### Recent Submissions

• Journal Article

#### Siberian larch (Larix sibirica Ledeb.) mitochondrial genome assembled using both short and long nucleotide sequence reads is currently the largest known mitogenome ﻿

BMC Genomics. 2020 Sep 23;21(1):654
Abstract Background Plant mitochondrial genomes (mitogenomes) can be structurally complex while their size can vary from ~ 222 Kbp in Brassica napus to 11.3 Mbp in Silene conica. To date, in comparison with the number of plant species, only a few plant mitogenomes have been sequenced and released, particularly for conifers (the Pinaceae family). Conifers cover an ancient group of land plants that includes about 600 species, and which are of great ecological and economical value. Among them, Siberian larch (Larix sibirica Ledeb.) represents one of the keystone species in Siberian boreal forests. Yet, despite its importance for evolutionary and population studies, the mitogenome of Siberian larch has not yet been assembled and studied. Results Two sources of DNA sequences were used to search for mitochondrial DNA (mtDNA) sequences: mtDNA enriched samples and nucleotide reads generated in the de novo whole genome sequencing project, respectively. The assembly of the Siberian larch mitogenome contained nine contigs, with the shortest and the largest contigs being 24,767 bp and 4,008,762 bp, respectively. The total size of the genome was estimated at 11.7 Mbp. In total, 40 protein-coding, 34 tRNA, and 3 rRNA genes and numerous repetitive elements (REs) were annotated in this mitogenome. In total, 864 C-to-U RNA editing sites were found for 38 out of 40 protein-coding genes. The immense size of this genome, currently the largest reported, can be partly explained by variable numbers of mobile genetic elements, and introns, but unlikely by plasmid-related sequences. We found few plasmid-like insertions representing only 0.11% of the entire Siberian larch mitogenome. Conclusions Our study showed that the size of the Siberian larch mitogenome is much larger than in other so far studied Gymnosperms, and in the same range as for the annual flowering plant Silene conica (11.3 Mbp). Similar to other species, the Siberian larch mitogenome contains relatively few genes, and despite its huge size, the repeated and low complexity regions cover only 14.46% of the mitogenome sequence.
• Journal Article

#### The central nervous system of Oweniidae (Annelida) and its implications for the structure of the ancestral annelid brain ﻿

Frontiers in Zoology. 2019 Mar 12;16(1):6
Abstract Background Recent phylogenomic analyses congruently reveal a basal clade which consists of Oweniidae and Mageloniidae as sister group to the remaining Annelida. These results indicate that the last common ancestor of Annelida was a tube-dwelling organism. They also challenge traditional evolutionary hypotheses of different organ systems, among them the nervous system. In textbooks the central nervous system is described as consisting of a ganglionic ventral nervous system and a dorsally located brain with different tracts that connect certain parts of the brain to each other. Only limited information on the fine structure, however, is available for Oweniidae, which constitute the sister group (possibly together with Magelonidae) to all remaining annelids. Results The brain of Oweniidae is ring- shaped and basiepidermal. Ganglia, higher brain centers or complex sensory organs do not exist; instead the central nervous system is medullary. Posterior to the brain the ventral medullary cord arises directly from the ventral region of the brain in Myriowenia sp. while in Owenia fusiformis two medullary cords arise perpendicular to the brain ring, extend caudally and fuse posterior. The central nervous system is composed of a central neuropil and surrounding somata of the neurons. According to ultrastructural and histological data only one type of neuron is present in the central nervous system. Conclusion The central nervous system of Oweniidae is the simplest in terms of enlargement of the dorsal part of the brain and neuron distribution found among Annelida. Our investigation suggests that neither ganglia nor commissures inside the brain neuropil or clusters of polymorphic neurons were present in the annelid stem species. These structures evolved later within Annelida, most likely in the stem lineage of Amphinomidae, Sipuncula and Pleistoannelida. Palps were supposedly present in the last common ancestor of annelids and innervated by two nerves originating in the dorsal part of the brain. A broader comparison with species of each major spiralian clade shows the medullary nervous system to be a common feature and thus possibly representing the ancestral state of the spiralian nervous system. Moreover, ganglia and clusters of polymorphic neurons seemingly evolved independently in the compared taxa of Spiralia and Annelida.
• Journal Article

