Biotite: new tools for a versatile Python bioinformatics library.

BACKGROUND: Biotite is a program library for sequence and structural bioinformatics written for the Python programming language. It implements widely used computational methods into a consistent and accessible package. This allows for easy combination of various data analysis, modeling and simulation methods. RESULTS: This article presents major functionalities introduced into Biotite since its original publication. The fields of application are shown using concrete examples. We show that the computational performance of Biotite for bioinformatics tasks is comparable to individual, special purpose software systems specifically developed for the respective single task. CONCLUSIONS: The results show that Biotite can be used as program library to either answer specific bioinformatics questions and simultaneously allow the user to write entire, self-contained software applications with sufficient performance for general application.

Clinical indicators of slow graft function and outcome after pediatric kidney transplantation.

BACKGROUND: Lesser degrees of perioperative ischemia-reperfusion injury that does not require dialysis may nonetheless influence allograft outcomes, necessitating evaluation of suitable surrogate indicators of perioperative allograft injury. METHODS: This retrospective analysis of pediatric kidney transplants evaluated two indicators representing pace and completeness of recovery, for association with 12-month estimated glomerular filtration rate (eGFR) and first-year rate of eGFR decline: time to creatinine nadir (TTN) and ratio of recipient/donor unadjusted GFR (uGFRR/D ) at 1-month post-transplant. Donor, recipient, and perioperative risk factors were tested further for association with these 2 indicators. RESULTS: 179 patients (190 transplants) aged 13 (IQR 7-17) years and 56% male were included. Twelve-month eGFR was strongly associated with unadjusted GFR at 1 month (uGFR1M , p < .001) and uGFRR/D (p = .003), but not with TTN. None of the indicators was associated with the rate of subsequent eGFR decline after 1-month post-transplant. As a potential surrogate indicator, uGFR1M is effectively modeled by TTN and uGFRR/D (adjusted R2  = 0.57) and is associated with 12-month eGFR (ß = 0.81 ± 0.08; p < .001). Clinical factors associated with uGFRR/D included donor uGFR (p < .001), BSA (p = .026), age (p = .074), and recipient BSA (p < .001). Factors associated with pace of recovery (TTN) included donor uGFR (p = .018), type (p = .019), and recipient BSA (p = .022). CONCLUSIONS: The uGFRR/D ratio, but not TTN, is a useful indicator of perioperative allograft damage that is associated with one-year functional outcome; and uGFR1M is a potential early surrogate outcome. Donor, recipient, and perioperative factors that are associated with slow allograft function are identified.

Large-sample-size assessment of socioeconomic predictors of community-level resource management occurrence.

Community-level resource management efforts are cornerstones in ensuring sustainable use of natural resources. Yet, understanding how community characteristics influence management practices remains contested. With a sample size of ≥725 communities, we assessed the effects of key community (i.e., socioeconomic) characteristics (human population size and density, market integration, and modernization) on the probability of occurrence of fisheries management practices, including gear, species, and spatial restrictions. The study was based in Solomon Islands, a Pacific Island country with a population that is highly dependent on coastal fisheries. People primarily dwell in small communities adjacent to the coastline dispersed across 6 island provinces and numerous smaller islands. We used nationally collected data in binomial logistic regression models to examine the likelihood of management occurrence, given socioeconomic context of communities. In contrast to prevailing views, we identified a positive and statistically significant association between both human population size and market integration and all 3 management practices. Human population density, however, had a statistically significant negative association and modernization a varied and limited association with occurrence of all management practices. Our method offers a way to remotely predict the occurrence of resource management practices based on key socioeconomic characteristics. It could be used to improve understanding of why some communities conduct natural resource management activities when statistical patterns suggest they are not likely to and thus improve understanding of how some communities of people beat the odds despite limited market access and high population density.

