Prognostic value of PCSK9 levels in patients with acute coronary syndromes.

AIMS Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

Prodromal Transient Ischemic Attack or Minor Stroke and Outcome in Basilar Artery Occlusion

BACKGROUND The presence of prodromal transient ischemic attacks (TIAs) has been associated with a favorable outcome in anterior circulation stroke. We aimed to determine the association between prodromal TIAs or minor stroke and outcomes at 1 month, in the Basilar Artery International Cooperation Study, a registry of patients presenting with an acute symptomatic and radiologically confirmed basilar artery occlusion. METHODS A total of 619 patients were enrolled in the registry. Information on prodromal TIAs was available for 517 patients and on prodromal stroke for 487 patients. We calculated risk ratios and corresponding 95% confidence intervals (CIs) for poor clinical outcome (modified Rankin Scale score ≥4) according to the variables of interest. RESULTS Prodromal minor stroke was associated with poor outcome (crude risk ratio [cRR], 1.26; 95% CI, 1.12-1.42), but TIAs were not (cRR, .93; 95% CI, .79-1.09). These associations remained essentially the same after adjustment for confounding variables. CONCLUSIONS Prodromal minor stroke was associated with an unfavorable outcome in patients with basilar artery occlusion, whereas prodromal TIA was not.

Connecteurs pragmatiques et métareprésentation: l’exemple de parce que

L’objectif principal de cet article est de montrer que certains emplois des connecteurs pragmatiques nécessitent la construction d’une métareprésentation. Nous verrons d’abord que les capacités humaines de métareprésentation sont diverses et montrerons ensuite que cette diversité se retrouve dans les différents types d’emplois des connecteurs. Nous proposerons une esquisse de modèle qui rend compte de cette propriété des connecteurs dans le cadre de la théorie de la pertinence. Enfin, nous testerons la validité de notre modèle en présentant des données dans le domaine de l’acquisition du langage, plus particulièrement sur la production de parce que chez des enfants entre deux et quatre ans.

Reduced foveal vision enhances peripheral monitoring and peripheral event detection

Introduction: Although it seems plausible that sports performance relies on high-acuity foveal vision, it could be empirically shown that myoptic blur (up to +2 diopters) does not harm performance in sport tasks that require foveal information pick-up like golf putting (Bulson, Ciuffreda, & Hung, 2008). How myoptic blur affects peripheral performance is yet unknown. Attention might be less needed for processing visual cues foveally and lead to better performance because peripheral cues are better processed as a function of reduced foveal vision, which will be tested in the current experiment. Methods: 18 sport science students with self-reported myopia volunteered as participants, all of them regularly wearing contact lenses. Exclusion criteria comprised visual correction other than myopic, correction of astigmatism and use of contact lenses out of Swiss delivery area. For each of the participants, three pairs of additional contact lenses (besides their regular lenses; used in the “plano” condition) were manufactured with an individual overcorrection to a retinal defocus of +1 to +3 diopters (referred to as “+1.00 D”, “+2.00 D”, and “+3.00 D” condition, respectively). Gaze data were acquired while participants had to perform a multiple object tracking (MOT) task that required to track 4 out of 10 moving stimuli. In addition, in 66.7 % of all trials, one of the 4 targets suddenly stopped during the motion phase for a period of 0.5 s. Stimuli moved in front of a picture of a sports hall to allow for foveal processing. Due to the directional hypotheses, the level of significance for one-tailed tests on differences was set at α = .05 and posteriori effect sizes were computed as partial eta squares (ηρ2). Results: Due to problems with the gaze-data collection, 3 participants had to be excluded from further analyses. The expectation of a centroid strategy was confirmed because gaze was closer to the centroid than the target (all p < .01). In comparison to the plano baseline, participants more often recalled all 4 targets under defocus conditions, F(1,14) = 26.13, p < .01, ηρ2 = .65. The three defocus conditions differed significantly, F(2,28) = 2.56, p = .05, ηρ2 = .16, with a higher accuracy as a function of a defocus increase and significant contrasts between conditions +1.00 D and +2.00 D (p = .03) and +1.00 D and +3.00 D (p = .03). For stop trials, significant differences could neither be found between plano baseline and defocus conditions, F(1,14) = .19, p = .67, ηρ2 = .01, nor between the three defocus conditions, F(2,28) = 1.09, p = .18, ηρ2 = .07. Participants reacted faster in “4 correct+button” trials under defocus than under plano-baseline conditions, F(1,14) = 10.77, p < .01, ηρ2 = .44. The defocus conditions differed significantly, F(2,28) = 6.16, p < .01, ηρ2 = .31, with shorter response times as a function of a defocus increase and significant contrasts between +1.00 D and +2.00 D (p = .01) and +1.00 D and +3.00 D (p < .01). Discussion: The results show that gaze behaviour in MOT is not affected to a relevant degree by a visual overcorrection up to +3 diopters. Hence, it can be taken for granted that peripheral event detection was investigated in the present study. This overcorrection, however, does not harm the capability to peripherally track objects. Moreover, if an event has to be detected peripherally, neither response accuracy nor response time is negatively affected. Findings could claim considerable relevance for all sport situations in which peripheral vision is required which now needs applied studies on this topic. References: Bulson, R. C., Ciuffreda, K. J., & Hung, G. K. (2008). The effect of retinal defocus on golf putting. Ophthalmic and Physiological Optics, 28, 334-344.

