclear overlap.
An excess of J/ψ yield at very low transverse momentum (pT<0.3 GeV/c), originating from coherent photoproduction, is observed in peripheral and semicentral hadronic Pb−Pb collisions at a center-of-mass energy per nucleon pair of sNN−−−√=5.02 TeV. The measurement is performed with the ALICE detector via the dimuon decay channel at forward rapidity (2.5<y<4). The nuclear modification factor at very low pT and the coherent photoproduction cross section are measured as a function of centrality down to the 10% most central collisions. These results extend the previous study at sNN−−−√=2.76 TeV, confirming the clear excess over hadronic production in the pT range 0−0.3 GeV/c and the centrality range 70−90%, and establishing an excess with a significance greater than 5σ also in the 50−70% and 30−50% centrality ranges. The results are compared with earlier measurements at sNN−−−√=2.76 TeV and with different theoretical predictions aiming at describing how coherent photoproduction occurs in hadronic interactions with nuclear overlap.
Introduction: Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis.
Methods: Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentrations of sodium, potassium, magnesium, calcium, chloride, lactate, albumin, and phosphate were measured at baseline, in shock, and during 3 hours post-therapy. Strong ion difference and the amount of weak plasma acid were calculated. To detect the presence of unmeasured anions, anion gap and strong ion gap were determined. Capillary electrophoresis was used to identify potential contributors to unmeasured anions.
Results: During induction of shock, pH decreased significantly from 7.41 to 7.19. The transient increase in lactate concentration from 1.5 to 5.5 mEq/L during shock was not sufficient to explain the transient increases in anion gap (+11.0 mEq/L) and strong ion gap (+7.1 mEq/L), suggesting that substantial amounts of unmeasured anions must have been generated. Capillary electrophoresis revealed increases in serum concentration of acetate (2.2 mEq/L), citrate (2.2 mEq/L), alpha-ketoglutarate (35.3 microEq/L), fumarate (6.2 microEq/L), sulfate (0.1 mEq/L), and urate (55.9 microEq/L) after shock induction.
Conclusion: Large amounts of unmeasured anions were generated after hemorrhage in this highly standardized model of hemorrhagic shock. Capillary electrophoresis suggested that the hitherto unmeasured anions citrate and acetate, but not sulfate, contributed significantly to the changes in strong ion gap associated with induction of shock.
Recent studies have suggested increased plasticity of differentiated cells within the intestine to act both as intestinal stem cells (ISCs) and tumour-initiating cells. However, little is known of the processes that regulate this plasticity. Our previous work has shown that activating mutations of Kras or the NF-κB pathway can drive dedifferentiation of intestinal cells lacking Apc. To investigate this process further, we profiled both cells undergoing dedifferentiation in vitro and tumours generated from these cells in vivo by gene expression analysis. Remarkably, no clear differences were observed in the tumours; however, during dedifferentiation in vitro we found a marked upregulation of TGFβ signalling, a pathway commonly mutated in colorectal cancer (CRC). Genetic inactivation of TGFβ type 1 receptor (Tgfbr1/Alk5) enhanced the ability of KrasG12D/+ mutation to drive dedifferentiation and markedly accelerated tumourigenesis. Mechanistically this is associated with a marked activation of MAPK signalling. Tumourigenesis from differentiated compartments is potently inhibited by MEK inhibition. Taken together, we show that tumours arising in differentiated compartments will be exposed to different suppressive signals, for example, TGFβ and blockade of these makes tumourigenesis more efficient from this compartment.
Mutations causing aberrant splicing are frequently implicated in human diseases including cancer. Here, we establish a high-throughput screen of randomly mutated minigenes to decode the cis-regulatory landscape that determines alternative splicing of exon 11 in the proto-oncogene MST1R (RON). Mathematical modelling of splicing kinetics enables us to identify more than 1000 mutations affecting RON exon 11 skipping, which corresponds to the pathological isoform RON∆165. Importantly, the effects correlate with RON alternative splicing in cancer patients bearing the same mutations. Moreover, we highlight heterogeneous nuclear ribonucleoprotein H (HNRNPH) as a key regulator of RON splicing in healthy tissues and cancer. Using iCLIP and synergy analysis, we pinpoint the functionally most relevant HNRNPH binding sites and demonstrate how cooperative HNRNPH binding facilitates a splicing switch of RON exon 11. Our results thereby offer insights into splicing regulation and the impact of mutations on alternative splicing in cancer.