Los esfuerzos por manejar los recursos a nivel comunitario son pilares para garantizar el uso sustentable de los recursos naturales. Aun así, el conocimiento sobre cómo las características comunitarias influyen sobre las prácticas de manejo todavía está en discusión. Con un tamaño de muestra de ≥725 comunidades, evaluamos los efectos de las características (tamaño y densidad poblacional humana, integración del mercado y modernización) comunitarias (es decir, socioeconómicas) clave sobre la probabilidad de incidencia de las prácticas de manejo de las pesquerías, incluyendo el equipamiento, las especies y las restricciones espaciales. El estudio se ubicó en las Islas Salomón, un país isleño del Pacífico con una población altamente dependiente de las pesquerías costeras. En este país, las personas habitan principalmente en comunidades pequeñas adyacentes a la costa y dispersas en las seis provincias isleñas y en numerosas islas más pequeñas. Usamos datos recolectados en todo el país en unos modelos de regresión logística binomial para examinar la probabilidad de incidencia del manejo, dado el contexto socioeconómico de las comunidades. Contrario a las opiniones predominantes, identificamos una asociación positiva y estadísticamente significativa entre el tamaño poblacional humano y la integración del mercado y entre las tres prácticas de manejo. La densidad poblacional humana, sin embargo, tuvo una asociación negativa estadísticamente significativa y la modernización una asociación variada y limitada con la incidencia de las prácticas de manejo. Nuestro método ofrece una manera para predecir remotamente la incidencia de las prácticas de manejo de recursos con base en características socioeconómicas importantes. El método podría utilizarse para incrementar el conocimiento sobre cómo algunas comunidades llevan a cabo actividades de manejo de recursos naturales cuando los patrones estadísticos sugieren lo contrario y así mejorar el entendimiento de cómo algunas comunidades humanas superan todos los pronósticos a pesar del acceso limitado al mercado y la alta densidad poblacional. Evaluación de Muestras de Gran Tamaño de Pronosticadores Socioeconómicos de la Incidencia del Manejo de Recursos a Nivel Comunitario.

Multisensory Proximity and Transition Cues for Improving Target Awareness in Narrow Field of View Augmented Reality Displays.

Augmented reality applications allow users to enrich their real surroundings with additional digital content. However, due to the limited field of view of augmented reality devices, it can sometimes be difficult to become aware of newly emerging information inside or outside the field of view. Typical visual conflicts like clutter and occlusion of augmentations occur and can be further aggravated especially in the context of dense information spaces. In this article, we evaluate how multisensory cue combinations can improve the awareness for moving out-of-view objects in narrow field of view augmented reality displays. We distinguish between proximity and transition cues in either visual, auditory or tactile manner. Proximity cues are intended to enhance spatial awareness of approaching out-of-view objects while transition cues inform the user that the object just entered the field of view. In study 1, user preference was determined for 6 different cue combinations via forced-choice decisions. In study 2, the 3 most preferred modes were then evaluated with respect to performance and awareness measures in a divided attention reaction task. Both studies were conducted under varying noise levels. We show that on average the Visual-Tactile combination leads to 63% and Audio-Tactile to 65% faster reactions to incoming out-of-view augmentations than their Visual-Audio counterpart, indicating a high usefulness of tactile transition cues. We further show a detrimental effect of visual and audio noise on performance when feedback included visual proximity cues. Based on these results, we make recommendations to determine which cue combination is appropriate for which application.

HEMORRHAGIC OCCLUSIVE RETINAL VASCULITIS AFTER INTRACAMERAL VANCOMYCIN USE IN CATARACT SURGERY AFTER INTRAVENOUS EXPOSURE.

PURPOSE: To report a case of hemorrhagic occlusive retinal vasculitis after cataract surgery. METHODS: A 74-year-old woman presented with blurry vision and distorted vision, which started 2 days after an uncomplicated cataract surgery in the left eye. Intracameral vancomycin was injected during the case. The patient reported being treated with systemic vancomycin in the past. RESULTS: The visual acuity was 20/80 in the left eye. She had trace cells in the anterior chamber with no hypopyon and intraocular lens implant within the capsular bag in the left eye. Dilated fundus examination revealed no vitritis, There were large patches of peripheral retinal hemorrhages and retinal ischemia. The patient was diagnosed with hemorrhagic occlusive retinal vasculitis likely secondary to hypersensitivity reaction to intracameral vancomycin. The patient was started on oral prednisone, and the topical difluprednate course was escalated. Within 3 weeks, vision improved to 20/30 in the left eye. She underwent pan retinal photocoagulation targeting the ischemic areas in the periphery. CONCLUSION: The patient had previous exposure to systemic vancomycin, which may have sensitized her immune system. Later on, the hypersensitivity reaction took place after exposure to intracameral vancomycin during cataract surgery. Our hemorrhagic occlusive retinal vasculitis case had a favorable visual outcome, and recognition of this entity will ensure that vancomycin will not be used for infection prophylaxis in the fellow eye at the time of cataract surgery.

