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3D source localization of interictal spikes in epilepsy patients with MRI lesions.

The present study aims to accurately localize epileptogenic regions which are responsible for epileptic activities in epilepsy patients by means of a new subspace source localization approach, i.e. first principle vectors (FINE), using scalp EEG recordings. Computer simulations were first performed to assess source localization accuracy of FINE in the clinical electrode set-up. The source localization results from FINE were compared with the results from a classic subspace source localization approach, i.e. MUSIC, and their differences were tested statistically using the paired t-test. Other factors influencing the source localization accuracy were assessed statistically by ANOVA. The interictal epileptiform spike data from three adult epilepsy patients with medically intractable partial epilepsy and well-defined symptomatic MRI lesions were then studied using both FINE and MUSIC. The comparison between the electrical sources estimated by the subspace source localization approaches and MRI lesions was made through the coregistration between the EEG recordings and MRI scans. The accuracy of estimations made by FINE and MUSIC was also evaluated and compared by R(2) statistic, which was used to indicate the goodness-of-fit of the estimated sources to the scalp EEG recordings. The three-concentric-spheres head volume conductor model was built for each patient with three spheres of different radii which takes the individual head size and skull thickness into consideration. The results from computer simulations indicate that the improvement of source spatial resolvability and localization accuracy of FINE as compared with MUSIC is significant when simulated sources are closely spaced, deep, or signal-to-noise ratio is low in a clinical electrode set-up. The interictal electrical generators estimated by FINE and MUSIC are in concordance with the patients' structural abnormality, i.e. MRI lesions, in all three patients. The higher R(2) values achieved by FINE than MUSIC indicate that FINE provides a more satisfactory fitting of the scalp potential measurements than MUSIC in all patients. The present results suggest that FINE provides a useful brain source imaging technique, from clinical EEG recordings, for identifying and localizing epileptogenic regions in epilepsy patients with focal partial seizures. The present study may lead to the establishment of a high-resolution source localization technique from scalp-recorded EEGs for aiding presurgical planning in epilepsy patients.

Action Potentials↗

Paradoxical shifts in human color sensitivity caused by constructive and destructive interference between signals from the same cone class.

Paradoxical shifts in human color (spectral) sensitivity occur on deep-red (658 nm) background fields. As the radiance of the deep-red background is increased from low to moderate levels, the spectral sensitivity for detecting 15-Hz flicker shifts toward shorter wavelengths, although by more than is predicted by selective chromatic adaptation (e.g., Eisner & MacLeod, 1981; Stromeyer et al., 1987; Stockman et al., 1993). Remarkably, though, at higher background radiances, the spectral sensitivity then shifts precipitously back towards longer wavelengths. Here, we show that both effects are due in large part to destructive and constructive interference between signals generated by the same cone type. Contrary to the conventional model of the human visual system, the M- and L-cone types contribute not just the customary fast signals to the achromatic or luminance pathway, but also slower signals of the same or opposite sign. The predominant signs of the slow M- and L-cone signals change with background radiance, but always remain spectrally opposed (M-L or L-M). Consequently, when the slow and fast signals from one cone type destructively interfere, as they do near 15 Hz, those from the other cone type constructively interfere, causing the paradoxical shifts in spectral sensitivity. The shift in spectral sensitivity towards longer wavelengths is accentuated at higher temporal frequencies by a suppression of fast M-cone signals by deep-red fields.

Adaptation, Ocular↗

Homology models of dipeptidyl peptidases 8 and 9 with a focus on loop predictions near the active site.

Dipeptidyl peptidase 4 (DP4) inhibitors are currently under intensive investigation in late-stage clinical trials as a treatment for type II diabetes. Lack of selectivity toward the related enzymes DP8 and DP9 has recently emerged as a possible source of drug-induced toxicity. Unlike DP4, X-ray structures of DP8 and DP9 are not yet available. As an aid to understanding the structural basis for selectivity, the authors have constructed homology models of DP8 and DP9 based on the X-ray coordinates of DP4. Accurate sequence alignment reveals common structural features indicative for a well-preserved overall fold comprising two domains, namely, a hydrolase domain and a so-called beta-propeller, which together form the active site deeply buried within the protein. The conformation of two loops inside this deep cavity is particularly relevant for the active sites. The authors used a published protocol for loop prediction based on conformational sampling and energy analysis to generate plausible solutions for these two loops. The predictive power of the approach was successfully evaluated for the template protein DP4 and two additional known structures from the same protein family, namely, FAP and DPX. The authors also show that inclusion of the covalent ligand NVP-728 greatly enhances the refinement. Based on the established evaluation protocol, the corresponding loops of DP8 and DP9 were predicted and the resulting active sites were compared with DP4. In particular, the authors conclude that differences in the P2-pocket are relevant for the design of selective DP4 inhibitors. The loss of key interactions in DP8 and DP9 as predicted from their models is consistent with the selectivity profile of the DP4 clinical candidate MK-431.

