Correction of erosion after suburethral sling insertion for stress incontinence: results and related sexual function

BACKGROUND: Suburethral slings are commonly used for the surgical treatment of female stress incontinence; occasionally they can cause erosion and dyspareunia. OBJECTIVES: The primary aim of this study is to determine the outcome after reclosure of the vaginal epithelium for suburethral sling erosion. Sexual function was assessed before and after intervention using the Female Sexual Function Index (FSFI) questionnaire. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective case-controlled study in which, between December 2005 and December 2007, we included patients who were referred to the Department of Urogynaecology because of vaginal erosion after suburethral sling insertion for urinary stress incontinence. For evaluation of sexual function, all patients filled in an FSFI questionnaire before intervention and at follow-up. All patients underwent gynaecological examination including colposcopy, and the site and size of the defect were noted. INTERVENTION: The edge of the vaginal epithelium was trimmed, mobilized, and closed with interrupted vertical Vicryl mattress sutures in a single layer. MEASUREMENTS: FSFI questionnaire and clinical findings. RESULTS AND LIMITATIONS: Twenty-one patients were included in the study. Eighteen patients with larger defects were operated on, and three defects healed after topical application of estrogen cream. In 16 patients, the defect had healed at follow-up; two patients with persisting defects were brought back to surgery and the procedure was repeated, paying particular attention to tension-free adaptation of vaginal tissue. In one patient, partial sling removal was performed after the second failed intervention. The domains of desire (p<0.0001), arousal (p<0.0003), lubrication (p<0.0001), satisfaction (p<0.0130), and pain (p<0.0001) improved significantly. Orgasm remained unchanged (p=0.4130; all two-tailed t-test). CONCLUSION: Suburethral erosion can be treated effectively by resuturing. Sexual function is improved in regard to desire, arousal, lubrication, satisfaction, and pain, but not orgasm. In septic patients and patients with a history of radiation, grossly infected tissue, or severe pain, excision of the mesh needs to be considered.

Accuracy and self correction of information received from an internet breast cancer list: content analysis.

OBJECTIVES: To determine the prevalence of false or misleading statements in messages posted by internet cancer support groups and whether these statements were identified as false or misleading and corrected by other participants in subsequent postings. DESIGN: Analysis of content of postings. SETTING: Internet cancer support group Breast Cancer Mailing List. MAIN OUTCOME MEASURES: Number of false or misleading statements posted from 1 January to 23 April 2005 and whether these were identified and corrected by participants in subsequent postings. RESULTS: 10 of 4600 postings (0.22%) were found to be false or misleading. Of these, seven were identified as false or misleading by other participants and corrected within an average of four hours and 33 minutes (maximum, nine hours and nine minutes). CONCLUSIONS: Most posted information on breast cancer was accurate. Most false or misleading statements were rapidly corrected by participants in subsequent postings.

Correction of dephasing oscillations in matter-wave interferometry

Vibrations, electromagnetic oscillations, and temperature drifts are among the main reasons for dephasing in matter-wave interferometry. Sophisticated interferometry experiments, e.g., with ions or heavy molecules, often require integration times of several minutes due to the low source intensity or the high velocity selection. Here we present a scheme to suppress the influence of such dephasing mechanisms—especially in the low-frequency regime—by analyzing temporal and spatial particle correlations available in modern detectors. Such correlations can reveal interference properties that would otherwise be washed out due to dephasing by external oscillating signals. The method is shown experimentally in a biprism electron interferometer where a perturbing oscillation is artificially introduced by a periodically varying magnetic field. We provide a full theoretical description of the particle correlations where the perturbing frequency and amplitude can be revealed from the disturbed interferogram. The original spatial fringe pattern without the perturbation can thereby be restored. The technique can be applied to lower the general noise requirements in matter-wave interferometers. It allows for the optimization of electromagnetic shielding and decreases the efforts for vibrational or temperature stabilization.

A large animal model of spinal muscular atrophy and correction of phenotype.