Risk Factors for Intracranial Haemorrhage in Accidents Associated with the Shower or Bathtub

BACKGROUND There has been little research on bathroom accidents. It is unknown whether the shower or bathtub are connected with special dangers in different age groups or whether there are specific risk factors for adverse outcomes. METHODS This cross-sectional analysis included all direct admissions to the Emergency Department at the Inselspital Bern, Switzerland from 1 January 2000 to 28 February 2014 after accidents associated with the bathtub or shower. Time, age, location, mechanism and diagnosis were assessed and special risk factors were examined. Patient groups with and without intracranial bleeding were compared with the Mann-Whitney U test.The association of risk factors with intracranial bleeding was investigated using univariate analysis with Fisher's exact test or logistic regression. The effects of different variables on cerebral bleeding were analysed by multivariate logistic regression. RESULTS Two hundred and eighty (280) patients with accidents associated with the bathtub or shower were included in our study. Two hundred and thirty-five (235) patients suffered direct trauma by hitting an object (83.9%) and traumatic brain injury (TBI) was detected in 28 patients (10%). Eight (8) of the 27 patients with mild traumatic brain injuries (GCS 13-15), (29.6%) exhibited intracranial haemorrhage. All patients with intracranial haemorrhage were older than 48 years and needed in-hospital treatment. Patients with intracranial haemorrhage were significantly older and had higher haemoglobin levels than the control group with TBI but without intracranial bleeding (p<0.05 for both).In univariate analysis, we found that intracranial haemorrhage in patients with TBI was associated with direct trauma in general and with age (both p<0.05), but not with the mechanism of the fall, its location (shower or bathtub) or the gender of the patient. Multivariate logistic regression analysis identified only age as a risk factor for cerebral bleeding (p<0.05; OR 1.09 (CI 1.01;1.171)). CONCLUSION In patients with ED admissions associated with the bathtub or shower direct trauma and age are risk factors for intracranial haemorrhage. Additional effort in prevention should be considered, especially in the elderly.

Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV.

Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ∼88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-α only (n=3). The most common malignancies (n⩾4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non-melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time.Leukemia advance online publication, 26 February 2016; doi:10.1038/leu.2016.20.

Is human herpesvirus 8 infection more common in men than in women? Systematic review and meta-analysis.

All forms of Kaposi sarcoma (KS) are more common in men than in women. It is unknown if this is due to a higher prevalence of human herpesvirus 8 (HHV-8), the underlying cause of KS, in men compared to women. We did a systematic review and meta-analysis to examine the association between HHV-8 seropositivity and gender in the general population. Studies in selected populations like for example, blood donors, hospital patients, and men who have sex with men were excluded. We searched Medline and Embase from January 1994 to February 2015. We included observational studies that recruited participants from the general population and reported HHV-8 seroprevalence for men and women or boys and girls. We used random-effects meta-analysis to pool odds ratios (OR) of the association between HHV-8 and gender. We used meta-regression to identify effect modifiers, including age, geographical region and type of HHV-8 antibody test. We included 22 studies, with 36,175 participants. Men from sub-Saharan Africa (SSA) (OR 1.21, 95% confidence interval [CI] 1.09-1.34), but not men from elsewhere (OR 0.94, 95% CI 0.83-1.06), were more likely to be HHV-8 seropositive than women (p value for interaction=0.010). There was no difference in HHV-8 seroprevalence between boys and girls from SSA (OR 0.90, 95% CI 0.72-1.13). The type of HHV-8 assay did not affect the overall results. A higher HHV-8 seroprevalence in men than women in SSA may partially explain why men have higher KS risk in this region. This article is protected by copyright. All rights reserved.

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6×10²⁰ protons on target

We report on measurements of neutrino oscillation using data from the T2K long-baseline neutrino experiment collected between 2010 and 2013. In an analysis of muon neutrino disappearance alone, we find the following estimates and 68% confidence intervals for the two possible mass hierarchies: Normal Hierarchy: sin²θ₂₃= 0.514+0.055−0.056 and ∆m²_32 = (2.51 ± 0.10) × 10⁻³ eV²/c⁴ Inverted Hierarchy: sin²θ₂₃= 0.511 ± 0.055 and ∆m²_13 = (2.48 ± 0.10) × 10⁻³ eV²/c⁴ The analysis accounts for multi-nucleon mechanisms in neutrino interactions which were found to introduce negligible bias. We describe our first analyses that combine measurements of muon neutrino disappearance and electron neutrino appearance to estimate four oscillation parameters, |∆m^2|, sin²θ₂₃, sin²θ₁₃, δCP , and the mass hierarchy. Frequentist and Bayesian intervals are presented for combinations of these parameters, with and without including recent reactor measurements. At 90% confidence level and including reactor measurements, we exclude the region δCP = [0.15, 0.83]π for normal hierarchy and δCP = [−0.08, 1.09]π for inverted hierarchy. The T2K and reactor data weakly favor the normal hierarchy with a Bayes Factor of 2.2. The most probable values and 68% 1D credible intervals for the other oscillation parameters, when reactor data are included, are: sin²θ₂₃= 0.528+0.055−0.038 and |∆m²_32| = (2.51 ± 0.11) × 10⁻³ eV²/c⁴.

