br Conclusion br Bladder exstrophy is a


Bladder exstrophy is a rare major birth defect with an incidence of 1 in 10,000-50,000 live births, which requires specialized surgical care. The goals of treatment are to preserve renal function, achieve urinary continence, gain adequate function of external genitalia, and attain acceptable cosmesis. Surgery for exstrophy is complex and challenging, and begins in the newborn period. Associated genitourinary tract anomalies play an important and impactful role in bladder exstrophy patients, directly affecting their treatment plan and surgical outcomes.
Case Report
A full-term newborn girl with a prenatal diagnosis of classic bladder exstrophy (CBE) was born to a 32-year old G1P0 woman via uncomplicated vaginal delivery. Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. Maternal history was significant for basal cell carcinoma and a carrier state of primary hyperoxaluria type 2. The pregnancy was otherwise uncomplicated except for prenatal ultrasonography findings of fetal bladder exstrophy with left hydronephrosis and hydroureter. Physical examination at birth revealed an abdominal wall defect with bladder found externally. Genitourinary tract examination showed a bifid clitoris, labia separated bilaterally and involved in the bladder defect, and a patent tropisetron (Fig. 1). Pelvic X-ray showed the pubic symphysis to be splayed, with a diastasis distance of 4.4 cm. Ultrasonography after birth revealed a right kidney of normal size, contour, and echogenicity. There was moderate dilation of the left renal pelvis and marked dilation of the left ureter, measuring up to 2.4 cm. Additionally, extraneous tissue in the left lower pole of the kidney was found, reflective of a duplicated collecting system.
On day 1 of life, the patient underwent examination under anesthesia, which revealed a 6 × 5 cm bladder template that was reducible into the abdomen, without significant polyps, and a malleable pelvis. Left retrograde pyelogram and renal ultrasound findings were consistent with a complete duplicated left collecting system with 2 left ureteral orifices very close together below the trigone, and hydroureteronephrosis of the left upper pole. Multisequence, multiplanar magnetic resonance imaging (MRI) was performed the day before exstrophy closure, confirming these renal anomaly findings (Fig. 2).
On day 7 of life, the patient underwent closure in the modern staged repair of exstrophy (MSRE) fashion with bilateral anterior innominate osteotomies. Utilizing intraoperative 3-Dimensional (3-D) MRI BrainLAB (Munich, Germany) imaging, the bladder was incised and dissected down to the urogenital diaphragm and the levator hiatus. Upon further dissection, an ectopic upper pole ureter from the left kidney was found to insert distally on the urethral plate (Fig. 3). A left common sheath ureteral reimplantation (UR) was performed using Politano-Leadbetter technique. The bladder was then closed and the urethral mucosa was closed over a 12-French sound. An umbilicoplasty was also undertaken. The pubic bones were brought together and secured using a nylon stitch. The bifid clitoral hood was joined in the midline and a monsplasty was performed. Per institutional practice, an external fixator and immobilization was applied for 4 weeks to allow healing. Surgical wounds healed nicely and the patient was discharged without any complications. Follow-up renal ultrasound at 1 month was unremarkable, with future imaging every 6 months, and examination under anesthesia with cystoscopy at 1 year to evaluate bladder capacity and anatomical sequelae.

Bladder exstrophy is a spectrum of anomalies involving the urinary genital, musculoskeletal, and gastrointestinal tract. Associated urinary tract anomalies are not uncommon. Stec et al reported that renal anomalies are present in 2.8% of children born with CBE. The most common renal malformation seen in the CBE population is a duplicated collecting system (1.3%), with a proportion of 1:77 among the exstrophy population, a 1.6-fold increase over the incidence in the general population. Other findings include an absent or hypoplastic kidney (0.6%), pelvic kidney (0.4%), multicystic dysplastic kidney (0.2%), and ureteropelvic junction obstruction (0.2%).

tropisetron As the science of research synthesis is a relatively

As the science of research synthesis is a relatively new one, precise terminology is still developing. We use the term ‘research synthesis’ to mean a summary of research studies, and the term ‘knowledge synthesis’ to mean a broader tool that includes non-research based sources such as local knowledge. Some groups consider research synthesis, evidence synthesis, and knowledge synthesis to be synonyms; others suggest they differ (Whittemore et al., 2014). Given the inconsistency in the use of these terms, we see no harm in referring to a research synthesis simply as a literature review, while acknowledging that a review could be conducted in many ways and for different purposes.

