Evolutionary forces shaping genomic islands of population differentiation in humans

Background Levels of differentiation among populations depend both on demographic and selective factors: genetic drift and local adaptation increase population differentiation, which is eroded by gene flow and balancing selection. We describe here the genomic distribution and the properties of genomic regions with unusually high and low levels of population differentiation in humans to assess the influence of selective and neutral processes on human genetic structure. Methods Individual SNPs of the Human Genome Diversity Panel (HGDP) showing significantly high or low levels of population differentiation were detected under a hierarchical-island model (HIM). A Hidden Markov Model allowed us to detect genomic regions or islands of high or low population differentiation. Results Under the HIM, only 1.5% of all SNPs are significant at the 1% level, but their genomic spatial distribution is significantly non-random. We find evidence that local adaptation shaped high-differentiation islands, as they are enriched for non-synonymous SNPs and overlap with previously identified candidate regions for positive selection. Moreover there is a negative relationship between the size of islands and recombination rate, which is stronger for islands overlapping with genes. Gene ontology analysis supports the role of diet as a major selective pressure in those highly differentiated islands. Low-differentiation islands are also enriched for non-synonymous SNPs, and contain an overly high proportion of genes belonging to the 'Oncogenesis' biological process. Conclusions Even though selection seems to be acting in shaping islands of high population differentiation, neutral demographic processes might have promoted the appearance of some genomic islands since i) as much as 20% of islands are in non-genic regions ii) these non-genic islands are on average two times shorter than genic islands, suggesting a more rapid erosion by recombination, and iii) most loci are strongly differentiated between Africans and non-Africans, a result consistent with known human demographic history.

Guidance for the preparation of neurological management guidelines by EFNS scientific task forces - revised recommendations 2012

This paper is meant to provide guidance to anyone wishing to write a neurological guideline for diagnosis or treatment, and is directed at the Scientist Panels and task forces of the European Federation of Neurological Societies (EFNS). It substitutes the previous guidance paper from 2004. It contains several new aspects: the guidance is now based on a change of the grading system for evidence and for the resulting recommendations, and has adopted The Grading of Recommendations, Assessment, Development and Evaluation system (GRADE). The process of grading the quality of evidence and strength of recommendations can now be improved and made more transparent. The task forces embarking on the development of a guideline must now make clearer and more transparent choices about outcomes considered most relevant when searching the literature and evaluating their findings. Thus, the outcomes chosen will be more critical, more patient-oriented and easier to translate into simple recommendations. This paper also provides updated practical recommendations for planning a guideline task force within the framework of the EFNS. Finally, this paper hopes to find the approval also by the relevant bodies of our future organization, the European Academy of Neurology.

Lordoplasty: report on early results with a new technique for the treatment of vertebral compression fractures to restore the lordosis

Cement augmentation using PMMA cement is known as an efficient treatment for osteoporotic vertebral compression fractures with a rapid release of pain in most patients and prevention of an ongoing kyphotic deformity of the vertebrae treated. However, after a vertebroplasty there is no chance to restore vertebral height. Using the technique of kyphoplasty a certain restoration of vertebral body height can be achieved. But there is a limitation of recovery due to loss of correction when deflating the kyphoplastic ballon and before injecting the cement. In addition, the instruments used are quite expensive. Lordoplasty is another technique to restore kyphosis by indirect fracture reduction as it is used with an internal fixateur. The fractured and the adjacent vertebrae are instrumented with bone cannulas bipediculary and the adjacent vertebrae are augmentated with cement. After curing of the cement the fractured vertebra is reduced by applying a lordotic moment via the cannulas. While maintaining the pretension the fractured vertebra is reinforced. We performed a prospective trial of 26 patients with a lordoplastic procedure. There was a pain relief of about 87% and a significant decrease in VAS value from 7.3 to 1.9. Due to lordoplasty there was a significant and permanent correction in vertebral and segmental kyphotic angle about 15.2 degrees and 10.0 degrees , respectively and also a significant restoration in anterior and mid vertebral height. Lordoplasty is a minimal invasive technique to restore vertebral body height. An immediate relief of pain is achieved in most patients. The procedure is safe and cost effective.

