Optical detection of single electron spin resonance in a quantum dot

We demonstrate optically detected spin resonance of a single electron confined to a self-assembled quantum dot. The dot is rendered dark by resonant optical pumping of the spin with a coherent laser. Contrast is restored by applying a radio frequency (rf) magnetic field at the spin resonance. The scheme is sensitive even to rf fields of just a few micro-T. In one case, the spin resonance behaves exactly as a driven 3-level quantum system (a lambda-system) with weak damping. In another, the dot exhibits remarkably strong (67% signal recovery) and narrow (0.34 MHz) spin resonances with fluctuating resonant positions, evidence of unusual dynamic processes of non-Markovian character.Comment: 4 pages, 5 figure

Dose reduction of epoetin-alpha in the prevention of chemotherapy-induced anaemia

Introduction: Anaemia during chemotherapy is often left untreated. Erythropoiesis-stimulating agents are frequently used to treat overt anaemia. Their prophylactic use, however, remains controversial and raises concerns about cost-effectiveness. Therefore, we assessed the efficacy of a dose-reduction schedule in anaemia prophylaxis. Materials and methods: The study included patients with untreated solid tumours about to receive platinum-based chemotherapy and had haemoglobin (Hb) levels ≥11g/dL. Epoetin-α was administered at a dose level of 3 × 10,000U weekly as soon as Hb descended to < 13g/dL. Dose reductions to 3 × 4,000U and 3 × 2,000U weekly were planned in 4-week intervals if Hb stabilised in the range of 11-13g/dL. Upon ascending to ≥13g/dL, epoetin was discontinued. Iron supplements of 100mg intravenous doses were given weekly. Of 37 patients who enrolled, 33 could be evaluated. Results and discussion: Their median Hb level was 13.7 (10.9-16.2) g/dL at baseline and descended to 11.0 (7.4-13.8) g/dL by the end of chemotherapy. Anaemia (Hb < 10g/dL) was prevented in 24 patients (73%). The mean dose requirement for epoetin-α was 3 × 5,866U per week per patient, representing a dose reduction of 41%. Treatment failed in nine patients (27%), in part due to epoetin-α resistance in four (12%) and blood transfusion in three (9%) patients. Conclusion: Dose reduction was as effective as fixed doses in anaemia prophylaxis but reduced the amount of prescribed epoetin substantiall

The CSHQ-DE Questionnaire Uncovers Relevant Sleep Disorders in Children and Adolescents with Long COVID

Acute SARS-CoV-2 infections in children and adolescents are usually mild. However, they can suffer from ongoing symptoms, generally referred to as long COVID. Sleep disorders are one of the most frequent complaints in long COVID although precise data are missing. We assessed the sleep behavior of children and adolescents who presented at our outpatient clinic between January 2021 and May 2022 with the Children’s Sleep Habits Questionnaire (CSHQ-DE). We compared the sleep behavior at three different time points: pre-COVID-19; post-COVID-19 at the initial presentation; and post-COVID-19 at re-presentation. Data from 45 patients were analyzed. Of those, 64% were female and the median age was 10 years (range: 0–18 years). Asymptomatic or mild COVID-19 disease was experienced in 89% of patients; 11% experienced moderate disease. The initial presentation occurred at a median of 20.4 weeks (6 weeks–14 months) after the infection. The CSHQ-DE score increased significantly from pre-COVID-19 (45.82 ± 8.7 points) to post-COVID-19 (49.40 ± 8.3 points; p ≤ 0.01). The score then normalized at re-presentation (46.98 ± 7.8; p = 0.1). The greatest changes were seen in the CSHQ-DE subscale score “daytime sleepiness”. Our data showed that children and adolescents with long COVID often suffer from sleep disturbances. For most children and adolescents, these sleep disorders decreased over time without any further medical intervention aside from a basic sleep consultation