Under the Kigali Amendment to the Montreal Protocol, new controls are being implemented to reduce emissions of HFC-23 (CHF3), a by-product during the manufacture of HCFC-22 (CHClF2). Starting in 2015, China and India, who dominate global HCFC-22 production (75% in 2017), set out ambitious programs to reduce HFC-23 emissions. Here, we estimate that these measures should have seen global emissions drop by 87% between 2014 and 2017. Instead, atmospheric observations show that emissions have increased and in 2018 were higher than at any point in history (15.9 ± 0.9 Gg yr−1). Given the magnitude of the discrepancy between expected and observation-inferred emissions, it is likely that the reported reductions have not fully materialized or there may be substantial unreported production of HCFC-22, resulting in unaccounted-for HFC-23 by-product emissions. The difference between reported and observation-inferred estimates suggests that an additional ~309 Tg CO2-equivalent emissions were added to the atmosphere between 2015 and 2017.
The use of phylogenies in ecology is increasingly common and has broadened our understanding of biological diversity. Ecological sub-disciplines, particularly conservation, community ecology and macroecology, all recognize the value of evolutionary relationships but the resulting development of phylogenetic approaches has led to a proliferation of phylogenetic diversity metrics. The use of many metrics across the sub-disciplines hampers potential meta-analyses, syntheses, and generalizations of existing results. Further, there is no guide for selecting the appropriate metric for a given question, and different metrics are frequently used to address similar questions. To improve the choice, application, and interpretation of phylo-diversity metrics, we organize existing metrics by expanding on a unifying framework for phylogenetic information.
Generally, questions about phylogenetic relationships within or between assemblages tend to ask three types of question: how much; how different; or how regular? We show that these questions reflect three dimensions of a phylogenetic tree: richness, divergence, and regularity. We classify 70 existing phylo-diversity metrics based on their mathematical form within these three dimensions and identify ‘anchor’ representatives: for α-diversity metrics these are PD (Faith's phylogenetic diversity), MPD (mean pairwise distance), and VPD (variation of pairwise distances). By analysing mathematical formulae and using simulations, we use this framework to identify metrics that mix dimensions, and we provide a guide to choosing and using the most appropriate metrics. We show that metric choice requires connecting the research question with the correct dimension of the framework and that there are logical approaches to selecting and interpreting metrics. The guide outlined herein will help researchers navigate the current jungle of indices.
Africa's protected areas (PAs) are the last stronghold of the continent's unique biodiversity, but they appear increasingly threatened by climate change, substantial human population growth, and land-use change. Conservation planning is challenged by uncertainty about how strongly and where these drivers will interact over the next few decades. We investigated the combined future impacts of climate-driven vegetation changes inside African PAs and human population densities and land use in their surroundings for 2 scenarios until the end of the 21st century. We used the following 2 combinations of the shared socioeconomic pathways (SSPs) and representative greenhouse gas concentration pathways (RCPs): the “middle-of-the-road” scenario SSP2–RCP4.5 and the resource-intensive “fossil-fueled development” scenario SSP5–RCP8.5. Climate change impacts on tree cover and biome type (i.e., desert, grassland, savanna, and forest) were simulated with the adaptive dynamic global vegetation model (aDGVM). Under both scenarios, most PAs were adversely affected by at least 1 of the drivers, but the co-occurrence of drivers was largely region and scenario specific. The aDGVM projections suggest considerable climate-driven tree cover increases in PAs in today's grasslands and savannas. For PAs in West Africa, the analyses revealed climate-driven vegetation changes combined with hotspots of high future population and land-use pressure. Except for many PAs in North Africa, future decreases in population and land-use pressures were rare. At the continental scale, SSP5–RCP8.5 led to higher climate-driven changes in tree cover and higher land-use pressure, whereas SSP2–RCP4.5 was characterized by higher future population pressure. Both SSP–RCP scenarios implied increasing challenges for conserving Africa's biodiversity in PAs. Our findings underline the importance of developing and implementing region-specific conservation responses. Strong mitigation of future climate change and equitable development scenarios would reduce ecosystem impacts and sustain the effectiveness of conservation in Africa.
