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This is an overview of the EAS Familial Hypercholesterolaemia (FH) Studies Collaboration (FHSC) global consortium and registry (established 2015), which broadly addresses the global burden of FH. Eighty-seven National Lead Investigators from 74 countries form this expanding global consortium, and this global registry currently includes pooled data on 70,000 participants from participating countries to facilitate FH surveillance. Published first results from this global registry concluded that FH is diagnosed late, and management of LDL-cholesterol falls below guideline recommendations, and therefore earlier detection of FH and wider use of combination therapy is required. Further FHSC studies will follow on updated data including new countries, participants and variables, and non-DNA genetic information, and on the remaining cohorts in the registry. FHSC cross-sectional collaborative global studies are expected to promote FH detection earlier in life to subsequently initiate early lipid lowering therapy to reduce lifelong exposure to cumulative LDL-cholesterol thus reducing cardiovascular disease risk.

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In this study, in operandi SAXS experiments were conducted on samples of human hair with a varying degree of strain (2% within the elastic region and 10% beyond). Four different features in the SAXS patterns were evaluated: The intermediate filament distance perpendicular to and the distance from the meridional arc in the load direction, as well as the distances of the lipid bilayer peak in and perpendicular to the load direction. From the literature, one concludes that polar lipids in the cuticle are the origin of the lipid peak in the SAXS pattern, and this study shows that the observed strain in the lipids is much lower than in the intermediate filaments. We support these findings with SEM micrographs, which show that the scales in the cuticle deform much less than the cortex. The observed deformation of the intermediate filaments is very high, about 70% of the macrostrain, and the ratio of the transverse strain to the longitudinal strain at the nanoscale gives a Poisson ratio of νnano = 0.44, which is typical for soft matter. This work also finds that by varying the time period between two strain cycles, the typical strain recovery time is about 1000 min, i.e., one day. After this period, the structure is nearly identical to the initial structure, which suggests an interpretation that this is the typical time for the self-healing of hair after mechanical treatment.

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Plastid sequences have long dominated phylogeny reconstruction at all time depths, predicated on a usually untested assumption that they accurately represent the evolutionary histories of phenotypically circumscribed species. We combined detailed in situ morphometrics (124 plants) and whole-plastome sequencing through genome skimming (71 plants) in order to better understand species-level diversity and speciation in arguably the most challenging monophyletic group within the taxonomically controversial, pseudo-copulatory bee orchid genus Ophrys. Using trees and ordinations, we interpreted the data at four nested demographic levels-macrospecies, mesospecies, microspecies, and local population-seeking the optimal level for bona fide species. Neither morphological nor molecular discontinuities are evident at any level below macrospecies, the observed overlap among taxa suggesting that both mesospecies and microspecies reflect arbitrary division of a continuum of variation. Plastomes represent geographic location more strongly than taxonomic assignment and correlate poorly with morphology, suggesting widespread plastid capture and possibly post-glacial expansion from multiple southern refugia. As they are rarely directly involved in the speciation process, plastomes depend on extinction of intermediate lineages to provide phylogenetic signal and so cannot adequately document evolutionary radiations. The popular 'ethological' evolutionary model recognizes as numerous 'ecological species' (microspecies) lineages perceived as actively diverging as a result of density-dependent selection on very few features that immediately dictate extreme pollinator specificity. However, it is assumed rather than demonstrated that the many microspecies are genuinely diverging. We conversely envisage a complex four-dimensional reticulate network of lineages, generated locally and transiently through a wide spectrum of mechanisms, but each unlikely to maintain an independent evolutionary trajectory long enough to genuinely speciate by escaping ongoing gene flow. The frequent but localized microevolution that characterizes the Ophrys sphegodes complex is often convergent and rarely leads to macroevolution. Choosing between the contrasting 'discontinuity' and 'ethology' models will require next-generation sequencing of nuclear genomes plus ordination of corresponding morphometric matrices, seeking the crucial distinction between retained ancestral polymorphism-consistent with lineage divergence-and polymorphisms reflecting gene flow through 'hybridization'-more consistent with lineage convergence.

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Yak belly hair was proposed as a cheap substitute for human hair for the development of hair dyes, as its chemical composition closely resembles human hair in Raman spectroscopy. The absence of melanin in yak belly hair also leads to a strong reduction of fluorescence in Raman measurements, which is advantageous for the investigation of the effectivity of hair dyes. To assess the suitability for replacing human hair, we analyzed similarities and differences of both hair types with a variety of methods: Raman spectroscopy, to obtain molecular information; small-angle X-ray scattering to determine the nanostructure, such as intermediate filament distance, distance of lipid layers and nanoporosity; optical and scanning electron microscopy of surfaces and cross sections to determine the porosity at the microstructural level; and density measurements and tensile tests to determine the macroscopic structure, macroporosity and mechanical properties. Both types of hair are similar on a molecular scale, but differ on other length scales: yak belly hair has a smaller intermediate filament distance on the nanoscale. Most striking is a higher porosity of yak belly hair on all hierarchical levels, and a lower Young's modulus on the macroscale. In addition to the higher porosity, yak belly hair has fewer overlapping scales of keratin, which further eases the uptake of coloring. This makes, on the other hand, a comparison of coloring processes difficult, and limits the usefulness of yak belly hair as a substitute for human hair.