What is the purpose of the literature review?
An approach to differentiating reviews that we have found useful is based on the aim of the review. One goal of a review might be to integrate all the science and ‘make sense of it’. Such reviews have a configuring aim, with the authors often presenting the results of the review within a conceptual model or theoretical framework. These reviews almost always aim to provide an overview of the area. The authors might also offer an opinion of the topic and how the literature supports that opinion, or how in the review author\’s opinion the ‘dots join up’. Such a review might also seek to explain controversies; therefore such reviews are not necessarily dismissive of the tropisetron of findings in the literature. Reviews of this nature are often called narrative integrative reviews (Whittemore et al., 2014) and often cover broad topics, such as the pathogenesis of an organism, the epidemiology of a disease, the ecology of an organism, or control and treatment options for a disease. Many reviews in veterinary science, including those used in textbooks and conferences and journals, have this integrative aim. Experts are frequently invited to write narrative integrative reviews for journals and conference proceedings. Students are also often required to write narrative integrative reviews for thesis projects or other educational activities (Gough et al., 2012). This article is an example of a narrative integrative review designed to introduce the area of research synthesis and includes our interpretation of prior work and how Heterochromatin relates to veterinary science.
A different goal for a review might be to summarize what is in the literature without inserting a perspective. The review authors might aim to summarize all the literature rather than espouse a view or, as described by Cooper et al. (2009), the aim of such a review is to provide ‘evidence that is neutral in perspective … less likely to be affected by bias or by their own subjective outlooks’. Gough et al. (2012) refer to this type of review as an aggregative review. The most commonly recognized forms of aggregative review are systematic reviews, meta-analyses, and scoping reviews. Aggregative reviews are often focused by necessity because the aim is to summarize everything. Examples of aggregative reviews often describe the comparative efficacy of treatment(s), the magnitude of association of an exposure with a disease, the characteristics of a diagnostic test(s), estimates of prevalence of disease, or the topics that had been studied in an area. If the purpose of this review was to conduct an aggregative review of research synthesis, we would most likely have compiled a list of the papers about research synthesis in veterinary science and described their scope without seeking to guide the reader on how we view the approaches i.e. just describe what is available. Such an aggregative review would not, however, serve our purpose. Given that a systematic review is a common example of an aggregative review, the steps of a systematic review are provided in Table 1 and compared to a narrative integrative review.
There are several proposed approaches to classifying reviews and descriptors for reviews including systematic reviews (with or without meta-analysis), quantitative syntheses, mixed-studies reviews, scoping reviews, integrative reviews, and umbrella reviews (Cooper et al., 2009; Grant and Booth, 2009). Currently, the distinctions between these classifications are too overlapping and rapidly evolving to warrant further discussion; interested readers are referred to other sources (Evans and Kowanko, 2000; Cooper et al., 2009).

br Source of financial support The writing of this

Source of financial support: The writing of this article was supported in part by Abbott. However, the authors summarized their independent professional opinion and take full responsibility for potential errors in the article.

clinical trials; online communities; patient-reported outcomes; social media


Patient-reported outcomes (PROs) are increasingly recognized as important tools in adding value to the drug review and evaluation process

because they provide unique perspectives on medical conditions or their therapies that are known only to the patient

. “Content validity” describes the extent to which a PRO intended to assess such subjective outcomes actually measures the concept of interest

and is an ongoing process that relies on the generation of qualitative and quantitative evidence. Crucially, PRO measures must reflect patient concerns relative to the concept being assessed and, therefore, documentation of content validity relies on patient input from the target tropisetron of patients

. Qualitative studies are used to generate appropriate items and domains; to ensure the instrument is comprehensive relative to its intended measurement concept, population, and context of use; and to ensure patient understanding of the instrument, that is, instructions, items, and response options through cognitive debriefing