Early surveillance biopsy utilization and management of pediatric renal allograft acute T cell-mediated rejection in Canadian centers: Observations from the PROBE multicenter cohort study.

BACKGROUND: Early TCMR surveillance with protocol kidney biopsy is used differentially among pediatric kidney transplant centers. Little has been reported about actual center-based differences, and this variability may influence TCMR ascertainment, treatment, and monitoring more broadly. METHODS: Data from the PROBE multicenter study were used to identify patients from centers conducting ESB or LSIB. ESB was defined as >50% of patients having at least 1 surveillance biopsy in the first 9 months. Patients were compared for number of biopsies, rejection episodes, treatment, and follow-up monitoring. RESULTS: A total of 261 biopsies were performed on 97 patients over 1-2 years of follow-up. A total of 228 (87%) of biopsies were performed in ESB centers. Compared to LSIB centers, ESB centers had 7-fold more episodes of TCMR diagnosed on any biopsy [0.8 ± 1.2 vs 0.1 ± 0.4; P < .001] and a 3-fold higher rate from indication biopsies [0.3 ± 0.9 vs 0.1 ± 0.3; P = .04]. The proportion of rejection treatment varied based on severity: Banff borderline i1t1 (40%);>i1t1 and < Banff 1A (86%); and ≥ Banff 1A (100%). Biopsies for follow-up were performed after treatment in 80% of cases (n = 28) of rejection almost exclusively at ESB centers, with 17 (61%) showing persistence of TCMR (≥i1t1). CONCLUSIONS: Practice variation exists across Canadian pediatric renal transplant centers with ESB centers identifying more episodes of rejection. Additionally, treatment of Banff borderline is not universal and varies with severity regardless of center type. Lastly, follow-up biopsies are performed inconsistently and invariably show persistence of rejection.

Comparing Non-Visual and Visual Guidance Methods for Narrow Field of View Augmented Reality Displays.

Current augmented reality displays still have a very limited field of view compared to the human vision. In order to localize out-of-view objects, researchers have predominantly explored visual guidance approaches to visualize information in the limited (in-view) screen space. Unfortunately, visual conflicts like cluttering or occlusion of information often arise, which can lead to search performance issues and a decreased awareness about the physical environment. In this paper, we compare an innovative non-visual guidance approach based on audio-tactile cues with the state-of-the-art visual guidance technique EyeSee360 for localizing out-of-view objects in augmented reality displays with limited field of view. In our user study, we evaluate both guidance methods in terms of search performance and situation awareness. We show that although audio-tactile guidance is generally slower than the well-performing EyeSee360 in terms of search times, it is on a par regarding the hit rate. Even more so, the audio-tactile method provides a significant improvement in situation awareness compared to the visual approach.

Risk factors associated with allograft failure in pediatric kidney transplant recipients with focal segmental glomerulosclerosis.

BACKGROUND: With improved outcomes for children transplanted with FSGS since previous NAPRTCS registry reports, this study re-evaluates the association of living donation, immunosuppression, and DGF on graft survival. SETTING: Patients transplanted between 2002 and 2016, comparing FSGS diagnosis vs other glomerular diseases. METHODS: Primary outcomes were allograft survival and FSGS recurrent-free graft survival. Potential risk factors were obtained at the time of transplant and up to 30 days post-transplantation. Analysis considered a priori that DGF may be a proxy for severe FSGS recurrence. Multivariable survival models for outcome were tested for sensitivity without/with DGF to determine features independent of recurrence. RESULTS: From the larger cohort of 3010 patients, 5-year graft survival in children with FSGS (n = 455) was worse (74.3%) compared with other glomerular diseases (87.1%, n = 690) (HR 1.45, P = 0.033). Modeling all glomerular diseases, survival risk was associated with deceased donor (HR 1.83, P = 0.002), re-transplantation (HR 1.58, P = 0.013), and recipient age (HR 1.06/y, P = 0.002). The living donor advantage was not confirmed in a FSGS model (HR 1.51 for deceased, P = 0.12). DGF was highly associated with graft failure (HR 4.39, P < 0.001) and independent of re-transplant history but not FSGS diagnosis. Induction agents or primary immunosuppression choices were not associated with survival. CONCLUSION: Graft survival rates have improved since the previous report. Living donor did not predict graft failure, but there remains no survival advantage. DGF was the primary independent predictor for graft loss secondary to FSGS recurrence, consistent with DGF being a proxy for severe recurrent disease.

