Trigeminal neuralgia related to megadolichobasilar artery compression: a prospective series of twenty-nine patients treated with gamma knife surgery, with more than one year of follow-up.

BACKGROUND: Trigeminal neuralgia (TN) secondary to megadolichobasilar artery (MBA) compression is considerably difficult to manage surgically. OBJECTIVE: This study aims to evaluate the safety/efficacy of Gamma Knife surgery (GKS) in this special group of patients. METHODS: Between July 1992 and November 2010, 29 patients with >1 year of follow-up presenting with MBA compression were treated with GKS at Timone University Hospital. Radiosurgery was performed using a Gamma Knife (model B, C or Perfexion). A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 9.1 mm (range: 6-18.2 mm) from the emergence. RESULTS: The median follow-up period was 46.1 months (range: 12.9-157.9 months). Initially, all patients (100%) were pain free; the average time to complete pain relief was 13.5 days (range: 0-240 days). Their actuarial probability of remaining pain free without medication at 0.5, 1 and 2 years was 93.1, 79.3 and 75.7%, respectively, and remained stable until 13 years after treatment. The actuarial probability of hypoesthesia onset at 6 months was 4.3%; at 1 year it reached 13% and remained stable until 13 years after treatment. CONCLUSIONS: GKS proved to be reasonably safe and effective on a long-term basis as a first- and/or second-line surgical treatment for TN due to MBA compression.

Prediction of free imatinib concentrations based on total plasma concentrations in patients with gastrointestinal stromal tumours.

AIM: Total imatinib concentrations are currently measured for the therapeutic drug monitoring of imatinib, whereas only free drug equilibrates with cells for pharmacological action. Due to technical and cost limitations, routine measurement of free concentrations is generally not performed. In this study, free and total imatinib concentrations were measured to establish a model allowing the confident prediction of imatinib free concentrations based on total concentrations and plasma proteins measurements. METHODS: One hundred and fifty total and free plasma concentrations of imatinib were measured in 49 patients with gastrointestinal stromal tumours. A population pharmacokinetic model was built up to characterize mean total and free concentrations with inter-patient and intrapatient variability, while taking into account α1 -acid glycoprotein (AGP) and human serum albumin (HSA) concentrations, in addition to other demographic and environmental covariates. RESULTS: A one compartment model with first order absorption was used to characterize total and free imatinib concentrations. Only AGP influenced imatinib total clearance. Imatinib free concentrations were best predicted using a non-linear binding model to AGP, with a dissociation constant Kd of 319 ng ml(-1) , assuming a 1:1 molar binding ratio. The addition of HSA in the equation did not improve the prediction of imatinib unbound concentrations. CONCLUSION: Although free concentration monitoring is probably more appropriate than total concentrations, it requires an additional ultrafiltration step and sensitive analytical technology, not always available in clinical laboratories. The model proposed might represent a convenient approach to estimate imatinib free concentrations. However, therapeutic ranges for free imatinib concentrations remain to be established before it enters into routine practice.

Tree edit distance as a baseline approach for paraphrase representation

Finding an adequate paraphrase representation formalism is a challenging issue in Natural Language Processing. In this paper, we analyse the performance of Tree Edit Distance as a paraphrase representation baseline. Our experiments using Edit Distance Textual Entailment Suite show that, as Tree Edit Distance consists of a purely syntactic approach, paraphrase alternations not based on structural reorganizations do not find an adequate representation. They also show that there is much scope for better modelling of the way trees are aligned.

Laser scanning evaluation of atrophy after autologous free muscle transfer.

Denervated muscle tissue undergoes morphologic changes that result in atrophy. The amount of muscle atrophy after denervation following free muscle transfer has not been measured so far. Therefore, the amount of muscle atrophy in human free muscle transfer for lower extremity reconstruction was measured in a series of 10 patients. Three-dimensional laser surface scanning was used to measure flap volume changes 2 weeks as well as 6 and 12 months after the operation. None of the muscles transferred was re-innervated.All muscles healed uneventfully without signs of compromised perfusion resulting in partial flap loss. The muscle volume decreased to 30 ± 4% and 19 ± 4% 6 and 12 months, respectively, after the operation, ie, the volume decreased by approximately 80% within a 12-month period.Denervated free muscle flap tissue undergoes massive atrophy of approximately 80%, mostly within the first 6 months.

Shall a free public library be established? : Iowa public library laws, 1914

This leaflet gives information on how to start a free public library in a community. Includes regulations and related laws dealing with libraries.

