Explore the vast range of titles available.

For a long time, global fits of the electroweak sector of the standard model (SM) have been used to exploit measurements of electroweak precision observables at lepton colliders (LEP, SLC), together with measurements at hadron colliders (Tevatron, LHC) and accurate theoretical predictions at multi-loop level, to constrain free parameters of the SM, such as the Higgs and top masses. Today, all fundamental SM parameters entering these fits are experimentally determined, including information on the Higgs couplings, and the global fits are used as powerful tools to assess the validity of the theory and to constrain scenarios for new physics. Future measurements at the Large Hadron Collider (LHC) and the International Linear Collider (ILC) promise to improve the experimental precision of key observables used in the fits. This paper presents updated electroweak fit results using the latest NNLO theoretical predictions and prospects for the LHC and ILC. The impact of experimental and theoretical uncertainties is analysed in detail. We compare constraints from the electroweak fit on the Higgs couplings with direct LHC measurements, and we examine present and future prospects of these constraints using a model with modified couplings of the Higgs boson to fermions and bosons.

Parkinson's disease is associated with an increased incidence of cognitive impairment and dementia. Predicting who is at risk of cognitive decline early in the disease course has implications for clinical prognosis and for stratification of participants in clinical trials. We assessed the use of clinical information and biomarkers as predictive factors for cognitive decline in patients with newly diagnosed Parkinson's disease. The Parkinson's Progression Markers Initiative (PPMI) study is a cohort study in patients with newly diagnosed Parkinson's disease. We evaluated cognitive performance (Montreal Cognitive Assessment [MoCA] scores), demographic and clinical data, APOE status, and biomarkers (CSF and dopamine transporter [DAT] imaging results). Using change in MoCA scores over 2 years, MoCA scores at 2 years' follow-up, and a diagnosis of cognitive impairment (combined mild cognitive impairment or dementia) at 2 years as outcome measures, we assessed the predictive values of baseline clinical variables and separate or combined additions of APOE status, DAT imaging, and CSF biomarkers. We did univariate and multivariate linear analyses with MoCA change scores between baseline and 2 years, and with MoCA scores at 2 years as dependent variables, using backwards linear regression analysis. Additionally, we constructed a prediction model for diagnosis of cognitive impairment using logistic regression analysis. 390 patients with Parkinson's disease recruited between July 1, 2010, and May 31, 2013, and for whom data on MoCA scores at baseline and 2 years were available. In multivariate analyses, baseline age, University of Pennsylvania Smell Inventory Test (UPSIT) scores, CSF amyloid — (Aβ42) to t-tau ratio, and APOE status were associated with change in MoCA scores over time. Baseline age, MoCA and UPSIT scores, and CSF Aβ42 to t-tau ratio were associated with MoCA score at 2 years (using a backwards p-removal threshold of 0·1). Accuracy of prediction of cognitive impairment using age alone (area under the curve 0·68, 95% CI 0·60–0·76) significantly improved by addition of clinical scores (UPSIT, Rapid Eye Movement Sleep Behaviour Disorder Screening Questionnaire [RBDSQ], Geriatric Depression Scale, and Movement Disorder Society Unified Parkinson's Disease Rating Scale motor scores; 0·76, 0·68–0·83), CSF variables (0·74, 0·68–0·81), or DAT imaging results (0·76, 0·68–0·83). In combination, the five variables showing the most significant associations with cognitive impairment (age, UPSIT, RBDSQ, CSF Aβ42, and caudate uptake on DAT imaging) allowed prediction of cognitive impairment at 2 years (0·80, 0·74–0·87; p=0·0003 compared to age alone). In newly diagnosed Parkinson's disease, the occurrence of cognitive impairment at 2 year follow-up can be predicted with good accuracy using a model combining information on age, non-motor assessments, DAT imaging, and CSF biomarkers. None.

Alzheimer’s disease (AD) is characterized pathologically by amyloid-beta (Aβ) deposition in brain parenchyma and blood vessels (as cerebral amyloid angiopathy (CAA)) and by neurofibrillary tangles of hyperphosphorylated tau. Compelling genetic and biomarker evidence supports Aβ as the root cause of AD. We previously reported human transmission of Aβ pathology and CAA in relatively young adults who had died of iatrogenic Creutzfeldt–Jakob disease (iCJD) after childhood treatment with cadaver-derived pituitary growth hormone (c-hGH) contaminated with both CJD prions and Aβ seeds. This raised the possibility that c-hGH recipients who did not die from iCJD may eventually develop AD. Here we describe recipients who developed dementia and biomarker changes within the phenotypic spectrum of AD, suggesting that AD, like CJD, has environmentally acquired (iatrogenic) forms as well as late-onset sporadic and early-onset inherited forms. Although iatrogenic AD may be rare, and there is no suggestion that Aβ can be transmitted between individuals in activities of daily life, its recognition emphasizes the need to review measures to prevent accidental transmissions via other medical and surgical procedures. As propagating Aβ assemblies may exhibit structural diversity akin to conventional prions, it is possible that therapeutic strategies targeting disease-related assemblies may lead to selection of minor components and development of resistance. A small number of patients who received growth hormone preparations contaminated with seeds of the amyloid-beta protein developed Alzheimer’s disease many years after treatment.