#### Agricultural trade policies and child nutrition in low- and middle-income countries: a cross-national analysis ﻿

Globalization and Health. 2019 Mar 15;15(1):21
Abstract Background There has been growing interest in understanding the role of agricultural trade policies in diet and nutrition. This cross-country study examines associations between government policies on agricultural trade prices and child nutrition outcomes, particularly undernutrition. Methods This study links panel data on government distortions to agricultural incentives to data from 212,258 children aged 6 to 35 months participating in Demographic and Health Surveys from 22 countries between 1991 and 2010. Country fixed-effects regression models were used to examine the association between within-country changes in nominal rates of assistance to tradable agriculture (government price distortions as a percentage of original prices) and child nutritional outcomes (height-for-age, weight-for-age, and weight-for-height Z-scores) while controlling for a range of time-varying country covariates. Results Five-year average nominal rates of assistance to tradable agriculture ranged from − 72.0 to 45.5% with a mean of − 5.0% and standard deviation of 18.9 percentage points. A 10-percentage point increase in five-year average rates of assistance to tradable agriculture was associated with improved height-for-age (0.02, 95% CI,0.00–0.05) and weight-for-age (0.05, 95% CI: 0.02–0.09) Z-scores. Improvements in nutritional status were greatest among children who had at least one parent earning wages in agriculture, and effects decreased as a country’s proportion of tradable agriculture increased, particularly for weight-for-age Z-scores. Conclusions Government assistance to tradable agriculture, such as through reduced taxation, was associated with small but significant improvements in child nutritional status, especially for children with a parent earning wages in agriculture when the share of tradable agriculture was not high.
• Journal Article

#### MetaCHIP: community-level horizontal gene transfer identification through the combination of best-match and phylogenetic approaches ﻿

Microbiome. 2019 Mar 04;7(1):36
Abstract Background Metagenomic datasets provide an opportunity to study horizontal gene transfer (HGT) on the level of a microbial community. However, current HGT detection methods cannot be applied to community-level datasets or require reference genomes. Here, we present MetaCHIP, a pipeline for reference-independent HGT identification at the community level. Results Assessment of MetaCHIP’s performance on simulated datasets revealed that it can predict HGTs with various degrees of genetic divergence from metagenomic datasets. The results also indicated that the detection of very recent gene transfers (i.e. those with low levels of genetic divergence) from metagenomics datasets is largely affected by the read assembly step. Comparison of MetaCHIP with a previous analysis on soil bacteria showed a high level of consistency for the prediction of recent HGTs and revealed a large number of additional non-recent gene transfers, which can provide new biological and ecological insight. Assessment of MetaCHIP’s performance on real metagenomic datasets confirmed the role of HGT in the spread of genes related to antibiotic resistance in the human gut microbiome. Further testing also showed that functions related to energy production and conversion as well as carbohydrate transport and metabolism are frequently transferred among free-living microorganisms. Conclusion MetaCHIP provides an opportunity to study HGTs among members of a microbial community and therefore has several applications in the field of microbial ecology and evolution. MetaCHIP is implemented in Python and freely available at https://github.com/songweizhi/MetaCHIP .
• Journal Article

#### Strain-encoded cardiac magnetic resonance imaging: a new approach for fast estimation of left ventricular function ﻿

BMC Cardiovascular Disorders. 2019 Mar 05;19(1):52
Abstract Background Recently introduced fast strain-encoded (SENC) cardiac magnetic resonance (CMR) imaging (fast-SENC) provides real-time acquisition of myocardial performance in a single heartbeat. We aimed to test the ability and accuracy of real-time strain-encoded CMR imaging to estimate left ventricular volumes, ejection fraction and mass. Methods Thirty-five subjects (12 healthy volunteers and 23 patients with known or suspected coronary artery disease) were investigated. All study participants were imaged at 1.5 Tesla MRI scanner (Achieva, Philips) using an advanced CMR study protocol which included conventional cine and fast-SENC imaging. A newly developed real-time free-breathing SENC imaging technique based on the acquisition of two images with different frequency modulation was employed. Results All parameters were successfully derived from fast-SENC images with total study time of 105 s (a 15 s scan time and a 90 s post-processing time). There was no significant difference between fast-SENC and cine imaging in the estimation of LV volumes and EF, whereas fast-SENC underestimated LV end-diastolic mass by 7%. Conclusion The single heartbeat fast-SENC technique can be used as a good alternative to cine imaging for the precise calculation of LV volumes and ejection fraction while the technique significantly underestimates LV end-diastolic mass.
• Journal Article

