The Environmental Protection Agencies (EPAs) of Denmark, Sweden, Norway, Germany and the Netherlands submitted a proposal to the European Chemical Agency (ECHA) in February 2023 calling for a ban in the use of toxic industrial chemicals per- and polyfluoroalkyl substances (PFAS). These chemicals are highly toxic causing elevated cholesterol, immune suppression, reproductive failure, cancer and neuro-endocrine disruption in humans and wildlife being a significant threat to biodiversity and human health. The main reason for the submitted proposal is recent findings of significant flaws in the transition to PFAS replacements that is leading to a widespread pollution. Denmark was the first country banning PFAS, and now other EU countries support the restrictions of these carcinogenic, endocrine disruptive and immunotoxic chemicals. The proposed plan is among the most extensive received by the ECHA for 50 years. Denmark is now the first EU country to initiate the establishment of groundwater parks to try and protect its drinking water. These parks are areas free of agricultural activities and nutritious sewage sludge to secure drinking water free of xenobiotic including PFAS. The PFAS pollution also reflects the lack of comprehensive spatial and temporal environmental monitoring programs in the EU. Such monitoring programs should include key indicator species across ecosystems of livestock, fish and wildlife, to facilitate detection of early ecological warning signals and sustain public health. Simultaneously with inferring a total PFAS ban, the EU should also push for more persistent, bioaccumulative and toxic (PBT) PFAS substances to be listed on the Stockholm Convention (SC) Annex A such as PFOS (perfluorooctane sulfonic acid) that is currently listed on the SCs Annex B. The combination of these regulative restrictions combined with groundwater parks and pan-European biomonitoring programs, would pave the way forward for a cleaner environment to sustain health across the EU.
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
The Baltic/Wadden Sea Flyway of common eiders has declined over the past three decades. Multiple factors such as contaminant exposure, global warming, hunting, white-tailed eagle predation, decreased agricultural eutrophication and infectious diseases have been suggested to explain the decline. We collected information on body mass, mercury (Hg) concentration, biochemistry and untargeted metabolomics of incubating birds in two colonies in the Danish Straits (Hov Røn, n = 100; Agersø, n = 29) and in one colony in the Baltic proper (Christiansø, n = 23) to look into their metabolisms and energy balance. Body mass was available from early and late incubation for Hov Røn and Christiansø, showing a significant decline (25-30%) in both colonies with late body mass at Christiansø being the lowest. Whole blood concentrations of total mercury Hg were significantly higher in birds at Christiansø in the east compared to Hov Røn in the west. All birds in the three colonies had Hg concentrations in the range of ≤1.0 μg/g ww, which indicates that the risk of effects on reproduction is in the no to low risk category for wild birds. Among the biochemical measures, glucose, fructosamine, amylase, albumin and protein decreased significantly from early to late incubation at Hov Røn and Christiansø, reflecting long-term fastening as supported by the decline in body mass. Untargeted metabolomics performed on Christiansø eiders revealed presence of 8,433 plasma metabolites. Of these, 3,179 metabolites changed significantly (log2-fold change ≥1, p ≤ 0.05) from the early to late incubation. For example, smaller peptides and vitamin B2 (riboflavin) were significantly down-regulated while 11-deoxycorticosterone and palmitoylcarnitine were significantly upregulated. These results show that cumulative stress including fasting during incubation affect the eiders' biochemical profile and energy metabolism and that this may be most pronounced for the Christiansø colony in the Baltic proper. This amplify the events of temperature increases and food web changes caused by global warming that eventually accelerate the loss in body weight. Future studies should examine the relationship between body condition, temperature and reproductive outcomes and include mapping of food web contaminant, energy and nutrient content to better understand, manage and conserve the populations.
Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.
The factor structure of DSM-5 posttraumatic stress disorder (PTSD) has been extensively debated with evidence supporting the recently proposed seven-factor Hybrid model. However, despite myriad studies examining PTSD symptom structure few have assessed the diagnostic implications of these proposed models. This study aimed to generate PTSD prevalence estimates derived from the 7 alternative factor models and assess whether pre-established risk factors associated with PTSD (e.g., transportation accidents and sexual victimisation) produce consistent risk estimates. Seven alternative models were estimated within a confirmatory factor analytic framework using the PTSD Checklist for DSM-5 (PCL-5). Data were analysed from a Malaysian adolescent community sample (n = 481) of which 61.7% were female, with a mean age of 17.03 years. The results indicated that all models provided satisfactory model fit with statistical superiority for the Externalising Behaviours and seven-factor Hybrid models. The PTSD prevalence estimates varied substantially ranging from 21.8% for the DSM-5 model to 10.0% for the Hybrid model. Estimates of risk associated with PTSD were inconsistent across the alternative models, with substantial variation emerging for sexual victimisation. These findings have important implications for research and practice and highlight that more research attention is needed to examine the diagnostic implications emerging from the alternative models of PTSD.
