Diagnostic Value of Lumbar Facet Joint Injection: A Prospective Triple Cross-Over Study

The diagnosis “lumbar facet syndrome” is common and often indicates severe lumbar spine surgery procedures. It is doubtful whether a painful facet joint (FJ) can be identified by a single FJ block. The aim of this study was to clarify the validity of a single and placebo controlled bilateral FJ blocks using local anesthetics. A prospective single blinded triple cross-over study was performed. 60 patients (31 f, 29 m, mean age 53.2 yrs (22–73)) with chronic low back pain (mean pain persistance 31 months, 6 months of conservative treatment without success) admitted to a local orthopaedic department for surgical or conservative therapy of chronic LBP, were included in the study. Effect on pain reduction (10 point rating scale) was measured. The 60 subjects were divided into six groups with three defined sequences of fluoroscopically guided bilateral monosegmental lumbar FJ test injections in “oblique needle” technique: verum-(local anaesthetic-), placebo-(sodium chloride-) and sham-injection. Carry-over and periodic effects were evaluated and a descriptive and statistical analysis regarding the effectiveness, difference and equality of the FJ injections and the different responses was performed. The results show a high rate of non-response, which documents the lack of reliable and valid predictors for a positive response towards FJ blocks. There was a high rate of placebo reactions noted, including subjects who previously or later reacted positively to verum injections. Equivalence was shown among verum vs. placebo and partly vs. sham also. With regard to test validity criteria, a single intraarticular FJ block with local anesthetics is not useful to detect the pain-responsible FJ and therefore is no valid and reliable diagostic tool to specify indication of lumbar spine surgery. Comparative FJ blocks with local anesthetics and placebo-controls have to be interpretated carefully also, because they solely give no proper diagnosis on FJ being main pain generator

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Search for Higgs boson decays to a Z boson and a photon in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2204.12945v2 [hep-ex], https://arxiv.org/abs/2204.12945v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/HIG-19-014 (CMS Public Pages). Report number: CMS-HIG-19-014, CERN-EP-2022-019.Results are presented from a search for the Higgs boson decay H → Zγ, where Z → ℓ+ℓ− with ℓ = e or μ. The search is performed using a sample of proton-proton (pp) collision data at a center-of-mass energy of 13 TeV, recorded by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138 fb^{−1}. Events are assigned to mutually exclusive categories, which exploit differences in both event topology and kinematics of distinct Higgs production mechanisms to enhance signal sensitivity. The signal strength μ, defined as the product of the cross section and the branching fraction [σ(pp → H)B(H → Zγ)] relative to the standard model prediction, is extracted from a simultaneous fit to the ℓ+ℓ−γ invariant mass distributions in all categories and is found to be μ = 2.4 ± 0.9 for a Higgs boson mass of 125.38 GeV. The statistical significance of the observed excess of events is 2.7 standard deviations. This measurement corresponds to σ(pp → H)B(H → Zγ) = 0.21 ± 0.08 pb. The observed (expected) upper limit at 95% confidence level on μ is 4.1 (1.8). The ratio of branching fractions B(H → Zγ)/B(H → γγ) is measured to be 1.5 +0.7−0.6, which agrees with the standard model prediction of 0.69 ± 0.04 at the 1.5 standard deviation level.SCOAP3

Search for direct production of GeV-scale resonances decaying to a pair of muons in proton-proton collisions at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2309.16003v2 [hep-ex], https://arxiv.org/abs/2309.16003v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables, including additional supplementary figures, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-21-005 (CMS Public Pages). Report number: CMS-EXO-21-005, CERN-EP-2023-165.A search for direct production of low-mass dimuon resonances is performed using s√ = 13 TeV proton-proton collision data collected by the CMS experiment during the 2017-2018 operation of the CERN LHC with an integrated luminosity of 96.6 fb−1. The search exploits a dedicated high-rate trigger stream that records events with two muons with transverse momenta as low as 3 GeV but does not include the full event information. The search is performed by looking for narrow peaks in the dimuon mass spectrum in the ranges of 1.1-2.6 GeV and 4.2-7.9 GeV. No significant excess of events above the expectation from the standard model background is observed. Model-independent limits on production rates of dimuon resonances within the experimental fiducial acceptance are set. Competitive or world's best limits are set at 90% confidence level for a minimal dark photon model and for a scenario with two Higgs doublets and an extra complex scalar singlet (2HDM+S). Values of the squared kinetic mixing coefficient ε2 in the dark photon model above 10−6 are excluded over most of the mass range of the search. In the 2HDM+S, values of the mixing angle sin(θH) above 0.08 are excluded over most of the mass range of the search with a fixed ratio of the Higgs doublets vacuum expectation tanβ = 0.5.SCOAP3