Transanal endoscopic microsurgery versus conventional transanal excision for patients with early rectal cancer.

OBJECTIVE: To compare transanal endoscopic microsurgery (TEMS) with conventional transanal excision (TAE) in terms of the quality of resection, local recurrence, and survival rates in patients with stage I rectal cancer. BACKGROUND: Although TEMS is often considered a superior surgical technique to TAE, it is poorly suited for excising tumors in the lower third of the rectum. Such tumors may confer a worse prognosis. METHODS: We retrospectively reviewed information on all patients with stage pT1 and pT2 rectal adenocarcinoma who underwent local excision from 1997 through mid-2006. We excluded patients with node-positive, metastatic, recurrent, previously irradiated, or snare-excised tumors. RESULTS: Our study included 42 TEMS and 129 TAE patients. We found no significant differences in patient characteristics, adjuvant therapy, tumor stage, or adverse histopathologic features. In the TAE group, 52 (40%) of tumors were <5 cm from the anal verge (AV); in the TEMS group, only 1 (2%) (P = 0.0001). Surgical margins were less often positive in the TEMS group (2%) than in the TAE group (16%) (P = 0.017). For patients with tumors > or =5 cm from the AV, the estimated 5-year disease-free survival (DFS) rate was similar between the TEMS group (84.1%) and the TAE group (76.1%) (P = 0.651). But within the TAE group, the estimated 5-year DFS rate was better for patients with tumors > or =5 cm from the AV (76.1%) vs. <5 cm from the AV (60.5%) (P = 0.029). In our multivariate analysis, the tumor distance from the anal verge, the resection margin status, the T stage, and the use of adjuvant therapy--but not the surgical technique (i.e., TEMS or TAE) itself--were independent predictors of local recurrence and DFS. CONCLUSIONS: The quality of resection is better with TEMS than with TAE. However, the apparently better oncologic outcomes with TEMS can be partly explained by case selection of lower-risk tumors of the upper rectum.

Formation of disclinations line near a free nematic interface

We have studied the nucleation and the physical properties of a -1/2 wedge disclination line near the free surface of a confined nematic liquid crystal. The position of the disclination line has been related to the material parameters (elastic constants, anchoring energy, and favored anchoring angle of the molecules at the free surface). The use of a planar model for the structure of the director field (whose predictions have been contrasted to those of a fully three-dimensional model) has allowed us to relate the experimentally observed position of the disclination line to the relevant properties of the liquid crystals. In particular, we have been able to observe the collapse of the disclination line due to a temperature-induced anchoring-angle transition, which has allowed us to rule out the presence of a real disclination line near the nematic/isotropic front in directional growth experiments.

Decision-making with distance measures and inducedaggregation operators

[spa] Se presenta un nuevo modelo para la toma de decisiones basado en el uso de medidas de distancia y de operadores de agregación inducidos. Se introduce la distancia media ponderada ordenada inducida (IOWAD). Es un nuevo operador de agregación que extiende el operador OWA a través del uso de distancias y un proceso de reordenación de los argumentos basado en variables de ordenación inducidas. La principal ventaja el operador IOWAD es la posibilidad de utilizar una familia parametrizada de operadores de agregación entre la distancia individual máxima y la mínima. Se estudian algunas de sus principales propiedades y algunos casos particulares. Se desarrolla un ejemplo numérico en un problema de toma de decisiones sobre selección de inversiones. Se observa que la principal ventaja de este modelo en la toma de decisiones es la posibilidad de mostrar una visión más completa del proceso, de forma que el decisor está capacitado para seleccionar la alternativa que está más cerca de sus intereses.

Decision-making with distance measures and inducedaggregation operators

[spa] Se presenta un nuevo modelo para la toma de decisiones basado en el uso de medidas de distancia y de operadores de agregación inducidos. Se introduce la distancia media ponderada ordenada inducida (IOWAD). Es un nuevo operador de agregación que extiende el operador OWA a través del uso de distancias y un proceso de reordenación de los argumentos basado en variables de ordenación inducidas. La principal ventaja el operador IOWAD es la posibilidad de utilizar una familia parametrizada de operadores de agregación entre la distancia individual máxima y la mínima. Se estudian algunas de sus principales propiedades y algunos casos particulares. Se desarrolla un ejemplo numérico en un problema de toma de decisiones sobre selección de inversiones. Se observa que la principal ventaja de este modelo en la toma de decisiones es la posibilidad de mostrar una visión más completa del proceso, de forma que el decisor está capacitado para seleccionar la alternativa que está más cerca de sus intereses.

