Computational ballistic analysis of the cranial shot to John F. Kennedy.

Almost 60 years after the assassination of President John F. Kennedy in 1963, the majority of Americans are still reluctant to believe official reports presented by the commissions gathered in 1964 and again in 1976 that determined the direction of the shot resulting in the fatal head injury. Long-withheld, confidential government files released in 2017 reignited the controversy. The present investigation computationally simulated projectile-skull-impacts from the direction specified in official reports and from three other directions. Detailed geometric models of the human head and ammunition, as well as known parameters from the assassination site served as the supportive base for analysis. Constitutive mathematical models for the impact of projectile material with skull tissues at supersonic speed were employed to analyze bone and bullet fragmentation mechanics. Simulated fracture characteristics of bone and bullet were compared with photographic and X-ray evidence. The most likely origin of the fatal shot was determined based on the degree of corresponding deformation and fragmentation between simulation and documented evidence. Computational corroboration could be established as physically consistent with high-speed impact from the rear, as established by the official commissions. Simulations of three other speculative shot origins did not correspond with the documented evidence.

New methodology for mechanical characterization of human superficial facial tissue anisotropic behaviour in vivo.

Mechanical characterization of human superficial facial tissue has important applications in biomedical science, computer assisted forensics, graphics, and consumer goods development. Specifically, the latter may include facial hair removal devices. Predictive accuracy of numerical models and their ability to elucidate biomechanically relevant questions depends on the acquisition of experimental data and mechanical tissue behavior representation. Anisotropic viscoelastic behavioral characterization of human facial tissue, deformed in vivo with finite strain, however, is sparse. Employing an experimental-numerical approach, a procedure is presented to evaluate multidirectional tensile properties of superficial tissue layers of the face in vivo. Specifically, in addition to stress relaxation, displacement-controlled multi-step ramp-and-hold protocols were performed to separate elastic from inelastic properties. For numerical representation, an anisotropic hyperelastic material model in conjunction with a time domain linear viscoelasticity formulation with Prony series was employed. Model parameters were inversely derived, employing finite element models, using multi-criteria optimization. The methodology provides insight into mechanical superficial facial tissue properties. Experimental data shows pronounced anisotropy, especially with large strain. The stress relaxation rate does not depend on the loading direction, but is strain-dependent. Preconditioning eliminates equilibrium hysteresis effects and leads to stress-strain repeatability. In the preconditioned state tissue stiffness and hysteresis insensitivity to strain rate in the applied range is evident. The employed material model fits the nonlinear anisotropic elastic results and the viscoelasticity model reasonably reproduces time-dependent results. Inversely deduced maximum anisotropic long-term shear modulus of linear elasticity is G∞,maxaniso=2.43kPa and instantaneous initial shear modulus at an applied rate of ramp loading is G0,maxaniso=15.38kPa. Derived mechanical model parameters constitute a basis for complex skin interaction simulation.

Plasma MR-proANP levels are associated with carotid intima-media thickness in the general community: the KORA F4 study.

OBJECTIVE: Subjects with metabolic syndrome (MetS) and individuals with type 2 diabetes are at high risk for vascular complications. Hormones acting on vascular endothelium may be involved in the atherogenic process associated with metabolic disorders. The objective of this study was to determine the correlation of pro-atrial natriuretic hormone (proANP) with the presence of subclinical atherosclerosis. METHODS: In 1272 subjects participating in the KORA F4 study, we determined plasma levels of mid-regional proANP (MR-proANP) and the intima-media thickness (IMT) of the carotid artery. We used logistic regression models to investigate the relation of MR-proANP with components of MetS and IMT. RESULTS: In multiple adjusted regression models, MR-proANP levels were inversely associated with MetS (OR = 0.66, 95% CI 0.47-0.93), central obesity (OR = 0.67, 95% CI 0.46-0.96), raised triglyceride levels (OR = 0.53, 95% CI 0.37-0.77), prediabetes (OR = 0.62, 95%, CI 0.44-0.87) and type 2 diabetes (OR = 0.55, 95% CI 0.35-0.88) when comparing the top quartile vs. the lower three quartiles. Furthermore, there was an inverse relationship between MR-proANP and IMT. After adjustment for traditional cardiovascular risk markers, individuals with high MR-proANP plasma levels in the top quartile (Q4) had significantly lower IMT values (Q4 vs. Q1-Q3: ß -0.0178, 95% CI -0.0344; -0.0013). CONCLUSIONS: In this population-based study, high plasma concentrations of MR-proANP were significantly associated with a lower incidence of MetS components and lower measures of early atherosclerosis. The data suggest a link between MR-proANP levels and the development of vascular complications.