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Here we show that the well-known ovalbumin epitope SIINFEKL that is routinely used to stimulate ovalbumin-specific T cells and to test new vaccine adjuvants can form a stable hydrogel. We investigate properties of this hydrogel by a range of spectroscopic and imaging techniques demonstrating that the hydrogel is stabilized by self-assembly of the peptide into nanofibres via stacking of ß-sheets. As peptide hydrogels are known to stimulate an immune response as adjuvants, the immunoactive properties of the SIINFEKL peptide may also originate from its propensity to self-assemble into a hydrogel. This finding requires a re-evaluation of this epitope in adjuvant testing.

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OBJECTIVE: The objective of this research was to identify the rate of unexpected malignancies after laparoscopic-assisted supracervical hysterectomies (LASH) and describe the therapy regime. METHODS: The research is based on a retrospective chart analysis of patients undergoing a simple hysterectomy in the gynecological endoscopy department of a general hospital in Germany. RESULTS: 2,577 simple hysterectomies conducted between March 2005 and March 2010 were sub-classified in different types of hysterectomies (vaginal-, abdominal-, total-, abdominal supracervical hysterectomy, LAVH, and LASH). This study focuses on the LASH sub-group of 1,584 patients and does not make any comparisons to other operative approaches. Out of the 1,584 patients, 87.8 % (n = 1,391) received preoperative screening to exclude dysplasia or malignancy based on the policy of the German Association for gynecology and obstetrics (DGGG). The screening includes cytology (Pap-smear) and preoperative ultrasound of the uterus or dilatation and curettage (d&c). Unexpected malignancies were found in 0.25 % (n = 4) of the patients pre-screened according to DGGG protocol. Out of the four malign patients, two had endometrial cancer. Two patients had leiomyosarcoma. CONCLUSION: The study shows that there is a small probability of unexpected malignancies even in correctly pre-screened patients for LASH procedures. Yet in the short-term (28-52 months), malign patients remain recurrence free after treatment. LASH is therefore a good procedure for assumed benign disease.

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The time taken to rupture in cyclic fatigue tests, to a stress of 45 MPa, was used to compare the fatigue quality of tendons from sheep of varying ages. Muscle and tendon cross-sectional areas were used to calculate the stress-in-life of each tendon. For any given age, high-stressed plantaris tendons were of a higher fatigue quality than low-stressed extensor tendons. Both fatigue quality and stress-in-life increased with age for each tendon type. High-stressed tendons are subjected to large increases in stress-in-life during growth, and fatigue quality increased significantly with this stress. This relationship was not seen, however, in low-stressed tendons, which are not subjected to a comparable range of stresses over time. It is possible that cells modify tendon fatigue quality in response to tendon loading history. Whilst Young's modulus was seen to increase with age, no difference was detected between high- and low-stressed tendons.

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Prilutsky (1999, target paper) reports that Crowninshield and Brand's (1981) criterion, minimization of the sum of the cubes of muscle stresses, works well as a predictor of the division of labor between muscles, for various tasks. However, no direct benefit from minimizing this particular sum is apparent, and it seems likely that it is merely a correlate of the criterion that actually drives muscle choice. In many tasks, there would be a clear, direct benefit from minimizing metabolic energy costs, as Prilutsky (1999) points out. Alexander (1997a, 1997b) and Minetti and Alexander (1997) have shown how the metabolic energy costs of muscle contraction can be estimated, and used to predict optimum muscle properties or optimal patterns of movement. This article explores the feasibility of using the same approach to predict optimum division of labor between one- and two-joint muscles.

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The guts of people and animals function like industrial chemical plants. They are assemblies of tubes and tanks in which foods are hydrolysed by enzyme-catalysed reactions, or fermented by microorganisms. Raw materials enter at one end, waste matter is voided at the other, and valuable products are abstracted on the way. A mill at the entrance end reduces the raw materials to small fragments, enabling the reactions to proceed faster. This paper shows how ideas from chemical engineering are guiding research on the gut, giving much clearer understanding of how foods respond to chewing, and of how guts are designed to process different foods. We will discuss the teeth as a grinding mill, and the digestive tube as a chain of chemical reactors.

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Calculation of the stresses exerted by human muscles requires knowledge of their physiological cross-sectional area (PCSA). Magnetic resonance imaging (MRI) has made it possible to measure PCSAs of leg muscles of healthy human subjects, which are much larger than the PCSAs of cadaveric leg muscles that have been used in previous studies. We have used published MRI data, together with our own force-plate records and films of running and jumping humans, to calculate stresses in the major groups of leg muscles. Peak stresses in the triceps surae ranged from 100 kN m-2 during take off for standing high jumps to 150 kN m-2 during running at 4 m s-1. In the quadriceps, peak stresses ranged from 190 kN m-2 during standing long jumps to 280 kN m-2 during standing high jumps. Similar stresses were calculated from published measurements of joint moments. These stresses are lower than those previously calculated from cadaveric data, but are in the range expected from physiological experiments on isolated muscles.