Reproducibility of electrical sensory testing in lower urinary tract at weekly intervals in healthy volunteers and women with non-neurogenic detrusor overactivity.

OBJECTIVE: To evaluate the reproducibility of a standardized technique of current perception threshold measurements with square wave and sine wave current, with monopolar and bipolar electrodes in a cohort of patients with overactive bladder (OAB) and healthy volunteers. METHODS: We enrolled 6 female nulliparous healthy volunteers and 11 female patients with OAB. Current perception threshold measurements of the bladder were performed using several techniques. The same sequence was used for all 3 measurements performed at weekly intervals to assess the reproducibility. An intraclass correlation coefficient >0.75 was considered as very good reproducibility. RESULTS: All the different stimulation forms were well tolerated by all participants and all experienced stimulation at 2.5-Hz and 95-Hz square wave current. The results with sine wave current showed less uniform results. The intraclass correlation showed the greatest reproducibility with bipolar stimulation at a current of 95 Hz. Sine wave current at 5 Hz and 250 Hz showed low reproducibility. Bipolar stimulation had significantly lower thresholds than monopolar stimulation (P < .0001). No significant differences were found between the healthy subjects and the patients with OAB for the 4 settings. CONCLUSION: In the healthy volunteers and patients with OAB, the determination of the current perception threshold in the bladder using a standardized method is feasible and well tolerated, with both bipolar and monopolar stimulation. In our study, square wave current showed strong reproducibility at weekly intervals at 2.5 Hz and 95 Hz. However, sinusoid current gave weak reproducibility.

Reproducibility of urodynamic filling sensation at weekly interval in healthy volunteers and in women with detrusor overactivity.

AIMS: To evaluate the reproducibility of bladder sensation during standardized filling cystometry in female volunteers and overactive bladder (OAB) patients, repeated with weekly interval. METHODS: We recruited 13 female nulliparous volunteers (age 21-47) and 17 female patients with OAB between (age 18-72). They participated in three investigation periods, each separated by 7 days to assess reproducibility of sensation related to standardized cystometry. Subjects were asked to report all sensations they felt during bladder filling. RESULTS: The previously described pattern of sensation was reported during bladder filling in all. Consecutive sensations corresponded to statistically higher bladder volumes. Volumes, at which different sensations of bladder filling were reported, were significantly higher in controls than in OAB patients [first sensation of filling (FSF) P = 0.003, first desire to void (FDV) P < 0.0001, and strong desire to void (SDV) P < 0.0001]. The sensation/volume ratios were significantly higher in patients with OAB than in the healthy volunteers: FSF occurred at mean 46% and FDV at mean 73% of SDV in OAB patients, compared to 36% and 64% in healthy volunteers. Sensations proved highly reproducible when determined with weekly interval. CONCLUSIONS: Our data demonstrate that cystometric filling sensation determined in a standardized way with weekly interval is highly reproducible in healthy and in OAB patients. This finding has, in our opinion, clinical importance as it shows that the technique is reliable both for a sensory evaluation of the LUT as to study influence of treatment aimed at changing this sensation.

Postoperative endophthalmitis caused by Candida parapsilosis: clinical features and treatment outcomes.

Three consecutive patients with postoperative Candida parapsilosis endophthalmitis presented from a single surgeon and surgery center after uncomplicated cataract surgery. All patients were treated with pars plana vitrectomy (PPV), intraocular lens removal, total capsulectomy, and intraoperative injection of intravitreal antifungal agent. Intraoperative cultures of undiluted vitreous and lens capsule were all positive for the fungus. All patients also received oral antifungal agents postoperatively. Two of these patients received several serial intravitreal antifungal injections after PPV. Following these treatments, all infections were resolved and vision outcomes were favorable at last follow-up.

The effect of intravesical oxybutynin on the ice water test and on electrical perception thresholds in patients with neurogenic detrusor overactivity.