Cytotoxicity on human cells of Cry1Ab and Cry1Ac Bt insecticidal toxins alone or with a glyphosate-based herbicide.

The study of combined effects of pesticides represents a challenge for toxicology. In the case of the new growing generation of genetically modified (GM) plants with stacked traits, glyphosate-based herbicides (like Roundup) residues are present in the Roundup-tolerant edible plants (especially corns) and mixed with modified Bt insecticidal toxins that are produced by the GM plants themselves. The potential side effects of these combined pesticides on human cells are investigated in this work. Here we have tested for the very first time Cry1Ab and Cry1Ac Bt toxins (10 ppb to 100 ppm) on the human embryonic kidney cell line 293, as well as their combined actions with Roundup, within 24 h, on three biomarkers of cell death: measurements of mitochondrial succinate dehydrogenase, adenylate kinase release by membrane alterations and caspase 3/7 inductions. Cry1Ab caused cell death from 100 ppm. For Cry1Ac, under such conditions, no effects were detected. The Roundup tested alone from 1 to 20 000 ppm is necrotic and apoptotic from 50 ppm, far below agricultural dilutions (50% lethal concentration 57.5 ppm). The only measured significant combined effect was that Cry1Ab and Cry1Ac reduced caspases 3/7 activations induced by Roundup; this could delay the activation of apoptosis. There was the same tendency for the other markers. In these results, we argue that modified Bt toxins are not inert on nontarget human cells, and that they can present combined side-effects with other residues of pesticides specific to GM plants.

[Update on type 1 diabetes]. / Update Typ-1-Diabetes.

Type 1a diabetes develops from a chronic autoimmune process leading to absolute insulin deficiency and proneness to ketosis. Prospective studies have clearly shown that intensive insulin therapy (ICT) results in improved quality of life and reduced development of diabetes-associated microvascular and macrovascular complications. The gold standard of therapy in type 1 diabetes is insulin injection with a basal bolus insulin regimen, in which patient daily routine and wishes are considered. The treatment goals should be determined on an individualized basis together with the patient. An HbA(1c) value < 7.0% is considered to be well controlled while values ≤ 6.5% indicate an excellent blood glucose control, as long as there are no episodes of severe hypoglycemia. As many adult patients with type 1 diabetes develop additional cardiovascular risk factors dyslipidemia and hypertension should also be considered and treated according to current treatment guidelines. A multimodal treatment may be the best way to preserve quality of life in patients with type 1 diabetes.

Method for characterizing viscoelasticity of human gluteal tissue.

Characterizing compressive transient large deformation properties of biological tissue is becoming increasingly important in impact biomechanics and rehabilitation engineering, which includes devices interfacing with the human body and virtual surgical guidance simulation. Individual mechanical in vivo behaviour, specifically of human gluteal adipose and passive skeletal muscle tissue compressed with finite strain, has, however, been sparsely characterised. Employing a combined experimental and numerical approach, a method is presented to investigate the time-dependent properties of in vivo gluteal adipose and passive skeletal muscle tissue. Specifically, displacement-controlled ramp-and-hold indentation relaxation tests were performed and documented with magnetic resonance imaging. A time domain quasi-linear viscoelasticity (QLV) formulation with Prony series valid for finite strains was used in conjunction with a hyperelastic model formulation for soft tissue constitutive model parameter identification and calibration of the relaxation test data. A finite element model of the indentation region was employed. Strong non-linear elastic but linear viscoelastic tissue material behaviour at finite strains was apparent for both adipose and passive skeletal muscle mechanical properties with orthogonal skin and transversal muscle fibre loading. Using a force-equilibrium assumption, the employed material model was well suited to fit the experimental data and derive viscoelastic model parameters by inverse finite element parameter estimation. An individual characterisation of in vivo gluteal adipose and muscle tissue could thus be established. Initial shear moduli were calculated from the long-term parameters for human gluteal skin/fat: G(∞,S/F)=1850 Pa and for cross-fibre gluteal muscle tissue: G(∞,M)=881 Pa. Instantaneous shear moduli were found at the employed ramp speed: G(0,S/F)=1920 Pa and G(0,M)=1032 Pa.

