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We discuss the potential of light-nuclei measurements in heavy-ion collisions at intermediate energies for the search of the hypothetical QCD critical end-point. A previous proposal based on neutron density fluctuations has brought appealing experimental evidences of a maximum in the ratio of the number of tritons times protons, divided over deuterons square, O tpd. However these results are difficult to reconcile with the state-of-the-art statistical thermal model predictions. Based on the idea that the QCD critical point can lead to a substantial attraction among nucleons, we propose new light-nuclei multiplicity ratios involving He in which the maximum would be more noticeable. We argue that the experimental extraction is feasible by presenting these ratios formed from actual measurements of total and differential yields at low and high collision energies from FOPI and ALICE experiments, respectively. We also illustrate the possible behavior of these ratios at intermediate energies applying a semiclassical method based on flucton paths using the preliminary NA49 and STAR data for O tpd as input.
This work presents, to our knowledge, the first completely passive imaging with human-body-emitted radiation in the lower THz frequency range using a broadband uncooled detector. The sensor consists of a Si CMOS field-effect transistor with an integrated log-spiral THz antenna. This THz sensor was measured to exhibit a rather flat responsivity over the 0.1–1.5-THz frequency range, with values of the optical responsivity and noise-equivalent power of around 40 mA/W and 42 pW/√Hz, respectively. These values are in good agreement with simulations which suggest an even broader flat responsivity range exceeding 2.0 THz. The successful imaging demonstratestheimpressivethermalsensitivitywhichcanbeachievedwithsuchasensor. Recording of a 2.3×7.5-cm2-sized image of the fingers of a hand with a pixel size of 1 mm2 at a scanning speed of 1 mm/s leads to a signal-to-noise ratio of 2 and a noise-equivalent temperature difference of 4.4 K. This approach shows a new sensing approach with field-effect transistors as THz detectors which are usually used for active THz detection.
Recent data have suggested that performing recanalizing therapies in ischemic stroke might lead to an increased risk of acute symptomatic seizures. This applies to both intravenous thrombolysis and mechanical thrombectomy. We therefore determined the frequency of acute symptomatic seizures attributable to these two recanalization therapies using a large, population-based stroke registry in Central Europe. We performed two matched 1:1 case–control analyses. In both analyses, patients were matched for age, stroke severity on admission and pre-stroke functional status. The first analysis compared patients treated with intravenous thrombolysis to a non-recanalization control group. To isolate the effect of mechanical thrombectomy, we compared patients with both mechanical thrombectomy and intravenous thrombolysis to those with only intravenous thrombolysis treatment in a second analysis. From 135,117 patients in the database, 13,356 patients treated with only intravenous thrombolysis, and 1013 patients treated with both intravenous thrombolysis and mechanical thrombectomy were each matched to an equivalent number of controls. Patients with intravenous thrombolysis did not suffer from clinically apparent acute symptomatic seizures significantly more often than non-recanalized patients (treatment = 199; 1.5% vs. control = 237; 1.8%, p = 0.07). Mechanical thrombectomy in addition to intravenous thrombolysis also was not associated with an increased risk of acute symptomatic seizures, as the same number of patients suffered from seizures in the treatment and control group (both n = 17; 1.7%, p = 1). In a large population-based stroke registry, the frequency of clinically apparent acute symptomatic seizures was not increased in patients who received either intravenous thrombolysis alone or in conjunction with mechanical thrombectomy.
The National Institutes of Health Stroke Scale (NIHSS) score is the most frequently used score worldwide for assessing the clinical severity of a stroke. Prior research suggested an association between acute symptomatic seizures after stroke and poorer outcome. We determined the frequency of acute seizures after ischemic stroke in a large population-based registry in a central European region between 2004 and 2016 and identified risk factors for acute seizures in univariate and multivariate analyses. Additionally, we determined the influence of seizures on morbidity and mortality in a matched case–control design. Our analysis of 135,117 cases demonstrated a seizure frequency of 1.3%. Seizure risk was 0.6% with an NIHSS score at admission <3 points and increased up to 7.0% with >31 score points. Seizure risk was significantly higher in the presence of acute non-neurological infections (odds ratio: 3.4; 95% confidence interval: 2.8–4.1). A lower premorbid functional level also significantly increased seizure risk (OR: 1.7; 95%CI: 1.4–2.0). Mortality in patients with acute symptomatic seizures was almost doubled when compared to controls matched for age, gender, and stroke severity. Acute symptomatic seizures increase morbidity and mortality in ischemic stroke. Their odds increase with a higher NIHSS score at admission.