Alcohol markers in hair: an issue of interpretation

Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) are metabolites of alcohol that when detected in hair can provide evidence of a person’s drinking behavior. The analysis of these compounds in hair has become commonplace in recent years and has been used as evidence in legal proceedings. Despite the routine use of such toxicological analysis, the correct interpretation of alcohol biomarker hair testing can be complex, and there may be debate as to the significance of the data. This paper considers whether the accepted norm of applying interpretative cut-off values to EtG and FAEE concentrations from hair samples is appropriate, and asks whether Bayesian theory, using a likelihood ratio approach may offer greater insight as to the strength of evidence. In addition to the complexity of result interpretation in this field, the sensitivity of alcohol biomarkers in hair to distinguish low level drinking from abstinence also represents a significant challenge. The use of fingernail EtG testing as an alternative to hair analysis is explored in this paper and it is proposed that fingernails may in theory show a higher uptake of EtG than hair, and thus show potential as a useful alternative matrix to document long-term low to moderate alcohol consumptio

Opportunities for farming in alpine countries – pathways to truly grassland-based beef and milk production in Austria and Switzerland

Farming in the alpine countries of Austria and Switzerland fulfils important economic, socio-cultural and ecological functions for society. At the same time, it is responsible for important environmental impacts, whereas nitrogen balance surpluses and related impacts play a central role. It is crucial to reduce nitrogen inputs and site-adapted production and closing material cycles are core elements of ecologically sustainable land use. The study analysed the effects of adapted beef and dairy systems on the environmental impact and the food production with the help of the SOL mass-flow model. This includes higher reliance on grassland-based feed by abandoning the use of concentrate feed and forage maize, locally adapted reduction of livestock numbers, increased use of nitrogen-fixing legumes, reduction in mineral nitrogen fertilization, site-specific plant production and increase in nitrogen efficiency in both animal husbandry and crop production. The implementation of such a grassland-based beef and milk production results in lower ammonia emissions, reduction of nitrogen balance surpluses and lower total greenhouse gas emissions from agriculture. These environmental improvements exceed the effects of the agricultural policy since the 1990s, even though the latter has increasingly focussed on environmental impacts. Moreover, the reduction in concentrate feed and forage maize releases arable land for alternative use. This allows for increased plant-based food production and therefore minimizes the competition between food and feed production. Other options for the use of the released land are less intensive farm operations, ecological compensation areas and/or nature conservation. Finally, the reduction in animal-based food production could be offset by changed dietary patterns and the increase of plant-based food production. The suggested transformation from a production focussed to an ecologically-oriented land use and food system requires a political framework and market conditions which cannot be implemented quickly but need awareness raising and fundamental societal change

The Treat-to-Target Project in Atopic Dermatitis: One Year On

Atopic dermatitis is a chronic skin condition for which a range of systemic treatments have recently been approved. A treat-to-target strategy has been deve loped previously alongside an algorithm to guide the management of patients with atopic dermatitis. Here, we review the strategy and algorithm in the context of the evolving therapeutic landscape, and identify areas for further refinement and development

Global Levels of Histone Modifications in Peripheral Blood Mononuclear Cells of Subjects with Exposure to Nickel

Background: Occupational exposure to nickel (Ni) is associated with an increased risk for lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, cause gene amplification, and disrupt cellular epigenetic homeostasis. However, the Ni-induced changes in global histone modification levels have only been tested in vitro

Intranasal delivery of bone marrow derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease

In view of the rapid preclinical development of cell-based therapies for neurodegenerative disorders, traumatic brain injury, and tumors, the safe and efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSCs) to the brain in the rat 6-hydroxydopamine model of Parkinson’s disease (PD). The present study examined delivery of bone marrow derived MSCs, macrophages, and microglia to the brain in a transgenic model of PD ((Thy1)-h[A30P] αS) and an APP/PS1 model of Alzheimer’s disease (AD) via intranasal application (INA). INA of microglia in naïve BL/6 mice led to targeted and effective delivery of cells to the brain. Quantitative PCR analysis of eGFP DNA showed that the brain contained the highest amount of eGFP-microglia (up to 2.1x104) after INA of 1x106 cells, while the total amount of cells detected in peripheral organs did not exceed 3.4x103. Seven days after INA, MSCs expressing eGFP were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem of (Thy1)-h[A30P] αS transgenic mice, showing predominant distribution within the OB and brainstem. INA of eGFP-expressing macrophages in 13 month-old APP/PS1 mice led to delivery of cells to the OB, hippocampus, cortex, and cerebellum. Both, MSCs and macrophages contained Iba-1-positive population of small microglia-like cells and Iba-1-negative large rounded cells showing either intracellular Amyloid beta (macrophages in APP/PS1 model) or α-Synuclein (MSCs in (Thy1)-h[A30P] αS model) immunoreactivity. Here we show, for the first time, intranasal delivery of cells to the brain of transgenic PD and AD mouse models. Additional work is needed to determine the optimal dosage (single treatment regimen or repeated administrations) to achieve functional improvement in these mouse models with intranasal microglia/macrophages and MSCs