Ligament balancing in TKA: Evaluation of a force-sensing device and the influence of patellar eversion and ligament release

Ligament balancing in total knee arthroplasty may have an important influence on joint stability and prosthesis lifetime. In order to provide quantitative information and assistance during ligament balancing, a device that intraoperatively measures knee joint forces and moments was developed. Its performance and surgical advantages were evaluated on six cadaver specimens mounted on a knee joint loading apparatus allowing unconstrained knee motion as well as compression and varus-valgus loading. Four different experiments were performed on each specimen. (1) Knee joints were axially loaded. Comparison between applied and measured compressive forces demonstrated the accuracy and reliability of in situ measurements (1.8N). (2) Assessment of knee stability based on condyle contact forces or varus-valgus moments were compared to the current surgical method (difference of varus-valgus loads causing condyle lift-off). The force-based approach was equivalent to the surgical method while the moment-based, which is considered optimal, showed a tendency of lateral imbalance. (3) To estimate the importance of keeping the patella in its anatomical position during imbalance assessment, the effect of patellar eversion on the mediolateral distribution of tibiofemoral contact forces was measured. One fourth of the contact force induced by the patellar load was shifted to the lateral compartment. (4) The effect of minor and major medial collateral ligament releases was biomechanically quantified. On average, the medial contact force was reduced by 20% and 46%, respectively. Large variation among specimens reflected the difficulty of ligament release and the need for intraoperative force monitoring. This series of experiments thus demonstrated the device's potential to improve ligament balancing and survivorship of total knee arthroplasty.

[Effectiveness of intermittent pneumatic compression (IPC) on thrombosis prophylaxis: a systematic literature review]

Despite changes in patient demographics and short-ened length of hospital stay deep vein thrombosis (DVT) remains a major health care problem which may lead to a variety of other high risk complications. Current treatment guidelines focus on preventive measures. Beside drug therapy, physical measures executed by nursing professionals exist, the outcomes of which are discussed controversially. Based on 25 studies that were found in MEDLINE and the Cochrane library, this systematic literature review identifies the effectiveness of intermittent pneumatic compression (IPC) on thrombosis prophylaxis. In almost all medical settings IPC contributes to a significant reduction of the incidence of DVT. At the same time, IPC has minimal negative side effects and is also cost effective. Correct application of IPC and patient compliance are essential to achieve its effectiveness. An increased awareness within the healthcare team in identifying the risk for and implementing measures against DVT is needed. Guidelines need to be developed in order to improve the effectiveness of thrombosis prophylaxis with the implementation of IPC.

Effects of glenoid component version on humeral head displacement and joint reaction forces: an experimental study

The purpose of this study was to determine whether changes in glenoid version are associated with humeral head displacement and changes in the joint reaction forces, as these might contribute to instability or loosening in total shoulder replacement. A total shoulder prosthesis was implanted in neutral version in 6 cadaveric shoulders. Glenoid version was then changed in steps of 4 degrees toward more anteversion and retroversion. An increase in anteversion resulted in anterior translation of the humeral head and in eccentric loading of the anterior part of the glenoid. Retroversion was associated with posterior displacement and posterior loading of the glenoid. A change in rotation of the humeral component did not compensate for altered version of the glenoid component. These results suggest that both instability and glenoid component loosening may be related to the version of the glenoid component. Therefore, assessment of loosening and instability justifies precise assessment of glenoid component version.

Integrity of venoarteriolar reflex determines level of microvascular skin flow enhancement with intermittent pneumatic compression

OBJECTIVE: To investigate whether intermittent pneumatic compression (IPC) augments skin blood flow through transient suspension of local vasoregulation, the veno-arteriolar response (VAR), in healthy controls and in patients with peripheral arterial disease (PAD). METHODS: Nineteen healthy limbs and twenty-two limbs with PAD were examined. To assess VAR, skin blood flow (SBF) was measured using laser Doppler fluxmetry in the horizontal and sitting positions and was defined as percentage change with postural alteration [(horizontal SBF--sitting SBF)/horizontal SBF x 100]. On IPC application to the foot, the calf, or both, SBF was measured with laser Doppler fluxmetry, the probe being attached to the pulp of the big toe. RESULTS: Baseline VAR was higher in the controls 63.8 +/- 6.4% than in patients with PAD (31.7 +/- 13.4%, P = .0162). In both groups SBF was significantly higher with IPC than at rest (P < .0001). A higher percentage increase with IPC was demonstrated in the controls (242 +/- 85% to 788 +/- 318%) than in subjects with PAD, for each one of the three different IPC modes investigated (98 +/- 33% to 275 +/- 72%) with IPC was demonstrated. The SBF enhancement with IPC correlated with VAR for all three compression modes (r = 0.58, P = .002 for calf compression, r = 0.65, P < .0001 for foot compression alone, and r = 0.64, P = .0002 for combined foot and calf compression). CONCLUSION: The integrity of the veno-arteriolar response correlates with the level of skin blood flow augmentation generated with intermittent pneumatic compression, indicating that this may be associated with a transient suspension of the autoregulatory vasoconstriction both in healthy controls and in patients with PAD.

