Ein Beitrag zur Vordimensionierung der Steifigkeitseigenschaften metallischer Bauteile durch die systematische Integration additiv gefertigter Meso-Strukturen

Die additive Fertigung ermöglicht es, Meso-Strukturen, auch Gitterstrukturen genannt, in Bauteile zu integrieren. Meso-Strukturen bestehen aus sich periodisch wiederholenden Elementarzellen mit vielfältigen Topologien, die durch die Merkmale Strukturdicke und Kantenlängen der Elementarzellen-Einhüllenden definiert sind. Die geometrische Vielfalt und die variablen Merkmale ergeben eine Vielzahl nutzbarer Eigenschaften. Besonders die hohe Leichtbaugüte der Meso-Strukturen ist von Bedeutung. Meso-Strukturen in Bauteile zu integrieren, erfordert eine gezielte Auslegung der Eigenschaften der Meso-Strukturen während des Produktentwicklungsprozesses (PEP). Zur Bewertung und Auswahl von Bauteilkonzepten mit und ohne Meso-Strukturen im Vergleich ist eine einfache und schnelle Vorauslegung der Meso-Strukturen zweckmäßig. Die Auslegung mittels simulationsgestützter Optimierung oder iterativer Dimensionierung, wie sie in der Literatur beschrieben wird, führt zu einem hohen Auslegungsaufwand und Einflüsse einzelner Merkmale auf die Bauteileigenschaften sind nicht direkt ersichtlich. Ziel der Arbeit ist es daher, eine Methode zur Vordimensionierung der Meso-Strukturen zu erarbeiten, in welcher die Zusammenhänge zwischen den leichtbaurelevanten Steifigkeitseigenschaften der Meso-Strukturen und den Merkmalen Topologie, Strukturdicke und Kantenlänge würfelförmiger Elementarzellen-Einhüllender, für eine beanspruchungsgerechte Dimensionierung mit einem Modell beschrieben werden. Dazu werden die Zusammenhänge für homogene Meso-Strukturen mittels Finite-Elemente-Methode (FEM) untersucht und eine Dimensionierungsgleichung für die Auslegung der Meso-Strukturen ermittelt, die eine Vordimensionierung der Steifigkeitseigenschaften ohne erneute Verwendung von Simulationen ermöglicht. Die Dimensionierungsgleichung beschreibt topologieweise die Normal- und Schubsteifigkeit der Meso-Struktur-Elementarzellen, abhängig vom Dimensionsverhältnis Strukturdicke zu Kantenlänge der Elementarzellen-Einhüllenden. Das FEM- und das Dimensionierungsmodell werden initial experimentell verifiziert. Die beanspruchungsgerechte Gestaltung erfordert lokal unterschiedliche Ausprägungen der Merkmale der Meso-Strukturen. Für die Anpassung an die lokale Beanspruchung wird eine Variation der Strukturdicke sowie deren Gradierung vorgesehen, um die Bereiche unterschiedlicher Strukturdicken ohne Steifigkeitssprünge zu verbinden. Die Auswirkung der Gradierung wird ebenfalls mittels FEM untersucht. Abhängig von der relativen Durchschnittsdichte werden die Steifigkeitseigenschaften durch die Gradierung verglichen mit einer homogenen Elementarzelle der gleichen Durchschnittsdichte reduziert. Anhand der Ergebnisse, wird ein Kriterium für die Dimensionierung von Gradienten, ausgehend von der lokal erforderlichen Dicke einer homogenen Elementarzelle, ermittelt. Die Anwendung des Modells zur Vorauslegung in der Konzeptphase des PEP wird durch ein methodisches Vorgehen systematisiert und beispielhaft evaluiert

Diagnostic uncertainty in pediatric chronic pain: Nature, prevalence, and consequences

Introduction: Diagnostic uncertainty (DU), which is the perception that a label or explanation for a patient's health problem is missing or inaccurate, has been linked to distress, anxiety, and difficulty coping among adults with pain. This study examined the prevalence of DU among youth with chronic pain and their parents and the relation of parent and youth DU with youth pain, pain-related constructs, and health-related quality of life (HRQoL).Methods: Participants included 174 youth with chronic pain (Mage = 14.28 years; 73% female) and one of their parents (91% mothers) recruited from a tertiary-level pediatric chronic pain program in Canada. Youth and parent DU was assessed using a brief measure of 3 empirically derived yes/no questions regarding whether the youth and parent had received a clear diagnosis/explanation for their/their child's pain and whether they believed there was something else happening with their/their child's pain that doctors had not yet found. Youth reported on their pain intensity, pain interference, pain catastrophizing, fear of pain, and HRQoL.Results: Thirty-one percent of youth and 28% of parents experienced DU. Seventy percent of parents and youth were in agreement regarding their experience of DU. Youth DU was linked to higher youth catastrophic thinking about their pain. Parent DU was linked to greater youth pain interference and intensity and lower youth HRQoL.Conclusion: Diagnostic uncertainty is experienced by nearly a third of youth with chronic pain and their parents and is linked to worse youth pain, pain catastrophizing, and HRQoL.Diagnostic uncertainty is common among youth with chronic pain and their parents and is linked to worse youth pain, pain catastrophizing, and quality of life