#### A constructive review of the State Forest Inventory in the Russian Federation ﻿

Forest Ecosystems. 2019 Mar 08;6(1):9
Abstract The State Forest Inventory (SFI) in the Russian Federation is a relatively new project that is little known in the English-language scientific literature. Following the stipulations of the Forest Act of 2006, the first SFI sample plots in this vast territory were established in 2007. The 34 Russian forest regions were the basic geographical units for all statistical estimates and served as a first-level stratification, while a second level was based on old inventory data and remotely sensed data. The sampling design was to consist of a simple random sample of 84,700 circular 500 m2 sample plots over forest land. Each sample plot consists of three nested concentric circular subplots with radii of 12.62, 5.64 and 2.82 m and additional subplots for assessing and describing undergrowth, regeneration and ground vegetation. In total, 117 variables were to be measured or assessed on each plot. Although field work has begun, the methodology has elicited some criticism. The simple random sampling design is less efficient than a systematic design featuring sample plot clusters and a mix of temporary and permanent plots. The second-level stratification is mostly ineffective for increasing precision. Qualitative variables, which are not always essential, are dominant, while important quantitative variables are under-represented. Because of very slow progress, in 2018 the original plan was adjusted by reducing the number of permanent sample plots from 84,700 to 68,287 so that the first SFI cycle could be completed by 2020.
• Journal Article

#### Guidelines for open peer review implementation ﻿

Research Integrity and Peer Review. 2019 Feb 27;4(1):4
Abstract Open peer review (OPR) is moving into the mainstream, but it is often poorly understood and surveys of researcher attitudes show important barriers to implementation. As more journals move to implement and experiment with the myriad of innovations covered by this term, there is a clear need for best practice guidelines to guide implementation. This brief article aims to address this knowledge gap, reporting work based on an interactive stakeholder workshop to create best-practice guidelines for editors and journals who wish to transition to OPR. Although the advice is aimed mainly at editors and publishers of scientific journals, since this is the area in which OPR is at its most mature, many of the principles may also be applicable for the implementation of OPR in other areas (e.g., books, conference submissions).
• Journal Article

#### Laquinimod, a prototypic quinoline-3-carboxamide and aryl hydrocarbon receptor agonist, utilizes a CD155-mediated natural killer/dendritic cell interaction to suppress CNS autoimmunity ﻿

Journal of Neuroinflammation. 2019 Feb 26;16(1):49
Abstract Background Quinoline-3-carboxamides, such as laquinimod, ameliorate CNS autoimmunity in patients and reduce tumor cell metastasis experimentally. Previous studies have focused on the immunomodulatory effect of laquinimod on myeloid cells. The data contained herein suggest that quinoline-3-carboxamides improve the immunomodulatory and anti-tumor effects of NK cells by upregulating the adhesion molecule DNAX accessory molecule-1 (DNAM-1). Methods We explored how NK cell activation by laquinimod inhibits CNS autoimmunity in experimental autoimmune encephalomyelitis (EAE), the most utilized model of MS, and improves immunosurveillance of experimental lung melanoma metastasis. Functional manipulations included in vivo NK and DC depletion experiments and in vitro assays of NK cell function. Clinical, histological, and flow cytometric read-outs were assessed. Results We demonstrate that laquinimod activates natural killer (NK) cells via the aryl hydrocarbon receptor and increases their DNAM-1 cell surface expression. This activation improves the cytotoxicity of NK cells against B16F10 melanoma cells and augments their immunoregulatory functions in EAE by interacting with CD155+ dendritic cells (DC). Noteworthy, the immunosuppressive effect of laquinimod-activated NK cells was due to decreasing MHC class II antigen presentation by DC and not by increasing DC killing. Conclusions This study clarifies how DNAM-1 modifies the bidirectional crosstalk of NK cells with CD155+ DC, which can be exploited to suppress CNS autoimmunity and strengthen tumor surveillance.
• Journal Article