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A simple model predicts the energy cost of bipedal locomotion for given speed, stride length, duty factor and shape factor. (The duty factor is the fraction of stride duration, for which a foot is on the ground, and the shape factor describes the pattern of force exerted on the ground). The parameters are varied to find the gait that minimizes metabolic energy cost, for each speed. A previous model by Alexander calculated the work that muscles have to do, but the metabolic cost (calculated in this paper) is more likely to be the principal criterion for gait selection. This model gives good predictions of human stride lengths, and of the speed at which we break into a run. It predicts lower duty factors and higher shape factors than are normally used, but the relationships between these gait parameters and speed parallel the empirical relationships.

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Many tasks require the arm to move from its initial position to a specified target position, but leave us free to choose the trajectory between them. This paper presents and tests the hypothesis that trajectories are chosen to minimize metabolic energy costs. Costs are calculated for the range of possible trajectories, for movements between the end points used in previously published experiments. Calculated energy minimizing trajectories for a model with biarticular elbow muscles agree well with observed trajectories for fast movements. Good agreement is also obtained for slow movements if they are assumed to be performed by slower muscles. A model in which all muscles are uniarticular is less successful in predicting observed trajectories. The effects of loads and of reversing the direction of movement are investigated.

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The skeleton of a leg is a chain of bones, breakage of any one of which makes the whole leg useless. The oxygen-transport system of mammals is a chain of processes, any one of which may limit the rate of use of oxygen. The simple argument that a chain is as strong as its weakest link suggests that chains both of structures and of processes would be best designed to have the strengths or capacities of all their links matched. However, this paper shows that if the performance of a link built to a given design is to some extent unpredictable, it may be better to design links for unequal performance. In chains of structures, links made from less expensive or more variable materials should be designed to be somewhat stronger than others. In chains of processes, the plant for less expensive or more predictable processes should be designed for higher maximum rates of working. These conclusions offer possible explanations for some observations regarding frequencies of fracture in horse leg bones and the diffusing capacities of mammalian lungs.

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Studies of the dynamics of locomotor performances depend on knowledge of the distribution of body mass within and between limb segments. However, these data are difficult to derive. Segment mass properties have generally been estimated by modelling limbs as truncated cones, but this approach fails to take into account that some segments are of elliptical, not circular, cross section; and further, the profiles of real segments are generally curved. Thus, they are more appropriately modelled as solids of revolution, described by the rotation in space of convex or concave curves, and the possibility of an elliptical cross section needs to be taken into account. In this project we have set out to develop a general geometric model which can take these factors into account, and permit segment inertial properties to be derived from cadavers by segmentation, and from living individuals using linear external measurements. We present a model which may be described by up to four parameters, depending on the profile and serial cross section (circular or ellipsoidal) of the individual segments. The parameters are obtained from cadavers using a simplified complex-pendulum technique, and from intact specimens by calculation from measurements of segment diameters and lengths. From the parameters, the center of mass, moments of interia, and radii of gyration may be derived, using simultaneous equations. Inertial properties of the body segments of four Pan troglodytes and a single Pongo were determined, and contrasted to comparable findings for humans. Using our approach, the mass distribution characteristics of any individual or species may be represented by a rigid-link segment model or "android." If this is made to move according to motion functions derived from a real performance of the individual represented, we show that recordings of resulting ground reaction forces may be quite closely simulated by predictive dynamic modelling.

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Bipedal walking by common chimpanzees is known to differ both kinematically and kinetically from human bipedalism, in particular by the adoption of flexed-knee gaits and characteristically single-peaked vertical ground reaction force curves. This study provides a test of the proposition that the two former mechanical characteristics are functionally related. Further, it examines the pattern of forces occurring during normal human bipedal walking at slow, normal and fast velocities; and during walking imitating bipedal walking of the common chimpanzee, by both male and female human adults and children. The data suggest naturally reared chimpanzees walk with greater lateral forces than do adult humans walking erect. Women show greater variance in force parameters than do men; and children more than do adults, but men walk with greater vertical accelerations of the centre of mass, and sharper peaks of sagittal acceleration and deceleration than women. Data from both forceplate and pressure-pad records suggest that young children (and a chimpanzee for which forceplate data was available) accelerate using the heel, rather than the anterior part of the foot. A principal component analysis of Fourier coefficients for the force curves shows that forces produced by adults imitating chimpanzee gaits are intermediate between those produced in normal human gait and those produced by 'real' chimpanzees, confirming a functional connection between knee and hip kinematics during bipedal walking and the shape of the vertical ground reaction force curve. Human flexed-knee, flexed-hip walking is found to produce in-phase fluctuations in potential and kinetic energies, preventing the energy exchange which obtains in erect walking. Finally, computer simulations of bipedal walking indicate that kinematics are more influential determinants of ground reaction forces than are body parameters.

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