85 research outputs found

    Unfolding Quantum Computer Readout Noise

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    In the current era of noisy intermediate-scale quantum (NISQ) computers, noisy qubits can result in biased results for early quantum algorithm applications. This is a significant challenge for interpreting results from quantum computer simulations for quantum chemistry, nuclear physics, high energy physics, and other emerging scientific applications. An important class of qubit errors are readout errors. The most basic method to correct readout errors is matrix inversion, using a response matrix built from simple operations to probe the rate of transitions from known initial quantum states to readout outcomes. One challenge with inverting matrices with large off-diagonal components is that the results are sensitive to statistical fluctuations. This challenge is familiar to high energy physics, where prior-independent regularized matrix inversion techniques (`unfolding') have been developed for years to correct for acceptance and detector effects when performing differential cross section measurements. We study various unfolding methods in the context of universal gate-based quantum computers with the goal of connecting the fields of quantum information science and high energy physics and providing a reference for future work. The method known as iterative Bayesian unfolding is shown to avoid pathologies from commonly used matrix inversion and least squares methods.Comment: 13 pages, 16 figures; v2 has a typo fixed in Eq. 3 and a series of minor modification

    G-CSF, rt-PA and combination therapy after experimental thromboembolic stroke

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    BACKGROUND: Granulocyte Colony-Stimulating Factor (G-CSF) has remarkable neuroprotective properties. Due to its proven safety profile, G-CSF is currently used in clinical stroke trials. As neuroprotectants are considered to be more effective in the early phase of cerebral ischemia and during reperfusion, G-CSF should to be tested in combination with thrombolysis. Therefore, combination therapy was investigated in an experimental model of thromboembolic stroke. METHODS: Male Wistar rats (n = 72) were subjected to a model of thromboembolic occlusion (TE) of the middle cerebral artery. Different groups (n = 12 each) treated by recombinant tissue-plasminogen activator (rt-PA) or/and G-CSF: group control (control), group early G-CSF (G-CSF 60 min after TE), group rt-PA (rt-PA 60 min after TE), group com (combination rt-PA/G-CSF), group delayed rt-PA (rt-PA after 180 min), group deco (G-CSF after 60 min, rt-PA after 180 min). Animals were investigated by magnetic resonance imaging (MRI) and silver infarct staining (SIS) 24 hours after TE. RESULTS: Early G-CSF or rt-PA reduced the infarct size compared to all groups (p \u3c 0.05 to p \u3c 0.01) with the exception of group com, (p = n.s.) as measured by T2, DWI, and SIS. Late administration of rt-PA lead to high mortality and larger infarcts compared to all other groups (p \u3c 0.05 to p \u3c 0.01). Pre-treatment by G-CSF (deco) reduced infarct site compared to delayed rt-PA treatment (p \u3c 0.05). G-CSF did not significantly influence PWI when combined with rt-PA. All animals treated by rt-PA showed improved parameters in PWI indicating reperfusion. CONCLUSIONS: G-CSF was neuroprotective when given early after TE. Early combination with rt-PA showed no additional benefit compared to rt-PA or G-CSF alone, but did not lead to side effects. Pretreatment by G-CSF was able to reduce deleterious effects of late rt-PA treatment