#### Protura are unique: first evidence of specialized feeding on ectomycorrhizal fungi in soil invertebrates ﻿

BMC Ecology. 2019 Feb 22;19(1):10
Abstract Background Ectomycorrhizal fungi (ECM) play a central role in nutrient cycling in boreal and temperate forests, but their role in the soil food web remains little understood. One of the groups assumed to live as specialised mycorrhizal feeders are Protura, but experimental and field evidence is lacking. We used a combination of three methods to test if Protura are specialized mycorrhizal feeders and compared their trophic niche with other soil invertebrates. Using pulse labelling of young beech and ash seedlings we analysed the incorporation of 13C and 15N into Acerentomon gallicum. In addition, individuals of Protura from temperate forests were collected for the analysis of neutral lipid fatty acids and natural variations in stable isotope ratios. Results Pulse labelling showed rapid incorporation of root-derived 13C, but no incorporation of root-derived 15N into A. gallicum. The transfer of 13C from lateral roots to ectomycorrhizal root tips was high, while it was low for 15N. Neutral lipid fatty acid (NLFA) analysis showed high amounts of bacterial marker (16:1ω7) and plant marker (16:0 and 18:1ω9) fatty acids but not of the fungal membrane lipid 18:2ω6,9 in A. gallicum. Natural variations in stable isotope ratios in Protura from a number of temperate forests were distinct from those of the great majority of other soil invertebrates, but remarkably similar to those of sporocarps of ECM fungi. Conclusions Using three in situ methods, stable isotope labelling, neutral lipid fatty acid analysis and natural variations of stable isotope ratios, we showed that Protura predominantly feed on mycorrhizal hyphae via sucking up hyphal cytoplasm. Predominant feeding on ectomycorrhizal mycelia by Protura is an exception; the limited consumption of ECM by other soil invertebrates may contribute to carbon sequestration in temperate and boreal forests.
• Journal Article

#### Identification of the recently described plasminogen gene mutation p.Lys330Glu in a family from Northern Germany with hereditary angioedema ﻿

Clinical and Translational Allergy. 2019 Feb 14;9(1):9
Abstract Hereditary angioedema (HAE) is a life-threatening disease characterized by recurrent episodes of subcutaneous and mucosal swellings and abdominal cramping. Corticosteroids and antihistamines, which are usually beneficial in histamine-induced acquired angioedema, are not effective in HAE. Therefore, diagnosing HAE correctly is crucial for affected patients. We report a family from Northern Germany with six individuals suffering from recurrent swellings, indicating HAE. Laboratory tests and genetic diagnostics of the genes SERPING1, encoding C1 esterase inhibitor (C1-INH), and F12, encoding coagulation factor XII, were unremarkable. In three affected and one yet unaffected member of the family, we were then able to identify the c.988A > G (also termed c.1100A > G) mutation in the plasminogen (PLG) gene, which has recently been described in several families with HAE. This mutation leads to a missense mutation with an amino acid exchange p.Lys330Glu in the kringle 3 domain of plasminogen. There was no direct relationship between the earlier described cases with this mutation and the family we report here. In all affected members of the family, the symptoms manifested in adulthood, with swellings of the face, tongue and larynx, including a fatal case of a 19 year-old female individual. The frequency of the attacks was variable, ranging between once per year to once a month. In one individual, we also found decreased serum levels of plasminogen as well as coagulation factor XII. As previously reported in patients with PLG defects, icatibant proved to be very effective in controlling acute attacks, indicating an involvement of bradykinin in the pathogenesis.
• Journal Article

#### Implementing a digital communication assistance tool to collect the medical history of refugee patients: DICTUM Friedland - an action-oriented mixed methods study protocol ﻿