Climate change and its impacts already pose considerable challenges for societies that will further increase with global warming (IPCC, 2014a, b). Uncertainties of the climatic response to greenhouse gas emissions include the potential passing of large-scale tipping points (e.g. Lenton et al., 2008; Levermann et al., 2012; Schellnhuber, 2010) and changes in extreme meteorological events (Field et al., 2012) with complex impacts on societies (Hallegatte et al., 2013). Thus climate change mitigation is considered a necessary societal response for avoiding uncontrollable impacts (Conference of the Parties, 2010). On the other hand, large-scale climate change mitigation itself implies fundamental changes in, for example, the global energy system. The associated challenges come on top of others that derive from equally important ethical imperatives like the fulfilment of increasing food demand that may draw on the same resources. For example, ensuring food security for a growing population may require an expansion of cropland, thereby reducing natural carbon sinks or the area available for bio-energy production. So far, available studies addressing this problem have relied on individual impact models, ignoring uncertainty in crop model and biome model projections. Here, we propose a probabilistic decision framework that allows for an evaluation of agricultural management and mitigation options in a multi-impact-model setting. Based on simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP), we outline how cross-sectorally consistent multi-model impact simulations could be used to generate the information required for robust decision making.
Using an illustrative future land use pattern, we discuss the trade-off between potential gains in crop production and associated losses in natural carbon sinks in the new multiple crop- and biome-model setting. In addition, crop and water model simulations are combined to explore irrigation increases as one possible measure of agricultural intensification that could limit the expansion of cropland required in response to climate change and growing food demand. This example shows that current impact model uncertainties pose an important challenge to long-term mitigation planning and must not be ignored in long-term strategic decision making.
In order to achieve climate change mitigation, long-term decisions are required that must be reconciled with other societal goals that draw on the same resources. For example, ensuring food security for a growing population may require an expansion of crop land, thereby reducing natural carbon sinks or the area available for bio-energy production. Here, we show that current impact-model uncertainties pose an important challenge to long-term mitigation planning and propose a new risk-assessment and decision framework that accounts for competing interests.
Based on cross-sectorally consistent simulations generated within the Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) we discuss potential gains and limitations of additional irrigation and trade-offs of the expansion of agricultural land as two possible response measures to climate change and growing food demand. We describe an illustrative example in which the combination of both measures may close the supply demand gap while leading to a loss of approximately half of all natural carbon sinks.
We highlight current limitations of available simulations and additional steps required for a comprehensive risk assessment.
National greenhouse gas inventories (GHGIs) are submitted annually to the United Nations Framework Convention on Climate Change (UNFCCC). They are estimated in compliance with Intergovernmental Panel on Climate Change (IPCC) methodological guidance using activity data, emission factors and facility-level measurements. For some sources, the outputs from these calculations are very uncertain. Inverse modelling techniques that use high-quality, long-term measurements of atmospheric gases have been developed to provide independent verification of national GHGIs. This is considered good practice by the IPCC as it helps national inventory compilers to verify reported emissions and to reduce emission uncertainty. Emission estimates from the InTEM (Inversion Technique for Emission Modelling) model are presented for the UK for the hydrofluorocarbons (HFCs) reported to the UNFCCC (HFC-125, HFC-134a, HFC-143a, HFC-152a, HFC-23, HFC-32, HFC-227ea, HFC-245fa, HFC-43-10mee and HFC-365mfc). These HFCs have high global warming potentials (GWPs), and the global background mole fractions of all but two are increasing, thus highlighting their relevance to the climate and a need for increasing the accuracy of emission estimation for regulatory purposes. This study presents evidence that the long-term annual increase in growth of HFC-134a has stopped and is now decreasing. For HFC-32 there is an early indication, its rapid global growth period has ended, and there is evidence that the annual increase in global growth for HFC-125 has slowed from 2018. The inverse modelling results indicate that the UK implementation of European Union regulation of HFC emissions has been successful in initiating a decline in UK emissions from 2018. Comparison of the total InTEM UK HFC emissions in 2020 with the average from 2009–2012 shows a drop of 35 %, indicating progress toward the target of a 79 % decrease in sales by 2030. The total InTEM HFC emission estimates (2008–2018) are on average 73 (62–83) % of, or 4.3 (2.7–5.9) Tg CO2-eq yr−1 lower than, the total HFC emission estimates from the UK GHGI. There are also significant discrepancies between the two estimates for the individual HFCs.