    Childhood and adult social conditions and risk of stroke

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    Background: Socioeconomic conditions may strongly influence the risk of stroke. We tested the hypotheses that indexes of social status in different life periods including childhood are inversely associated with stroke risk and that there is a cumulative effect of social conditions during lifetime on the risk of stroke. Furthermore, we investigated whether social advancement compared to the parental generation is associated with reduced stroke risk. Methods: In a case-control study, we assessed parental professional status, highest school degree, professional education and the last professional activity in 370 consecutive patients with ischemic or hemorrhagic stroke or transient ischemic attack [TIA; age 60.7 +/- 12.8 years (mean +/- standard deviation); 31.1% women] and 370 age-and sex-matched control subjects randomly selected from the general population of the same area. Results: Higher level of school exams [odds ratio (OR) 0.58, 95% confidence interval (CI) 0.39-0.86], university or polytechnic high school degrees (OR 0.39, 95% CI 0.24-0.63), nonmanual (last or current) professional activity (OR 0.51, 95% CI 0.37-0.71) and father’s nonmanual professional activity (OR 0.64, 95% 0.43-0.97) were associated with a lower risk of stroke/TIA. Adjustment for vascular risk factors including current smoking and alcohol consumption reduced the strength of these associations and rendered them nonsignificant except for university or polytechnic high school degrees (OR 0.49, 95% CI 0.27-0.87). Additional adjustment for regular sports activity further attenuated the association between academic degrees and risk of stroke/TIA (OR 0.56, 95% CI 0.31-1.02). A score summarizing 4 lifetime social indexes was not independently associated with stroke risk (OR 0.67, 95% CI 0.39-1.16). Social advancement as assessed by changes from paternal manual work to nonmanual work in the index generation was more common among control subjects (23.5%) than patients (15.3%; p = 0.0097), but such advancement was not independently associated with stroke/TIA after adjustment for all covariables (OR 0.82, 95% CI 0.50–1.33). Conclusions: Socioeconomic conditions were inversely linked to the risk of stroke/TIA. These associations were strongly influenced by lifestyle factors such as smoking, alcohol consumption and mainly sports activity. Stroke preventive strategies may have a particularly large potential if they focus on such lifestyle habits in socially disadvantaged groups. Copyright © 2012 S. Karger AG, Base

    Serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase and myeloperoxidase in ischemic stroke

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    Background and aims: Matrix metalloproteinase (MMP)-8 and myeloperoxidase (MPO) may contribute to cerebral damage in acute ischemic stroke. We tested the hypothesis that levels of MPO, MMP-8 and the ratio between MMP-8 and its regulator, tissue inhibitor of metalloproteinase (TIMP-1), are increased in acute ischemic stroke and its etiologic subgroups and they correlate with stroke severity. Methods: In a cross-sectional case-control study, serum concentrations of MMP-8, MPO and TIMP-1 were assessed within 24 h after admission in 470 first-ever ischemic stroke patients and 809 age-and sex-matched controls, randomly selected from the population. Odds ratios (OR) per decade of log transformed dependent variables were calculated and adjusted for age, sex and vascular risk factors. Results: Levels of MMP-8 (OR 4.9; 95% CI 3.4-7.2), MMP-8/TIMP-1 ratio (3.0; 2.2-4.1) and MPO (6.6; 4.0-11.0) were independently associated with ischemic stroke. MMP-8 levels differed between etiologic stroke subgroups (p = 0.019, ANOVA), with higher levels in cardioembolic stroke and stroke due to large vessel disease, and lower levels in microangiopathic stroke. MMP-8, MMP-8/TIMP-1 ratio and MPO (p <0.001) concentrations showed positive associations with stroke severity independent of stroke etiology. Conclusions: Concentrations of serum neutrophil markers are increased after ischemic stroke and associate with stroke severity and etiology. The value of these biomarkers in diagnostics and prognostics is worth being evaluated. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

    Association between infectious burden, socioeconomic status, and ischemic stroke

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    Background and aims: Infectious diseases contribute to stroke risk, and are associated with socioeconomic status (SES). We tested the hypotheses that the aggregate burden of infections increases the risk of ischemic stroke (IS) and partly explains the association between low SES and ischemic stroke. Methods: In a case-control study with 470 ischemic stroke patients and 809 age- and sex-matched controls, randomly selected from the population, antibodies against the periodontal microbial agents Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, against Chlamydia pneumonia, Mycoplasma pneumoniae (IgA and IgG), and CagA-positive Helicobacter pylori (IgG) were assessed. Results: IgA seropositivity to two microbial agents was significantly associated with IS after adjustment for SES (OR 1.45 95% CI 1.01-2.08), but not in the fully adjusted model (OR 1.32 95% CI 0.86-2.02). By trend, cumulative IgA seropositivity was associated with stroke due to large vessel disease (LVD) after full adjustment (OR 1.88, 95% CI 0.96e3.69). Disadvantageous childhood SES was associated with higher cumulative seropositivity in univariable analyses, however, its strong impact on stroke risk was not influenced by seroepidemiological data in the multivariable model. The strong association between adulthood SES and stroke was rendered nonsignificant when factors of dental care were adjusted for. Conclusions: Infectious burden assessed with five microbial agents did not independently contribute to ischemic stroke consistently, but may contribute to stroke due to LVD. High infectious burden may not explain the association between childhood SES and stroke risk. Lifestyle factors that include dental negligence may contribute to the association between disadvantageous adulthood SES and stroke. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

    Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen stroke study, a population-based stroke registry

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    Background: Stroke etiology in ischemic stroke guides preventive measures and etiological stroke subgroups may show considerable differences between both sexes. In a population-based stroke registry we analyzed etiological subgroups of ischemic stroke and calculated sex-specific incidence and mortality rates. Methods: The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke registry. Multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Modified TOAST ( Trial of Org 10172 in Acute Stroke Treatment) criteria were applied for subgroup analysis in ischemic stroke. Results: Out of 626 patients with first-ever ischemic stroke in 2006 and 2007, women (n = 327) were older (73.5 8 12.6 years) than men (n = 299; 69.7 8 11.5 years; p < 0.001). The age-adjusted incidence rate of ischemic stroke was significantly higher in men (1.37; 95% CI 1.20–1.56) than in women (1.12; 95% CI 0.97–1.29; p = 0.04). Cardioembolism (n = 219; 35.0%), smallartery occlusion (n = 164; 26.2%), large-artery atherosclerosis (n = 98; 15.7%) and ‘probable atherothrombotic stroke’ (n = 84; 13.4%) were common subgroups of ischemic stroke. Stroke due to large-artery atherosclerosis (p = 0.025), current smoking (p = 0.008), history of smoking (p 85 years) was detected. Conclusions: Cardioembolism is the main source for ischemic stroke in our population. Etiology of ischemic stroke differs between sexes, with large-artery atherosclerotic stroke and associated diseases (coronary artery disease and peripheral artery disease) being more common in men

    Low self-reported sports activity before stroke predicts poor one-year-functional outcome after first-ever ischemic stroke in a population-based stroke register

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    Background: Physical activity (PA) is associated with lower risk of stroke. We tested the hypothesis that lack of pre-stroke PA is an independent predictor of poor outcome after first-ever ischemic stroke. Methods: We assessed recent self-reported PA and other potential predictors for loss of functional independence - modified Rankin Scale (mRS) &gt; 2 - one year after first-ever ischemic stroke in 1370 patients registered between 2006 and 2010 in the Ludwigshafen Stroke Study, a population-based stroke registry. Results: After 1 year, 717 (52.3%) of patients lost their independence including 251 patients (18.3%) who had died. In multivariate logistic regression analysis lack of regular PA prior to stroke (Odds Ratio (OR) 1.7, Confidence Interval (CI) 1.1–2.5), independently predicted poor outcome together with higher age (65–74: OR 1.7; CI 1.1–2.8, 75–84 years: OR 3.3; CI 2.1–5.3; ≥85 years OR 14.5; CI 7.4–28.5), female sex (OR 1.5; CI 1.1–2.1), diabetes mellitus (OR 1.8; CI 1.3–2.5), stroke severity (OR 1.2; CI 1.1–1.2), probable atherothrombotic stroke etiology (OR 1.8; CI 1.1–2.8) and high leukocyte count (&gt; 9.000/mm3; OR 1.4; CI 1.0–1.9) at admission. Subclassifying unknown stroke etiology, embolic stroke of unknown source (ESUS; n = 40, OR 2.2; CI 0.9–5.5) tended to be associated with loss of independence. Conclusion: In addition to previously reported factors, lack of PA prior to stroke as potential indicator of worse physical condition, high leukocyte count at admission as indicator of the inflammatory response and probable atherothrombotic stroke etiology might be independent predictors for non-functional independence in first-ever ischemic stroke

