tropisetron Dans notre s rie le grade II est

Dans notre série le grade II est un grade abondant avec 54,8% des cas. Cette observation est également révélée dans d’autres études [8]. Concernant l’examen clinique, Benjelloun et al. [14] ont montré que le diagnostic était basé sur l’échographie chez 77,4% des patients et sur la tomodensitométrie chez tous les patients. Dans notre série, L’échographie a été utilisée chez 26,08% des cas et la tomodensitométrie chez 100% des cas. Nous avons constaté que la néphrectomie était le traitement de référence ce qui rejoint l’étude de Fall et al. [16] où la néphrectomie a été pratiquée chez 43 (58,1%) patients.

Conclusion

Conflit d’intérêt

Introduction

Observation
Il s’agit d’un patient âgé de 61ans, tabagique chronique à 20 PA et qui fut initialement admis dans notre structure pour anémie sur hématurie totale caillotante. Cette dernière évoluait depuis 7 mois sans qu’il puisse consulter. Le patient a bénéficié d’une résection trans-urétrale biopsique objectivant une grosse tumeur à large tropisetron d’implantation dont l’étude anatomopathologique a conclu à un carcinome urothélial infiltrant le muscle classé pt2. Un bilan d’extension consistant en une TDM thoraco-abdomino-pelvienne a été réalisé et n’a objectivé aucune métastase. Le patient a bénéficié par la suite d’une cystoprostatectomie avec un curage ganglionnaire ilio-obturateur bilatéral étendu et une dérivation urinaire trans-cutanée bilatérale.
Ce patient fut perdu de vue avant de se présenter 2ans plus tard à la consultation d’urologie après l’altération de son état général. A l’examen clinique ont été notées des lésions cutanées maculeuses pigmentées à surfaces finement squameuses, en placard non prurigineuses et en regard de la cicatrice chirurgicale, de l’aisselle et l’hémithorax gauches (Figures 1 and 2). Les urétérostomies cutanées étaient en revanche fonctionnelles.

Discussion
Le premier cas de métastases cutanées secondaires à une tumeur de vessie a été rapporté dans la littérature en 1909 [1]. Les cas relevés sont rares. En effet, l’incidence de ces manifestations est de 0.84% sur une série de Block et al. [2].
L’incidence des métastases des tumeurs de vessie est directement liée au degré d’infiltration tumorale, à la dimension et au grade tumoral, mais l’infiltration garde néanmoins l’impact le plus important [3]. Cependant, les métastases peuvent également apparaitre dans les tumeurs superficielles [3].
La dissémination des cellules cancéreuses à la peau se fait selon 4 mécanismes: envahissement par contiguïté de proche en proche, une extension hématogène, lymphatique ou une manipulation iatrogène (siège en regard de la cicatrice) [4].
Les métastases cutanées ont la particularité d’apparaitre tardivement après le geste opératoire [5]. Schmiedecke et al. ont rapporté dans leur étude un délai moyen d’apparition estimé à 18 moins, tout en rapportant un cas de métastase cutanée survenu 10ans après la découverte du site initial [5].
L’aspect clinique de la métastase peut revêtir plusieurs formes. Brownstein et al ont décrit 3 principaux aspects cliniques: la lésion nodulaire, la lésion scléreuse et la lésion inflammatoire (qui représente le cas de notre patient) [6]. Les métastases cutanées peuvent siéger préférentiellement au niveau de la face, le cou, le tronc et les extrémités [3].
La biopsie, geste simple, permet d’établir le diagnostic, mais l’origine urothéliale reste parfois difficile à affirmer [7]. Le diagnostic différentiel se fait essentiellement avec les malformations lymphatiques, le zona, la cellulite, le lymphome et la dermite radique [5].
L’étude anatomo-pathologique montre des nids de cellules malignes avec un cytoplasme éosinophile. La plupart de ces cellules expriment à l’étude immuno-histochimique les cytokératines 7 et 20. Des études récentes ont montré que l’uroplakine III est détectée dans 50 à 60% des carcinomes urothéliaux primaires et des carcinomes métastasiques d’origine urothéliale [8]. Le pronostic est péjoratif avec une espérance de vie de moins d’un an immovable joint [3]. Devant le peu de cas rapportés dans la littérature et la survie limitée, il est difficile d’élaborer un schéma thérapeutique.

