Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
4,385
result(s) for
"Schaefer, D."
Sort by:
Quantification of biological aging in young adults
Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their \"biological aging\" (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.
Journal Article
Polygenic scores for smoking and educational attainment have independent influences on academic success and adjustment in adolescence and educational attainment in adulthood
Educational success is associated with greater quality of life and depends, in part, on heritable cognitive and non-cognitive traits. We used polygenic scores (PGS) for smoking and educational attainment to examine different genetic influences on facets of academic adjustment in adolescence and educational attainment in adulthood. PGSs were calculated for participants of the Minnesota Twin Family Study ( N = 3225) and included as predictors of grades, academic motivation, and discipline problems at ages 11, 14, and 17 years-old, cigarettes per day from ages 14 to 24 years old, and educational attainment in adulthood (mean age 29.4 years). Smoking and educational attainment PGSs had significant incremental associations with each academic variable and cigarettes per day. About half of the adjusted effects of the smoking and education PGSs on educational attainment in adulthood were mediated by the academic variables in adolescence. Cigarettes per day from ages 14 to 24 years old did not account for the effect of the smoking PGS on educational attainment, suggesting the smoking PGS indexes genetic influences related to general behavioral disinhibition. In sum, distinct genetic influences measured by the smoking and educational attainment PGSs contribute to academic adjustment in adolescence and educational attainment in adulthood.
Journal Article
Tissue engineering of bone: the reconstructive surgeon's point of view
Bone defects represent a medical and socioeconomic challenge. Different types of biomaterials are applied for reconstructive indications and receive rising interest. However, autologous bone grafts are still considered as the gold standard for reconstruction of extended bone defects. The generation of bioartificial bone tissues may help to overcome the problems related to donor site morbidity and size limitations. Tissue engineering is, according to its historic definition, an “interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function”. It is based on the understanding of tissue formation and regeneration and aims to rather grow new functional tissues than to build new spare parts. While reconstruction of small to moderate sized bone defects using engineered bone tissues is technically feasible, and some of the currently developed concepts may represent alternatives to autologous bone grafts for certain clinical conditions, the reconstruction of largevolume defects remains challenging. Therefore vascularization concepts gain on interest and the combination of tissue engineering approaches with flap prefabrication techniques may eventually allow application of bone‐tissue substitutes grown in vivo with the advantage of minimal donor site morbidity as compared to conventional vascularized bone grafts. The scope of this review is the introduction of basic principles and different components of engineered bioartificial bone tissues with a strong focus on clinical applications in reconstructive surgery. Concepts for the induction of axial vascularization in engineered bone tissues as well as potential clinical applications are discussed in detail.
Journal Article
PDGF-BB regulates splitting angiogenesis in skeletal muscle by limiting VEGF-induced endothelial proliferation
VEGF induces normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo. This transition depends on the balance between VEGF-induced endothelial stimulation and PDGF-BB-mediated pericyte recruitment, and co-expression of PDGF-BB normalizes aberrant angiogenesis despite high VEGF doses. We recently found that VEGF over-expression induces angiogenesis in skeletal muscle through an initial circumferential vascular enlargement followed by longitudinal splitting, rather than sprouting. Here we investigated the cellular mechanism by which PDGF-BB co-expression normalizes VEGF-induced aberrant angiogenesis. Monoclonal populations of transduced myoblasts, expressing similarly high levels of VEGF alone or with PDGF-BB, were implanted in mouse skeletal muscles. PDGF-BB co-expression did not promote sprouting and angiogenesis that occurred through vascular enlargement and splitting. However, enlargements were significantly smaller in diameter, due to a significant reduction in endothelial proliferation, and retained pericytes, which were otherwise lost with high VEGF alone. A time-course of histological analyses and repetitive intravital imaging showed that PDGF-BB co-expression anticipated the initiation of vascular enlargement and markedly accelerated the splitting process. Interestingly, quantification during in vivo imaging suggested that a global reduction in shear stress favored the initiation of transluminal pillar formation during VEGF-induced splitting angiogenesis. Quantification of target gene expression showed that VEGF-R2 signaling output was significantly reduced by PDGF-BB co-expression compared to VEGF alone. In conclusion, PDGF-BB co-expression prevents VEGF-induced aberrant angiogenesis by modulating VEGF-R2 signaling and endothelial proliferation, thereby limiting the degree of circumferential enlargement and enabling efficient completion of vascular splitting into normal capillary networks despite high VEGF doses.