    Socioeconomic decline and advancement within and between generations and the risk of stroke - a case-control study

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    Background: Disadvantageous socioeconomic conditions (SEC) in both childhood and adulthood increase the risk of stroke. We investigated whether intergenerational and lifetime social advancement decreases and/or social descent increases stroke risk. Methods: In a case-control study with 466 patients with first-ever ischemic stroke and 807 controls randomly selected from the general population, we compared paternal profession to subjects’ professional education in adolescence and their last profession in adulthood. Furthermore, we constructed a socioeconomic risk score for childhood (based on paternal and maternal profession and occupation, familial, living and material conditions), adolescence (based on highest school degree and professional education), and adulthood (based on last profession, periods of unemployment, and marital status), and compared subjects´ positions at different life stages. Odds ratios were derived based on conditional logistic regression conditioning on age and sex only, after adjustment for medical and lifestyle risk factors, and after additional adjustment for socioeconomic risk score values. Results: Intergenerational upward mobility between paternal profession and subject’s professional education was associated with lower ischemic stroke risk independent of medical and lifestyle risk factors (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.41–0.81) and after additional adjustment for socioeconomic conditions in all three life stages (OR 0.67; 95% CI 0.45–0.99). Advancement between fathers´ profession and subject’s last profession was associated with reduced odds of stroke after adjustment for risk factors (OR 0.65; 95% CI 0.47–0.89), but not significantly after additional adjustment for SEC (OR 0.77; 95% CI 0.52–1.13). Social descent between adolescence and adulthood indicated by the transition into a more disadvantageous tertile of socioeconomic risk score was associated with increased odds of stroke after adjustment for all risk factor (OR 2.93; 95% CI 1.21–7.13). Analyses by sex revealed mostly similar results in men and women with only few potential differences. Conclusions: Our study results indicate that aspects of social downward mobility during adulthood may be associated with increased risk of stroke, whereas intergenerational upward mobility may be linked to a lower stroke risk. If confirmed by future studies, such results may help to focus stroke prevention measures at high risk populations

    Decline in the number of patients with meningitis in German hospitals during the COVID-19 pandemic

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    BACKGROUND AND OBJECTIVES: In 2020, a wide range of hygiene measures was implemented to mitigate infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In consequence, pulmonary infections due to other respiratory pathogens also decreased. Here, we evaluated the number of bacterial and viral meningitis and encephalitis cases during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a multicentre retrospective analysis of data from January 2016 until December 2020, numbers of patients diagnosed with bacterial meningitis and other types of CNS infections (such as viral meningitis and encephalitis) at 26 German hospitals were studied. Furthermore, the number of common meningitis-preceding ear-nose-throat infections (sinusitis, mastoiditis and otitis media) was evaluated. RESULTS: Compared to the previous years, the total number of patients diagnosed with pneumococcal meningitis was reduced (n = 64 patients/year in 2020 vs. n = 87 to 120 patients/year between 2016 and 2019, all p < 0.05). Additionally, the total number of patients diagnosed with otolaryngological infections was significantly lower (n = 1181 patients/year in 2020 vs. n = 1525 to 1754 patients/year between 2016 and 2019, all p < 0.001). We also observed a decline in viral meningitis and especially enterovirus meningitis (n = 25 patients/year in 2020 vs. n = 97 to 181 patients/year between 2016 and 2019, all p < 0.001). DISCUSSION: This multicentre retrospective analysis demonstrates a decline in the number of patients treated for viral and pneumococcal meningitis as well as otolaryngological infections in 2020 compared to previous years. Since the latter often precedes pneumococcal meningitis, this may point to the significance of the direct spread of pneumococci from an otolaryngological focus such as mastoiditis to the brain as one important pathophysiological route in the development of pneumococcal meningitis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11034-w

    Activated Met Signalling in the Developing Mouse Heart Leads to Cardiac Disease

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    BACKGROUND: The Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF) or the constitutively activated Tpr-Met kinase to explore: i) the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii) the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43) in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease
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