. Best practices usually include either individual interviews or focus groups with participants who are experiencing the target condition or have recent experience with it. These traditional methods of collecting qualitative data to support the content validity of a new or existing PRO instrument, however, are labor intensive, time consuming, and relatively expensive. Although detailed figures are not available for specific parts of the instrument, development estimates from the New England Research Institutes suggest that developing a PRO from beginning to end takes at least 24 months and costs between

decision making; dynamic simulation modeling; health care delivery; methods

Background to the Task ForceIn October 2013, the ISPOR Health Science Policy Council recommended to the ISPOR Board of Directors that an ISPOR Emerging Good Practices for Outcomes Research Task Force be established to focus on dynamic simulation modeling methods that can be applied in health care delivery research and recommendations on how these simulation techniques can assist health care decision makers to evaluate interventions to improve the effectiveness and efficiency of health care delivery. The Board of Directors approved the ISPOR Simulation Modeling Emerging Good Practices Task Force in November 2013.The task force leadership group is composed of experts in modeling, epidemiology, research, systems and industrial engineering, economics, and health technology assessment. Task force members were selected to represent a diverse range of perspectives. They work in hospital health systems, research organizations, academia, and the pharmaceutical industry. In addition, the task force had international representation with members from Canada, The Netherlands, Colombia, and the United States.The task force met approximately every five weeks by teleconference to develop an outline and discuss issues to be included in the report. In addition, task force members met in person at ISPOR International meetings and European congresses. All task force members reviewed many drafts of the report and provided frequent feedback in both oral and written comments.Preliminary findings and recommendations were presented in forum and workshop presentations at the 2014 ISPOR Annual International Meeting in Montreal and ISPOR Annual European Congress in Amsterdam. In addition, written feedback was received from the first and final draft reports’ circulation to the 190-member ISPOR Modeling Review Group.Comments were discussed by the task force on a series of teleconferences and during a 1.5-day task force face-to-face consensus meeting. All comments were considered, and most were substantive and constructive. Comments were addressed as appropriate in subsequent versions of the report. All written comments are published at the ISPOR Web site on the task force’s Webpage: The task force report and Webpage may also be accessed from the ISPOR homepage ( via the purple Research Tools menu, ISPOR Good Practices for Outcomes Research, heading: Modeling MethodsIn the course of task force deliberations, in response to specific comments and suggestions from reviewers, and a growing concern about length, sclerenchyma became apparent that two task force reports would be needed to be thorough, covering the essential points, yet keep the report readable and digestible. With Value in Health’s permission, the material has been split into two articles.This first article is a primer on how dynamic simulation modeling methods can be applied to health system problems. It provides the fundamentals and definitions, and discusses why dynamic simulation modeling methods are different from typical models used in economic evaluation and relevant to health care delivery research. It includes a basic description of each method (system dynamics, discrete event simulation, agent-based modeling), and provides guidance on how to ascertain whether these simulation methods are appropriate for a specific problem via the SIMULATE checklist developed by the task force.The second report will provide more depth, delving into the technical specifications related to the three dynamic simulation modeling methods. It will systematically compare each method across a number of features and provide a guide for good research practices for the conduct of dynamic simulation modeling. This report will appear in the March/April 2015 issue of Value in Health.

br Figure thinsp xA Representative sequential chest radiographs

Figure 2. Representative sequential chest radiographs and the graphs of excursion and peak motion of the diaphragms obtained by chest dynamic radiography (“dynamic X-ray phrenicography”). (a) Radiograph of the resting end-expiratory position. (b) Radiograph of the resting end-inspiratory position. (c) Graph showing the vertical excursions and the peak motion speeds of the bilateral diaphragm. A board-certified radiologist placed a point of interest (red point) on the highest point of each tropisetron on the radiograph at the resting end-expiratory position (a). These points were automatically traced by the template-matching technique throughout the respiratory phase (double arrows in b) (Supplementary Video S1); red double arrow indicates the vertical excursion of the right diaphragm and blue double arrow indicates that of the left diaphragm. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (c). The lowest point (0 mm) of the excursion on the graph indicated that the highest point of each diaphragm was at the resting end-expiratory position (ie, null point was set at the end-expiratory phase) (c). (Color version of figure is available online.)Figure optionsDownload full-size imageDownload high-quality image (305 K)Download as PowerPoint slide

Pulmonary Function Tests

The pulmonary function tests were performed in all participants on the same day of the imaging study. Parameters of pulmonary function tests were measured according to the American Thoracic Society guidelines 20 ;  21 using a pulmonary function instrument with computer processing (DISCOM-21 FX, Chest MI Co, Tokyo, Japan).