OBJECTIVES Spinal muscular atrophy (SMA) is caused by reduced levels of survival motor neuron (SMN) protein, which results in motoneuron loss. Therapeutic strategies to increase SMN levels including drug compounds, antisense oligonucleotides, and scAAV9 gene therapy have proved effective in mice. We wished to determine whether reduction of SMN in postnatal motoneurons resulted in SMA in a large animal model, whether SMA could be corrected after development of muscle weakness, and the response of clinically relevant biomarkers. METHODS Using intrathecal delivery of scAAV9 expressing an shRNA targeting pig SMN1, SMN was knocked down in motoneurons postnatally to SMA levels. This resulted in an SMA phenotype representing the first large animal model of SMA. Restoration of SMN was performed at different time points with scAAV9 expressing human SMN (scAAV9-SMN), and electrophysiology measurements and pathology were performed. RESULTS Knockdown of SMN in postnatal motoneurons results in overt proximal weakness, fibrillations on electromyography indicating active denervation, and reduced compound muscle action potential (CMAP) and motor unit number estimation (MUNE), as in human SMA. Neuropathology showed loss of motoneurons and motor axons. Presymptomatic delivery of scAAV9-SMN prevented SMA symptoms, indicating that all changes are SMN dependent. Delivery of scAAV9-SMN after symptom onset had a marked impact on phenotype, electrophysiological measures, and pathology. INTERPRETATION High SMN levels are critical in postnatal motoneurons, and reduction of SMN results in an SMA phenotype that is SMN dependent. Importantly, clinically relevant biomarkers including CMAP and MUNE are responsive to SMN restoration, and abrogation of phenotype can be achieved even after symptom onset.

U7 snRNAs induce correction of mutated dystrophin pre-mRNA by exon skipping.

Most cases of Duchenne muscular dystrophy are caused by dystrophin gene mutations that disrupt the mRNA reading frame. Artificial exclusion (skipping) of a single exon would often restore the reading frame, giving rise to a shorter, but still functional dystrophin protein. Here, we analyzed the ability of antisense U7 small nuclear (sn)RNA derivatives to alter dystrophin pre-mRNA splicing. As a proof of principle, we first targeted the splice sites flanking exon 23 of dystrophin pre-mRNA in the wild-type muscle cell line C2C12 and showed precise exon 23 skipping. The same strategy was then successfully adapted to dystrophic immortalized mdx muscle cells where exon-23-skipped dystrophin mRNA rescued dystrophin protein synthesis. Moreover, we observed a stimulation of antisense U7 snRNA expression by the murine muscle creatine kinase enhancer. These results demonstrate that alteration of dystrophin pre-mRNA splicing could correct dystrophin gene mutations by expression of specific U7 snRNA constructs.

Correction of aberrant FGFR1 RNA splicing through blocking intronic regulatory elements

Analysis of the human genome has revealed that more than 74% of human genes undergo alternative RNA splicing. Aberrations in alternative RNA splicing have been associated with several human disorders, including cancer. ^ We studied the aberrant expression of alternative RNA splicing isoforms of the Fibroblast Growth Factor Receptor 1 (FGFR1) gene in a human glioblastoma cancer model. Normal glial cells express the FGFR1α, which contains three extracellular domains. In tumors the most abundant isoform is the FGFR1β, which lacks the first extracellular domain due to the skipping of a single exon, termed alpha. The skipping of the α-exon is regulated by two intronic silencing sequences within the precursor mRNA. Since we observed no mutations on these elements in tumor cells, we hypothesized that the over-expression of regulatory proteins that recognize these sequences is responsible for the aberrant expression of splicing isoforms. Hence, we blocked the formation of protein complexes on the ISS using antisense RNA oligonucleotides in vitro. We also evaluated the impact of the ISS antisense oligonucleotides on the endogenous FGFR1 splicing, in a glioblastoma cell model. By targeting intronic regulatory elements we were able to increase the level of alpha exon inclusion up to 90% in glioblastoma cells. The effect was dose dependent, sequence specific and reproducible in glioblastoma and other cancer cells, which also exhibit an alpha exon skipping phenotype. Targeting FGFR1 endogenous ISS1 and ISS2 sequences did not have an additive or synergistic effect, which suggest a regulatory splicing mechanism that requires the interaction of complexes formed on these elements. An increase in the levels of the FGFR1α isoform resulted in a reduction in cell invasiveness. Also, a significant increase in the levels of caspase 3/7 activities, which is indicative of an elevation in apoptosis levels, suggests that expression of FGFR1β might be relevant for tumor survival. These studies demonstrate that it is possible to prevent aberrant expression of exon skipping events through the targeting of intronic regulatory elements, providing an important new therapeutic tool for the correction of human disease caused by alternative RNA splicing. ^