Nocardia infection in solid organ transplant recipients: a multicenter European case-control study.

BACKGROUND  Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplantation (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients. METHODS  We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis. RESULTS  One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 [range 2-244] months after transplantation. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (OR=6.11 [2.58-14.51]), use of tacrolimus (OR=2.65 [1.17-6.00]) and corticosteroid dose (OR=1.12 [1.03-1.22]) at the time of diagnosis, patient age (OR=1.04 [1.02-1.07]) and length of stay in intensive care unit after SOT (OR=1.04 [1.00-1.09]) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms. CONCLUSIONS  We identified five risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.

Sleep-disordered breathing among acute ischemic stroke patients in Brazil.

OBJECTIVES Sleep-disordered breathing (SDB) is very common in acute stroke patients and has been related to poor outcome. However, there is a lack of data about the association between SDB and stroke in developing countries. The study aims to characterize the frequency and severity of SDB in Brazilian patients during the acute phase of ischemic stroke; to identify clinical and laboratorial data related to SDB in those patients; and to assess the relationship between sleep apnea and functional outcome after six months of stroke. METHODS Clinical data and laboratorial tests were collected at hospital admission. The polysomnography was performed on the first night after stroke symptoms onset. Functional outcome was assessed by the modified Rankin Scale (mRS). RESULTS We prospectively evaluated 69 patients with their first-ever acute ischemic stroke. The mean apnea-hypopnea index (AHI) was 37.7 ± 30.2. Fifty-three patients (76.8%) exhibited an AHI ≥ 10 with predominantly obstructive respiratory events (90.6%), and thirty-three (47.8%) had severe sleep apnea. Age (OR: 1.09; 95% CI: 1.03-1.15; p= 0.004) and hematocrit (OR: 1.18; 95% CI: 1.03-1.34; p= 0.01) were independent predictors of sleep apnea. Age (OR: 1.13; 95% CI: 1.03-1.24; p= 0.01), body mass index (OR: 1.54; 95% CI: 1.54-2.18; p= 0.01), and hematocrit (OR: 1.19; 95% CI: 1.01-1.40; p= 0.04) were independent predictors of severe sleep apnea. The National Institutes of Health Stroke Scale (NIHSS; OR: 1.30; 95% CI: 1.1-1.5; p= 0.001) and severe sleep apnea (OR: 9.7; 95% CI: 1.3-73.8; p= 0.03) were independently associated to mRS >2 at six months, after adjusting for confounders. CONCLUSION Patients with acute ischemic stroke in Brazil have a high frequency of SDB. Severe sleep apnea is associated with a poor long-term functional outcome following stroke in that population.

Percutaneous mitral valve edge-to-edge repair: in-hospital results and 1-year follow-up of 628 patients of the 2011-2012 Pilot European Sentinel Registry.

BACKGROUND The use of transcatheter mitral valve repair (TMVR) has gained widespread acceptance in Europe, but data on immediate success, safety, and long-term echocardiographic follow-up in real-world patients are still limited. OBJECTIVES The aim of this multinational registry is to present a real-world overview of TMVR use in Europe. METHODS The Transcatheter Valve Treatment Sentinel Pilot Registry is a prospective, independent, consecutive collection of individual patient data. RESULTS A total of 628 patients (mean age 74.2 ± 9.7 years, 63.1% men) underwent TMVR between January 2011 and December 2012 in 25 centers in 8 European countries. The prevalent pathogenesis was functional mitral regurgitation (FMR) (n = 452 [72.0%]). The majority of patients (85.5%) were highly symptomatic (New York Heart Association functional class III or higher), with a high logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation) (20.4 ± 16.7%). Acute procedural success was high (95.4%) and similar in FMR and degenerative mitral regurgitation (p = 0.662). One clip was implanted in 61.4% of patients. In-hospital mortality was low (2.9%), without significant differences between groups. The estimated 1-year mortality was 15.3%, which was similar for FMR and degenerative mitral regurgitation. The estimated 1-year rate of rehospitalization because of heart failure was 22.8%, significantly higher in the FMR group (25.8% vs. 12.0%, p[log-rank] = 0.009). Paired echocardiographic data from the 1-year follow-up, available for 368 consecutive patients in 15 centers, showed a persistent reduction in the degree of mitral regurgitation at 1 year (6.0% of patients with severe mitral regurgitation). CONCLUSIONS This independent, contemporary registry shows that TMVR is associated with high immediate success, low complication rates, and sustained 1-year reduction of the severity of mitral regurgitation and improvement of clinical symptoms.