AIMS: The C-fiber-mediated bladder-cooling reflex and the determination of the current perception thresholds (CPTs) permit to investigate afferent LUT pathways. They have both been proposed to detect and differentiate neurologic bladder dysfunction. This study evaluates, prospectively, the effect of oxybutynin, an antimuscarinic with direct antispasmodic effect on smooth muscle, on repeated ice water test (IWT) and CPTs in patients with a known incomplete neurogenic bladder. METHODS: Patients with a known incomplete lesion of the bladder innervation, detrusor overactivity during cystometric bladder filling and a continuous positive response to repeated IWT were included. After the initial tests, 30 mg intravesical oxybutynin (1 mg/ml) was instilled and left in the bladder for 15 min. Afterwards CPTs and IWT were re-assessed. RESULTS: After the drug application, the bladder-cooling reflex could not be initiated, even after three instillations, in 16/17 patients. The bladder CPT increased from 29.7 +/- 11.3 to 39.1 +/- 15.7 mA after oxybutynin (P = 0.001). No difference was found in CPT of the left forearm (P = 0.208). CONCLUSIONS: Intravesical oxybutynin blocks the bladder-cooling reflex and increases but does not block CPT sensation in the bladder in most patients with incomplete neurogenic lesion and detrusor overactivity. These results help explain the clinical effect of intravesical oxybutynin in neurogenic patients. They also indicate that a pharmacological local influence on C-fiber-related activity can give different clinical effects.

The concurrent presentation of minimal change nephrotic syndrome and aplastic anemia.

Minimal change nephrotic syndrome (MCNS) has been associated with primary immunological disorders, such as lymphoma and thymoma. While several different explanations have been proposed, much of the literature has implicated activated T-lymphocytes in the pathogenesis. We report a patient with minimal change nephrotic syndrome presenting concurrently with thrombocytopenia and anemia, with a subsequent diagnosis of aplastic anemia. To our knowledge, this is the first such case described in the literature.

Can a faked cystometry deceive patients in their perception of filling sensations? A study on the reliability of spontaneously reported cystometric filling sensations in patients with non-neurogenic lower urinary tract dysfunction.

AIMS: To evaluate the reliability of spontaneously reported bladder sensations during real and faked cystometry in patients with non-neurogenic lower urinary tract dysfunction. METHODS: Fifty-nine patients with non-neurogenic lower urinary tract dysfunction were submitted to a real and faked filling cystometry and were asked to describe all bladder-related sensations they experienced during the investigations. All patients were told that the bladder had to be filled twice, but during the faked cystometry, no water was infused in the bladder. RESULTS: During the real cystometry, the normal pattern of filling sensation was reported by 88%. During the faked cystometry, none of the patients reported the normal pattern of filling sensations. Five patients reported first sensation of filling, one first desire to void (FDV). None of the patients reported a strong desire to void (SDV) during the faked cystometry. CONCLUSIONS: Asking patients with a non-neurogenic lower urinary tract dysfunction to report on the bladder filling sensations during cystometry is a valid method for sensory evaluation. A minority of patients may report some sensation of bladder filling even without actual bladder filling. Memory and habituation may play a role in the perception of bladder sensation and one should be aware of this. However, reporting some sensation during faked cystometry not necessarily means the evaluation of the perception of bladder filling is unreliable.

Repeated ice water tests and electrical perception threshold determination to detect a neurologic cause of detrusor overactivity.

OBJECTIVES: To explore the added value of a repeated ice water test (IWT) and electrical perception threshold (EPT) measurement in the search for a neurologic cause of idiopathic detrusor overactivity (DOA). METHODS: The IWT, if originally negative, was repeated up to three times, and EPT measurements were done in 63 patients with neurologic DOA, 117 patients with idiopathic DOA without outflow obstruction, and 30 women with stress urinary incontinence without DOA. RESULTS: Although the IWT was positive in 46% of the neurologic patients if used once, this percentage became 86% when the IWT was repeated. In nonneurologic patients, one IWT was positive in only 7% and when repeated, the positive test rate increased to 24%. IWT, even repeated, remained negative in the women with stress urinary incontinence. The EPTs were not significantly different between the neurologic and nonneurologic patients with a positive IWT, except after the third instillation. In those with negative IWTs, the EPTs were significantly different between the neurologic and nonneurologic patients, independent of the number of IWTs done. If the EPTs were compared within each group between those with positive and negative IWTs, the difference was not significant at the first IWT. However, the difference became statistically significant after two IWTs for the nonneurologic group and after three IWTs for both groups. CONCLUSIONS: Our results have shown that repeating the IWT will increase its positivity. Combining the IWT and EPT will reinforce the results of both tests and can indicate more clearly the possibility of an unsuspected neurologic pathologic finding in patients with idiopathic DOA.