Correction of systematic errors in Wide Area Multilateration

This work presents a method to estimate and correct slow time-dependent position errors due to non perfect ground station synchronization and tropospheric propagation. It uses opportunity traffic emissions, i.e. signals transmitted from the aircrafts within the coverage zone. This method is used to overcome the difficulty of installing reference beacons simultaneously visible by all the base stations in a given Wide Area Multilateration (WAM) system.

Fast Correction of Tiled Display Systems on Planar Surfaces

A method for fast colour and geometric correction of a tiled display system is presented in this paper. Such kind of displays are a common choice for virtual reality applications and simulators, where a high resolution image is required. They are the cheapest and more flexible alternative for large image generation but they require a precise geometric and colour correction. The purpose of the proposed method is to correct the projection system as fast as possible so in case the system needs to be recalibrated it doesn’t interfere with the normal operation of the simulator or virtual reality application. This technique makes use of a single conventional webcam for both geometric and photometric correction. Some previous assumptions are made, like planar projection surface and negligibleintra-projector colour variation and black-offset levels. If these assumptions hold true, geometric and photometric seamlessness can be achievedfor this kind of display systems. The method described in this paper is scalable for an undefined number of projectors and completely automatic.

Correction of one unstable embankment in Spain

During the years 1992-1996 a climatic change took place in the Iberian Peninsula, changing from dry years to humid years, giving place to numerous and abundant rainfalls that, in the zone of Andalusia caused enough problems in embankments of the roads.

Effects of the correction of particle microbial contamination and particle transit model in the rumen on in situ protein evaluation of grass hays.

Effects of considering the particle comminution rate -kc- in addition to particle rumen outflow -kp- and the ruminal microbial contamination on estimates of by-pass and intestinal digestibility of DM, organic matter and crude protein were examined in perennial ryegrass and oat hays. By-pass kc-kp-based values of amino acids were also determined. This study was performed using particle transit, in situ and 15N techniques on three rumen and duodenum-cannulated wethers. The above estimates were determined using composite samples from rumen-incubated residues representative of feed by-pass. Considering the comminution rate, kc, modified the contribution of the incubated residues to these samples in both hays and revealed a higher microbial contamination, consistently in oat hay and only as a tendency for crude protein in ryegrass hay. Not considering kc or rumen microbial contamination overvalued by-pass and intestinal digestibility in both hays. Therefore, non-microbial-corrected kp-based values of intestinal digested crude protein were overestimated as compared with corrected and kc-kp-based values in ryegrass hay -17.4 vs 4.40%- and in oat hay -5.73 vs 0.19%-. Both factors should be considered to obtain accurate in situ estimates in grasses, as the protein value of grasses is very conditioned by the microbial synthesis derived from their ruminal fermentation. Consistent overvaluations of amino acid by-pass due to not correcting microbial contamination were detected in both hays, with large variable errors among amino acids. A similar degradation pattern of amino acids was recorded in both hays. Cysteine, methionine, leucine and valine were the most degradation-resistant amino acids.