Visual rating scales, developed to assess atrophy in patients with cognitive impairment, offer a cost-effective diagnostic tool that is ideally suited for implementation in clinical practice. By focusing attention on brain regions susceptible to change in dementia and enforcing structured reporting of these findings, visual rating can improve the sensitivity, reliability and diagnostic value of radiological image interpretation. Brain imaging is recommended in all current diagnostic guidelines relating to dementia, and recent guidelines have also recommended the application of medial temporal lobe atrophy rating. Despite these recommendations, and the ease with which rating scales can be applied, there is still relatively low uptake in routine clinical assessments. Careful consideration of atrophy rating scales is needed to verify their diagnostic potential and encourage uptake among clinicians. Determining the added value of combining scores from visual rating in different brain regions may also increase the diagnostic value of these tools.

In view of the discovery of a new boson by the ATLAS and CMS Collaborations at the LHC, we present an update of the global Standard Model (SM) fit to electroweak precision data. Assuming the new particle to be the SM Higgs boson, all fundamental parameters of the SM are known allowing, for the first time, to overconstrain the SM at the electroweak scale and assert its validity. Including the effects of radiative corrections and the experimental and theoretical uncertainties, the global fit exhibits a p -value of 0.07. The mass measurements by ATLAS and CMS agree within 1.3 σ with the indirect determination . Within the SM the W boson mass and the effective weak mixing angle can be accurately predicted to be M W =80.359±0.011 GeV and from the global fit. These results are compatible with, and exceed in precision, the direct measurements. For the indirect determination of the top quark mass we find , in agreement with the kinematic and cross-section-based measurements.

On 7 June , the FDA approved aducanumab, the first new drug for Alzheimer’s disease in almost 20 years—and notably, the first drug with a putative disease‐modifying mechanism for the treatment of this devastating disorder, namely the removal of β‐amyloid (or Aβ) plaques from the brain. Graphical Abstract G. Lalli, J. Schott, J. Hardy, and B De Strooper comment on the FDA approval of aducanumab and provide some interesting points to consider.

Midlife hypertension confers increased risk for cognitive impairment in late life. The sensitive period for risk exposure and extent that risk is mediated through amyloid or vascular-related mechanisms are poorly understood. We aimed to identify if, and when, blood pressure or change in blood pressure during adulthood were associated with late-life brain structure, pathology, and cognition. Participants were from Insight 46, a neuroscience substudy of the ongoing longitudinal Medical Research Council National Survey of Health and Development, a birth cohort that initially comprised 5362 individuals born throughout mainland Britain in one week in 1946. Participants aged 69–71 years received T1 and FLAIR volumetric MRI, florbetapir amyloid-PET imaging, and cognitive assessment at University College London (London, UK); all participants were dementia-free. Blood pressure measurements had been collected at ages 36, 43, 53, 60–64, and 69 years. We also calculated blood pressure change variables between ages. Primary outcome measures were white matter hyperintensity volume (WMHV) quantified from multimodal MRI using an automated method, amyloid-β positivity or negativity using a standardised uptake value ratio approach, whole-brain and hippocampal volumes quantified from 3D-T1 MRI, and a composite cognitive score—the Preclinical Alzheimer Cognitive Composite (PACC). We investigated associations between blood pressure and blood pressure changes at and between 36, 43, 53, 60–64, and 69 years of age with WMHV using generalised linear models with a gamma distribution and log link function, amyloid-β status using logistic regression, whole-brain volume and hippocampal volumes using linear regression, and PACC score using linear regression, with adjustment for potential confounders. Between May 28, 2015, and Jan 10, 2018, 502 individuals were assessed as part of Insight 46. 465 participants (238 [51%] men; mean age 70·7 years [SD 0·7]; 83 [18%] amyloid-β-positive) were included in imaging analyses. Higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) at age 53 years and greater increases in SBP and DBP between 43 and 53 years were positively associated with WMHV at 69–71 years of age (increase in mean WMHV per 10 mm Hg greater SBP 7%, 95% CI 1–14, p=0·024; increase in mean WMHV per 10 mm Hg greater DBP 15%, 4–27, p=0·0057; increase in mean WMHV per one SD change in SBP 15%, 3–29, p=0·012; increase in mean WMHV per 1 SD change in DBP 15%, 3–30, p=0·017). Higher DBP at 43 years of age was associated with smaller whole-brain volume at 69–71 years of age (−6·9 mL per 10 mm Hg greater DBP, −11·9 to −1·9, p=0·0068), as were greater increases in DBP between 36 and 43 years of age (−6·5 mL per 1 SD change, −11·1 to −1·9, p=0·0054). Greater increases in SBP between 36 and 43 years of age were associated with smaller hippocampal volumes at 69–71 years of age (−0·03 mL per 1 SD change, −0·06 to −0·001, p=0·043). Neither absolute blood pressure nor change in blood pressure predicted amyloid-β status or PACC score at 69–71 years of age. High and increasing blood pressure from early adulthood into midlife seems to be associated with increased WMHV and smaller brain volumes at 69–71 years of age. We found no evidence that blood pressure affected cognition or cerebral amyloid-β load at this age. Blood pressure monitoring and interventions might need to start around 40 years of age to maximise late-life brain health. Alzheimer's Research UK, Medical Research Council, Dementias Platform UK, Wellcome Trust, Brain Research UK, Wolfson Foundation, Weston Brain Institute, Avid Radiopharmaceuticals.