The effect of pulsed jet lavage in vertebroplasty on injection forces of polymethylmethacrylate bone cement, material distribution, and potential fat embolism: a cadaver study

STUDY DESIGN: In vitro testing of vertebroplasty techniques including pulsed jet-lavage for fat and marrow removal in human cadaveric lumbar and thoracic vertebrae. OBJECTIVE: To develop jet-lavage techniques for vertebroplasty and investigate their effect on cement distribution, injection forces, and fat embolism. SUMMARY OF BACKGROUND DATA: The main complications of cement vertebroplasty are cement leakage and pulmonary fat embolism, which can have fatal consequences and are difficult to prevent reliably by current vertebroplasty techniques. METHODS: Twenty-four vertebrae (Th8-L04) from 5 osteoporotic cadaver spines were grouped in triplets depending on bone mineral density (BMD). Before polymethylmethacrylate (PMMA) vertebroplasty, a pulsatile jet-lavage for removal of intertrabecular fat and bone marrow was performed in 2 groups with 8 specimens each, performing radial and axial irrigation from the biopsy needles. One hundred mL of Ringer solution were injected through 1 pedicle and regained by low vacuum via the contralateral pedicle. Eight control vertebrae were not irrigated. All specimens underwent standardized PMMA cement augmentation injecting 20% of the vertebral volume. Injection forces, cement distribution, and extravasations were quantified. RESULTS: All irrigation solution could be retrieved with the vacuum applied. A Kruskal-Wallis test revealed significantly higher injection forces of the control group as compared with the irrigated groups (P = 0.021). Dilatation of the syringe at forces above 300 N occurred in 75% of the untreated compared with 12.5% of the lavaged specimens. CT distribution analysis showed more homogenous cement distribution of the cement and significantly less extravasation in the irrigated specimens. CONCLUSION: The developed lavage technique for vertebroplasty showed to be feasible and reproducible. The reduction of injection forces would allow the use of more viscous PMMA cement lowering the risk for cement embolization and results in a safer procedure. The wash-out of bone marrow and the possible reduction of pulmonary fat embolism have to be verified with in vivo models.

A patient-specific finite element methodology to predict damage accumulation in vertebral bodies under axial compression, sagittal flexion and combined loads

Due to the inherent limitations of DXA, assessment of the biomechanical properties of vertebral bodies relies increasingly on CT-based finite element (FE) models, but these often use simplistic material behaviour and/or single loading cases. In this study, we applied a novel constitutive law for bone elasticity, plasticity and damage to FE models created from coarsened pQCT images of human vertebrae, and compared vertebral stiffness, strength and damage accumulation for axial compression, anterior flexion and a combination of these two cases. FE axial stiffness and strength correlated with experiments and were linearly related to flexion properties. In all loading modes, damage localised preferentially in the trabecular compartment. Damage for the combined loading was higher than cumulated damage produced by individual compression and flexion. In conclusion, this FE method predicts stiffness and strength of vertebral bodies from CT images with clinical resolution and provides insight into damage accumulation in various loading modes.

Quantification of relativistic perturbation forces on spacecraft trajectories

The intent of the work presented in this thesis is to show that relativistic perturbations should be considered in the same manner as well known perturbations currently taken into account in planet-satellite systems. It is also the aim of this research to show that relativistic perturbations are comparable to standard perturbations in speciffc force magnitude and effects. This work would have been regarded as little more then a curiosity to most engineers until recent advancements in space propulsion methods { e.g. the creation of a artiffcial neutron stars, light sails, and continuous propulsion techniques. These cutting-edge technologies have the potential to thrust the human race into interstellar, and hopefully intergalactic, travel in the not so distant future. The relativistic perturbations were simulated on two orbit cases: (1) a general orbit and (2) a Molniya type orbit. The simulations were completed using Matlab's ODE45 integration scheme. The methods used to organize, execute, and analyze these simulations are explained in detail. The results of the simulations are presented in graphical and statistical form. The simulation data reveals that the speciffc forces that arise from the relativistic perturbations do manifest as variations in the classical orbital elements. It is also apparent from the simulated data that the speciffc forces do exhibit similar magnitudes and effects that materialize from commonly considered perturbations that are used in trajectory design, optimization, and maintenance. Due to the similarities in behavior of relativistic versus non-relativistic perturbations, a case is made for the development of a fully relativistic formulation for the trajectory design and trajectory optimization problems. This new framework would afford the possibility of illuminating new more optimal solutions to the aforementioned problems that do not arise in current formulations. This type of reformulation has already showed promise when the previously unknown Space Superhighways arose as a optimal solution when classical astrodynamics was reformulated using geometric mechanics.

Implementation of a Variable Compression Ratio Mechanism in a Four Cylinder Engine

Ever since the invention of the internal combustion engine, generating more power and achieving better efficiency has been a major goal for the designers. Variable compression ratio technology is way to achieve those goals. This paper will discuss the method of varying the compression ratio of an inline 4-cylinder engine through the use of a 4-bar linkage and gear mechanism. This mechanism was proven to easily vary the compression ratio of the engine and shows promise of becoming a technology used for future engine designer.