Adenosine Deaminase↗

New pentasaccharides for prophylaxis of deep vein thrombosis: pharmacology.

Fondaparinux is the first of a new class of antithrombotic compounds, the synthetic pentasaccharides. By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Fondaparinux does not bind to platelets. Its antithrombotic effect has been demonstrated in several animal models of arterial and venous thrombosis. At equivalent antithrombotic concentrations, fondaparinux induced less bleeding than unfractionated heparin in experimental bleeding models. Furthermore, it did not cross-react with sera from patients with heparin-induced thrombocytopenia. Administered subcutaneously, the absorption of fondaparinux is complete, rapid, and independent of dose. It has a linear pharmacokinetic profile, and its half-life of approximately 17 h allows for once-daily dosing. Fondaparinux is almost completely excreted by the kidneys. Owing to the limited intrasubject and intersubject variability, routine monitoring and dose adjustments should not be required for most patients. Fondaparinux has been approved for use in thromboprophylaxis after major orthopedic surgery, where it has demonstrated its efficacy compared to a low-molecular-weight heparin. Its clinical development in other indications is ongoing.

Factor Xa Inhibitors↗

An independent evaluation of second generation suction microkeratomes.

BACKGROUND: Microkeratome designs for lamellar refractive surgery have changed significantly in recent years. Three microkeratome systems (Automatic Corneal Shaper (Steinway Instrument Company, Inc, San Diego, Calif), Draeger Lamellar Keratome (Storz Instrument GmbH, Heidelberg, Germany), and Microprecision test model (Microprecision Instrument Company, Inc, Phoenix, Ariz) were subjected to a concurrent and independent evaluation. METHODS: Three types of keratectomies (primary superficial stromal, secondary intrastromal, and primary deep stromal) were performed under identical conditions in human cadaver eyes. The resected discs and the beds were observed for uniformity, accuracy, centering, and smoothness. Scanning electron microscopy of the corneal beds and cutting blades was done. RESULTS: The three systems produced irregular surfaces with chatter lines that appeared least rough with the Draeger rotating machine. The average primary and secondary section diameters were undersized by 10% in all three systems. The average primary keratectomy thickness was more accurate with Steinway, but the variability was over 20 microns in all three systems. Regarding the average secondary keratectomy thickness, Steinway tended to cut thicker, whereas Draeger and Microprecision tended to cut thinner than attempted. The Draeger blade presented the smoothest edge. CONCLUSIONS: All three systems need substantial improvements to produce more accurate, reproducible, and smooth resections. More reliable methods to accurately measure the thickness of the resected cornea should be developed.

Cornea↗

Distinct mechanisms of bidirectional activity-dependent synaptic plasticity in superficial and deep layers of rat entorhinal cortex.

The entorhinal cortex plays a key role in processing memory information in the brain; superficial layers relay information to, and deep layers receive information from, the hippocampus. The cellular mechanisms of memory are thought to include a number that produce long-term potentiation (LTP) and depression (LTD) of synaptic strength. Our work presents evidence that LTP and LTD occur simultaneously at memory-relevant synapses. We report here that low frequency stimulation generates NMDA receptor-dependent LTD in Wistar rat superficial (layers II and III), and LTP in the deep entorhinal cortex layers (layers V and VI). LTP in deep layers is masked by simultaneously occurring voltage-gated calcium channel-dependent LTD. Our data support a novel mechanism for the sliding-threshold (BCM) model of synaptic plasticity: The sliding thresholds for induction of LTP and LTD in entorhinal cortex deep layers will be driven by the relative activation state of NMDA receptors and voltage-gated calcium channels. The co-expression of LTD and LTP at presynaptic sites in the entorhinal cortex deep layers reveals an intriguing mechanism for differential processing of synaptic information, which may underlie the vast dynamic capacity for information storage by this cortical structure.

