When and How Can Endpoints Be Changed after Initiation of a Randomized Clinical Trial?

Contains fulltext : 52680.pdf ( ) (Open Access)OBJECTIVES: It is unclear whether insulin-like growth factor (IGF) function is involved in the pathophysiology of chronic fatigue syndrome (CFS). Unpublished data and reports in patient organization newsletters suggest that Acclydine, a food supplement, could be effective in the treatment of CFS by increasing biologically active IGF1 levels. Here we aimed to measure the IGF1 and IGF binding protein (IGFBP) 3 status of CFS patients compared to age- and gender-matched neighborhood controls, and to assess the effect of Acclydine on fatigue severity, functional impairment, and biologically active IGF1 level (IGFBP3/IGF1 ratio). DESIGN: A randomized, placebo-controlled, double-blind clinical trial. SETTING: Radboud University Nijmegen Medical Centre, The Netherlands. PARTICIPANTS: Fifty-seven adult patients who fulfilled the US Centers for Disease Control and Prevention criteria for CFS. IGF status of 22 CFS patients was compared to that of 22 healthy age- and gender-matched neighborhood control individuals. INTERVENTION: Acclydine or placebo for 14 wk. OUTCOME MEASURES: Outcomes were fatigue severity (Checklist Individual Strength, subscale fatigue severity [CIS-fatigue]), functional impairment (Sickness Impact Profile-8 [SIP-8]), and biologically active IGF1 serum concentrations. Analyses were on an intention-to-treat basis. RESULTS: There was no difference in IGF status in 22 CFS patients compared to healthy age- and gender-matched control individuals. Treatment with Acclydine did not result in significant differences compared with the placebo group on any of the outcome measures: CIS-fatigue +1.1 (95% CI -4.4 to +6.5, p = 0.70), SIP-8 +59.1 (95% CI -201.7 to +319.8, p = 0.65), and IGFBP3/IGF1 ratio -0.5 (95% CI -2.8 to +1.7, p = 0.63). CONCLUSION: We found no differences in IGF1 status in CFS patients compared to healthy matched neighborhood controls. In addition, the results of this clinical trial do not demonstrate any benefit of Acclydine over placebo in the treatment of CFS

Postępowanie w chorobach tarczycy u kobiet w ciąży

The management of thyroid disorders during pregnancy is one of the most frequently disputed problems in modern endocrinology. It is widely known that thyroid dysfunction may result in subfertility, and, if inadequately treated during pregnancy, may cause obstetrical complications and influence fetal development. The 2007 Endocrine Society Practice Guideline endorsed with the participation of the Latino America Thyroid Association, the American Thyroid Association, the Asia and Oceania Thyroid Association and the European Thyroid Association, greatly contributed towards uniformity of the management of thyroid disorders during pregnancy and postpartum. Despite the tremendous progress in knowledge on the mutual influence of pregnancy and thyroid in health and disease, there are still important areas of uncertainty. There have been at least a few important studies published in the last 3 years, which influenced the thyroidal care of the expecting mother. It should also be remembered that guidelines may not always be universally applied in all populations with different ethnical, socio-economical, nutritional (including iodine intake) background or exposed to different iodine prophylaxis models. The Task Force for development of guidelines for thyroid dysfunction management in pregnant women was established in 2008. The expert group has recognized the following tasks: development of the coherent model of the management of thyroid dysfunction in pregnant women, identification of the group of women at risk of thyroid dysfunction, who may require endocrine care in the preconception period, during pregnancy and postpartum – that is in other words, the development of Polish recommendations for targeted thyroid disorder case finding during pregnancy, and the development of Polish trimester-specific reference values of thyroid hormones. Comprehensive Polish guidelines developed by the Task Force are to systematize the management of the thyroid disorders in pregnant women in Poland. (Pol J Endocrinol 2011; 62 (4): 362–381)Jednym z aktualnie szeroko dyskutowanych problemów współczesnej endokrynologii jest opieka tyreologiczna nad kobietą ciężarną. Powszechnie wiadomo, że dysfunkcja tarczycy może być przyczyną zaburzeń płodności, a nieleczona prawidłowo w czasie ciąży zwiększa ryzyko powikłań położniczych oraz ma wpływ na rozwój płodu. Opublikowane w 2007 roku wytyczne Towarzystwa Endokrynologicznego (Endocrine Society), opracowane przy współudziale Towarzystwa Tyreologicznego Ameryki Łacińskiej (LATS), Towarzystwa Tyreologicznego Azji i Oceanii (AOTA), Amerykańskiego Towarzystwa Tyreologicznego (ATA) oraz Europejskiego Towarzystwa Tyreologicznego (ETA), w dużym stopniu usystematyzowały zasady postępowania w chorobach tarczycy w czasie ciąży i w okresie poporodowym. Pomimo ogromnego postępu wiedzy na temat wzajemnego wpływu ciąży i funkcji gruczołu tarczowego w zdrowiu i chorobie, jaki osiągnięto w ciągu ostatnich kilkunastu lat, nadal pewne obszary wymagają dalszych badań. W ciągu 3 lat, które minęły od publikacji wytycznych, przybyło danych, które wpłynęły na niektóre zasady prowadzenia ciężarnej z chorobą tarczycy. Wytyczne nie zawsze mają charakter uniwersalny i nie mogą być w prosty sposób transponowane na społeczeństwa zróżnicowane etnicznie i ekonomicznie, o odmiennych zwyczajach dietetycznych, w tym w spożyciu nośników jodu, oraz stosujące odmienne modele profilaktyki jodowej. W 2008 roku powołano Zespół Ekspertów do spraw Opieki Tyreologicznej w Ciąży. Za cele prac Zespołu przyjęto: opracowanie modelu opieki nad ciężarną z zaburzeniami funkcji tarczycy, określenie grupy kobiet z ryzykiem zaburzeń funkcji tarczycy wymagających oceny tyreologicznej podczas planowania ciąży, w trakcie jej trwania oraz w okresie poporodowym — czyli przygotowanie polskich wskazań do badań przesiewowych oraz ustalenie wartości referencyjnych stężeń hormonów tarczycy w poszczególnych trymestrach ciąży. Opracowane przez Zespół wytyczne systematyzują zasady opieki tyreologicznej nad kobietą ciężarną w Polsce. (Endokrynol Pol 2011; 62 (4): 362–381