A systematic review on the burden of illness in individuals with tuberous sclerosis complex (TSC)
(2020)
Objective: This review will summarize current knowledge on the burden of illness (BOI) in tuberous sclerosis complex (TSC), a multisystem genetic disorder manifesting with hamartomas throughout the body, including mainly the kidneys, brain, skin, eyes, heart, and lungs.
Methods: We performed a systematic analysis of the available literature on BOI in TSC according to the PRISMA guidelines. All studies irrespective of participant age that reported on individual and societal measures of disease burden (e.g. health care resource use, costs, quality of life) were included.
Results: We identified 33 studies reporting BOI in TSC patients. Most studies (21) reported health care resource use, while 14 studies reported quality of life and 10 studies mentioned costs associated with TSC. Only eight research papers reported caregiver BOI. Substantial BOI occurs from most manifestations of the disorder, particularly from pharmacoresistant epilepsy, neuropsychiatric, renal and skin manifestations. While less frequent, pulmonary complications also lead to a high individual BOI. The range for the mean annual direct costs varied widely between 424 and 98,008 International Dollar purchasing power parities (PPP-$). Brain surgery, end-stage renal disease with dialysis, and pulmonary complications all incur particularly high costs. There is a dearth of information regarding indirect costs in TSC. Mortality overall is increased compared to general population; and most TSC related deaths occur as a result of complications from seizures as well as renal complications. Long term studies report mortality between 4.8 and 8.3% for a follow-up of 8 to 17.4 years.
Conclusions: TSC patients and their caregivers have a high burden of illness, and TSC patients incur high costs in health care systems. At the same time, the provision of inadequate treatment that does not adhere to published guidelines is common and centralized TSC care is received by no more than half of individuals who need it, especially adults. Further studies focusing on the cost effectiveness and BOI outcomes of coordinated TSC care as well as of new treatment options such as mTOR inhibitors are necessary.
The purpose of this study was to identify distinctive mental health profiles for industrial psychologists based on the Mental Health Continuum. Further, it aimed to determine how these profiles differ with respect to work-role fit, meaningfulness and work engagement. It also aimed to investigate whether industrial psychologists within managerial or specialist differ in respect of different types of mental health. An online cross-sectional survey design was employed to draw a census sample (n = 274) from all South African industrial psychologists. A biographical questionnaire, the Work-Role Fit Scale, the Psychological Meaningfulness Scale, the Work Engagement Scale, and the Mental Health Continuum–Short Form were administered. Descriptive statistics, correlations, latent profile analysis, MANOVAs and ANOVAs were computed. Three mental health profiles for industrial psychologists were identified: languishing, moderately mentally healthy and flourishing. Significant differences between the three mental health profiles and experiences of meaningful work-role fit and work engagement were found, but not between experiences of managerial roles. The results show that individuals with different mental health profiles, experience work and its related outcomes, differently. Therefore, in order to enhance meaningful work-role fit and work engagement of industrial psychologists, a one-size-fits-all model may not be appropriate.
Editorial: Positive organizational interventions: contemporary theories, approaches and applications
(2020)
Despite the popularity of the term Positive Psychological Coaching within the literature, there is no consensus as to how it should be defined (framed) or what the components of a positive coaching “model” should include. The aim of this systematic review was to define positive psychological coaching and to construct a clear demarcated positive psychological coaching model based on the literature. A systematic literature review led to the extraction of 2,252 records. All records were screened using specific inclusion/exclusion criteria, which resulted in the exclusion of records based on duplicates (n = 1,232), titles (n = 895), abstracts (n = 78), and criteria violations (n = 23). Twenty-four academic, peer-reviewed publications on positive psychological coaching were included. Data relating to conceptual definitions and coaching models/phases/frameworks were extracted and processed through thematic content analysis. Our results indicate that positive psychological coaching can be defined as a short to medium term professional, collaborative relationship between a client and coach, aimed at the identification, utilization, optimization, and development of personal strengths and resources in order to enhance positive states, traits and behaviors. Utilizing Socratic goal setting and positive psychological evidence-based approaches to facilitate personal growth, optimal functioning, enhanced wellbeing, and the actualization of people's potential. Further, eight critical components of a positive psychological coaching model were identified and discussed. The definition and coaching process identified in this study will provide coaches with a fundamental positive psychological framework for optimizing people's potential.
