Global solar wind variations over the last four centuries

The most recent “grand minimum” of solar activity, the Maunder minimum (MM, 1650–1710), is of great interest both for understanding the solar dynamo and providing insight into possible future heliospheric conditions. Here, we use nearly 30 years of output from a data-constrained magnetohydrodynamic model of the solar corona to calibrate heliospheric reconstructions based solely on sunspot observations. Using these empirical relations, we produce the first quantitative estimate of global solar wind variations over the last 400 years. Relative to the modern era, the MM shows a factor 2 reduction in near-Earth heliospheric magnetic field strength and solar wind speed, and up to a factor 4 increase in solar wind Mach number. Thus solar wind energy input into the Earth’s magnetosphere was reduced, resulting in a more Jupiter-like system, in agreement with the dearth of auroral reports from the time. The global heliosphere was both smaller and more symmetric under MM conditions, which has implications for the interpretation of cosmogenic radionuclide data and resulting total solar irradiance estimates during grand minima

Return to play with hypertrophic cardiomyopathy: are we moving too fast? A critical review.

The diagnosis of a potentially lethal cardiovascular disease in a young athlete presents a complex dilemma regarding athlete safety, patient autonomy, team or institutional risk tolerance and medical decision-making. Consensus cardiology recommendations previously supported the 'blanket' disqualification of athletes with hypertrophic cardiomyopathy (HCM) from competitive sport. More recently, epidemiological studies examining the relative contribution of HCM as a cause of sudden cardiac death (SCD) in young athletes and reports from small cohorts of older athletes with HCM that continue to exercise have fueled debate whether it is safe to play with HCM. Shared decision-making is endorsed within the sports cardiology community in which athletes can make an informed decision about treatment options and potentially elect to continue competitive sports participation. This review critically examines the available evidence relevant to sports eligibility decisions in young athletes diagnosed with HCM. Histopathologically, HCM presents an unstable myocardial substrate that is vulnerable to ventricular tachyarrhythmias during exercise. Studies support that young age and intense competitive sports are risk factors for SCD in patients with HCM. We provide an estimate of annual mortality based on our understanding of disease prevalence and the incidence of HCM-related SCD in different athlete populations. Adolescent and young adult male athletes and athletes participating in a higher risk sport such as basketball, soccer and American football exhibit a greater risk. This review explores the potential harms and benefits of sports disqualification in athletes with HCM and details the challenges and limitations of shared decision-making when all parties may not agree

Multi-component based cross correlation beat detection in electrocardiogram analysis

BACKGROUND: The first stage in computerised processing of the electrocardiogram is beat detection. This involves identifying all cardiac cycles and locating the position of the beginning and end of each of the identifiable waveform components. The accuracy at which beat detection is performed has significant impact on the overall classification performance, hence efforts are still being made to improve this process. METHODS: A new beat detection approach is proposed based on the fundamentals of cross correlation and compared with two benchmarking approaches of non-syntactic and cross correlation beat detection. The new approach can be considered to be a multi-component based variant of traditional cross correlation where each of the individual inter-wave components are sought in isolation as opposed to being sought in one complete process. Each of three techniques were compared based on their performance in detecting the P wave, QRS complex and T wave in addition to onset and offset markers for 3000 cardiac cycles. RESULTS: Results indicated that the approach of multi-component based cross correlation exceeded the performance of the two benchmarking techniques by firstly correctly detecting more cardiac cycles and secondly provided the most accurate marker insertion in 7 out of the 8 categories tested. CONCLUSION: The main benefit of the multi-component based cross correlation algorithm is seen to be firstly its ability to successfully detect cardiac cycles and secondly the accurate insertion of the beat markers based on pre-defined values as opposed to performing individual gradient searches for wave onsets and offsets following fiducial point location

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Reusable Components of Semantic Specifications

Semantic specifications of programming languages typically have poor modularity. This hinders reuse of parts of the semantics of one language when specifying a different language – even when the two languages have many constructs in common – and evolution of a language may require major reformulation of its semantics. Such drawbacks have discouraged language developers from using formal semantics to document their designs. In the PLanCompS project, we have developed a component-based approach to semantics. Here, we explain its modularity aspects, and present an illustrative case study: a component-based semantics for Caml Light. We have tested the correctness of the semantics by running programs on an interpreter generated from the semantics, comparing the output with that produced on the standard implementation of the language. Our approach provides good modularity, facilitates reuse, and should support co-evolution of languages and their formal semantics. It could be particularly useful in connection with domain-specific languages and language-driven software development

Diagnostic accuracy of post-mortem MRI for thoracic abnormalities in fetuses and children