Intranasal delivery of bone marrow derived mesenchymal stem cells, macrophages, and microglia to the brain in mouse models of Alzheimer's and Parkinson's disease

In view of the rapid preclinical development of cell-based therapies for neurodegenerative disorders, traumatic brain injury, and tumors, the safe and efficient delivery and targeting of therapeutic cells to the central nervous system is critical for maintaining therapeutic efficacy and safety in the respective disease models. Our previous data demonstrated therapeutically efficacious and targeted delivery of mesenchymal stem cells (MSCs) to the brain in the rat 6-hydroxydopamine model of Parkinson’s disease (PD). The present study examined delivery of bone marrow derived MSCs, macrophages, and microglia to the brain in a transgenic model of PD ((Thy1)-h[A30P] αS) and an APP/PS1 model of Alzheimer’s disease (AD) via intranasal application (INA). INA of microglia in naïve BL/6 mice led to targeted and effective delivery of cells to the brain. Quantitative PCR analysis of eGFP DNA showed that the brain contained the highest amount of eGFP-microglia (up to 2.1x104) after INA of 1x106 cells, while the total amount of cells detected in peripheral organs did not exceed 3.4x103. Seven days after INA, MSCs expressing eGFP were detected in the olfactory bulb (OB), cortex, amygdala, striatum, hippocampus, cerebellum, and brainstem of (Thy1)-h[A30P] αS transgenic mice, showing predominant distribution within the OB and brainstem. INA of eGFP-expressing macrophages in 13 month-old APP/PS1 mice led to delivery of cells to the OB, hippocampus, cortex, and cerebellum. Both, MSCs and macrophages contained Iba-1-positive population of small microglia-like cells and Iba-1-negative large rounded cells showing either intracellular Amyloid beta (macrophages in APP/PS1 model) or α-Synuclein (MSCs in (Thy1)-h[A30P] αS model) immunoreactivity. Here we show, for the first time, intranasal delivery of cells to the brain of transgenic PD and AD mouse models. Additional work is needed to determine the optimal dosage (single treatment regimen or repeated administrations) to achieve functional improvement in these mouse models with intranasal microglia/macrophages and MSCs

The incidence function model as a tool for landscape ecological impact assessments

Landscape-scale approaches to assessing the impact of land-use change on species' persistence are necessary because species depend on processes acting at varying scales, yet existing approaches to ecological impact assessment tend only to be site-based. A further major criticism of current ecological impact assessments is that they tend to be qualitative. Here we develop methods that apply the Incidence Function Model (IFM) in real urban planning contexts, by generating repeatable and comparable quantitative measures of ecological impacts. To demonstrate the methods for a case study (Nottingham, UK), we estimated landscape-scale measures of species' persistence that indicate metapopulation viability. We based these on Nottingham’s landscape when urban developments were recently proposed, then adjust the land cover to include the proposed developments, and also for two projected landscapes where 10% and 20% of the original natural or semi-natural land cover is lost. We find that the IFM shows promise as a tool for quantitative landscape-scale ecological impact assessment, depending on the size of the impact. We detected minimal differences in the species' viability measures between the original and post-development landscapes. This suggests that for small (around 2%) cumulative losses of natural/ semi-natural space, current site-based approaches are sufficient. However, when the cumulative effect of continued development was modelled by increasing the losses of natural/semi-natural land cover to 10–20% of existing cover, the impact on many of the species studied was more substantial. This indicates that a landscape-scale approach is necessary for larger, prolonged and cumulative habitat losses