Journal Article
Propagation of forcing and model uncertainties on to hydrological drought characteristics in a multi-model century-long experiment in large river basins
Recent climate change impact studies studies have presented conflicting results regarding the largest source of uncertainty in essential hydrological variables, especially streamflow and derived characteristics that describe the evolution of drought events. Part of the problem arises from the lack of a consistent framework to address compatible initial conditions for the impact models and a set of standardized historical and future forcings. The ISI-MIP2 project provides a good opportunity to advance our understanding of the propagation of forcing and model uncertainties on to century-long time series of drought characteristics using an ensemble of hydrological model (HM) projections across a broad range of climate scenarios and regions. To achieve this goal, we used six regional preconditioned hydrological models set up in seven large river basins: Upper-Amazon, Blue-Nile, Ganges, Upper-Niger, Upper-Mississippi, Rhine, and Upper-Yellow. These models were forced with bias-corrected outputs from five CMIP5 general circulation models (GCMs) under two extreme representative concentration pathway scenarios (i.e., RCP2.6 and RCP8.5) for the period 1971-2099. The simulated streamflow was transformed into a monthly runoff index (RI) to analyze the attributions of the GCM and HM uncertainties on to drought magnitudes and durations over time. The results indicated that GCM uncertainty mostly dominated over HM uncertainty for the projections of runoff drought characteristics, irrespective of the selected RCP and region. In general, the overall uncertainty increased with time. The uncertainty in the drought characteristics increased as the radiative forcing of the RCP increased, but the propagation of the GCM uncertainty on to a drought characteristic depended largely upon the hydro-climatic regime. Although our study emphasizes the need for multi-model ensembles for the assessment of future drought projections, the agreement between the GCM forcings was still too weak to draw conclusive recommendations.
Journal Article
Measurement of Interlaminar Tensile Strength and Elastic Properties of Composites Using Open-Hole Compression Testing and Digital Image Correlation
Advanced polymeric composites are increasingly used in high-performance aircraft structures to reduce weight and improve efficiency. However, a major challenge delaying the implementation of the advanced composites is the lack of accurate methods for material characterization. Accurate measurement of three-dimensional mechanical properties of composites, stress–strain response, strength, fatigue, and toughness properties, is essential in the development of validated analysis techniques accelerating design and certification of composite structures. In particular, accurate measurement of the through-thickness constitutive properties and interlaminar tensile (ILT) strength is needed to capture delamination failure, which is one of the primary failure modes in composite aircraft structures. A major technical challenge to accurate measurement of ILT properties is their strong sensitivity to manufacturing defects that often leads to unacceptable scatter in standard test results. Unacceptable failure mode in standard test methods is another common obstacle to accurate ILT strength measurement. Characterization methods based on non-contact full-field measurement of deformation have emerged as attractive alternative techniques allowing more flexibility in test configuration to address some of the limitations inherent to strain gauge-based standard testing. In this work, a method based on full-field digital image correlation (DIC) measurement of surface deformation in unidirectional open-hole compression (OHC) specimens is proposed and investigated as a viable alternative to assessing ILT stress–strain, strength, and fatigue properties. Inverse identification using a finite element model updating (FEMU) method is used for simultaneous measurement of through-thickness elastic constants with recovery of the maximum ILT stress at failure for characterization of strength and fatigue S–N curves.
Journal Article
A contemporary case series of Fournier’s gangrene at a Swiss tertiary care center—can scoring systems accurately predict mortality and morbidity?
Background
Fournier’s gangrene (FG) is a life-threatening infection of the genital, perineal, and perianal regions with a morbidity range between 3 and 67%. Our aim is to report our experience in treatment of FG and to assess whether three different scoring systems can accurately predict mortality and morbidity in FG patients.