BMC Health Services Research. 2019 Feb 06;19(1):103
Abstract Background Language barriers play a decisive role in determining the outcomes of medical consultations between healthcare providers and their foreign patients. This issue is a significant challenge to the German healthcare system, especially with the rising number of refugees in recent years. The communication gap between healthcare professionals and their non-German speaking patients sometimes leads to unnecessary medical re-admission, insufficient medical history, incorrect diagnosis, and treatment plans. In this study, we aim to assess the usability and accuracy of a novel digital translation tool in collecting medical history from patients in their native language and to check its effects on healthcare outcomes. Methods The study aims to monitor the implementation of a new digital communication assistance tool (DCAT) and to investigate its impact on the mutual understanding between refugee patients and their German general practitioners (GPs). In the first study phase, an action-oriented approach is used to implement DCAT. In the second study phase, DCAT use will be evaluated with a mixed methods design. The main outcome assesses the re-consultation rates of patients before and after using DCAT. Secondary outcomes include the usability of the tool, its acceptance and perceived quality by patients, the accuracy of the information collected as determined from analysing the reasons for the consultation (ICPC-2 codes), and diagnosis (ICD-10 codes). The acceptance by patients, socio-demographic factors and native language are also taken into account. The research designs for both study phases include questionnaires, semi-structured interviews, non-participant observation and analysis of collected patients’ data. All the collected data is pseudonymised. Discussion The DCAT study is one of the new research projects in primary healthcare investigating the usability, accuracy, and acceptance of digital translation tools during medical encounters. We aim to eliminate significant communication errors and misunderstandings in medical consultations, thereby improving the quality of healthcare outcomes. By applying an action research design, we will attain a more comprehensive evaluation of DCAT scopes and limits. The results of this study are expected to give an in-depth understanding of possible applications and benefits of digital translation tools for patient care. Trial registration German Clinical Trials Register DRKS00013076 , 29/09/2017.
• Journal Article

#### Somatic and sociodemographic predictors of depression outcome among depressed patients with coronary artery disease - a secondary analysis of the SPIRR-CAD study ﻿

BMC Psychiatry. 2019 Feb 04;19(1):57
• Journal Article

#### Stepwise large genome assembly approach: a case of Siberian larch (Larix sibirica Ledeb) ﻿

BMC Bioinformatics. 2019 Feb 05;20(Suppl 1):37
Background De novo assembling of large genomes, such as in conifers (~ 12–30 Gbp), which also consist of ~ 80% of repetitive DNA, is a very complex and computationally intense endeavor. One of the main problems in assembling such genomes lays in computing limitations of nucleotide sequence assembly programs (DNA assemblers). As a rule, modern assemblers are usually designed to assemble genomes with a length not exceeding the length of the human genome (3.24 Gbp). Most assemblers cannot handle the amount of input sequence data required to provide sufficient coverage needed for a high-quality assembly. Results An original stepwise method of de novo assembly by parts (sets), which allows to bypass the limitations of modern assemblers associated with a huge amount of data being processed, is presented in this paper. The results of numerical assembling experiments conducted using the model plant Arabidopsis thaliana, Prunus persica (peach) and four most popular assemblers, ABySS, SOAPdenovo, SPAdes, and CLC Assembly Cell, showed the validity and effectiveness of the proposed stepwise assembling method. Conclusion Using the new stepwise de novo assembling method presented in the paper, the genome of Siberian larch, Larix sibirica Ledeb. (12.34 Gbp) was completely assembled de novo by the CLC Assembly Cell assembler. It is the first genome assembly for larch species in addition to only five other conifer genomes sequenced and assembled for Picea abies, Picea glauca, Pinus taeda, Pinus lambertiana, and Pseudotsuga menziesii var. menziesii.
• Journal Article

#### Complementary and alternative medicine use in adults with autism spectrum disorder in Germany: results from a multi-center survey ﻿