Seismological structure of the 1.8 Ga Trans-Hudson Orogen of North America

Precambrian tectonic processes are debated: what was the nature and scale of orogenic events on the younger, hotter, and more ductile Earth? Northern Hudson Bay records the Paleoproterozoic collision between the Western Churchill and Superior plates—the ∼1.8 Ga Trans-Hudson Orogeny (THO)—and is an ideal locality to study Precambrian tectonic structure. Integrated field, geochronological, and thermobarometric studies suggest that the THO was comparable to the present-day Himalayan-Karakoram-Tibet Orogen (HKTO). However, detailed understanding of the deep crustal architecture of the THO, and how it compares to that of the evolving HKTO, is lacking. The joint inversion of receiver functions and surface wave data provides new Moho depth estimates and shear velocity models for the crust and uppermost mantle of the THO. Most of the Archean crust is relatively thin (∼39 km) and structurally simple, with a sharp Moho; upper-crustal wave speed variations are attributed to postformation events. However, the Quebec-Baffin segment of the THO has a deeper Moho (∼45 km) and a more complex crustal structure. Observations show some similarity to recent models, computed using the same methods, of the HKTO crust. Based on Moho character, present-day crustal thickness, and metamorphic grade, we support the view that southern Baffin Island experienced thickening during the THO of a similar magnitude and width to present-day Tibet. Fast seismic velocities at >10 km below southern Baffin Island may be the result of partial eclogitization of the lower crust during the THO, as is currently thought to be happening in Tibet

Genome-Wide Mapping of Susceptibility to Coronary Artery Disease Identifies a Novel Replicated Locus on Chromosome 17

Coronary artery disease (CAD) is a leading cause of death world-wide, and most cases have a complex, multifactorial aetiology that includes a substantial heritable component. Identification of new genes involved in CAD may inform pathogenesis and provide new therapeutic targets. The PROCARDIS study recruited 2,658 affected sibling pairs (ASPs) with onset of CAD before age 66 y from four European countries to map susceptibility loci for CAD. ASPs were defined as having CAD phenotype if both had CAD, or myocardial infarction (MI) phenotype if both had a MI. In a first study, involving a genome-wide linkage screen, tentative loci were mapped to Chromosomes 3 and 11 with the CAD phenotype (1,464 ASPs), and to Chromosome 17 with the MI phenotype (739 ASPs). In a second study, these loci were examined with a dense panel of grid-tightening markers in an independent set of families (1,194 CAD and 344 MI ASPs). This replication study showed a significant result on Chromosome 17 (MI phenotype; p = 0.009 after adjustment for three independent replication tests). An exclusion analysis suggests that further genes of effect size λ(sib) > 1.24 are unlikely to exist in these populations of European ancestry. To our knowledge, this is the first genome-wide linkage analysis to map, and replicate, a CAD locus. The region on Chromosome 17 provides a compelling target within which to identify novel genes underlying CAD. Understanding the genetic aetiology of CAD may lead to novel preventative and/or therapeutic strategies

Recommendations for the surveillance of education and employment outcomes in survivors of childhood, adolescent, and young adult cancer: A report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Educational achievement and employment outcomes are critical indicators of quality of life in survivors of childhood, adolescent, and young adult (CAYA) cancer. This review is aimed at providing an evidence-based clinical practice guideline (CPG) with internationally harmonized recommendations for the surveillance of education and employment outcomes in survivors of CAYA cancer diagnosed before the age of 30 years. The CPG was developed by a multidisciplinary panel under the umbrella of the International Late Effects of Childhood Cancer Guideline Harmonization Group. After evaluating concordances and discordances of 4 existing CPGs, the authors performed a systematic literature search through February 2021. They screened articles for eligibility, assessed quality, and extracted and summarized the data from included articles. The authors formulated recommendations based on the evidence and clinical judgment. There were 3930 articles identified, and 83 of them, originating from 17 countries, were included. On a group level, survivors were more likely to have lower educational achievement and more likely to be unemployed than comparisons. Key risk factors for poor outcomes included receiving a primary diagnosis of a central nervous system tumor and experiencing late effects. The authors recommend that health care providers be aware of the risk of educational and employment problems, implement regular surveillance, and refer survivors to specialists if problems are identified. In conclusion, this review presents a harmonized CPG that aims to facilitate evidence-based care, positively influence education and employment outcomes, and ultimately minimize the burden of disease and treatment-related late adverse effects for survivors of CAYA cancers. LAY SUMMARY: A multidisciplinary panel has developed guidelines for the surveillance of education and employment outcomes among survivors of childhood, adolescent, and young adult cancer. On the basis of evidence showing that survivors are at risk for lower educational achievement and unemployment, it is recommended that all survivors receive regular screening for educational and employment outcomes