A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at [Formula: see text][Formula: see text]. The analysis exploits the [Formula: see text] decay in data corresponding to an integrated luminosity of 19.7[Formula: see text] collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities [Formula: see text], and with the photon of largest and next-to-largest transverse momentum ([Formula: see text]) divided by the diphoton mass [Formula: see text] satisfying the respective conditions of [Formula: see text] and [Formula: see text], the total fiducial cross section is [Formula: see text][Formula: see text].
A measurement of the W boson pair production cross section in proton-proton collisions at [Formula: see text] TeV is presented. The data collected with the CMS detector at the LHC correspond to an integrated luminosity of 19.4[Formula: see text]. The [Formula: see text] candidates are selected from events with two charged leptons, electrons or muons, and large missing transverse energy. The measured [Formula: see text] cross section is [Formula: see text], consistent with the standard model prediction. The [Formula: see text] cross sections are also measured in two different fiducial phase space regions. The normalized differential cross section is measured as a function of kinematic variables of the final-state charged leptons and compared with several perturbative QCD predictions. Limits on anomalous gauge couplings associated with dimension-six operators are also given in the framework of an effective field theory. The corresponding 95 % confidence level intervals are [Formula: see text], [Formula: see text], [Formula: see text], in the HISZ basis.
The normalized differential cross section for top quark pair ([Formula: see text]) production is measured in pp collisions at a centre-of-mass energy of 8[Formula: see text] at the CERN LHC using the CMS detector in data corresponding to an integrated luminosity of 19.7[Formula: see text]. The measurements are performed in the lepton[Formula: see text]jets ([Formula: see text][Formula: see text]jets) and in the dilepton ([Formula: see text], [Formula: see text], and [Formula: see text]) decay channels. The [Formula: see text] cross section is measured as a function of the kinematic properties of the charged leptons, the jets associated to b quarks, the top quarks, and the [Formula: see text] system. The data are compared with several predictions from perturbative quantum chromodynamic up to approximate next-to-next-to-leading-order precision. No significant deviations are observed relative to the standard model predictions.
Measurements of the [Formula: see text][Formula: see text] production cross sections in proton-proton collisions at center-of-mass energies of 7 and 8[Formula: see text] are presented. Candidate events for the leptonic decay mode [Formula: see text], where [Formula: see text] denotes an electron or a muon, are reconstructed and selected from data corresponding to an integrated luminosity of 5.1 (19.6)[Formula: see text] at 7 (8)[Formula: see text] collected with the CMS experiment. The measured cross sections, [Formula: see text] at 7[Formula: see text], and [Formula: see text] at 8[Formula: see text], are in good agreement with the standard model predictions with next-to-leading-order accuracy. The selected data are analyzed to search for anomalous triple gauge couplings involving the [Formula: see text][Formula: see text] final state. In the absence of any deviation from the standard model predictions, limits are set on the relevant parameters. These limits are then combined with the previously published CMS results for [Formula: see text][Formula: see text] in 4[Formula: see text] final states, yielding the most stringent constraints on the anomalous couplings.
Stringent limits are set on the long-lived lepton-like sector of the phenomenological minimal supersymmetric standard model (pMSSM) and the anomaly-mediated supersymmetry breaking (AMSB) model. The limits are derived from the results presented in a recent search for long-lived charged particles in proton-proton collisions, based on data collected by the CMS detector at a centre-of-mass energy of 8 TeV at the Large Hadron Collider. In the pMSSM parameter sub-space considered, 95.9 % of the points predicting charginos with a lifetime of at least 10 ns are excluded. These constraints on the pMSSM are the first obtained at the LHC. Charginos with a lifetime greater than 100 ns and masses up to about 800 GeV in the AMSB model are also excluded. The method described can also be used to set constraints on other models.
This paper presents distributions of topological observables in inclusive three- and four-jet events produced in pp collisions at a centre-of-mass energy of 7[Formula: see text] with a data sample collected by the CMS experiment corresponding to a luminosity of 5.1[Formula: see text]. The distributions are corrected for detector effects, and compared with several event generators based on two- and multi-parton matrix elements at leading order. Among the considered calculations, MadGraph interfaced with pythia6 displays the overall best agreement with data.
The inclusive jet cross section for proton-proton collisions at a centre-of-mass energy of 7[Formula: see text] was measured by the CMS Collaboration at the LHC with data corresponding to an integrated luminosity of 5.0[Formula: see text]. The measurement covers a phase space up to 2[Formula: see text] in jet transverse momentum and 2.5 in absolute jet rapidity. The statistical precision of these data leads to stringent constraints on the parton distribution functions of the proton. The data provide important input for the gluon density at high fractions of the proton momentum and for the strong coupling constant at large energy scales. Using predictions from perturbative quantum chromodynamics at next-to-leading order, complemented with electroweak corrections, the constraining power of these data is investigated and the strong coupling constant at the Z boson mass [Formula: see text] is determined to be [Formula: see text], which is in agreement with the world average.