BMC Psychiatry. 2019 Feb 01;19(1):53
• Journal Article

#### Positive association between forest management, environmental change, and forest bird abundance ﻿

Forest Ecosystems. 2019 Jan 29;6(1):3
Abstract Background The global decrease in wildlife populations, especially birds, is mainly due to land use change and increasing intensity of land use (Parmesan and Yohe 2003). However, impacts of management tools to mitigate biodiversity loss at regional and global scales are less apparent in forest regions that have a constant forest area, and which did not suffer from habitat degradation, and where forests are sustainably managed, such as in Central Europe or the northeastern USA. A biodiversity assessment for Germany suggested, for example, that bird populations were constant (Bundesamt für Naturschutz 2015). Results This study shows that changes in the environment and in forest management over the past 45 years have had a significant, positive effect on the abundance of non-migratory forest bird species in Central Europe. Economy (timber prices and GDP), forest management (timber harvest and mixed forest area), and environmental factors (atmospheric CO2 concentration and nitrogen deposition) were investigated together with changes in abundances of migratory and non-migratory forest birds using partial least squares path modeling. Climate change, resulting in longer seasons and milder winters, and forest management, promoting tree diversity, were significantly positively related to the abundance of non-migratory forest birds and explained 92% of the variation in their abundance in Europe. Regionally-migrating forest birds had stable populations with large variation, while birds migrating across continents declined in recent decades, suggesting significant, contrasting changes in bird populations in Europe. In northeastern North America we also found evidence that non-migratory forests have experienced long-term increases in abundance, and this increase was related to management. The increase of populations of non-migratory forest birds in Europe and North America is associated with an increase in structural diversity and disturbances at the landscape level. Conclusions Our results suggest that reports about bird decline in forests should separate between migratory and non-migratory bird species. Efforts to mitigate the general decline in bird abundance should focus on land-use systems other than forests and support sustainable forest management independent of economic conditions.
• Journal Article

#### Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery – a sub-analysis of the RIPHeart-Study ﻿

BMC Cardiovascular Disorders. 2019 Jan 24;19(1):26
Abstract Background The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery. Methods We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery. Results A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10− 8) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10− 5 from the GWAS. Conclusions We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery. Trial registration The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.
• Journal Article

#### Study protocol for a multi-methods study: SAVOIR - evaluation of specialized outpatient palliative care (SAPV) in Germany: outcomes, interactions, regional differences ﻿

BMC Palliative Care. 2019 Jan 26;18(1):12
Abstract Background Since 2007, the German statutory health insurance covers Specialized Outpatient Palliative Care (SAPV). SAPV offers team-based home care for patients with advanced and progressive disease, complex symptoms and life expectancy limited to days, weeks or months. The introduction of SAPV is ruled by a directive (SAPV directive). Within this regulation, SAPV delivery models can and do differ regarding team structures, financing models, cooperation with other care professionals and processes of care. The research project SAVOIR is funded by G-BA’s German Innovations Fund to evaluate the implementation of the SAPV directive. Methods The processes, content and quality of SAPV will be evaluated from the perspectives of patients, SAPV teams, general practitioners and other care givers and payers. The influence of different contracts, team and network structures and regional and geographic settings on processes and results including patient-reported outcomes will be analyzed in five subprojects: [1] structural characteristics of SAPV and their impact on patient care, [2] quality of care from the perspective of patients, [3] quality of care from the perspective of SAPV teams, hospices, ambulatory nursing services, nursing homes and other care givers, content and extent of care from [4] the perspective of General Practitioners and [5] from the perspective of payers. The evaluation will be based on different types of data: team and organizational structures, treatment data based on routine documentation with electronic medical record systems, prospective assessment of patient-reported outcomes in a sample of SAPV teams, qualitative interviews with other stakeholders like nursing and hospice services, a survey in general practitioners and a retrospective analysis of claims data of all SAPV patients, covered by the health insurance fund BARMER in 2016. Discussion Data analysis will allow identification of variables, associated with quality of SAPV. Based on these findings, the SAVOIR study group will develop recommendations for the Federal Joint Committee for a revision of the SAPV directive. Trial registration German Clinical Trials Register (DRKS): DRKS00013949 (retrospectively registered, 14.03.2018), DRKS00014726 (14.05.2018), DRKS00014730 (30.05.2018). Subproject 3 is an interview study with professional caregivers and therefore not registered in DRKS as a clinical study.
• Journal Article

#### “An odyssey without receiving proper care” – experts’ views on palliative care provision for patients with migration background in Germany ﻿