Combined 23 Na and 13 C imaging at 3.0 Tesla using a single‐tuned large FOV birdcage coil

Purpose: An unmet need in carbon‐13 (13C)‐MRI is a transmit system that provides uniform excitation across a large FOV and can accommodate patients of wide‐ranging body habitus. Due to the small difference between the resonant frequencies, sodium‐23 (23Na) coil developments can inform 13C coil design while being simpler to assess due to the higher naturally abundant 23Na signal. Here we present a removable 23Na birdcage, which also allows operation as a 13C abdominal coil. Methods: We demonstrate a quadrature‐driven 4‐rung 23Na birdcage coil of 50 cm in length for both 23Na and 13C abdominal imaging. The coil transmit efficiencies and B 1 + maps were compared to a linearly driven 13C Helmholtz‐based (clamshell) coil. SNR was investigated with 23Na and 13C data using an 8‐channel 13C receive array within the 23Na birdcage. Results: The 23Na birdcage longitudinal FOV was > 40 cm, whereas the 13C clamshell was < 32 cm. The transmit efficiency of the birdcage at the 23Na frequency was 0.65 µT/sqrt(W), similar to the clamshell for 13C. However, the coefficient of variation of 23Na‐ B 1 + was 16%, nearly half that with the 13C clamshell. The 8‐channel 13C receive array combined with the 23Na birdcage coil generated a greater than twofold increase in 23Na‐SNR from the central abdomen compared with the birdcage alone. Discussion: This 23Na birdcage coil has a larger FOV and improved B 1 + uniformity when compared to the widely used clamshell coil design while also providing similar transmit efficiency. The coil has the potential to be used for both 23Na and 13C imaging

The threat of the COVID-19 pandemic on reversing global life-saving gains in the survival of childhood cancer: A call for collaborative action from SIOP, IPSO, PROS, WCC, CCI, st jude global, UICC and WHPCA

The COVID-19 pandemic poses an unprecedented health crisis in all socio-economic regions across the globe. While the pandemic has had a profound impact on access to and delivery of health care by all services, it has been particularly disruptive for the care of patients with life-threatening noncommunicable diseases (NCDs) such as the treatment of children and young people with cancer. The reduction in child mortality from preventable causes over the last 50 years has seen childhood cancer emerge as a major unmet health care need. Whilst survival rates of 85% have been achieved in high income countries, this has not yet been translated into similar outcomes for children with cancer in resource-limited settings where survival averages 30%. Launched in 2018, by the World Health Organization (WHO), the Global Initiative for Childhood Cancer (GICC) is a pivotal effort by the international community to achieve at least 60% survival for children with cancer by 2030. The WHO GICC is already making an impact in many countries but the disruption of cancer care during the COVID-19 pandemic threatens to set back this global effort to improve the outcome for children with cancer, wherever they may live. As representatives of the global community committed to fostering the goals of the GICC, we applaud the WHO response to the COVID-19 pandemic, in particular we support the WHO's call to ensure the needs of patients with life threatening NCDs including cancer are not compromised during the pandemic. Here, as collaborative partners in the GICC, we highlight specific areas of focus that need to be addressed to ensure the immediate care of children and adolescents with cancer is not disrupted during the pandemic; and measures to sustain the development of cancer care so the long-term goals of the GICC are not lost during this global health crisis.Fil: Pritchard Jones, Kathy. University College London; Estados UnidosFil: de Abib, Simone C.V.. International Society Of Paediatric Surgical Oncology; Surinam. Universidade Federal de Sao Paulo; BrasilFil: Esiashvili, Natia. University of Emory; Estados UnidosFil: Kaspers, Gertjan J.L.. Princess Máxima Center for Pediatric Oncology; Países BajosFil: Rosser, Jon. No especifíca;Fil: van Doorninck, John A.. Rocky Mountain Hospital for Children; Estados UnidosFil: Braganca, João M.L.. No especifíca;Fil: Hoffman, Ruth I.. No especifíca;Fil: Rodriguez Galindo, Carlos. St Jude Children’s Research Hospital; Estados UnidosFil: Adams, Cary. Union for International Cancer Control; SuizaFil: Connor, Stephen R.. Worldwide Hospice Palliative Care Alliance; Estados UnidosFil: Abdelhafeez, Abdelhafeez H.. International Society of Paediatric Surgical Oncology; Suiza. St. Jude Children’s Research Hospital; Estados UnidosFil: Bouffet, Eric. University Of Toronto. Hospital For Sick Children; Canadá. International Society of Paediatric Surgical Oncology; SuizaFil: Howard, Scott C.. International Society of Paediatric Surgical Oncology; Suiza. University of Tennessee; Estados UnidosFil: Challinor, Julia M.. International Society of Paediatric Surgical Oncology; Suiza. University of California; Estados UnidosFil: Hessissen, Laila. Children Hospital of Rabat; Marruecos. International Society of Paediatric Surgical Oncology; SuizaFil: Dalvi, Rashmi B.. Bombay Hospital Institute of Medical Sciences; India. International Society of Paediatric Surgical Oncology; SuizaFil: Kearns, Pamela. International Society of Paediatric Surgical Oncology; SuizaFil: Chantada, Guillermo Luis. International Society of Paediatric Surgical Oncology; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Frazier, Lindsay A.. International Society of Paediatric Surgical Oncology; Suiza. Dana-Farber Cancer Institute; Estados UnidosFil: Sullivan, Michael J.. University of Melbourne; Australia. International Society of Paediatric Surgical Oncology; SuizaFil: Schulte, Fiona S.M.. University of Calgary; Canadá. International Society of Paediatric Surgical Oncology; SuizaFil: Morrissey, Lisa K.. Boston Children’s Hospital; Estados Unidos. International Society of Paediatric Surgical Oncology; SuizaFil: Kozhaeva, Olga. European Society for Paediatric Oncology; BélgicaFil: Luna Fineman, Sandra. Children’s Hospital Colorado; Estados Unidos. International Society of Paediatric Oncology; SuizaFil: Khan, Muhammad S.. Tawam Hospital; Emiratos Arabes Unido