Methods
All patients that were treated for FG at the Department of Urology of the University Hospital Basel between June 2012 and March 2017 were included and assessed retrospectively by chart review. Furthermore, we calculated Fournier’s Gangrene Severity Index (FGSI), the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC), and the neutrophil–lymphocyte ratio (NLR) in every patient and assessed whether those scores correlate with the patients’ morbidity and mortality.
Results
Twenty patients were included, with a median (IQR) age of 66 (46–73) years. Fifteen of twenty (75%) patients required treatment on an intensive care unit, and three died (mortality rate: 15%). The mean FGSI, LRINEC, and NLR scores were 13.0, 9.3, and 45.3 for non-survivors and 7.7, 6.5, and 26 for survivors, respectively. None of the risk scores correlated significantly with mortality; however, all three significantly correlated with infection- and surgically-induced morbidity.
Conclusions
In our series, Fournier’s gangrene was associated with a mortality rate of 15% despite maximum multidisciplinary therapy at a specialized center. All risk scores were able to predict the morbidity of the disease in terms of local extent and the required surgical measures.
Journal Article
Difficulties with emotion regulation as a transdiagnostic mechanism linking child maltreatment with the emergence of psychopathology
Childhood maltreatment is associated with increased risk for most forms of psychopathology. We examine emotion dysregulation as a transdiagnostic mechanism linking maltreatment with general psychopathology. A sample of 262 children and adolescents participated; 162 (61.8%) experienced abuse or exposure to domestic violence. We assessed four emotion regulation processes (cognitive reappraisal, attention bias to threat, expressive suppression, and rumination) and emotional reactivity. Psychopathology symptoms were assessed concurrently and at a 2-year longitudinal follow-up. A general psychopathology factor (p factor), representing co-occurrence of psychopathology symptoms across multiple internalizing and externalizing domains, was estimated using confirmatory factor analysis. Maltreatment was associated with heightened emotional reactivity and greater use of expressive suppression and rumination. The association of maltreatment with attention bias varied across development, with maltreated children exhibiting a bias toward threat and adolescents a bias away from threat. Greater emotional reactivity and engagement in rumination mediated the longitudinal association between maltreatment and increased general psychopathology over time. Emotion dysregulation following childhood maltreatment occurs at multiple stages of the emotion generation process, in some cases varies across development, and serves as a transdiagnostic mechanism linking child maltreatment with general psychopathology.
Journal Article
The Mercury Dual Imaging System on the MESSENGER Spacecraft
The Mercury Dual Imaging System (MDIS) on the MESSENGER spacecraft will provide critical measurements tracing Mercury's origin and evolution. MDIS consists of a monochrome narrow-angle camera (NAC) and a multispectral wide-angle camera (WAC). The NAC is a 1.5 degree field-of-view (FOV) off-axis reflector, coaligned with the WAC, a four-element refractor with a 10.5 degree FOV and 12-color filter wheel. The focal plane electronics of each camera are identical and use a 1,024 x 1,024 Atmel (Thomson) TH7888A charge-coupled device detector. Only one camera operates at a time, allowing them to share a common set of control electronics. The NAC and the WAC are mounted on a pivoting platform that provides a 90 degree field-of-regard, extending 40 degree sunward and 50 degree anti-sunward from the spacecraft +Z-axis-the boresight direction of most of MESSENGER's instruments. Onboard data compression provides capabilities for pixel binning, remapping of 12-bit data into 8 bits, and lossless or lossy compression. MDIS will acquire four main data sets at Mercury during three flybys and the two-Mercury-solar-day nominal mission: a monochrome global image mosaic at near-zero emission angles and moderate incidence angles, a stereo-complement map at off-nadir geometry and near-identical lighting, multicolor images at low incidence angles, and targeted high-resolution images of key surface features. These data will be used to construct a global image base map, a digital terrain model, global maps of color properties, and mosaics of high-resolution image strips. Analysis of these data will provide information on Mercury's impact history, tectonic processes, the composition and emplacement history of volcanic materials, and the thickness distribution and compositional variations of crustal materials. This paper summarizes MDIS's science objectives and technical design, including the common payload design of the MDIS data processing units, as well as detailed results from ground and early flight calibrations and plans for Mercury image products to be generated from MDIS data.
Journal Article