Animals↗

Characteristics of scalp electrical fields associated with deep medial temporal epileptiform discharges.

OBJECTIVE: To determine scalp characteristics of epileptiform discharges arising from medial temporal structures (MT). METHODS: Signal-to-noise ratio was increased by averaging simultaneous recordings from intracranial and scalp electrodes synchronised on discharges recorded by foramen ovale (FO) electrodes. The topography, amplitude and distribution of averaged scalp signals were analysed. RESULTS: Four thousand three hundred and twenty-seven discharges from 20 patients were averaged into 77 patterns. Before averaging, only 9% of discharges were detectable on the scalp without the need of simultaneous FO recordings (SED). A further 72.3% of discharges fell into averaged patterns that could be detected on the scalp as small transients before or after averaging (STBA or STAA). In 18.7% of discharges, no scalp signal was seen after averaging. Whereas most SED patterns had largest amplitude on the scalp at anterior temporal electrodes, STBA and STAA patterns showed greater variability and more widespread scalp fields, suggesting a deeper source. Dipole source localisation modelled the majority of SED patterns as radial dipoles located just behind the eye. In contrast, dipoles corresponding to STBA or STAA patterns showed greater variability in location and orientation and tended to be located at MT. CONCLUSIONS: SED patterns seem to arise from widespread subtemporal and/or superficial neocortical activation, generating EEG fields that are distorted by the high electrical conductivity of anterior cranial foramina. In contrast, STBA and STAA patterns represent electrical fields from neuronal activity more restricted to MT, that reach the scalp highly attenuated by volume-conduction and less distorted by cranial foramina. SIGNIFICANCE: Low amplitude scalp signals can be related to MT activity and must be taken into consideration for the diagnosis of temporal lobe epilepsy, pre-surgical assessment and for valid modelling of deep sources from the scalp EEG and magnetoencephalogram.

Adolescent↗

Preliminary studies of a new stochastic human death function involving small integers.

We propose a new mathematical function for the analyses of age-related human deaths due to single causes. Like the earlier Gompertz and power law functions, it is a two parameter function. Unlike them, one of the parameters is an integer in the range of 5-13. The function is the integral gamma distribution raised to a combinatoric power (GDCP). The function has a deep relation to the power law, and this explains the past successes of the power law. The GDCP function generates highly accurate distributions for ages at death due to specific diseases, and also the means and variances for the distributions. It is possible now to assign unambiguously an integer to each cause of death. In model systems, the alpha integers are the number of "events" necessary to commit the organism to death. Different diseases with the same integer have the same age distribution at death. The major remaining problem is the relative sizes of the populations dying of each single cause. The solution to this must be model derived. The analysis of 24 single causes of death for males and females in the U.S.A., white population over the years 1968-1978 show: (1) the alpha integer is eight for almost all digestive organ carcinomas in both males and females; (2) cancers at other sites have various values for alpha; and (3) for vascular diseases females have alpha integers higher by one or two than males. If the combinatoric power is multiplied by a constant then the second number in the function, tau, the time constant, which is different for each disease, takes on an approximately constant value, which we call the "characteristic age" of the species. Thus, with one number, the "characteristic age" and the nine integers, we can predict, using the GDCP function, the relevant distributions of deaths due to all the different diseases.

Age Factors↗

A deep dynamo generating Mercury's magnetic field.

Mercury has a global magnetic field of internal origin and it is thought that a dynamo operating in the fluid part of Mercury's large iron core is the most probable cause. However, the low intensity of Mercury's magnetic field--about 1% the strength of the Earth's field--cannot be reconciled with an Earth-like dynamo. With the common assumption that Coriolis and Lorentz forces balance in planetary dynamos, a field thirty times stronger is expected. Here I present a numerical model of a dynamo driven by thermo-compositional convection associated with inner core solidification. The thermal gradient at the core-mantle boundary is subadiabatic, and hence the outer region of the liquid core is stably stratified with the dynamo operating only at depth, where a strong field is generated. Because of the planet's slow rotation the resulting magnetic field is dominated by small-scale components that fluctuate rapidly with time. The dynamo field diffuses through the stable conducting region, where rapidly varying parts are strongly attenuated by the skin effect, while the slowly varying dipole and quadrupole components pass to some degree. The model explains the observed structure and strength of Mercury's surface magnetic field and makes predictions that are testable with space missions both presently flying and planned.

