Hochschulbibliothekszentrum des Landes Nordrhein-Westfalen (hbz)
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Biomarkers in Ataxia-Telangiectasia: a Systematic Review
No full text<jats:title>Abstract</jats:title>
<jats:p>Ataxia-Telangiectasia (A-T) is a very rare multisystem disease of DNA repair, associated with progressive disabling neurological symptoms, respiratory failure, immunodeficiency and cancer predisposition, leading to premature death. There are no curative treatments available for A-T but clinical trials have begun. A major limiting factor in effectively evaluating therapies for A-T is the lack of suitable outcome measures and biomarkers. We have performed a systematic review to collect the information currently available on biomarkers for A-T both in patients and preclinical studies. We have identified 56 reports discussing potential A-T biomarkers in both pre-clinical models and patients. These studies report on diagnostic biomarkers but prognostic biomarkers and responsive markers of clinical status are currently lacking. Some biomarkers of neurodegeneration in A-T show promise, including non-invasive neuroimaging biomarkers. Some biomarkers of oxidative stress and responsive markers to radiotherapy and steroid treatment have potential value in clinical trials. The formation of the A-T biomarker working group with international experts is an important step forward to facilitate the sharing of materials, data and expertise with the common goal of finding effective biomarkers for A-T.</jats:p>
Living Lab Dementia: process evaluation of an academic-practice partnership in German long term care for people living with dementia - study protocol
No full text<jats:title>Abstract</jats:title>
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<jats:title>Background</jats:title>
<jats:p>Living Labs, as a type of academic-practice partnerships, possess the potential to transform care and research into a participatory partnership and narrow the research-practice gap to improve evidence-based and Person-centred care. Given the lack of systematic investigations of Living Labs in healthcare, we will establish a dementia-specific academic-practice partnership (<jats:italic>Living Lab Dementia)</jats:italic> in Germany and conduct a process evaluation. The aim of this study is to gain insights into the intervention itself (mechanisms of impact) and its implementation process (degree of implementation, barriers, and facilitators).</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>This process evaluation of the multi-center research project PraWiDem (German acronym for linking professional nursing practice and research in dementia) will be conducted applying a convergent mixed methods design and will be based on the Medical Research Council (MRC) framework for the development and evaluation of complex interventions. The intervention is presented in a logic model which describes relevant basic theoretical assumptions, intervention components, implementation aspects, mechanisms of impact, relevant outcomes, and the context in which the intervention is delivered. Data will be collected before the intervention (T<jats:sub>0</jats:sub>), during the intervention period, and at follow-up after 18 months (T<jats:sub>1</jats:sub>). Qualitative data will be collected through semi-structured interviews and focus groups. Quantitative data sources will be process documents and questionnaires.</jats:p>
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<jats:title>Discussion</jats:title>
<jats:p>Our study will provide important insights into the <jats:italic>Living Lab Dementia</jats:italic> intervention and its implementation processes. The results of this evaluation will contribute to the refinement of the intervention and its implementation processes, and will enable to measure the impact of these processes in future studies.</jats:p>
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International expert consensus on micronutrient supplement use during the early life course
No full text<jats:title>Abstract</jats:title>
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<jats:title>Background</jats:title>
<jats:p>Growing evidence demonstrates that maternal nutrition is crucial for the health of the mother-to-be, and early life course of the offspring. However, for most micronutrients, guidelines are inconsistent. This Delphi study aimed to investigate the level of expert consensus on maternal nutrition and micronutrient needs during preconception, pregnancy and lactation.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>We conducted a two-round web-based Delphi survey on various topics including general approaches to diet and supplement use, and existing guidelines. For the periods of preconception, pregnancy and lactation, questions focused on the importance and strength of evidence for supplement use with the following micronutrients for low- and high-risk populations: folic acid, choline, iodine, magnesium, calcium, iron, selenium, docosahexaenoic acid (DHA), and vitamins B1, B2, B6, B12, D and K.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>Thirty-five experts participated in the panel, who were healthcare professionals (HCPs), researchers and joint HCP-researchers with expertise in nutrition, gynaecology and/or obstetrics. Panellists reached consensus on the importance of diet and dietary supplement use during pregnancy and agreed on the lack of clarity and consistency in current guidelines, and the need for education in these areas for HCPs, pregnant people and the general population. For general low-risk populations, there was consensus on the importance of supplement use with iron and vitamin D from preconception through lactation, with folic acid and iodine from preconception through the second and third trimesters, respectively, with DHA from the first trimester through lactation and with calcium during lactation. Panellists agreed that the evidence for supplement use with each of these micronutrients during these phases to improve outcomes and/or foetal development is strong, except for vitamin D (preconception), DHA (first trimester), and iron (both periods). There was also consensus that supplement use advice should be tailored for people following vegan/vegetarian diets, restricted diets due to food intolerances, obesity, polycystic ovary syndrome, diabetes mellitus, and previous nutrition-related pregnancy complications.</jats:p>