Studies of new Higgs boson interactions through nonresonant HH production in the b¯bγγ fnal state in pp collisions at √s = 13 TeV with the ATLAS detector

A search for nonresonant Higgs boson pair production in the b ¯bγγ fnal state is performed using 140 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. This analysis supersedes and expands upon the previous nonresonant ATLAS results in this fnal state based on the same data sample. The analysis strategy is optimised to probe anomalous values not only of the Higgs (H) boson self-coupling modifer κλ but also of the quartic HHV V (V = W, Z) coupling modifer κ2V . No signifcant excess above the expected background from Standard Model processes is observed. An observed upper limit µHH < 4.0 is set at 95% confdence level on the Higgs boson pair production cross-section normalised to its Standard Model prediction. The 95% confdence intervals for the coupling modifers are −1.4 < κλ < 6.9 and −0.5 < κ2V < 2.7, assuming all other Higgs boson couplings except the one under study are fxed to the Standard Model predictions. The results are interpreted in the Standard Model efective feld theory and Higgs efective feld theory frameworks in terms of constraints on the couplings of anomalous Higgs boson (self-)interactions

Searches for lepton-flavour-violating decays of the Higgs boson into eτ and μτ in \sqrt{s} = 13 TeV pp collisions with the ATLAS detector

Abstract This paper presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ, performed using data collected with the ATLAS detector at the LHC. The searches are based on a data sample of proton-proton collisions at a centre-of-mass energy s $$\sqrt{s}$$ = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. Leptonic (τ → ℓνℓντ) and hadronic (τ → hadrons ντ) decays of the τ-lepton are considered. Two background estimation techniques are employed: the MC-template method, based on data-corrected simulation samples, and the Symmetry method, based on exploiting the symmetry between electrons and muons in the Standard Model backgrounds. No significant excess of events is observed and the results are interpreted as upper limits on lepton-flavour-violating branching ratios of the Higgs boson. The observed (expected) upper limits set on the branching ratios at 95% confidence level, B $$\mathcal{B}$$ (H → eτ) < 0.20% (0.12%) and B $$\mathcal{B}$$ (H → μτ ) < 0.18% (0.09%), are obtained with the MC-template method from a simultaneous measurement of potential H → eτ and H → μτ signals. The best-fit branching ratio difference, B $$\mathcal{B}$$ (H → μτ) → B $$\mathcal{B}$$ (H → eτ), measured with the Symmetry method in the channel where the τ-lepton decays to leptons, is (0.25 ± 0.10)%, compatible with a value of zero within 2.5σ