A search for a standard model Higgs boson produced in association with a top-quark pair and decaying to bottom quarks is presented. Events with hadronic jets and one or two oppositely charged leptons are selected from a data sample corresponding to an integrated luminosity of 19.5[Formula: see text] collected by the CMS experiment at the LHC in [Formula: see text] collisions at a centre-of-mass energy of 8[Formula: see text]. In order to separate the signal from the larger [Formula: see text] + jets background, this analysis uses a matrix element method that assigns a probability density value to each reconstructed event under signal or background hypotheses. The ratio between the two values is used in a maximum likelihood fit to extract the signal yield. The results are presented in terms of the measured signal strength modifier, [Formula: see text], relative to the standard model prediction for a Higgs boson mass of 125[Formula: see text]. The observed (expected) exclusion limit at a 95 % confidence level is [Formula: see text] (3.3), corresponding to a best fit value [Formula: see text].
Results are presented from a search for particle dark matter (DM), extra dimensions, and unparticles using events containing a jet and an imbalance in transverse momentum. The data were collected by the CMS detector in proton-proton collisions at the LHC and correspond to an integrated luminosity of 19.7[Formula: see text]at a centre-of-mass energy of 8[Formula: see text]. The number of observed events is found to be consistent with the standard model prediction. Limits are placed on the DM-nucleon scattering cross section as a function of the DM particle mass for spin-dependent and spin-independent interactions. Limits are also placed on the scale parameter [Formula: see text] in the Arkani-Hamed, Dimopoulos, and Dvali (ADD) model of large extra dimensions, and on the unparticle model parameter [Formula: see text]. The constraints on ADD models and unparticles are the most stringent limits in this channel and those on the DM-nucleon scattering cross section are an improvement over previous collider results.
Transverse momentum spectra of charged particles are measured by the CMS experiment at the CERN LHC in pPb collisions at [Formula: see text][Formula: see text], in the range [Formula: see text][Formula: see text] and pseudorapidity [Formula: see text] in the proton-nucleon center-of-mass frame. For [Formula: see text][Formula: see text], the charged-particle production is asymmetric about [Formula: see text], with smaller yield observed in the direction of the proton beam, qualitatively consistent with expectations from shadowing in nuclear parton distribution functions (nPDF). A pp reference spectrum at [Formula: see text][Formula: see text] is obtained by interpolation from previous measurements at higher and lower center-of-mass energies. The [Formula: see text] distribution measured in pPb collisions shows an enhancement of charged particles with [Formula: see text][Formula: see text] compared to expectations from the pp reference. The enhancement is larger than predicted by perturbative quantum chromodynamics calculations that include antishadowing modifications of nPDFs.
Properties of the Higgs boson with mass near 125[Formula: see text] are measured in proton-proton collisions with the CMS experiment at the LHC. Comprehensive sets of production and decay measurements are combined. The decay channels include [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] pairs. The data samples were collected in 2011 and 2012 and correspond to integrated luminosities of up to 5.1[Formula: see text] at 7[Formula: see text] and up to 19.7[Formula: see text] at 8[Formula: see text]. From the high-resolution [Formula: see text] and [Formula: see text] channels, the mass of the Higgs boson is determined to be [Formula: see text]. For this mass value, the event yields obtained in the different analyses tagging specific decay channels and production mechanisms are consistent with those expected for the standard model Higgs boson. The combined best-fit signal relative to the standard model expectation is [Formula: see text] at the measured mass. The couplings of the Higgs boson are probed for deviations in magnitude from the standard model predictions in multiple ways, including searches for invisible and undetected decays. No significant deviations are found.
This paper presents a measurement of the inclusive 3-jet production differential cross section at a proton-proton centre-of-mass energy of 7 TeV using data corresponding to an integrated luminosity of 5[Formula: see text]collected with the CMS detector. The analysis is based on the three jets with the highest transverse momenta. The cross section is measured as a function of the invariant mass of the three jets in a range of 445-3270 GeV and in two bins of the maximum rapidity of the jets up to a value of 2. A comparison between the measurement and the prediction from perturbative QCD at next-to-leading order is performed. Within uncertainties, data and theory are in agreement. The sensitivity of the observable to the strong coupling constant [Formula: see text] is studied. A fit to all data points with 3-jet masses larger than 664 GeV gives a value of the strong coupling constant of [Formula: see text].
A search has been performed for long-lived particles that could have come to rest within the CMS detector, using the time intervals between LHC beam crossings. The existence of such particles could be deduced from observation of their decays via energy deposits in the CMS calorimeter appearing at times that are well separated from any proton-proton collisions. Using a data set corresponding to an integrated luminosity of 18.6[Formula: see text] of 8[Formula: see text] proton-proton collisions, and a search interval corresponding to 281 h of trigger livetime, 10 events are observed, with a background prediction of [Formula: see text] events. Limits are presented at 95 % confidence level on gluino and top squark production, for over 13 orders of magnitude in the mean proper lifetime of the stopped particle. Assuming a cloud model of R-hadron interactions, a gluino with mass [Formula: see text]1000[Formula: see text] and a top squark with mass [Formula: see text]525[Formula: see text] are excluded, for lifetimes between 1 [Formula: see text]s and 1000[Formula: see text]. These results are the most stringent constraints on stopped particles to date.