Large submacular hemorrhage following PDT with verteporfin in patients with occult CNVM secondary to age-related macular degeneration.

A review of the charts for all patients who developed large submacular hemorrhages following photodynamic therapy for choroidal neovascular membranes secondary to age-related macular degeneration yielded three patients who met the criteria for a large submacular hemorrhage. All three patients were treated for exudative age-related macular degeneration and were taking warfarin for chronic anticoagulation. Before photodynamic therapy, the international normalized ratio ranged from 1.2 to 1.6. All three patients had received at least one previous verteporfin treatment in the study eye. All three hemorrhages were not noted immediately after photodynamic therapy and were documented within 1 to 2 weeks following the procedure. Patients with age-related macular degeneration who are receiving warfarin therapy and undergoing repeat verteporfin treatments appear to be at risk for submacular hemorrhages.

Triple therapy of intravitreal triamcinolone, photodynamic therapy, and pegaptanib sodium for choroidal neovascularization.

PURPOSE: To report the six-month results of subfoveal choroidal neovascularization that had been treated with combined therapy of high-dose intravitreal triamcinolone acetonide (HDIVTA), photodynamic therapy (PDT), and pegaptanib sodium injection. DESIGN: Retrospective, interventional case series study. METHODS: Medical files of 16 patients with this treatment were reviewed (22 eyes); 13 eyes had had previous treatment with HDIVTA and PDT; nine eyes were newly diagnosed choroidal neovascularization. Patients were treated with an injection of HDIVTA (10 mg), followed by PDT and pegabtanib sodium injection at two-week intervals. The main outcome variables were visual acuity (VA) and macular thickness by optical coherence tomography (OCT). RESULTS: The mean VA improved 2.2 lines (P = .013 in the new treatment group); the previous treatment group (HDIVTA + PDT) improved only 0.7 lines (P = 0.55, Wilcoxon ranked test). The mean of macular thickness before and after treatment was statistically significant in both groups. CONCLUSION: This combination therapy showed improvement and/or stabilization in VA, particularly when used as first-line therapy.

Biopsy-proven acute tubular necrosis in a child attributed to vancomycin intoxication.

Acute renal failure in children treated with vancomycin typically presents with interstitial nephritis. There is debate as to the extent of direct tubular toxicity attributable to vancomycin, especially in the absence of aminoglycoside treatment. We report a case of acute tubular necrosis (ATN) associated with vancomycin toxicity in an 8-year-old boy where there is no likely alternate explanation for toxic or ischemic injury. Treatment with hemodialysis resulted in the elimination of vancomycin from the circulation and subsequent improvement in renal function.

Detrusor overactivity. Does it represent a difference if patients feel the involuntary contractions?

PURPOSE: We evaluated the differences between patients with overactive bladder (OAB) who felt involuntary detrusor contractions during cystometry (detrusor overactivity [DO]) and those who did not feel them. MATERIALS AND METHODS: We prospectively studied 45 patients with symptoms of nonneurogenic, nonobstructed overactive bladder and with DO on cystometry. All patients underwent videourodynamics, the ice water test and electrical perception threshold determination. Continence, urodynamic parameters, data from specific sensory evaluation and outcome of drug treatment were examined. RESULTS: Almost half of our patients did feel the contractions of DO and half did not. The groups differed significantly. Those without DO sensation were more frequently incontinent, had more involuntary detrusor contractions and these occurred earlier during bladder filling. They had involuntary start of voiding more frequently, more pathological sensation of bladder filling and lower electrical sensory thresholds. The results of drug treatment were better in the group who felt DO. CONCLUSIONS: Contractions of DO are felt by some of the patients and they differ from those patients who do not feel such contractions. It is likely that this finding reflects the existence of different OAB conditions with a different neuropathological cause and a different treatment outcome. Therefore, we suggest that specific tests for the evaluation of sensation in the lower urinary tract should be part of the diagnosis of patients with DO and symptoms of OAB.