National Greenhouse Gas Inventories (GHGI) are submitted annually to the United Nations Framework Convention on Climate Change (UNFCCC). They are estimated in compliance with Intergovernmental Panel on Climate Change (IPCC) methodological guidance using activity data, emission factors and facility-level measurements. For some sources, the outputs from these calculations are very uncertain. Inverse modelling techniques that use high-quality, long-term measurements of atmospheric gases have been developed to provide independent verification of national GHGI. This is considered good practice by the IPCC as it helps national inventory compilers to verify reported emissions and to reduce emission uncertainty. Emission estimates from the InTEM (Inversion Technique for Emissions Modelling) model are presented for the UK for the hydrofluorocarbons (HFCs) reported to the UNFCCC (HFC-125, HFC-134a, HFC-143a, HFC-152a, HFC-23, HFC-32, HFC-227ea, HFC-245fa, HFC-43-10mee and HFC-365mfc). These HFCs have high Global Warming Potentials (GWPs) and the global background mole fractions of all but two are increasing, thus highlighting their relevance to the climate and a need for increasing the accuracy of emission estimation for regulatory purposes. This study presents evidence that the long-term annual increase in growth of HFC-134a has stopped and is now decreasing. For HFC-32 there is an early indication its rapid global growth period has ended, and there is evidence that the annual increase in global growth for HFC-125 has slowed from 2018. The inverse modelling results indicate that the UK implementation of European Union regulation of HFC emissions has been successful in initiating a decline in UK emissions in the since 2018. Comparison of the total InTEM UK HFC emissions in 2020 with the average from 2009–2012 shows a drop of 35%, indicating progress toward the target of a 79% decrease in sales by 2030. The total InTEM HFC emission estimates (2008–2018) are on average 73 (62–83)% of, or 4.3 (2.7–5.9) Tg CO2-eq yr−1 lower than, the total HFC emission estimates from the UK GHGI inventory. There are also significant discrepancies between the two estimates for the individual HFCs.
The International Halocarbons in Air Comparison Experiment (IHALACE) was conducted to document relationships between calibration scales among various laboratories that measure atmospheric greenhouse and ozone depleting gases. Six stainless steel cylinders containing natural and modified natural air samples were circulated among 19 laboratories. Results from this experiment reveal relatively good agreement among commonly used calibration scales for a number of trace gases present in the unpolluted atmosphere at pmol mol−1 (parts per trillion) levels, such as chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), and hydrofluorocarbons (HFCs). Some scale relationships were found to be consistent with those derived from bi-lateral experiments or from analysis of atmospheric data, while others revealed discrepancies. The transfer of calibration scales among laboratories was found to be problematic in many cases, meaning that measurements tied to a common scale may not, in fact, be compatible. These results reveal substantial improvements in calibration over previous comparisons. However there is room for improvement in communication and coordination of calibration activities with respect to the measurement of halogenated and related trace gases.
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in the reduced spectral resolution nominal observation mode. The data cover the period from January 2005 to April 2012 and the altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of modelled spectra to the measured limb spectral radiances. The spectral ν4-band at 816.5 ± 13 cm−1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The rate of linear growth in the lower latitudes lower stratosphere was about 6 to 7 pptv year−1 in the period 2005–2012. The profiles obtained were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and cryosampler balloon measurements. Between 13 and 22 km, average agreement within −3 to +5 pptv (MIPAS – ACE) with ACE-FTS v3.5 profiles is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15–50 pptv below 24 km and less than 10 pptv above 28 km. MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from the NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data. This is attributed to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10°-latitude/1-to-2-km-altitude bins. The relative linear variation was always positive, with relative increases of 40–70 % decade−1 in the tropics and global lower stratosphere, and up to 120 % decade−1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. Asian HCFC-22 emissions have become the major source of global upper tropospheric HCFC-22. In the upper troposphere, monsoon air, rich in HCFC-22, is instantaneously mixed into the tropics. In the middle stratosphere, between 20 and 30 km, the observed trend is inconsistent with the trend at the surface (corrected for the age of stratospheric air), hinting at circulation changes. There exists a stronger positive trend in HCFC-22 in the Southern Hemisphere and a more muted positive trend in the Northern Hemisphere, implying a potential change in the stratospheric circulation over the observation period.