The purpose of this study was to examine the psychometric properties (i.e., factorial validity, measurement invariance, and reliability) of the Grit-Original scale (Grit-O) within the Netherlands. The Grit-O scale was subjected to a competing measurement modeling strategy that sequentially compared both independent cluster model confirmatory factor analytical- and exploratory structural equation modeling approaches. The results showed that both a two first order, bi-factor structure as well as a less restrictive two factor ESEM factorial structure best-fitted the data. The instrument showed to be reliable at both a lower- (Cronbach’s alpha) and upper-level (composite reliability) limit. However, measurement invariance between genders could only be established for the B-ICM-CFA model. Finally, concurrent validity was established through relating the GRIT-O to task performance. The linear use of the Grit-O scale should therefore carefully be considered.
This article examines whether autonomy as an educational aim should be defended at the global scale. It begins by identifying the normative issues at stake in global autonomy education by distinguishing them from the problems of autonomy education in multicultural nation-states. The article then explains why a planet-wide expansion of the ideal of autonomy is conceivable on the condition that the concept of autonomy is widened in a way that renders its precise meaning flexibly adjustable to a variety of distinct social and cultural contexts. A context-transcendent, core meaning of autonomy remains in place, however, according to which a person is only autonomous if she relates to the values and goals that direct her life in a way so that she sees them as her own and is able to identify and critically assess her principal reasons for action. Finally, the article addresses two challenges to the global expansion of autonomy education: the objection that autonomy is presently not the most important educational aim and the objection that global autonomy education is a form of cultural imperialism. It finds both objections wanting.
Background: Berotralstat (BCX7353) is an oral, once-daily inhibitor of plasma kallikrein in development for the prophylaxis of hereditary angioedema (HAE) attacks.
Objective: Our aim was to determine the efficacy, safety, and tolerability of berotralstat in patients with HAE over a 24-week treatment period (the phase 3 APeX-2 trial).
Methods: APeX-2 was a double-blind, parallel-group study that randomized patients at 40 sites in 11 countries 1:1:1 to receive once-daily berotralstat in a dose of 110 mg or 150 mg or placebo (Clinicaltrials.gov identifier NCT03485911). Patients aged 12 years or older with HAE due to C1 inhibitor deficiency and at least 2 investigator-confirmed HAE attacks in the first 56 days of a prospective run-in period were eligible. The primary efficacy end point was the rate of investigator-confirmed HAE attacks during the 24-week treatment period.
Results: A total of 121 patients were randomized; 120 of them received at least 1 dose of the study drug (n = 41, 40, and 39 in the 110-mg dose of berotralstat, 150-mg of dose berotralstat, and placebo groups, respectively). Berotralstat demonstrated a significant reduction in attack rate at both 110 mg (1.65 attacks per month; P = .024) and 150 mg (1.31 attacks per month; P < .001) relative to placebo (2.35 attacks per month). The most frequent treatment-emergent adverse events that occurred more with berotralstat than with placebo were abdominal pain, vomiting, diarrhea, and back pain. No drug-related serious treatment-emergent adverse events occurred.
Conclusion: Both the 110-mg and 150-mg doses of berotralstat reduced HAE attack rates compared with placebo and were safe and generally well tolerated. The most favorable benefit-to-risk profile was observed at a dose of 150 mg per day.
Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.
Personalized campaign styles are of increasing importance in contemporary election campaigns at all levels of politics. Surprisingly, we know little about their implications for the behavior of successful candidates once they take public office. This paper aims to fill this gap in empirical and theoretical ways. It shows that campaign personalization results in legislative personalization. Legislators that ran personalized campaigns are found to be more likely to deviate in roll call votes and to take independent positions on the floor. These findings result from a novel dataset that matches survey evidence on candidates’ campaign styles in the 2009 German Federal Elections with the legislative behavior of successful candidates in the 17th German Bundestag (2009–2013). Combining data from the campaign and legislative arenas allows us to explore the wider consequences of campaign personalization.