Journal Article↗

[Changes in the environment of medical practice].

Changes in medical practice have been very deep in the last 50 years. These changes have happened together with other external variations in the economy, demography, culture and information, generating a sense of uneasiness and unhappiness among the medical profession. This problem is visible when interviewing clinicians in a wide range of medical settings, independently of their contractual arrangement. The medical work model in Chile has changed from a situation in which there was a sole employer, the National Health Service, one single training school, the University of Chile, and a small minority of powerful and influential intellectual leaders. At the beginning of the XXI century, there are several modes of medical work, distant and unconnected among them. On the other side of the problem many factors add complexity, such as the demographic and epidemiological transition, technological advance, the dual rich-poor medical care, the emergence of malpractice procedures and the new, better informed and more demanding medical consumer. On top of this, different health care systems reform initiatives appear, providing more uncertainty to a nearly unbearable situation. This bibliographic review shows us that similar feelings are experienced in advanced countries and in developing societies such as Chile.

Career Choice↗

Three-dimensional printing and porous metallic surfaces: a new orthopedic application.

As-cast, porous surfaced CoCr implants were tested for bone interfacial shear strength in a canine transcortical model. Three-dimensional printing (3DP) was used to create complex molds with a dimensional resolution of 175 microm. 3DP is a solid freeform fabrication technique that can generate ceramic pieces by printing binder onto a bed of ceramic powder. A printhead is rastered across the powder, building a monolithic mold, layer by layer. Using these 3DP molds, surfaces can be textured "as-cast," eliminating the need for additional processing as with commercially available sintered beads or wire mesh surfaces. Three experimental textures were fabricated, each consisting of a surface layer and deep layer with distinct individual porosities. The surface layer ranged from a porosity of 38% (Surface Y) to 67% (Surface Z), whereas the deep layer ranged from 39% (Surface Z) to 63% (Surface Y). An intermediate texture was fabricated that consisted of 43% porosity in both surface and deep layers (Surface X). Control surfaces were commercial sintered beaded coatings with a nominal porosity of 37%. A well-documented canine transcortical implant model was utilized to evaluate these experimental surfaces. In this model, five cylindrical implants were placed in transverse bicortical defects in each femur of purpose bred coonhounds. A Latin Square technique was used to randomize the experimental implants left to right and proximal to distal within a given animal and among animals. Each experimental site was paired with a porous coated control site located at the same level in the contralateral limb. Thus, for each of the three time periods (6, 12, and 26 weeks) five dogs were utilized, yielding a total of 24 experimental sites and 24 matched pair control sites. At each time period, mechanical push-out tests were used to evaluate interfacial shear strength. Other specimens were subjected to histomorphometric analysis. Macrotexture Z, with the highest surface porosity, failed at a significantly higher shear stress (p = 0.05) than the porous coated controls at 26 weeks. It is postulated that an increased volume of ingrown bone, resulting from a combination of high surface porosity and a high percentage of ingrowth, was responsible for the observed improvement in strength. Macrotextures X and Y also had significantly greater bone ingrowth than the controls (p = 0.05 at 26 weeks), and displayed, on average, greater interfacial shear strengths than controls, although they were not statistically significant.

Animals↗

Population-based study of risk of venous thromboembolism associated with various oral contraceptives.