Long-distance wolf recolonization of France and Switzerland inferred from non-invasive genetic sampling over a period of 10 years

In the early 1900s, the wolf (Canis lupus) was extirpated from France and Switzerland. There is growing evidence that the species is presently recolonizing these countries in the western Alps. By sequencing the mitochondrial DNA (mtDNA) control region of various samples mainly collected in the field (scats, hairs, regurgitates, blood or tissue; n = 292), we could (1) develop a non-invasive method enabling the unambiguous attribution of these samples to wolf, fox (Vulpes vulpes) or dog (Canis familiaris), among others; (2) demonstrate that Italian, French and Swiss wolves share the same mtDNA haplotype, a haplotype that has never been found in any other wolf population world-wide. Combined together, field and genetic data collected over 10 years corroborate the scenario of a natural expansion of wolves from the Italian source population. Furthermore, such a genetic approach is of conservation significance, since it has important consequences for management decisions. This first long-term report using non-invasive sampling demonstrates that long-distance dispersers are common, supporting the hypothesis that individuals may often attempt to colonize far from their native pack, even in the absence of suitable corridors across habitats characterized by intense human activities.

Analytical interference of 4-hydroxy-3-methoxymethamphetamine with the measurement of plasma free normetanephrine by ultra-high pressure liquid chromatography-tandem mass spectrometry.

OBJECTIVES: The diagnosis of pheochromocytoma relies on the measurement of plasma free metanephrines assay whose reliability has been considerably improved by ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Here we report an analytical interference occurring between 4-hydroxy-3-methoxymethamphetamine (HMMA), a metabolite of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), and normetanephrine (NMN) since they share a common pharmacophore resulting in the same product ion after fragmentation. DESIGN AND METHODS: Synthetic HMMA was spiked into plasma samples containing various concentrations of NMN and the intensity of the interference was determined by UPLC-MS/MS before and after improvement of the analytical method. RESULTS: Using a careful adjustment of chromatographic conditions including the change of the UPLC analytical column, we were able to distinguish both compounds. HMMA interference for NMN determination should be seriously considered since MDMA activates the sympathetic nervous system and if confounded with NMN may lead to false-positive tests when performing a differential diagnostic of pheochromocytoma.

Creation and Validation of Chronojump-Boscosystem: A Free Tool to Measure Vertical Jumps

Measuring the height of the vertical jump is an indicator of the strength and power of the lower body. The technological tools available to measure the vertical jump are black boxes and are not open to third-party verification or adaptation. We propose the creation of a measurement system called Chronojump-Boscosystem, consisting of open hardware and free software. Methods: A microcontroller was created and validated using a square wave generator and an oscilloscope. Two types of contact platforms were developed using different materials. These platforms were validated by the minimum pressure required for activation at different points by a strain gauge, together with the on/off time of our platforms in respect of the Ergojump-Boscosystem platform by a sample of 8 subjects performing submaximal jumps with one foot on each platform. Agile methodologies were used to develop and validate the software. Results: All the tools fall under the free software / open hardware guidelines and are, in that sense, free. The microcontroller margin of error is 0.1%. The validity of the fiberglass platform is 0.95 (ICC). The management software contains nearly 113.000 lines of code and is available in 7 languages.

Outcome evaluation of ankle osteoarthritis treatments using spatio-temporal gait parameters and plantar pressure during unconstrained long distance walking : P25

Introduction: Ankle arthrodesis (AD) and total ankle replacement (TAR) are typical treatments for ankle osteoarthritis (AO). Despite clinical interest, there is a lack of their outcome evaluation using objective criteria. Gait analysis and plantar pressure assessment are appropriate to detect pathologies in orthopaedics but they are mostly used in lab with few gait cycles. In this study, we propose an ambulatory device based on inertial and plantar pressure sensors to compare the gait during long-distance trials between healthy subjects (H) and patients with AO or treated by AD and TAR. Methods: Our study included four groups: 11 patients with AO, 9 treated by TAR, 7 treated by AD and 6 control subjects. An ambulatory system (Physilog®, CH) was used for gait analysis; plantar pressure measurements were done using a portable insole (Pedar®-X, DE). The subjects were asked to walk 50 meters in two trials. Mean value and coefficient of variation of spatio-temporal gait parameters were calculated for each trial. Pressure distribution was analyzed in ten subregions of foot. All parameters were compared among the four groups using multi-level model-based statistical analysis. Results: Significant difference (p <0.05) with control was noticed for AO patients in maximum force in medial hindfoot and forefoot and in central forefoot. These differences were no longer significant in TAR and AD groups. Cadence and speed of all pathologic groups showed significant difference with control. Both treatments showed a significant improvement in double support and stance. TAR decreased variability in speed, stride length and knee ROM. Conclusions: In spite of a small sample size, this study showed that ankle function after AO treatments can be evaluated objectively based on plantar pressure and spatio-temporal gait parameters measured during unconstrained walking outside the lab. The combination of these two ambulatory techniques provides a promising way to evaluate foot function in clinics.

