Abstract
In the course of the preliminary planning of the new Gelnhausen–Fulda railway line which is part of the railway project Hanau–Würzburg/Fulda, two route options with tunnels, bridges, cuts ...and embankments are to be investigated and assessed as efficiently as possible with regard to potential geotechnical risk areas. Due to the geological and hydrogeological conditions within the north‐eastern Hessian Buntsandsteingebirge, several groundwater levels, landslides in tunnel portal areas and karstification structures are to be expected on the two route options, each of which is approx. 45 km long. In order to obtain detailed and, above all, large‐scale knowledge of geotechnical hazards of each route = in the preliminary stage of the exploration programme, geophysical surface investigations are a cost‐ and time‐optimized exploration method in addition to standard drilling. These findings as well as existing subsurface information are combined by means of BIM, so that risk areas can be identified at an early stage of the project and taken into account when selecting the most affordable route.
Abstract
Im Zuge der Vorplanung der DB‐Neubaustrecke Gelnhausen–Fulda als Teilmaßnahme des Projekts Hanau–Würzburg/Fulda sollen zwei Trassenvarianten mit Tunneln, Brücken, Einschnitten sowie Dämmen untersucht und möglichst effizient hinsichtlich potenzieller geotechnischer Risikobereiche abgeschätzt werden. Aufgrund der geologischen und hydrogeologischen Gegebenheiten innerhalb des nordosthessischen Buntsandsteingebirges ist auf den beiden zu untersuchenden jeweils ca. 45 km langen Trassen mit etlichen Grundwasserstockwerken, Rutschungen in Portalbereichen und Verkarstungsstrukturen zu rechnen. Um bereits in der Vorstufe des Erkundungsprogramms detaillierte und vor allem großräumige Erkenntnisse über die geotechnischen Gefährdungsbilder der einzelnen Trassen zu erhalten, bieten sich zusätzlich zu einem punktuellen Bohrprogramm oberflächengeophysikalische Untersuchungen Erkundungen an. Diese Erkenntnisse sowie geologische und hydrogeoglogische Bestandsunterlagen werden in einem BIM‐Gesamtmodell eingebunden, sodass Risikobereiche möglichst frühzeitig erkannt und bei der Trassenoptimierung berücksichtigt werden können.
We recently reported on the use of defocused imaging for single molecule localization microscopy close to the coverslip
Biomed. Opt. Express
,
11
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775
(
2020
)
10.1364/BOE.375678
. The original ...manuscript contains an error in the description of the Cramér-Rao lower bound (CRLB) calculations for SALM/DONALD, which affected the corresponding precision plot in Figure 2(b). We present a corrected description and plot.
Genome sequencing (GS) is expected to reduce the diagnostic gap in rare disease genetics. We aimed to evaluate a scalable framework for genome-based analyses 'beyond the exome' in regular care of ...patients with inherited retinal degeneration (IRD) or inherited optic neuropathy (ION).
PCR-free short-read GS was performed on 1000 consecutive probands with IRD/ION in routine diagnostics. Complementary whole-blood RNA-sequencing (RNA-seq) was done in a subset of 74 patients. An open-source bioinformatics analysis pipeline was optimised for structural variant (SV) calling and combined RNA/DNA variation interpretation.
A definite genetic diagnosis was established in 57.4% of cases. For another 16.7%, variants of uncertain significance were identified in known IRD/ION genes, while the underlying genetic cause remained unresolved in 25.9%. SVs or alterations in non-coding genomic regions made up for 12.7% of the observed variants. The RNA-seq studies supported the classification of two unclear variants.
GS is feasible in clinical practice and reliably identifies causal variants in a substantial proportion of individuals. GS extends the diagnostic yield to rare non-coding variants and enables precise determination of SVs. The added diagnostic value of RNA-seq is limited by low expression levels of the major IRD disease genes in blood.
Objective
The efficacy of bariatric surgery has been proven; however, a subset of patients fails to achieve expected long‐term weight loss postoperatively. As differences in surgery outcome may be ...influenced by heterogeneous psychological profiles in prebariatric patients, previous subtyping models differentiated patients based on temperament traits. The objective of this study was to expand these models by additionally considering emotion dysregulation and disinhibited eating behaviors for subtyping, as these factors were associated with maladaptive eating behaviors and poor postbariatric weight loss outcome.
Method
Within a prospective multicenter registry, N = 370 prebariatric patients were examined using interview and self‐report questionnaires. A latent profile analysis was performed to identify subtypes based on temperament traits, emotion dysregulation, and disinhibited eating behaviors.
Results
Five prebariatric subtypes were identified with specific profiles regarding self‐control, emotion dysregulation, and disinhibited eating behaviors. Subtypes were associated with different levels of eating disorder psychopathology, depression, and quality of life. The expanded model increased variance explanation compared to temperament‐based models.