BACKGROUND: Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens. However, confounding and bias in the design of these studies may have affected the findings. The aim of our study was to re-examine the association between risk of VTE and OC use with a different study design and analysis to avoid some of the bias and confounding of the earlier studies. METHODS: We used computer records of patients from 143 general practices in the UK. The study was based on the medical records of about 540,000 women born between 1941 and 1981. All women who had a recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise specified, or pulmonary embolus during the study period, and who had been treated with an anticoagulant were identified as potential cases of VTE. We did a cohort analysis to estimate and compare incidence of VTE in users of the main OC preparations, and a nested case-control study to calculate the odds ratios of VTE associated with use of different types of OC, after adjustment for potential confounding factors. In the case-control study, we matched cases to controls by exact year of birth, practice, and current use of OCs. We used a multiple logistic regression model that included body-mass index, number of cycles, change in type of OC prescribed within 3 months of the event, previous pregnancy, and concurrent disease. FINDINGS: 85 women met the inclusion criteria for VTE, two of whom were users of progestagen-only OCs. Of the 83 cases of VTE associated with use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary thrombosis, and five as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation preparations. After adjustment for age, the rate ratio of VTE in users of third-generation relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic regression showed no significant difference in the risk of VTE between users of third-generation and second-generation OCs. Among users of third-generation progestagens, the risk of VTE was higher in users of desogestrel with 20 g ethinyloestradiol than in users of gestodene or desogestrel with 30 g ethinyloestradiol. With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens. INTERPRETATION: The previously reported increase in odds ratio associated with third-generation OCs when compared with second-generation products is likely to have been the result of residual confounding by age. The increased odds ratio associated with products containing 20 micrograms ethinyloestradiol and desogestrel compared with the 30 micrograms product is biologically implausible, and is likely to be the result of preferential prescribing and, thus, confounding.

Adolescent↗

Simulating the embolization of blood vessels using magnetic microparticles and acupuncture needle in a magnetic field.

Computer models were developed to simulate the capture and subsequent deposition of magnetic microparticles (MMPs) in a blood vessel adjacent to a ferromagnetic wire (e.g., acupuncture needle) magnetized by a uniform external magnetic field. Process parameter conditions were obtained to enable optimal capture of MMPs into the deposit. It was found that the maximum capture distance of the MMPs was within 0.5-2.0 mm when the particles were superparamagnetic and had large size (>1.0 microm) and relative large flow rates (2.5-5.0 cm/s) as in a healthy artery. It was also found that the deposits were asymmetrical and that their size was between 1.0 and 2.0 mm. For the case of lower flow rates as can be found in a tumor (<1.0 mm/s) and using small magnetite particles (0.25-2.0 microm) the maximum capture distance was larger, ranging between approximately 0.5 and 6.4 mm, depending on the blood flow rate, the radius of wire, and particle clustering. The range of embolization (deposition) in this later case was between 0.5 and 5.9 mm. The potential of this technique to generate MMPs deposits to embolize blood vessels inhibiting the blood supply and thus facilitating necrosis of tumors located deep within the patient (3-7 cm) is discussed.

Acupuncture Therapy↗

The differential cardioprotective effects of nucleoside transport inhibitor on moderate and deep hypothermic ischemia with cold cardioplegia.

The differences in the cardioprotective effects of nucleoside transport inhibitor (NTI) which is known to accumulate endogenous adenosine, on moderate and deep hypothermic ischemia, were examined. Using the Langendorff model, isolated, perfused rat hearts were arrested with cold cardioplegia and subjected to 90 min of global ischemia followed by 40 min of reperfusion. The temperature during ischemia was maintained at either 10 degrees C (groups 1 and 2) or 25 degrees C (groups 3 and 4). In groups 2 and 4, NTI in the form of R75231, 1 mg/l, was added to the cardioplegic solution. The intramyocardial adenosine triphosphate content at the end of ischemia was significantly lower in the moderate hypothermia groups than in the deep hypothermia groups. In the moderate hypothermia groups, NTI significantly enhanced the adenosine accumulation at the end of ischemia. Moreover, the recovery of both the contractile function and coronary flow rate in group 4 was superior to that in group 3, and was similar to those in groups 1 and 2. The addition of NTI to the cardioplegic solution generated a sufficient cardioprotective effect in moderate hypothermic ischemia, but not in deep hypothermic ischemia. The mechanism of this discrepancy is attributed to the differences in the levels of endogenous adenosine accumulated during ischemia.

Adenine Nucleotides↗

Acinar flow irreversibility caused by perturbations in reversible alveolar wall motion.