Free and total plasma levels of lopinavir during pregnancy, at delivery and postpartum: implications for dosage adjustments in pregnant women.

BACKGROUND: Physiological changes associated with pregnancy may alter antiretroviral plasma concentrations and might jeopardize prevention of mother-to-child HIV transmission. Lopinavir is one of the protease inhibitors more frequently prescribed during pregnancy in Europe. We described the free and total pharmacokinetics of lopinavir in HIV-infected pregnant and non-pregnant women, and evaluated whether significant alterations in its disposition and protein binding warrant systematic dosage adjustment. METHODS: Plasma samples were collected at first, second and third trimester of pregnancy, at delivery, in umbilical cord and postpartum. Lopinavir free and total plasma concentrations were measured by HPLC-MS/MS. Bayesian calculations were used to extrapolate total concentrations to trough (Cmin). RESULTS: A total of 42 HIV-positive pregnant women and 37 non-pregnant women on lopinavir/ritonavir were included in the study. Compared to postpartum and control values, total lopinavir Cmin was decreased moderately (31-39%) during pregnancy, and free Cmin minimally, showing significant alteration only at delivery (-35%). However, total and free Cmin remained in all patients above the target concentrations for wild-type virus of 1,000 ng/ml, and above the unbound IC50(WT) of 0.64-0.77 ng/ml of lopinavir, respectively. Lopinavir free fractions remained higher during pregnancy compared to postpartum and controls, and were influenced by α-1-acid-glycoprotein and albumin decrease. Free cord-to-mother ratio (0.43) was 2.7-fold higher than total cord-to-mother ratio (0.16), suggesting higher fetal exposure. CONCLUSIONS: The moderate decrease of total lopinavir concentrations during pregnancy is not associated with proportional decrease in free concentrations. Both reach a nadir at delivery, albeit not to an extent that would put treatment-naive women at risk of insufficient exposure to the free, pharmacologically active concentrations of lopinavir. No dosage adjustment is therefore needed during pregnancy as it is unlikely to further enhance treatment efficacy but could potentially increase the risk of maternal and fetal toxicity. Nonetheless, in case of viral resistance in treatment-experienced pregnant women, loss of virological control or questionable adherence, it is justified to consider lopinavir dosage adjustment based on total plasma concentration measurement.

Testing the effects of genetic crossing distance on embryo survival within a metapopulation of brown trout (Salmo trutta)

Predicting progeny performance from parental genetic divergence can potentially enhance the efficiency of supportive breeding programmes and facilitate risk assessment. Yet, experimental testing of the effects of breeding distance on offspring performance remains rare, especially in wild populations of vertebrates. Recent studies have demonstrated that embryos of salmonid fish are sensitive indicators of additive genetic variance for viability traits. We therefore used gametes of wild brown trout (Salmo trutta) from five genetically distinct populations of a river catchment in Switzerland, and used a full factorial design to produce over 2,000 embryos in 100 different crosses with varying genetic distances (FST range 0.005-0.035). Customized egg capsules allowed recording the survival of individual embryos until hatching under natural field conditions. Our breeding design enabled us to evaluate the role of the environment, of genetic and nongenetic parental contributions, and of interactions between these factors, on embryo viability. We found that embryo survival was strongly affected by maternal environmental (i.e. non-genetic) effects and by the microenvironment, i.e. by the location within the gravel. However, embryo survival was not predicted by population divergence, parental allelic dissimilarity, or heterozygosity, neither in the field nor under laboratory conditions. Our findings suggest that the genetic effects of inter-population hybridization within a genetically differentiated meta-population can be minor in comparison to environmental effects.