In higher concentrations, the blood pressure regulating hormone angiotensin II leads to vasoconstriction, hypertension, and oxidative stress by activating NADPH oxidases which are a major enzymatic source of reactive oxygen species (ROS). With the help of knockout animals, the impact of the three predominant NADPH oxidases present in the kidney, i.e., Nox1, Nox2 and Nox4 on angiotensin II-induced oxidative damage was studied. Male wildtype (WT) C57BL/6 mice, Nox1-, Nox2- and Nox4-deficient mice were equipped with osmotic minipumps, delivering either vehicle (PBS) or angiotensin II, for 28 days. Angiotensin II increased blood pressure and urinary albumin levels significantly in all treated mouse strains. In Nox1 knockout mice these increases were significantly lower than in WT, or Nox2 knockout mice. In WT mice, angiotensin II also raised systemic oxidative stress, ROS formation and DNA lesions in the kidney. A local significantly increased ROS production was also found in Nox2 and Nox4 knockout mice but not in Nox1 knockout mice who further had significantly lower systemic oxidative stress and DNA damage than WT animals. Nox2 and Nox4 knockout mice had increased basal DNA damage, concealing possible angiotensin II-induced increases. In conclusion, in the kidney, Nox1 seemed to play a role in angiotensin II-induced DNA damage.
Highlights
• PUR, PVC and PLA microplastics affect life-history parameters of Daphnia magna.
• Natural kaolin particles are less toxic than microplastics.
• Microplastic toxicity is material-specific, e.g. PVC is most toxic on reproduction.
• In case of PVC, plastic chemicals are the main driver of microplastic toxicity.
• PLA bioplastics are similarly toxic as conventional plastics.
Abstract
Given the ubiquitous presence of microplastics in aquatic environments, an evaluation of their toxicity is essential. Microplastics are a heterogeneous set of materials that differ not only in particle properties, like size and shape, but also in chemical composition, including polymers, additives and side products. Thus far, it remains unknown whether the plastic chemicals or the particle itself are the driving factor for microplastic toxicity. To address this question, we exposed Daphnia magna for 21 days to irregular polyvinyl chloride (PVC), polyurethane (PUR) and polylactic acid (PLA) microplastics as well as to natural kaolin particles in high concentrations (10, 50, 100, 500 mg/L, ≤ 59 μm) and different exposure scenarios, including microplastics and microplastics without extractable chemicals as well as the extracted and migrating chemicals alone. All three microplastic types negatively affected the life-history of D. magna. However, this toxicity depended on the endpoint and the material. While PVC had the largest effect on reproduction, PLA reduced survival most effectively. The latter indicates that bio-based and biodegradable plastics can be as toxic as their conventional counterparts. The natural particle kaolin was less toxic than microplastics when comparing numerical concentrations. Importantly, the contribution of plastic chemicals to the toxicity was also plastic type-specific. While we can attribute effects of PVC to the chemicals used in the material, effects of PUR and PLA plastics were induced by the mere particle. Our study demonstrates that plastic chemicals can drive microplastic toxicity. This highlights the importance of considering the individual chemical composition of plastics when assessing their environmental risks. Our results suggest that less studied polymer types, like PVC and PUR, as well as bioplastics are of particular toxicological relevance and should get a higher priority in ecotoxicological studies.
Geoffrey Burnstock will be remembered as the scientist who set up an entirely new field of intercellular communication, signaling via nucleotides. The signaling cascades involved in purinergic signaling include intracellular storage of nucleotides, nucleotide release, extracellular hydrolysis, and the effect of the released compounds or their hydrolysis products on target tissues via specific receptor systems. In this context ectonucleotidases play several roles. They inactivate released and physiologically active nucleotides, produce physiologically active hydrolysis products, and facilitate nucleoside recycling. This review briefly highlights the development of our knowledge of two types of enzymes involved in extracellular nucleotide hydrolysis and thus purinergic signaling, the ectonucleoside triphosphate diphosphohydrolases, and ecto-5′-nucleotidase.