Measurement of the H → γ γ and H → ZZ∗ → 4 cross-sections in pp collisions at √s = 13.6 TeV with the ATLAS detector

The inclusive Higgs boson production cross section is measured in the di-photon and the Z Z∗ → 4 decay channels using 31.4 and 29.0 fb−1 of pp collision data respectively, collected with the ATLAS detector at a centre of-mass energy of √s = 13.6 TeV. To reduce the model dependence, the measurement in each channel is restricted to a particle-level phase space that closely matches the chan nel’s detector-level kinematic selection, and it is corrected for detector effects. These measured fiducial cross-sections are σfid,γ γ = 76+14 −13 fb, and σfid,4 = 2.80 ± 0.74 fb, in agreement with the corresponding Standard Model predic tions of 67.6±3.7 fb and 3.67±0.19 fb. Assuming Standard Model acceptances and branching fractions for the two chan nels, the fiducial measurements are extrapolated to the full phase space yielding total cross-sections of σ (pp → H) = 67+12 −11 pb and 46±12 pb at 13.6 TeV from the di-photon and Z Z∗ → 4 measurements respectively. The two measure ments are combined into a total cross-section measurement of σ (pp → H) = 58.2±8.7 pb, to be compared with the Stan dard Model prediction of σ (pp → H)SM = 59.9 ± 2.6 p

Model-independent search for the presence of new physics in events including H → γγ with s \sqrt{s} = 13 TeV pp data recorded by the ATLAS detector at the LHC

Abstract A model-independent search for new physics leading to final states containing a Higgs boson, with a mass of 125.09 GeV, decaying to a pair of photons is performed with 139 fb−1 of s $$\sqrt{s}$$ = 13 TeV pp collision data recorded by the ATLAS detector at the Large Hadron Collider at CERN. This search examines 22 final states categorized by the objects that are produced in association with the Higgs boson. These objects include isolated electrons or muons, hadronically decaying τ-leptons, additional photons, missing transverse momentum, and hadronic jets, as well as jets that are tagged as containing a b-hadron. No significant excesses above Standard Model expectations are observed and limits on the production cross section at 95% confidence level are set. Detector efficiencies are reported for all 22 signal regions, which can be used to convert detector-level cross-section limits reported in this paper to particle-level cross-section constraints

Inclusive-photon production and its dependence on photon isolation in pp collisions at s \sqrt{s} = 13 TeV using 139 fb−1 of ATLAS data

Measurements of differential cross sections are presented for inclusive isolated-photon production in pp collisions at a centre-of-mass energy of 13 TeV provided by the LHC and using 139 fb−1 of data recorded by the ATLAS experiment. The cross sections are measured as functions of the photon transverse energy in different regions of photon pseudorapidity. The photons are required to be isolated by means of a fixed-cone method with two different cone radii. The dependence of the inclusive-photon production on the photon isolation is investigated by measuring the fiducial cross sections as functions of the isolation-cone radius and the ratios of the differential cross sections with different radii in different regions of photon pseudorapidity. The results presented in this paper constitute an improvement with respect to those published by ATLAS earlier: the measurements are provided for different isolation radii and with a more granular segmentation in photon pseudorapidity that can be exploited in improving the determination of the proton parton distribution functions. These improvements provide a more in-depth test of the theoretical predictions. Next-to-leading-order QCD predictions from JETPHOX and SHERPA and next-to-next-to-leading-order QCD predictions from NNLOJET are compared to the measurements, using several parameterisations of the proton parton distribution functions. The measured cross sections are well described by the fixed-order QCD predictions within the experimental and theoretical uncertainties in most of the investigated phase-space region

Combination of searches for invisible decays of the Higgs boson using 139 fb−1 of proton-proton collision data at root s=13 TeV collected with the ATLAS experiment

Many extensions of the Standard Model predict the production of dark matter particles at the LHC. Sufficiently light dark matter particles may be produced in decays of the Higgs boson that would appear invisible to the detector. This Letter presents a statistical combination of searches for H→invisible decays where multiple production modes of the Standard Model Higgs boson are considered. These searches are performed with the ATLAS detector using 139 fb−1of proton–proton collisions at a centre–of–mass energy of √s=13TeV at the LHC. In combination with the results at √s=7TeV and 8TeV, an upper limit on the H→invisible branching ratio of 0.107 (0.077) at the 95% confidence level is observed (expected). These results are also interpreted in the context of models where the 125GeV Higgs boson acts as a portal to dark matter, and limits are set on the scattering cross-section of weakly interacting massive particles and nucleons