Correction of the Colour Variations under Uncontrolled Lighting Conditions

Esta tesis trata sobre métodos de corrección que compensan la variación de las condiciones de iluminación en aplicaciones de imagen y video a color. Estas variaciones hacen que a menudo fallen aquellos algoritmos de visión artificial que utilizan características de color para describir los objetos. Se formulan tres preguntas de investigación que definen el marco de trabajo de esta tesis. La primera cuestión aborda las similitudes que se dan entre las imágenes de superficies adyacentes en relación a su comportamiento fotométrico. En base al análisis del modelo de formación de imágenes en situaciones dinámicas, esta tesis propone un modelo capaz de predecir las variaciones de color de la región de una determinada imagen a partir de las variaciones de las regiones colindantes. Dicho modelo se denomina Quotient Relational Model of Regions. Este modelo es válido cuando: las fuentes de luz iluminan todas las superficies incluídas en él; estas superficies están próximas entre sí y tienen orientaciones similares; y cuando son en su mayoría lambertianas. Bajo ciertas circunstancias, la respuesta fotométrica de una región se puede relacionar con el resto mediante una combinación lineal. No se ha podido encontrar en la literatura científica ningún trabajo previo que proponga este tipo de modelo relacional. La segunda cuestión va un paso más allá y se pregunta si estas similitudes se pueden utilizar para corregir variaciones fotométricas desconocidas en una región también desconocida, a partir de regiones conocidas adyacentes. Para ello, se propone un método llamado Linear Correction Mapping capaz de dar una respuesta afirmativa a esta cuestión bajo las circunstancias caracterizadas previamente. Para calcular los parámetros del modelo se requiere una etapa de entrenamiento previo. El método, que inicialmente funciona para una sola cámara, se amplía para funcionar en arquitecturas con varias cámaras sin solape entre sus campos visuales. Para ello, tan solo se necesitan varias muestras de imágenes del mismo objeto capturadas por todas las cámaras. Además, este método tiene en cuenta tanto las variaciones de iluminación, como los cambios en los parámetros de exposición de las cámaras. Todos los métodos de corrección de imagen fallan cuando la imagen del objeto que tiene que ser corregido está sobreexpuesta o cuando su relación señal a ruido es muy baja. Así, la tercera cuestión se refiere a si se puede establecer un proceso de control de la adquisición que permita obtener una exposición óptima cuando las condiciones de iluminación no están controladas. De este modo, se propone un método denominado Camera Exposure Control capaz de mantener una exposición adecuada siempre y cuando las variaciones de iluminación puedan recogerse dentro del margen dinámico de la cámara. Los métodos propuestos se evaluaron individualmente. La metodología llevada a cabo en los experimentos consistió en, primero, seleccionar algunos escenarios que cubrieran situaciones representativas donde los métodos fueran válidos teóricamente. El Linear Correction Mapping fue validado en tres aplicaciones de re-identificación de objetos (vehículos, caras y personas) que utilizaban como caracterísiticas la distribución de color de éstos. Por otra parte, el Camera Exposure Control se probó en un parking al aire libre. Además de esto, se definieron varios indicadores que permitieron comparar objetivamente los resultados de los métodos propuestos con otros métodos relevantes de corrección y auto exposición referidos en el estado del arte. Los resultados de la evaluación demostraron que los métodos propuestos mejoran los métodos comparados en la mayoría de las situaciones. Basándose en los resultados obtenidos, se puede decir que las respuestas a las preguntas de investigación planteadas son afirmativas, aunque en circunstancias limitadas. Esto quiere decir que, las hipótesis planteadas respecto a la predicción, la corrección basada en ésta y la auto exposición, son factibles en aquellas situaciones identificadas a lo largo de la tesis pero que, sin embargo, no se puede garantizar que se cumplan de manera general. Por otra parte, se señalan como trabajo de investigación futuro algunas cuestiones nuevas y retos científicos que aparecen a partir del trabajo presentado en esta tesis. ABSTRACT This thesis discusses the correction methods used to compensate the variation of lighting conditions in colour image and video applications. These variations are such that Computer Vision algorithms that use colour features to describe objects mostly fail. Three research questions are formulated that define the framework of the thesis. The first question addresses the similarities of the photometric behaviour between images of dissimilar adjacent surfaces. Based on the analysis of the image formation model in dynamic situations, this thesis proposes a model that predicts the colour variations of the region of an image from the variations of the surrounded regions. This proposed model is called the Quotient Relational Model of Regions. This model is valid when the light sources illuminate all of the surfaces included in the model; these surfaces are placed close each other, have similar orientations, and are primarily Lambertian. Under certain circumstances, a linear combination is established between the photometric responses of the regions. Previous work that proposed such a relational model was not found in the scientific literature. The second question examines whether those similarities could be used to correct the unknown photometric variations in an unknown region from the known adjacent regions. A method is proposed, called Linear Correction Mapping, which is capable of providing an affirmative answer under the circumstances previously characterised. A training stage is required to determine the parameters of the model. The method for single camera scenarios is extended to cover non-overlapping multi-camera architectures. To this extent, only several image samples of the same object acquired by all of the cameras are required. Furthermore, both the light variations and the changes in the camera exposure settings are covered by correction mapping. Every image correction method is unsuccessful when the image of the object to be corrected is overexposed or the signal-to-noise ratio is very low. Thus, the third question refers to the control of the acquisition process to obtain an optimal exposure in uncontrolled light conditions. A Camera Exposure Control method is proposed that is capable of holding a suitable exposure provided that the light variations can be collected within the dynamic range of the camera. Each one of the proposed methods was evaluated individually. The methodology of the experiments consisted of first selecting some scenarios that cover the representative situations for which the methods are theoretically valid. Linear Correction Mapping was validated using three object re-identification applications (vehicles, faces and persons) based on the object colour distributions. Camera Exposure Control was proved in an outdoor parking scenario. In addition, several performance indicators were defined to objectively compare the results with other relevant state of the art correction and auto-exposure methods. The results of the evaluation demonstrated that the proposed methods outperform the compared ones in the most situations. Based on the obtained results, the answers to the above-described research questions are affirmative in limited circumstances, that is, the hypothesis of the forecasting, the correction based on it, and the auto exposure are feasible in the situations identified in the thesis, although they cannot be guaranteed in general. Furthermore, the presented work raises new questions and scientific challenges, which are highlighted as future research work.