OBJECTIVES: To compare the diagnostic accuracy of post-mortem magnetic resonance imaging (PMMR) specifically for non-cardiac thoracic pathology in fetuses and children, compared with conventional autopsy. METHODS: Institutional ethics approval and parental consent was obtained. A total of 400 unselected fetuses and children underwent PMMR before conventional autopsy, reported blinded to the other dataset. RESULTS: Of 400 non-cardiac thoracic abnormalities, 113 (28 %) were found at autopsy. Overall sensitivity and specificity (95 % confidence interval) of PMMR for any thoracic pathology was poor at 39.6 % (31.0, 48.9) and 85.5 % (80.7, 89.2) respectively, with positive predictive value (PPV) 53.7 % (42.9, 64.0) and negative predictive value (NPV) 77.0 % (71.8, 81.4). Overall agreement was 71.8 % (67.1, 76.2). PMMR was most sensitive at detecting anatomical abnormalities, including pleural effusions and lung or thoracic hypoplasia, but particularly poor at detecting infection. CONCLUSIONS: PMMR currently has relatively poor diagnostic detection rates for the commonest intra-thoracic pathologies identified at autopsy in fetuses and children, including respiratory tract infection and diffuse alveolar haemorrhage. The reasonable NPV suggests that normal thoracic appearances at PMMR exclude the majority of important thoracic lesions at autopsy, and so could be useful in the context of minimally invasive autopsy for detecting non-cardiac thoracic abnormalities. KEY POINTS: • PMMR has relatively poor diagnostic detection rates for common intrathoracic pathology • The moderate NPV suggests that normal PMMR appearances exclude most important abnormalities • Lung sampling at autopsy remains the "gold standard" for pulmonary pathology

Risk factors for failure to return to the pre-fracture place of residence after hip fracture: a prospective longitudinal study of 444 patients

Introduction: Long-term place of residence after hip fracture is not often described in literature. The goal of this study was to identify risk factors, known at admission, for failure to return to the pre-fracture place of residence of hip fracture patients in the Wrst year after a hip fracture. Methods: This is a prospective longitudinal study of 444 consecutive admissions of hip fracture patients aged ≥65 years. Place of residence prior to admission, at discharge, after 3 and 12 months was registered. Patients admitted from a nursing home (n = 49) were excluded from statistical analysis. Multivariable logistic regression analysis was performed, using age, gender, presence of a partner, ASAscore, dementia, anaemia at admission, type of fracture, pre-fracture level of mobility and level of activities of daily living (ADL) as possible risk factors. Results: Two hundred eighty-nine patients lived in their own home, 31.8% returned at discharge, 72.9% at 3 months and 72.8% at 12 months. Age, absence of a partner, dementia, and a lower pre-fracture level of ADL or mobility were independent contributors to failure to return to their own home at discharge, 3 or 12 months. 106 patients lived in a residential home; 33.3% returned at discharge, 68.4% at 3 months and 64.4% at 12 months. Age was an independent contributor to failure to return to a residential home. Conclusions: Age, dementia and a lower pre-fracture level of ADL were the main signiWcant risk factors for failure to return to the pre-fracture residence. As the 3- and 12-month return-rates were similar, 3-month follow-up might be used as an endpoint in future research

Sex differential in mortality trends of old-aged Danes: a nation wide study of age, period and cohort effects

Objective Over the last half century the mortality rates in Denmark for females above age 80 have declined dramatically whereas the decline for males have been modest, resulting in a change in sex-ratio for centenarians from 2 to 5. Here we investigate whether this mortality pattern is mainly explained by period effects, cohort effects or both. This can provide clues for where to search for causes behind the changes in sex differential in mortality seen in many Western countries during the last decades. Methods Age-period-cohort study of mortality for all Danish women and men aged 79–98 during the period 1949–2006. Outcome measures Relative risks for deaths and second order differences for exploration of the nonlinear variation. Results Both the overall trends in mortality differences and the fluctuations in mortality for both men and women were better explained by period effects than by cohort effects. The observed rates were better described by the age, period and cohort model than by other models. Conclusions Our results suggest that causes for both the overall increased difference in mortality and the short term fluctuations in mortality rates are primarily to be found in the period dimension. Cohort effects on the mortality of the oldest Danish women and men played a significant but minor role compared to period effects

High precision determination of the gluon fusion Higgs boson cross-section at the LHC

We present the most precise value for the Higgs boson cross-section in the gluon-fusion production mode at the LHC. Our result is based on a perturbative expansion through N$^3$LO in QCD, in an effective theory where the top-quark is assumed to be infinitely heavy, while all other Standard Model quarks are massless. We combine this result with QCD corrections to the cross-section where all finite quark-mass effects are included exactly through NLO. In addition, electroweak corrections and the first corrections in the inverse mass of the top-quark are incorporated at three loops. We also investigate the effects of threshold resummation, both in the traditional QCD framework and following a SCET approach, which resums a class of $\pi^2$ contributions to all orders. We assess the uncertainty of the cross-section from missing higher-order corrections due to both perturbative QCD effects beyond N$^3$LO and unknown mixed QCD-electroweak effects. In addition, we determine the sensitivity of the cross-section to the choice of parton distribution function (PDF) sets and to the parametric uncertainty in the strong coupling constant and quark masses. For a Higgs mass of $m_H = 125~{\rm GeV}$ and an LHC center-of-mass energy of $13~{\rm TeV}$, our best prediction for the gluon fusion cross-section is \[ \sigma = 48.58\,{\rm pb} {}^{+2.22\, {\rm pb}\, (+4.56\%)}_{-3.27\, {\rm pb}\, (-6.72\%)} \mbox{ (theory)} \pm 1.56 \,{\rm pb}\, (3.20\%) \mbox{ (PDF+$\alpha_s$)} \