BMC Palliative Care. 2019 Jan 21;18(1):8
Abstract Background Migrants seem to be underrepresented in palliative care in Germany. Access barriers and challenges in care remain unclear. We aimed to provide a comprehensive insight into palliative care for migrants, using expert interviews. Methods Interviews with experts on palliative and general health care for migrants were audiotaped and transcribed. Data analysis followed a qualitative content analysis method for expert interviews proposed by Meuser and Nagel. Results In total, 13 experts from various fields (palliative and hospice care, other care, research and training) were interviewed. Experts identified access barriers on the health care system and the patient level as well as the sociopolitical level. Services don’t address migrants, who may use parallel structures. Patients may distrust the health care system, be oriented towards their home country and expect the family to care for them. In care, poor adaptation and inflexibility of health care services regarding needs of migrant patients because of scarce resources, patients’ preferences which may contradict professionals' values, and communication both on the verbal and nonverbal level were identified as the main challenges. Conflicts between patients, families and professionals are at risk to be interpreted exclusively as cultural conflicts. Palliative care providers should use skilled interpreters instead of family interpreters or unskilled staff members, and focus on training cultural competence. Furthermore, intercultural teams could enhance palliative care provision for migrants. Conclusions Though needs and wishes of migrant patients are often found to be similar to those of non-migrant patients, there are migration-specific aspects that can influence care provision at the end of life. Migration should be regarded as a biographical experience that has a severe and ongoing impact on the life of an individual and their family. Language barriers have to be considered, especially regarding patients' right to informed decision making. The reimbursement of interpreters in health care remains an open question.
• Journal Article

#### Prevalence of abnormal Alzheimer’s disease biomarkers in patients with subjective cognitive decline: cross-sectional comparison of three European memory clinic samples ﻿

Alzheimer's Research & Therapy. 2019 Jan 17;11(1):8
Abstract Introduction Subjective cognitive decline (SCD) in cognitively unimpaired older individuals has been recognized as an early clinical at-risk state for Alzheimer’s disease (AD) dementia and as a target population for future dementia prevention trials. Currently, however, SCD is heterogeneously defined across studies, potentially leading to variations in the prevalence of AD pathology. Here, we compared the prevalence and identified common determinants of abnormal AD biomarkers in SCD across three European memory clinics participating in the European initiative on harmonization of SCD in preclinical AD (Euro-SCD). Methods We included three memory clinic SCD samples with available cerebrospinal fluid (CSF) biomaterial (IDIBAPS, Barcelona, Spain, n = 44; Amsterdam Dementia Cohort (ADC), The Netherlands, n = 50; DELCODE multicenter study, Germany, n = 42). CSF biomarkers (amyloid beta (Aβ)42, tau, and phosphorylated tau (ptau181)) were centrally analyzed in Amsterdam using prespecified cutoffs to define prevalence of pathological biomarker concentrations. We used logistic regression analysis in the combined sample across the three centers to investigate center effects with regard to likelihood of biomarker abnormality while taking potential common predictors (e.g., age, sex, apolipoprotein E (APOE) status, subtle cognitive deficits, depressive symptoms) into account. Results The prevalence of abnormal Aβ42, but not tau or ptau181, levels was different across centers (64% DELCODE, 57% IDIBAPS, 22% ADC; p < 0.001). Logistic regression analysis revealed that the likelihood of abnormal Aβ42 (and also abnormal tau or ptau181) levels was predicted by age and APOE status. For Aβ42 abnormality, we additionally observed a center effect, indicating between-center heterogeneity not explained by age, APOE, or the other included covariates. Conclusions While heterogeneous frequency of abnormal Aβ42 was partly explained by between-sample differences in age range and APOE status, the additional observation of center effects indicates between-center heterogeneity that may be attributed to different recruitment procedures. These findings highlight the need for the development of harmonized recruitment protocols for SCD case definition in multinational studies to achieve similar enrichment rates of preclinical AD.
• Journal Article

#### Upper and lower bounds for the Bregman divergence ﻿

Journal of Inequalities and Applications. 2019 Jan 08;2019(1):4
Abstract In this paper we study upper and lower bounds on the Bregman divergence Δ F ξ ( y , x ) : = F ( y ) − F ( x ) − ⟨ ξ , y − x ⟩ $\Delta_{\mathcal {F}}^{\xi }(y,x):=\mathcal {F}(y)-\mathcal {F}(x)- \langle \xi , y-x \rangle$ for some convex functional F $\mathcal {F}$ on a normed space X $\mathcal {X}$ , with subgradient ξ ∈ ∂ F ( x ) $\xi \in\partial \mathcal {F}(x)$ . We give a considerably simpler new proof of the inequalities by Xu and Roach for the special case F ( x ) = ∥ x ∥ p $\mathcal {F}(x)= \Vert x \Vert ^{p}$ , p > 1 $p>1$ . The results can be transferred to more general functions as well.