Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72

A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for similar to 40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic lateral sclerosis cases (21 of Sardinian ancestry) and 41 German index familial amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On average, children developed disease 7.0 years earlier than their parents [children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation 10.9); P = 0.003]. Parental phenotype influenced the type of clinical symptoms manifested by the child: of the 13 cases where the affected parent had an amyotrophic lateral sclerosis-frontotemporal dementia or frontotemporal dementia, the affected child also developed amyotrophic lateral sclerosis-frontotemporal dementia in nine cases. When compared with patients carrying mutations of other amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non-C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6-7.2) and longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7-2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most frequent mutation in our large cohort of patients with familial amyotrophic lateral sclerosis of Italian, Sardinian and German ancestry. Together with mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for similar to 60% of familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72 hexanucleotide repeat expansions present some phenotypic differences compared with patients with mutations of other genes or with unknown mutations, namely a high incidence of bulbar-onset disease and comorbidity with frontotemporal dementia. Their pedigrees typically display a high frequency of cases with pure frontotemporal dementia, widening the concept of familial amyotrophic lateral sclerosis

Pain and Frailty in Hospitalized Older Adults

Introduction: Pain and frailty are prevalent conditions in the older population. Many chronic diseases are likely involved in their origin, and both have a negative impact on quality of life. However, few studies have analysed their association. Methods: In light of this knowledge gap, 3577 acutely hospitalized patients 65 years or older enrolled in the REPOSI register, an Italian network of internal medicine and geriatric hospital wards, were assessed to calculate the frailty index (FI). The impact of pain and some of its characteristics on the degree of frailty was evaluated using an ordinal logistic regression model after adjusting for age and gender. Results: The prevalence of pain was 24.7%, and among patients with pain, 42.9% was regarded as chronic pain. Chronic pain was associated with severe frailty (OR = 1.69, 95% CI 1.38–2.07). Somatic pain (OR = 1.59, 95% CI 1.23–2.07) and widespread pain (OR = 1.60, 95% CI 0.93–2.78) were associated with frailty. Osteoarthritis was the most common cause of chronic pain, diagnosed in 157 patients (33.5%). Polymyalgia, rheumatoid arthritis and other musculoskeletal diseases causing chronic pain were associated with a lower degree of frailty than osteoarthritis (OR = 0.49, 95%CI 0.28–0.85). Conclusions: Chronic and somatic pain negatively affect the degree of frailty. The duration and type of pain, as well as the underlying diseases associated with chronic pain, should be evaluated to improve the hospital management of frail older people

Search for a vector-like quark T′ → tH via the diphoton decay mode of the Higgs boson in proton-proton collisions at s \sqrt{s} = 13 TeV

A search for the electroweak production of a vector-like quark T′, decaying to a top quark and a Higgs boson is presented. The search is based on a sample of proton-proton collision events recorded at the LHC at = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. This is the first T′ search that exploits the Higgs boson decay to a pair of photons. For narrow isospin singlet T′ states with masses up to 1.1 TeV, the excellent diphoton invariant mass resolution of 1–2% results in an increased sensitivity compared to previous searches based on the same production mechanism. The electroweak production of a T′ quark with mass up to 960 GeV is excluded at 95% confidence level, assuming a coupling strength κT = 0.25 and a relative decay width Γ/MT′ < 5%

Measurement of the Higgs boson inclusive and differential fiducial production cross sections in the diphoton decay channel with pp collisions at s \sqrt{s} = 13 TeV

The measurements of the inclusive and differential fiducial cross sections of the Higgs boson decaying to a pair of photons are presented. The analysis is performed using proton-proton collisions data recorded with the CMS detector at the LHC at a centre-of-mass energy of 13 TeV and corresponding to an integrated luminosity of 137 fb$^{−1}$. The inclusive fiducial cross section is measured to be $σ_{fid}$=73.4$^{+5.4}_{−5.3}$(stat)$^{+2.4}_{−2.2}$(syst) fb, in agreement with the standard model expectation of 75.4 ± 4.1 fb. The measurements are also performed in fiducial regions targeting different production modes and as function of several observables describing the diphoton system, the number of additional jets present in the event, and other kinematic observables. Two double differential measurements are performed. No significant deviations from the standard model expectations are observed

Measurement of the Dependence of the Hadron Production Fraction Ratios fs/fuf_s / f_u and fd/fuf_d / f_u on BB Meson Kinematic Variables in Proton-Proton Collisions at s=13TeV\sqrt{s} = 13 TeV

The dependence of the ratio between the $B^0_s$ and $B^+$ hadron production fractions, $f_s/f_u$, on the transverse momentum $(p_T)$ and rapidity of the $B$ mesons is studied using the decay channels $B^0_s→J/ψϕ$ and $B^+→J/ψK^+$. The analysis uses a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of $61.6  fb^{−1}$. The $f_s/f_u$ ratio is observed to depend on the $B$ $p_T$ and to be consistent with becoming asymptotically constant at large $p_T$. No rapidity dependence is observed. The ratio of the $B^0$ to $B^+$ meson production fractions, $f_d/f_u$, is also measured, for the first time in proton-proton collisions, using the $B^0→J/ψK^{*0}$ decay channel. The result is found to be within 1 standard deviation of unity and independent of $pT$ and rapidity, as expected from isospin invariance

Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

A search for new physics in central exclusive production using the missing mass technique with the CMS detector and the CMS-TOTEM precision proton spectrometer

A generic search is presented for the associated production of a Z boson or a photon with an additional unspecified massive particle X, pp → pp + Z/γ + X, in proton-tagged events from proton–proton collisions at √s = 13 TeV, recorded in 2017 with the CMS detector and the CMS-TOTEM precision proton spectrometer. The missing mass spectrum is analysed in the 600–1600 GeV range and a fit is performed to search for possible deviations from the background expectation. No significant excess in data with respect to the background predictions has been observed. odelindependent upper limits on the visible production cross section of pp → pp + Z/γ + X are set