Mechanical gluteal soft tissue material parameter validation under complex tissue loading.

BACKGROUND: Finite element (FE) simulations of mechanical tissue loading help provide insight into internal tissue stress and strain distribution. Thus, better understanding of pressure sore aetiology and pressure sore prophylaxis can be acquired. Indispensable in the simulation process is adequate mechanical description of interacting soft tissue and body support materials. Sufficient verification of employed material parameters is required. METHOD OF APPROACH: Gluteal soft tissue material parameters, previously derived from experimental tissue indentation of a geometrically limited buttock sub-domain are shown to be suitable in simulating complex deformation of the entire buttocks. In the context of parameter verification, defined tissue loading via a soft foam material specimen was performed. Making use of magnetic resonance imaging (MRI), the scenario was scanned to gain tissue displacement information. Anatomical surface data was reconstructed and an FE-model of the experimental situation was generated and simulated. MR-image information was compared with simulation results. RESULTS: Deformation of gluteal skin/fat and passive muscle tissue and support material under loading was in good agreement with the corresponding MR-image data. Visual accordance was found for deformed skin boundary as well as for internal fat-muscle tissue boundaries by superimposing experimental and numerical output. In addition, section surface boundaries of the MR-images and the FE-model of skin/fat and muscle at the deformed state were discretized and sufficient sample points were provided. A correlation factor of R2= 0.998 for skin/fat deformation was derived, comparing simulation with MRI output. CONCLUSION: Reliability of employed tissue material parameters for use in realistic loading scenarios at finite strains including complex tissue and bone anatomy, non-linear tissue support material, multiple tissue types and contact interactions is shown.

Deriving ozone dose-response of photosynthesis in adult forest trees from branch-level cuvette gas exchange assessment.

Branch-level gas exchange provided the basis for assessing ozone flux in order to derive the dose-response relationship between cumulative O3 uptake (COU) and carbon gain in the upper sun crown of adult Fagus sylvatica. Fluxes of ozone, CO2 and water vapour were monitored simultaneously by climatized branch cuvettes. The cuvettes allowed branch exposure to an ambient or twice-ambient O3 regime, while tree crowns were exposed to the same O3 regimes (twice-ambient generated by a free-air canopy O3 exposure system). COU levels higher than 20mmolm(-2) led to a pronounced decline in carbon gain under elevated O3. The limiting COU range is consistent with findings on neighbouring branches exposed to twice-ambient O3 through free-air fumigation. The cuvette approach allows to estimate O3 flux at peripheral crown positions, where boundary layers are low, yielding a meso-scale within-crown resolution of photosynthetic foliage sensitivity under whole-tree free-air O3 fumigation.

Analysis of mechanical interaction between human gluteal soft tissue and body supports.

Pressure sores are the most common complication associated with patient immobilization. They develop through sustained localized tissue strain and stress, primarily caused by body supports. Modifying support design can reduce the risk and extent of pressure sore development with computational simulations helping to provide insight into tissue stress-strain distribution. Appropriate material parameters for human soft tissue and support material, as well as precise anatomical modelling, are indispensable in this process. A finite element (FE) model of the human gluteal region based on magnetic resonance imaging (MRI) data has been developed. In vivo human gluteal skin/fat and muscle long-term material parameters as well as open-cell polyurethane foam support long-term material parameters have been characterised. The Ogden form for slightly compressible materials was employed to describe human gluteal soft tissue behaviour. Altering support geometries and support materials, effects on human gluteal soft tissue could be quantified. FE-analysis indicated maximal tissue stress at the muscle-bone interface, not at the skin. Shear strain maxima were found in the muscle layer near the fat-muscle interface. Maximum compressive stress magnitude at the sacral bone depended strongly on the behaviour of the pelvic diaphragm musculature. We hypothesize that the compliance of the muscles forming the pelvic diaphragm govern the relative motion of the buttock tissue to the adjacent bone structure under compression, thus influencing tissue stress magnitudes.

A method for a mechanical characterisation of human gluteal tissue.