Azimuthal anisotropy of dijet events in PbPb collisions at √sNN = 5.02TeV

A preprint version of the article is available at arXiv - https://arxiv.org/abs/2210.08325The path-length dependent parton energy loss within the dense partonic medium created in lead-lead collisions at a nucleon-nucleon center-of-mass energy of √sNN = 5.02TeV is studied by determining the azimuthal anisotropies for dijets with high transverse momentum. The data were collected by the CMS experiment in 2018 and correspond to an integrated luminosity of 1.69nb−1. For events containing back-to back jets, correlations in relative azimuthal angle and pseudorapidity (η) between jets and hadrons, and between two hadrons, are constructed. The anisotropies are expressed as the Fourier expansion coefficients vn, n = 2–4 of these azimuthal distributions. The dijet vn values are extracted from long-range (1.5 < |∆η| < 2.5) components of these correlations, which suppresses the background contributions from jet fragmentation processes. Positive dijet v2 values are observed which increase from central to more peripheral events, while the v3 and v4 values are consistent with zero within experimental uncertainties.SCOAP

Search for W′ bosons decaying to a top and a bottom quark in leptonic final states in proton-proton collisions at s \sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2310.19893v1 [hep-ex], https://arxiv.org/abs/2310.19893v1 . Comments: Submitted to the Journal of High Energy Physics. All figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/B2G-20-012 (CMS Public Pages). Report number: CMS-B2G-20-012, CERN-EP-2023-213.A search for W' bosons decaying to a top and a bottom quark in final states including an electron or a muon is performed with the CMS detector at the LHC. The analyzed data correspond to an integrated luminosity of 138 fb^{-1} of proton-proton collisions at a center-of-mass energy of 13 Tev. Good agreement with the standard model expectation is observed and no evidence for the existence of the W' boson is found over the mass range examined. The largest observed deviation from the standard model expectation is found for a W' boson mass (mW′) hypothesis of 3.8 TeV with a relative decay width of 1%, with a local (global) significance of 2.6 (2.0) standard deviations. Upper limits on the production cross sections of W' bosons decaying to a top and a bottom quark are set. Left- and right-handed W' bosons with mW′ below 3.9 and 4.3 TeV, respectively, are excluded at the 95% confidence level, under the assumption that the new particle has a narrow decay width. Limits are also set for relative decay widths up to 30%. These are the most stringent limits to date on this W' boson decay channel.SCOAP3

Search for electroweak production of charginos and neutralinos at s\sqrt{s} = 13 TeV in final states containing hadronic decays of WW, WZ, or WH and missing transverse momentum

Data availability: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “CMS data preservation, re-use and open access policy”.A preprint version of this article is archived at: arXiv:2205.09597v2 [hep-ex], https://arxiv.org/abs/2205.09597v2 . Comments: Replaced with the published version. Added the journal reference. All the figures and tables, including additional supplementary figures and tables, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/SUS-21-002 (CMS Public Pages). Report number: CMS-SUS-21-002, CERN-EP-2022-031This Letter presents a search for direct production of charginos and neutralinos via electroweak interactions. The results are based on data from proton-proton collisions at a center-of-mass energy of 13 TeV collected with the CMS detector at the LHC, corresponding to an integrated luminosity of 137 fb^{-1}. The search considers final states with large missing transverse momentum and pairs of hadronically decaying bosons WW, WZ, and WH, where H is the Higgs boson. These bosons are identified using novel algorithms. No significant excess of events is observed relative to the expectations from the standard model. Limits at the 95% confidence level are placed on the cross section for production of mass-degenerate wino-like supersymmetric particles χ~±1 and χ~02, and mass-degenerate higgsino-like supersymmetric particles χ~±1, χ~02, and χ~03. In the limit of a nearly-massless lightest supersymmetric particle χ~01, wino-like particles with masses up to 870 and 960 GeV are excluded in the cases of χ~02 → Zχ~01 and χ~02 → Hχ~01, respectively, and higgsino-like particles are excluded between 300 and 650 GeV.SCOAP3