Mixing associated with "stretch-and-fold" convective flow patterns has recently been demonstrated to play a potentially important role in aerosol transport and deposition deep in the lung (J. P. Butler and A. Tsuda. J. Appl. Physiol. 83: 800-809, 1997), but the origin of this potent mechanism is not well characterized. In this study we hypothesized that even a small degree of asynchrony in otherwise reversible alveolar wall motion is sufficient to cause flow irreversibility and stretch-and-fold convective mixing. We tested this hypothesis using a large-scale acinar model consisting of a T-shaped junction of three short, straight, square ducts. The model was filled with silicone oil, and alveolar wall motion was simulated by pistons in two of the ducts. The pistons were driven to generate a low-Reynolds-number cyclic flow with a small amount of asynchrony in boundary motion adjusted to match the degree of geometric (as distinguished from pressure-volume) hysteresis found in rabbit lungs (H. Miki, J. P. Butler, R. A. Rogers, and J. Lehr. J. Appl. Physiol. 75: 1630-1636, 1993). Tracer dye was introduced into the system, and its motion was monitored. The results showed that even a slight asynchrony in boundary motion leads to flow irreversibility with complicated swirling tracer patterns. Importantly, the kinematic irreversibility resulted in stretching of the tracer with narrowing of the separation between adjacent tracer lines, and when the cycle-by-cycle narrowing of lateral distance reached the slowly growing diffusion distance of the tracer, mixing abruptly took place. This coupling of evolving convective flow patterns with diffusion is the essence of the stretch-and-fold mechanism. We conclude that even a small degree of boundary asynchrony can give rise to stretch-and-fold convective mixing, thereby leading to transport and deposition of fine and ultrafine aerosol particles deep in the lung.

Aerosols↗

The thermochemical structure and evolution of Earth's mantle: constraints and numerical models.

Geochemical observations place several constraints on geophysical processes in the mantle, including a requirement to maintain several distinct reservoirs. Geophysical constraints limit plausible physical locations of these reservoirs to a thin basal layer, isolated deep 'piles' of material under large-scale mantle upwellings, high-viscosity blobs/plums or thin strips throughout the mantle, or some combination of these. A numerical model capable of simulating the thermochemical evolution of the mantle is introduced. Preliminary simulations are more differentiated than Earth but display some of the proposed thermochemical processes, including the generation of a high-mu mantle reservoir by recycling of crust, and the generation of a high-(3)He/(4)He reservoir by recycling of residuum, although the resulting high-(3)He/(4)He material tends to aggregate near the top, where mid-ocean-ridge melting should sample it. If primitive material exists as a dense basal layer, it must be much denser than subducted crust in order to retain its primitive (e.g. high-(3)He) signature. Much progress is expected in the near future.

Computer Simulation↗

Medial hamstring tendon regeneration following harvest for anterior cruciate ligament reconstruction: fact, myth, and clinical implication.

It has been demonstrated that the medial hamstring tendons regenerate in the majority of patients following their harvest for anterior cruciate ligament reconstruction. The anatomy and morphology of these regenerated tendons have been radiographically and surgically documented. The neotendons originate within the appropriate muscle belly but display an altered insertion anatomy. Their histological composition is largely tendinous but has regions that resemble scar tissue. Concordantly, an animal model indicates that the neotendon has decreased mechanical strength, which has implications for tendon re-harvest. The regenerated tendons do restore a muscle tendon complex that is able to generate force; however, strength testing indicates that the function of the hamstring muscles is altered by harvest and regeneration. The most significant strength deficits are present in deep knee flexion and internal rotation of the tibia, whereas the peak torque of knee flexion is minimally affected. Additional harvest of the gracilis tendon results in greater deficits. The current literature indicates that hamstring tendon regeneration does indeed occur, but with structural and functional alterations.

Animals↗

A simulation study of the reliability of recombination detection methods.

There exist many methods to detect recombination or mosaic structure in a sample of DNA sequences. But how reliable are they? Four methods were investigated with respect to their power to detect recombination in simulated samples with different amounts of recombination and mutation. In addition, we investigated the impact of the shape of the underlying genealogy on their performances. We found that the methods detected far fewer recombinations than were theoretically possible and that methods based on the principle of incompatibility in general had more power than methods that did not make use of this principle explicitly. This seemed, in particular, to be the case for phylogenies generated under population expansion scenarios which result in long branches at the tips and small deep branches. In addition to the results obtained through simulations, a series of new theoretical results on recombination is presented.

Algorithms↗