The most common complication associated with immobilization is pressure sores caused by sustained localized tissue strain and stress. Computational simulations have provided insight into tissue stress-strain distribution, subject to loading conditions. In the simulation process, adequate soft tissue material parameters are indispensable. An in vivo procedure to characterise material parameters of human gluteal skin/fat and muscle tissue has been developed. It employs a magnetic resonance imaging (MRI) device together with an MRI compatible loading device. Using the derived data as constraints in an iterative optimization process the inverse finite element (FE) method was applied. FE-models were built and the material constants describing skin/fat and muscle tissue were parameterized and optimized. Separate parameter sets for human gluteal skin/fat and muscle were established. The long-term shear modulus for human gluteal skin/fat was G_{infinity, S/F}= 1182 Pa and for muscle G_{infinity, M} = 1025 Pa. The Ogden form for slightly compressible materials was chosen to define passive human gluteal soft tissue material behaviour. To verify the approach, the human skin/fat-muscle tissue compound was simulated using the derived material parameter sets and the simulation result was compared to empirical values. A correlation factor of R;{2} = 0.997 was achieved.

Gas exchange and antioxidative compounds in young beech trees under free-air ozone exposure and comparisons to adult trees.

Three-year-old beech (Fagus sylvatica) seedlings growing in containers were placed into the sun and shade crown of a mature beech stand exposed to ambient (1 x O(3)) and double ambient (2 x O(3)) ozone concentrations at a free-air exposure system ("Kranzberg Forst", Germany). Pigments, alpha-tocopherol, glutathione, ascorbate, and gas exchange were measured in leaves during 2003 (a drought year) and 2004 (an average year). Sun-exposed seedlings showed higher contents of antioxidants, xanthophylls, and beta-carotene and lower contents of chlorophyll, alpha-carotene, and neoxanthin than shade-exposed seedlings. In 2003 sun-exposed seedlings showed higher contents of carotenoids and total glutathione and lower net photosynthesis rates (A(max)) compared to 2004. O(3) exposure generally affected the content of chlorophyll, the xanthophyll cycle, and the intercellular CO(2) concentration (c(i)). Seedlings differed from the adjacent adult trees in most biochemical and physiological parameters investigated: Sun exposed seedlings showed higher contents of alpha-tocopherol and xanthophylls and lower contents of ascorbate, chlorophyll, neoxanthin, and alpha-carotene compared to adult trees. Shade exposed seedlings had lower contents of xanthophylls, alpha-carotene, and alpha-tocopherol than shade leaves of old-growth trees. In 2003, seedlings had higher A(max), stomatal conductance (g(s)), and c(i) under 2 x O(3) than adult trees. The results showed that shade acclimated beech seedlings are more sensitive to O(3), possibly due to a lower antioxidative capacity per O(3) uptake. We conclude that beech seedlings are uncertain surrogates for adult beech trees.

CASIROZ: Root parameters and types of ectomycorrhiza of young beech plants exposed to different ozone and light regimes.

Tropospheric ozone (O(3)) triggers physiological changes in leaves that affect carbon source strength leading to decreased carbon allocation below-ground, thus affecting roots and root symbionts. The effects of O(3) depend on the maturity-related physiological state of the plant, therefore adult and young forest trees might react differently. To test the applicability of young beech plants for studying the effects of O(3) on forest trees and forest stands, beech seedlings were planted in containers and exposed for two years in the Kranzberg forest FACOS experiment (Free-Air Canopy O(3) Exposure System, http://www.casiroz.de ) to enhanced ozone concentration regime (ambient [control] and double ambient concentration, not exceeding 150 ppb) under different light conditions (sun and shade). After two growing seasons the biomass of the above- and below-ground parts, beech roots (using WinRhizo programme), anatomical and molecular (ITS-RFLP and sequencing) identification of ectomycorrhizal types and nutrient concentrations were assessed. The mycorrhization of beech seedlings was very low ( CA. 5 % in shade, 10 % in sun-grown plants), no trends were observed in mycorrhization (%) due to ozone treatment. The number of Cenococcum geophilum type of ectomycorrhiza, as an indicator of stress in the forest stands, was not significantly different under different ozone treatments. It was predominantly occurring in sun-exposed plants, while its majority share was replaced by Genea hispidula in shade-grown plants. Different light regimes significantly influenced all parameters except shoot/root ratio and number of ectomycorrhizal types. In the ozone fumigated plants the number of types, number of root tips per length of 1 to 2 mm root diameter, root length density per volume of soil and concentration of Mg were significantly lower than in control plants. Trends to a decrease were found in root, shoot, leaf, and total dry weights, total number of root tips, number of vital mycorrhizal root tips, fine root (mass) density, root tip density per surface, root area index, concentration of Zn, and Ca/Al ratio. Due to the general reduction in root growth indices and nutrient cycling in ozone-fumigated plants, alterations in soil carbon pools could be predicted.