We report on HCFC-22 data acquired by the Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) in reduced spectral resolution nominal mode in the period from January 2005 to April 2012 from version 5.02 level-1b spectral data and covering an altitude range from the upper troposphere (above cloud top altitude) to about 50 km. The profile retrieval was performed by constrained nonlinear least squares fitting of measured limb spectral radiances to modelled spectra. The spectral v4-band at 816.5 ± 13 cm-1 was used for the retrieval. A Tikhonov-type smoothing constraint was applied to stabilise the retrieval. In the lower stratosphere, we find a global volume mixing ratio of HCFC-22 of about 185 pptv in January 2005. The linear growth rate in the lower latitudes lower stratosphere was about 6 to 7 pptv yr-1 in the period 2005–2012. The obtained profiles were compared with ACE-FTS satellite data v3.5, as well as with MkIV balloon profiles and in situ cryosampler balloon measurements. Between 13 and 22 km, average agreement within -3 to +5 pptv (MIPAS–ACE) with ACE-FTS v3.5 pro files is demonstrated. Agreement with MkIV solar occultation balloon-borne measurements is within 10–20 pptv below 30 km and worse above, while in situ cryosampler balloon measurements are systematically lower over their full altitude range by 15– 50 pptv below 24 km and less than 10 pptv above 28 km. Obtained MIPAS HCFC-22 time series below 10 km altitude are shown to agree mostly well to corresponding time series of near-surface abundances from NOAA/ESRL and AGAGE networks, although a more pronounced seasonal cycle is obvious in the satellite data, probably due to tropopause altitude fluctuations and subsidence of polar winter stratospheric air into the troposphere. A parametric model consisting of constant, linear, quasi-biennial oscillation (QBO) and several sine and cosine terms with different periods has been fitted to the temporal variation of stratospheric HCFC-22 for all 10° latitude/1 to 2 km altitude bins. The relative linear variation was always positive, with relative increases of 40–70%decade-1 in the tropics and global lower stratosphere, and up to 120%decade-1 in the upper stratosphere of the northern polar region and the southern extratropical hemisphere. In the middle stratosphere between 20 and 30 km, the observed trend is not consistent with the age of stratospheric air-corrected trend at ground, but stronger positive at the Southern Hemisphere and less strong increasing in the Northern Hemisphere, hinting towards changes in the stratospheric circulation over the observation period.
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Background: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data.
Methods: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z > 3.1, cluster-level P < 0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research (GENDAAR).
Results: Discovery analyses in ABIDE revealed significant main effects across the intrinsic functional connectivity (iFC) of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples – EU-AIMS LEAP.
Limitations: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability.
Conclusions: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies.
Competing Interest Statement: ADM receives royalties from the publication of the Italian version of the Social Responsiveness Scale Child Version by Organization Speciali, Italy. JKB has been a consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice, Roche, and Servier. He is not an employee of any of these companies and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, or royalties. CFB is director and shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and received book royalties from Guildford Press and Sage. DM has been a consultant to, and advisory board member, for Roche and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm. He received conference support or speakers fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. JT is a consultant to Roche. The remaining authors declare no competing interests.
A recent randomized study of whipworm Trichuris suis ova (TSO) in ileal Crohn’s disease failed to demonstrate a clinical benefit compared to placebo after 12 weeks. Nonetheless, it has recently been shown that the spontaneous small intestinal inflammatory changes in Nod2-/- (Nucleotide-binding oligomerization domain 2) mice could be substantially ameliorated when these mice were colonized by Trichuris muris. Those and complementary epidemiologic findings in humans lead to the hypothesis that helminths may be advantageous only in patients carrying defective NOD2 variants. Thus, 207 participants of the TSO trial were retrospectively genotyped for six functional NOD2 genetic variants to evaluate whether the treatment outcome differed in patients carrying NOD2 variants. We observed no significant association of the NOD2 variants or their haplotypes with clinical outcome after TSO treatment.