Osteoporosis (OP) is a major public health concern, but still OP care does not meet guidelines. Interventions have been developed to improve appropriate OP management. The objective of the present study was to systematically review the current literature to ascertain the efficacy of interventions to improve OP care and characterize interventions taking into account elements related to their potential cost and feasibility. Studies published from 2003 to 2018 were retrieved from PubMed/MEDLINE, Science Direct, Web of Science, Cochrane, and Wiley Online Library databases. Screening of references and quality assessment were independently performed by two reviewers. We classified interventions into three types according to the target of the intervention: health system (structural interventions), healthcare professional (HCP), and patient. Meta-analysis was performed by type of intervention and their effect on two outcomes: prescription of BMD measurement and prescription of OP therapy. A total of 4268 records were screened; 32 studies were included in the qualitative analysis and 29 studies in the quantitative analysis. Structural interventions strongly and significantly improved prescription of BMD measurement (OR = 9.99, 95% CI 2.05; 48.59) and treatment prescription (OR = 3.82, 95% CI 2.16; 6.75). The impact of HCP-centered interventions on BMD measurement prescription did not reach statistical significance (OR = 2.19, 95% CI 0.84; 5.73) but significantly improved treatment prescription (OR = 3.82, 95% CI 2.16; 6.75). Interventions involving patients significantly improved the prescription of BMD measurement (OR = 2.16, 95% CI 1.62; 2.89) and treatment prescription (OR = 1.70, 95% CI 1.35; 2.14). Interventions to improve OP management had a significant positive impact on prescription of BMD measurement but a more limited impact on treatment prescription.

The neurodegenerative disorder Alzheimer's disease is characterised by the formation of β-amyloid plaques and neurofibrillary tangles in the brain parenchyma, which cause synapse and neuronal loss. This leads to clinical symptoms, such as progressive memory deficits. Clinically, these pathological changes can be detected in the cerebrospinal fluid and with brain imaging, although reliable blood tests for plaque and tangle pathologies remain to be developed. Plaques and tangles often co-exist with other brain pathologies, including aggregates of transactive response DNA-binding protein 43 and Lewy bodies, but the extent to which these contribute to the severity of Alzheimer's disease is currently unknown. In this ‘At a glance’ article and poster, we summarise the molecular biomarkers that are being developed to detect Alzheimer's disease and its related pathologies. We also highlight the biomarkers that are currently in clinical use and include a critical appraisal of the challenges associated with applying these biomarkers for diagnostic and prognostic purposes of Alzheimer's disease and related neurodegenerative disorders, also in their prodromal clinical phases.

ObjectiveTo establish the minimal clinically relevant change (MCRC) on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) for patients with mild Alzheimer's disease (AD).DesignCohort study.Setting59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative.PatientsOutpatients with AD in the Alzheimer's Disease Neuroimaging Initiative.Main outcome measuresThe authors applied anchor-based MCRC methodology comparing ADAS-Cog change against clinicians' judgement of clinically relevant worsening between baseline and 6 months in four domains: memory and non-memory cognitive performance; Clinical Dementia Rating Scale; and Functional Assessment Questionnaire. The analysis was repeated for the 6–12-month interval. To support these findings, the authors calculated distribution-based measures including half-baseline SD (1/2 SD) and SEM.Results181 patients (baseline ADAS-Cog score 18.5±6.4) had ADAS-Cog data at 0 and 6 months. Those undergoing clinically significant worsening on any of the four anchor questions (n=41–47) had an average ADAS-Cog change of 3.1–3.8 points. Similar results were found for the 177 patients with 6–12-month data. The average 1/2 SD for the baseline ADAS-Cog score was 3.2, and the SEM was 3.7.Conclusions3 points decline on the ADAS-Cog may be an appropriate MCRC for clinical trials of patients with early AD. However, further studies assessing the MCRC for improvement on the ADAS-Cog, using patient-based judgement as an anchor, and determining the minimal clinically relevant difference between change on two treatments are required.Clinical trial registration numberhttp://clinicalTrials.gov Identifier: NCT00106899.