Evidence that branch cuvettes are reasonable surrogates for estimating O3 effects in entire tree crowns.

Within the scope of quantifying ozone (O(3)) effects on forest tree crowns it is still an open question whether cuvette branches of adult trees are reasonable surrogates for O(3) responses of entire tree crowns and whether twigs exhibit autonomy in defense metabolism in addition to carbon autonomy. Therefore, cuvette-enclosed branches of mature beech (Fagus sylvatica) trees were compared with branches exposed to the same and different ozone regimes by a free-air fumigation system under natural stand conditions by means of a VICE VERSA experiment. For this purpose, cuvettes receiving 1 x O(3) air were mounted in trees exposed to 2 x O(3) and cuvettes receiving 2 x O(3) air were mounted in trees exposed to 1 x O (3) in the upper sun crown. At the end of the fumigation period in September 2004, leaves were examined for differences in gas exchange parameters, pigments, antioxidants, carbohydrates, and stable isotope ratios. No significant differences in foliar gas exchange, total carbohydrates, stable isotope ratios, pigment, and antioxidant contents were found as a consequence of cuvette enclosure (cuvette versus free-air branches) of the same O(3) concentrations besides increase of glucose inside the cuvettes and reduction of the de-epoxidation state of the xanthophyll cycle pigments. No significant ozone effect was found for the investigated gas exchange and most biochemical parameters. The total and oxidized glutathione level of the leaves was increased by the 2 x O(3) treatment in the cuvette and the free-air branches, but this effect was significant only for the free-air branches. From these results we conclude that cuvette branches are useful surrogates for examining the response of entire tree crowns to elevated O(3) and that the defence metabolism of twigs seems to be at least partially autonomous.

Modelling ozone effects on adult beech trees through simulation of defence, damage, and repair costs: Implementation of the CASIROZ ozone model in the ANAFORE forest model.

Ozone affects adult trees significantly, but effects on stem growth are hard to prove and difficult to correlate with the primary sites of ozone damage at the leaf level. To simulate ozone effects in a mechanistic way, at a level relevant to forest stand growth, we developed a simple ozone damage and repair model (CASIROZ model) that can be implemented into mechanistic photosynthesis and growth models. The model needs to be parameterized with cuvette measurements on net photosynthesis and dark respiration. As the CASIROZ ozone sub-model calculates effects of the ozone flux, a reliable representation of stomatal conductance and therefore ozone uptake is necessary to allow implementation of the ozone sub-model. In this case study the ozone sub-model was used in the ANAFORE forest model to simulate gas exchange, growth, and allocation. A preliminary run for adult beech (FAGUS SYLVATICA) under different ozone regimes at the Kranzberg forest site (Germany) was performed. The results indicate that the model is able to represent the measured effects of ozone adequately, and to distinguish between immediate and cumulative ozone effects. The results further help to understand ozone effects by distinguishing defence from damage and repair. Finally, the model can be used to extrapolate from the short-term results of the field study to long-term effects on tree growth. The preliminary simulations for the Kranzberg beech site show that, although ozone effects on yearly growth are variable and therefore insignificant when measured in the field, they could become significant at longer timescales (above 5 years, 5 % reduction in growth). The model offers a possible explanation for the discrepancy between the significant effects on photosynthesis (10 to 30 % reductions simulated), and the minor effects on growth. This appears to be the result of the strong competition and slow growth of the Kranzberg forest, and the importance of stored carbon for the adult beech (by buffering effects on carbon gain). We finally conclude that inclusion of ozone effects into current forest growth and yield models can be an important improvement into their overall performance, especially when simulating younger and less dense forests.