Borrelia recurrentis, the etiologic agent of louse-borne relapsing fever in humans, has evolved strategies, including antigenic variation, to evade immune defence, thereby causing severe diseases with high mortality rates. Here we identify for the first time a multifunctional surface lipoprotein of B. recurrentis, termed HcpA, and demonstrate that it binds human complement regulators, Factor H, CFHR-1, and simultaneously, the host protease plasminogen. Cell surface bound factor H was found to retain its activity and to confer resistance to complement attack. Moreover, ectopic expression of HcpA in a B. burgdorferi B313 strain, deficient in Factor H binding proteins, protected the transformed spirochetes from complement-mediated killing. Furthermore, HcpA-bound plasminogen/plasmin endows B. recurrentis with the potential to resist opsonization and to degrade extracellular matrix components. Together, the present study underscores the high virulence potential of B. recurrentis. The elucidation of the molecular basis underlying the versatile strategies of B. recurrentis to escape innate immunity and to persist in human tissues, including the brain, may help to understand the pathological processes underlying louse-borne relapsing fever.
Anthropogenic climate change is expected to impact ecosystem structure, biodiversity and ecosystem services in Africa profoundly. We used the adaptive Dynamic Global Vegetation Model (aDGVM), which was originally developed and tested for Africa, to quantify sources of uncertainties in simulated African potential natural vegetation towards the end of the 21st century. We forced the aDGVM with regionally downscaled high‐resolution climate scenarios based on an ensemble of six general circulation models (GCMs) under two representative concentration pathways (RCPs 4.5 and 8.5). Our study assessed the direct effects of climate change and elevated CO2 on vegetation change and its plant‐physiological drivers. Total increase in carbon in aboveground biomass in Africa until the end of the century was between 18% to 43% (RCP4.5) and 37% to 61% (RCP8.5) and was associated with woody encroachment into grasslands and increased woody cover in savannas. When direct effects of CO2 on plants were omitted, woody encroachment was muted and carbon in aboveground vegetation changed between –8 to 11% (RCP 4.5) and –22 to –6% (RCP8.5). Simulated biome changes lacked consistent large‐scale geographical patterns of change across scenarios. In Ethiopia and the Sahara/Sahel transition zone, the biome changes forecast by the aDGVM were consistent across GCMs and RCPs. Direct effects from elevated CO2 were associated with substantial increases in water use efficiency, primarily driven by photosynthesis enhancement, which may relieve soil moisture limitations to plant productivity. At the ecosystem level, interactions between fire and woody plant demography further promoted woody encroachment. We conclude that substantial future biome changes due to climate and CO2 changes are likely across Africa. Because of the large uncertainties in future projections, adaptation strategies must be highly flexible. Focused research on CO2 effects, and improved model representations of these effects will be necessary to reduce these uncertainties.
Although global- and catchment-scale hydrological models are often shown to accurately simulate long-term runoff time-series, far less is known about their suitability for capturing hydrological extremes, such as droughts. Here we evaluated simulations of hydrological droughts from nine catchment scale hydrological models (CHMs) and eight global scale hydrological models (GHMs) for eight large catchments: Upper Amazon, Lena, Upper Mississippi, Upper Niger, Rhine, Tagus, Upper Yangtze and Upper Yellow. The simulations were conducted within the framework of phase 2a of the Inter-Sectoral Impact Model Intercomparison Project (ISIMIP2a). We evaluated the ability of the CHMs, GHMs and their respective ensemble means (Ens-CHM and Ens-GHM) to simulate observed hydrological droughts of at least one month duration, over 31 years (1971–2001). Hydrological drought events were identified from runoff-deficits and the Standardised Runoff Index (SRI). In all catchments, the CHMs performed relatively better than the GHMs, for simulating monthly runoff-deficits. The number of drought events identified under different drought categories (i.e. SRI values of -1 to -1.49, -1.5 to -1.99, and ≤-2) varied significantly between models. All the models, as well as the two ensemble means, have limited abilities to accurately simulate drought events in all eight catchments, in terms of their occurrence and magnitude. Overall, there are opportunities to improve both CHMs and GHMs for better characterisation of hydrological droughts.