Magnetic resonance fingerprinting of the pancreas at 1.5 T and 3.0 T

Funder: GlaxoSmithKline; doi: http://dx.doi.org/10.13039/100004330Funder: National Institute of Health Research (NIHR) Cambridge Biomedical Research CentreFunder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; doi: http://dx.doi.org/10.13039/501100002927Abstract: Magnetic resonance imaging of the pancreas is increasingly used as an important diagnostic modality for characterisation of pancreatic lesions. Pancreatic MRI protocols are mostly qualitative due to time constraints and motion sensitivity. MR Fingerprinting is an innovative acquisition technique that provides qualitative data and quantitative parameter maps from a single free‐breathing acquisition with the potential to reduce exam times. This work investigates the feasibility of MRF parameter mapping for pancreatic imaging in the presence of free-breathing exam. Sixteen healthy participants were prospectively imaged using MRF framework. Regions-of-interest were drawn in multiple solid organs including the pancreas and T1 and T2 values determined. MRF T1 and T2 mapping was performed successfully in all participants (acquisition time:2.4–3.6 min). Mean pancreatic T1 values were 37–43% lower than those of the muscle, spleen, and kidney at both 1.5 and 3.0 T. For these organs, the mean pancreatic T2 values were nearly 40% at 1.5 T and < 12% at 3.0 T. The feasibility of MRF at 1.5 T and 3 T was demonstrated in the pancreas. By enabling fast and free-breathing quantitation, MRF has the potential to add value during the clinical characterisation and grading of pathological conditions, such as pancreatitis or cancer

Genomic Targets of Brachyury (T) in Differentiating Mouse Embryonic Stem Cells

The T-box transcription factor Brachyury (T) is essential for formation of the posterior mesoderm and the notochord in vertebrate embryos. Work in the frog and the zebrafish has identified some direct genomic targets of Brachyury, but little is known about Brachyury targets in the mouse.Here we use chromatin immunoprecipitation and mouse promoter microarrays to identify targets of Brachyury in embryoid bodies formed from differentiating mouse ES cells. The targets we identify are enriched for sequence-specific DNA binding proteins and include components of signal transduction pathways that direct cell fate in the primitive streak and tailbud of the early embryo. Expression of some of these targets, such as Axin2, Fgf8 and Wnt3a, is down regulated in Brachyury mutant embryos and we demonstrate that they are also Brachyury targets in the human. Surprisingly, we do not observe enrichment of the canonical T-domain DNA binding sequence 5'-TCACACCT-3' in the vicinity of most Brachyury target genes. Rather, we have identified an (AC)(n) repeat sequence, which is conserved in the rat but not in human, zebrafish or Xenopus. We do not understand the significance of this sequence, but speculate that it enhances transcription factor binding in the regulatory regions of Brachyury target genes in rodents.Our work identifies the genomic targets of a key regulator of mesoderm formation in the early mouse embryo, thereby providing insights into the Brachyury-driven genetic regulatory network and allowing us to compare the function of Brachyury in different species