Identification and correction of besouro's faults: impact on test‐driven development experiments

Context. This thesis is framed in experimental software engineering. More concretely, it addresses the problems arisen when assessing process conformance in test-driven development experiments conducted by UPM's Experimental Software Engineering group. Process conformance was studied using the Eclipse's plug-in tool Besouro. It has been observed that Besouro does not work correctly in some circumstances. It creates doubts about the correction of the existing experimental data which render it useless. Aim. The main objective of this work is the identification and correction of Besouro's faults. A secondary goal is fixing the datasets already obtained in past experiments to the maximum possible extent. This way, existing experimental results could be used with confidence. Method. (1) Testing Besouro using different sequences of events (creation methods, assertions etc..) to identify the underlying faults. (2) Fix the code and (3) fix the datasets using code specially created for this purpose. Results. (1) We confirmed the existence of several fault in Besouro's code that affected to Test-First and Test-Last episode identification. These faults caused the incorrect identification of 20% of episodes. (2) We were able to fix Besouro's code. (3) The correction of existing datasets was possible, subjected to some restrictions (such us the impossibility of tracing code size increase to programming time. Conclusion. The results of past experiments dependent upon Besouro's data could no be trustable. We have the suspicion that more faults remain in Besouro's code, whose identification requires further analysis.

Sustained correction of bleeding disorder in hemophilia B mice by gene therapy

Mice generated by disrupting the clotting factor IX gene exhibit severe bleeding disorder and closely resemble the phenotype seen in hemophilia B patients. Here we demonstrate that a single intraportal injection of a recombinant adeno-associated virus (AAV) vector encoding canine factor IX cDNA under the control of a liver-specific enhancer/promoter leads to a long-term and complete correction of the bleeding disorder. High level expression of up to 15–20 μg/ml of canine factor IX was detected in the plasma of mice injected with 5.6 × 1011 particles of an AAV vector for >5 months. The activated partial thromboplastin time of the treated mice was fully corrected to higher than normal levels. Liver-specific expression of canine factor IX was confirmed by immunofluorescence staining, and secreted factor IX protein was identified in the mouse plasma by Western blotting. All treated mice survived the tail clip test without difficulty. Thus, a single intraportal injection of a recombinant adeno-associated virus vector expressing factor IX successfully cured the bleeding disorder of hemophilia B mice, proving the feasibility of using AAV-based vectors for liver-targeted gene therapy of genetic diseases.