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<jats:title>Conclusion</jats:title>
<jats:p>The findings revealed robust consensus on various aspects of maternal nutrition, including the need for education, the lack of consistency in current guidelines on supplement use, the importance of supplement use across specific phases of pregnancy and the at-risk groups requiring tailored approaches.</jats:p>
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Correction: Cancer care in German centers of excellence during the first 2 years of the COVID-19 pandemic
No full textComparison of integrated versus parallel continuous renal replacement therapy combined with veno-venous extracorporeal membrane oxygenation in patients with COVID-19 ARDS
No full text<jats:title>Abstract</jats:title>
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<jats:title>Introduction</jats:title>
<jats:p>Acute kidney injury (AKI) is a common complication of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS) in patients receiving extracorporeal membrane oxygenation (ECMO) support, leading to requirement of continuous renal replacement therapy (CRRT) in 70% of ECMO patients. Parallel arrangement of CRRT and ECMO circuits is common in adult patients. However, CRRT may also be integrated directly into the ECMO circuit. This study compares the safety of both approaches.</jats:p>
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<jats:title>Methods</jats:title>
<jats:p>This retrospective analysis included 105 patients treated with continuous veno-venous haemodiafiltration and veno-venous ECMO (Cardiohelp©) for COVID-19-induced ARDS between April 2020 and December 2021. Of these, 48 patients received a parallel connected CRRT running independently from ECMO (parallel approach), while in 57 patients, CRRT was integrated into the ECMO circuit (integrated approach) by connecting the CRRT access line to the post-oxygenator port and the CRRT return line to the pre-oxygenator position. Local protocol for risk assessment of this device combination mandated a maximum return line pressure below 250 mmHg in the CRRT system.</jats:p>
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<jats:title>Results</jats:title>
<jats:p>At CRRT initiation, the integrated group had significantly higher median pressures in CRRT lines compared to the parallel approach group (access line 110 mmHg vs. -25 mmHg, return line 170 mmHg vs. 50 mmHg; <jats:italic>p</jats:italic> &lt; 0.01). However, median transmembrane pressures were similar between both groups (20 mmHg vs. 20 mmHg, <jats:italic>p</jats:italic> = 0.16). In-hospital mortality (<jats:italic>p</jats:italic> = 0.99), catheter associated infections (<jats:italic>p</jats:italic> = 0.47), bacteraemia (<jats:italic>p</jats:italic> = 0.96), filter clotting (<jats:italic>p</jats:italic> = 0.58) and unplanned CRRT system changes (<jats:italic>p</jats:italic> = 0.45) within the first 72 h of CRRT were comparable between both groups. The integrated group exhibited higher rates of bleeding events (37% vs. 23%; <jats:italic>p</jats:italic> = 0.08). Thromboembolism occurred in four cases in the integrated group, while one pneumothorax was observed in the parallel group. No cases of air embolism, device associated haemolysis or blood leakage was documented.</jats:p>
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<jats:title>Conclusions</jats:title>
<jats:p>Despite higher pressures in CRRT lines, the integrated approach provided comparable safety to the parallel approach. In case of hygienically challenging settings (such as the COVID-19 pandemic), the minimization of extracorporeal accesses and the streamlining of alarm management are decisive factors in providing intensive care medicine. Therefore, the integrated configuration of CRRT into the ECMO circuit can be advantageous in daily intensive care medicine.</jats:p>
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Characterization of the adaptive immune response in a mouse model for HPV-positive head and neck squamous cell carcinoma with implications to human disease
No full text<jats:title>Abstract</jats:title>
<jats:p>Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with a poor prognosis for survival. Risk factors include alcohol and tobacco abuse and infection with human papilloma virus (HPV). To enhance anti-tumor immune responses immunotherapeutic approaches are approved for recurrent metastatic disease but only approx. 20% of patients respond to checkpoint blockade of the PD-1/PD-L1 axis. Therefore, preclinical research is needed to better understand molecular and cellular processes and to identify new therapeutic targets. Immunocompetent mouse models can serve these purposes but only few are currently available for HPV-positive HNSCC. Here, we established a mouse cell line overexpressing the oncogenes <jats:italic>E6</jats:italic>/<jats:italic>E7</jats:italic> of the HPV16 genome as well as a constitutively active form of H-Ras and studied the anti-tumor immune response upon orthotopic tumor growth at the floor of the mouth. Moreover, we analyzed the same immunoregulatory pathways in samples of HPV-positive cancer patients. T cells in the tumor of mice and humans exhibited high expression of CD39 and CD73, two ectoenzymes involved in the production of immunosuppressive adenosine from ATP, along with increased expression of PD-1, LAG-3 and GITR. Additionally, B cell responses were elevated in tumor-bearing mice, seen as an increase of germinal center, immunoregulatory marginal zone and follicular B cell subtypes. Taken together, this study suggests that the generated mouse model shares characteristics with human disease and can thus be used as a platform to study anti-tumor responses in HPV-positive HNSCC which will help to identify novel therapeutic targets.</jats:p>