Conclusion
By adding emotion dysregulation and disinhibited eating behaviors to previous subtyping models, specific prebariatric subtypes emerged with distinct psychological deficit patterns. Future investigations should test the predictive value of these subtypes for postbariatric weight loss and health‐related outcomes.
O presente artigo examina a Medida Provisória 746/2016, convertida na Lei 13.415, situando-a no debate sobre as finalidades e o formato do “novo” Ensino Médio brasileiro. Seu intuito é apresentar os ...principais desdobramentos da reforma e problematizar ao menos três de seus mais notáveis abusos: i) o de tornar a escola servil aos organismos internacionais e às demandas do mercado financeiro; ii) o de colocar em risco o princípio democrático e universal da educação republicana; iii) o de autorizar os adultos a se eximirem da formação das novas gerações, transferindo tal responsabilidade para as próprias crianças e jovens. O suposto é de que os alunos terão plenas condições emocionais e intelectuais para isso. Contudo, crianças e jovens estão sendo constrangidos a tomar decisões prematuramente. Em síntese, oficialmente desamparados, tornados órfãos por decisão estatal e com amparo legal.
Different tumor microenvironments (TMEs) induce stromal cell plasticity that affects tumorigenesis. The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is ...unclear. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). Transcriptome analyses identified markedly different gene clusters that reflected the tumorigenic and angiogenic activities of the respective TMEs. The gene encoding the matricellular protein SPARCL1 was most strongly upregulated in Th1-TME TECs. It was also highly expressed in ECs in healthy colon tissues and Th1-TME CRCs but low in control-TME CRCs. In vitro, SPARCL1 expression was induced in confluent, quiescent ECs and functionally contributed to EC quiescence by inhibiting proliferation, migration, and sprouting, whereas siRNA-mediated knockdown increased sprouting. In human CRC tissues and mouse models, vessels with SPARCL1 expression were larger and more densely covered by mural cells. SPARCL1 secretion from quiescent ECs inhibited mural cell migration, which likely led to stabilized mural cell coverage of mature vessels. Together, these findings demonstrate TME-dependent intertumoral TEC heterogeneity in CRC. They further indicate that TEC heterogeneity is regulated by SPARCL1, which promotes the cell quiescence and vessel homeostasis contributing to the favorable prognoses associated with Th1-TME CRCs.
IMPORTANCE: Climate change, pollution, urbanization, socioeconomic inequality, and psychosocial effects of the COVID-19 pandemic have caused massive changes in environmental conditions that affect ...brain health during the life span, both on a population level as well as on the level of the individual. How these environmental factors influence the brain, behavior, and mental illness is not well known. OBSERVATIONS: A research strategy enabling population neuroscience to contribute to identify brain mechanisms underlying environment-related mental illness by leveraging innovative enrichment tools for data federation, geospatial observation, climate and pollution measures, digital health, and novel data integration techniques is described. This strategy can inform innovative treatments that target causal cognitive and molecular mechanisms of mental illness related to the environment. An example is presented of the environMENTAL Project that is leveraging federated cohort data of over 1.5 million European citizens and patients enriched with deep phenotyping data from large-scale behavioral neuroimaging cohorts to identify brain mechanisms related to environmental adversity underlying symptoms of depression, anxiety, stress, and substance misuse. CONCLUSIONS AND RELEVANCE: This research will lead to the development of objective biomarkers and evidence-based interventions that will significantly improve outcomes of environment-related mental illness.
Antimicrobial resistance (AMR) is a serious global health threat with extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales as the most critical ones. Studies on AMR in wild birds imply ...a possible dissemination function and indicate their potential role as sentinel animals. This study aimed to gain a deeper insight into the AMR burden of wild waterfowl by sampling semi-wild mallard ducks used as sentinels and to identify if AMR bacteria could be recommended to be added to the pathogens of public health risks to be screened for. In total, 376 cloacal and pooled fecal samples were collected from the sentinel plant over a period of two years. Samples were screened for ESBL-carrying E. coli and isolates found further analyzed using antimicrobial susceptibility testing and whole-genome sequencing. Over the sampling period, 4.26% (16/376) of the samples were positive for ESBL-producing E. coli. Blasub.CTX-M-1 and blasub.CTX-M-32 were the most abundant CTX-M types. Although none of the top global sequence types (ST) could be detected, poultry-derived ST115 and non-poultry-related STs were found and could be followed over time. The current study revealed low cases of ESBL-producing E. coli in semi-wild mallard ducks, which proves the suitability of sentinel surveillance for AMR detection in water-associated wildlife.
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