Statistical Analysis

Descriptive statistics are expressed as mean ± standard deviation for continuous variables and as frequency and percentages for nominal variables. A paired t test was used to compare the excursion and peak motion speed between the right diaphragm and the left diaphragm. The associations between the excursions of the diaphragms and participants\’ characteristics were evaluated by means of the Pearson\’s correlation coefficient and a simple linear regression or Student\’s t test depending on the type of variable (ie, continuous or nominal variable). Continuous variables were height, weight, BMI, tidal volume, vital capacity (VC, %VC), forced expiratory volume (FEV1, FEV1%, and %FEV1), and nominal variables were gender and smoking history. The robustness of the results of the univariate analyses was assessed with multiple linear regression models. The significance level for all tests was 5% (two sided). All data were analyzed using a commercially available software program (JMP; version 12, SAS, Cary, NC, USA).


Participants\’ Characteristics

Table 1 shows the clinical characteristics of all the participants (n = 172).

Excursions and Peak Motion Speeds of the Bilateral Diaphragm

Univariate Analysis of Associations Between the Diaphragmatic Excursions and Participants\’ Demographics

Figure 3. Estimated regression line of the excursion of the diaphragm on BMI or tidal volume. (a) Association between BMI and excursion of the right diaphragm. (b) Association between BMI and excursion of the left diaphragm. (c) Association between tidal volume and excursion of the right diaphragm. (d) Association between tidal volume and excursion of the left diaphragm. Lines show estimated regression (a–d). tropisetron All scatterplots show correlations (P < 0.05). BMI, body mass index.Figure optionsDownload full-size imageDownload high-quality image (226 K)Download as PowerPoint slide

Multivariate Analysis of Associations Between the Excursions and Participants\’ Demographics

Multiple linear regression analysis using all variables as factors (Model 1) demonstrated that weight, BMI, and tidal volume were independently associated with the bilateral excursion of the diaphragms (all P < 0.05) after adjusting for other clinical variables, including age, gender, smoking history, height, VC, %VC, FEV1, FEV1%, and %FEV1. There were no significant associations between the excursion of the diaphragms and variables including age, gender, smoking history, height, VC, %VC, FEV1, FEV1%, and %FEV1 (Table 4). Additionally, a multiple linear regression model using age, gender, BMI, tidal volume, VC, FEV1, and smoking history as factors (Model 2) was also fit as a sensitivity analysis, taking into account the correlation among variables (eg, BMI, height, and weight; VC and %VC; FEV1, FEV1%, and %FEV1). Model 2 (Supplementary Data S1) gave results consistent with Model 1 (Table 4): higher### BMI and higher tidal volume were independently associated with the increased bilateral excursion of the diaphragms (all P < 0.05). The adjusted R2 in Model 1 was numerically higher than that in Model 2 (right, 0.19 vs. 0.16, respectively; left, 0.16 vs. 0.13, respectively).

In order to achieve this science can benefit from

In order to achieve this, science can benefit from a large body of existing literature on the quality of new modes of research. Our impression, however, is that the relevant discourses about inter- and transdisciplinarity, sustainability science, team science, participatory research or post-normal science largely run parallel to each other. It is our conviction that exchange and systematic comparison between these different discourses would be beneficial, not only in terms of quality assurance but also with respect to creating a momentum for the proliferation of a critical and self-reflexive transdisciplinarity.
1. Context: a collective mind in a changing world
A rapidly changing world with its major shifts in electronic communication has put the standard 20th century construction of knowledge to the test (Gibbons et al., 1994). In this tropisetron changing world of global warming, ethnic violence, increasing pollution, and food insecurity, a positive future for humankind has become increasingly hard to imagine. On the other hand, global flows of people, natural resources, finance, and ideas offer a wide range of possible futures, both positive and negative (Falk, 1999). The sum of the changes produces transformational change: business will not be as usual, tomorrow will not be the same as yesterday. The transformational changes in both society and environment mean that the future remains chaotic and uncertain and knowledge about the future is under review (Nowotny, Scott, & Gibbons, 2001).
Yet accounts of the future continue to present contrasting courses of action, moving towards a self-sufficient utopia in which all will be well (Hopkins, 2008 and Hopkins, 2012)1 as against moving to prevent a catastrophic dystopia in which human-initiated changes make the planet uninhabitable (for example, Diamond, 2006). Such futures thinking remains in line with the long-dominant compartmentalised form of knowledge construction, a forced choice between opposites, packaged within the tropisetron academic disciplines and seeking certainty (Meadows, Meadows, & Randers, 1992). Healing the divisions created by genes polarised thinking requires access to a more comprehensive system of thought within a hopeful vision of a world not so divided.