Frontal theta oscillations and cognitive flexibility: Age-related modulations in EEG activity
No full textCognitive flexibility, the ability to adapt one's behaviour in changing environments, declines during aging. Electroencephalography (EEG) studies have implicated midfrontal theta oscillations in attentional set-shifting, a measure of cognitive flexibility. Little is known about the electrocortical underpinnings of set-shifting in aging. Here, we investigated aging effects on set-shifting performance by analysing theta power in 20 young (mean age: 22.5 ± 2.9 years) and 19 older (mean age: 69.4 ± 6.1 years) adults. Increasing shift difficulty (i.e., intra- vs. extra-dimensional shifts) elicited worse performance in both age groups, with older adults showing overall longer reaction times (RTs) and increased RT variability. Young adults exhibited amplified midfrontal theta power increases with higher shift difficulty whereas older adults showed overall lower theta power and no task-related midfrontal theta power modulation, indicating potentially distinct underlying neural mechanisms
Large-scale flood risk assessment in data-scarce areas: an application to Central Asia
No full text<jats:p>Abstract. The countries of Kazakhstan, Kyrgyz Republic, Tajikistan, Turkmenistan, and Uzbekistan in Central Asia are highly prone to natural hazards, particularly floods, earthquakes, and landslides. The European Union, in collaboration with the World Bank and the Global Facility for Disaster Reduction and Recovery (GFDRR), created the programme Strengthening Financial Resilience and Accelerating Risk Reduction in Central Asia (SFRARR) to advance disaster and climate resilience in the region. As part of the SFRARR project, the “Regionally consistent risk assessment for earthquakes and floods and selective landslide scenario analysis for strengthening financial resilience and accelerating risk reduction in Central Asia” was developed to achieve the project's objectives. This article presents the data, model, methodology, and results for the five Central Asian countries of the flood risk assessment, which represents the first high-resolution regional-scale transboundary risk assessment study in the area aiming to provide tools for decision-making. The output information will inform and enable the World Bank to initiate a policy dialogue. A fully probabilistic risk assessment for fluvial floods has been carried out for these countries to support regional and national risk financing and insurance applications, including potential indemnity and/or parametric risk financing solutions for a regional programme. A homogenised risk assessment methodology for the five countries and across multiple hazards (floods and earthquakes) and asset types has been adopted to obtain strategic financial solutions consistent across geographical areas and economic sectors. The largest relative (to the total exposed value) expected annual damages are found in Kazakhstan and Tajikistan, with values above 6 ‰. In the five considered countries, the largest relative expected annual damages by sector are found for the transport and agricultural sectors. Climate change is expected to have contrasting impacts, with increases in risk for some regions (the most severe increase is found in the Mangistauskaya region in Kazakhstan) and decreases for other regions (Lebap, Turkmenistan; Khatlon, Tajikistan; Samarkand, Uzbekistan; and Batken, Kyrgyz Republic).
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Air temperature and precipitation constraining the modelled wetland methane emissions in a boreal region in northern Europe
No full text<jats:p>Abstract. Wetland methane responses to temperature and precipitation are studied in a boreal wetland-rich region in northern Europe using ecosystem process models. Six ecosystem models (JSBACH-HIMMELI, LPX-Bern, LPJ-GUESS, JULES, CLM4.5, and CLM5) are compared to multi-model means of ecosystem models and atmospheric inversions from the Global Carbon Project and upscaled eddy covariance flux results for their temperature and precipitation responses and seasonal cycles of the regional fluxes. Two models with contrasting response patterns, LPX-Bern and JSBACH-HIMMELI, are used as priors in atmospheric inversions with Carbon Tracker Europe–CH4 (CTE-CH4) in order to find out how the assimilation of atmospheric concentration data changes the flux estimates and how this alters the interpretation of the flux responses to temperature and precipitation. Inversion moves wetland emissions of both models towards co-limitation by temperature and precipitation. Between 2000 and 2018, periods of high temperature and/or high precipitation often resulted in increased emissions. However, the dry summer of 2018 did not result in increased emissions despite the high temperatures. The process models show strong temperature and strong precipitation responses for the region (51 %–91 % of the variance explained by both). The month with the highest emissions varies from May to September among the models. However, multi-model means, inversions, and upscaled eddy covariance flux observations agree on the month of maximum emissions and are co-limited by temperature and precipitation. The setup of different emission components (peatland emissions, mineral land fluxes) has an important role in building up the response patterns. Considering the significant differences among the models, it is essential to pay more attention to the regional representation of wet and dry mineral soils and periodic flooding which contribute to the seasonality and magnitude of methane fluxes. The realistic representation of temperature dependence of the peat soil fluxes is also important. Furthermore, it is important to use process-based descriptions for both mineral and peat soil fluxes to simulate the flux responses to climate drivers.
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