tropisetron There is now compelling evidence indicating that

There is now compelling evidence indicating that both the EMP and definitive programs derive from progenitors known as hemogenic endothelial tropisetron (HECs) that display endothelial markers and are associated with the arterial vasculature (Bertrand et al., 2005; Boisset et al., 2010; Clarke et al., 2013; Kissa and Herbomel, 2010). Live imaging and histological analyses have demonstrated that hematopoietic progenitors develop from the HECs through a process known as the endothelial to hematopoietic transition (EHT) (Boisset et al., 2010; Kissa and Herbomel, 2010). Currently, there are no markers to distinguish EMP-HECs from definitive HECs. As the EMP program develops earlier than the definitive program, the EMP-derived lineages can predominate the PSC differentiation cultures and are often misinterpreted as representing definitive hematopoiesis. Developing strategies to distinguish definitive- from EMP-derived hematopoiesis in the PSC differentiation cultures is essential for identifying the signaling pathways that regulate the development of definitive HECs and their specification to HSCs.
We have previously shown that SOX17 is expressed in definitive HECs and that it is required for the establishment of the definitive, but not the primitive, hematopoietic program (Clarke et al., 2013). Our analysis of differentiated hematopoietic progeny from HECs generated from SOX17-null mouse embryonic stem cells (mESCs) revealed the presence of primitive erythroid progenitors, myeloid progenitors, and erythroid progenitors that gave rise to large colonies distinct from the primitive erythroid colonies. The presence of this population of erythroid progenitors suggests that the EMP program may also be Sox17 independent. Our goals in the present study were to define the role of Sox17 in EMP hematopoiesis, understand how Sox17 regulates the generation of definitive hemogenic endothelium, and identify additional markers to distinguish these programs. To achieve these goals, we deciphered the proteome of AGM-derived HECs and of HECs generated from Sox17-wild-type and Sox17-knockout mESCs using label-free quantitative proteomics. The findings from these studies demonstrate the overall utility of analyzing the proteome of small numbers of cells and show that expression of the transcription factor Stat1 and dependency on Sox17 distinguish the definitive erythroid lineage from the primitive and EMP-derived erythroid lineages.

Results

Discussion
Label-free proteomics represents an emerging technology for identifying and quantifying patterns of protein expression. While differences in patterns of protein expression have previously been shown to correlate with differentiated cell types, it has been much more challenging to develop technologies that can detect regulatory proteins such as transcription factors that specify specific cellular fates. Emerging embryonic HSCs and their progeny have been comprehensively examined via global transcriptional profiling, which revealed key insights into hematopoietic specification and leukemogenesis (Boisset et al., 2010; McKinney-Freeman et al., 2012). The direct precursor to the HSC, the HEC, has not been extensively examined, as only an abbreviated transcriptional profile of HECs within the murine embryo was recently elucidated using a Fluidigm-based approach (Swiers et al., 2013). Here, we have utilized label-free proteomics to decipher key regulators of embryonic hematopoiesis both in vivo and during the directed differentiation of ESCs in vitro. This approach to cellular profiling has the distinct advantage of identifying only translated functional proteins present in the cell, thus eliminating the unknown effects of post-transcriptional modification that may affect mRNA translation.
Our first analysis focused on the proteomic landscape of E10.5 and E11.5 VEC+ populations that contain ECs, HECs, and pre-HSCs (Rybtsov et al., 2011). With this approach, we were able to accurately identify and quantify known regulators of the early hematopoietic programs such as SCL/TAL1 and ALDH1A2, as well as a small cohort of proteins that exhibited dramatic expression changes between E10.5 and E11.5, providing a focused and manageable list of candidates to interrogate as putative regulators of the generation of type I pre-HSCs. To date, the generation of PSC-derived HSCs has been difficult, likely due to the undefined nature of PSC differentiation culture conditions and the lack of accurate comparison of the in vitro populations to potential equivalent in vivo embryonic stages. Comparison of D7 mESC-derived HEC populations to the E10.5 and E11.5 HEC populations revealed that our D7 HEC population represents a developmental intermediate. Therefore, interrogation of this dataset will help identify the absence of key regulatory proteins, thus providing a potential explanation for the inability of these cells to faithfully generate HSCs in vitro.

br Experimental procedures br Results br Discussion Between groups

Experimental procedures

Results

Discussion
Between-groups differences in pattern of activity in the l-MFG and r-MFG were largest in the two experimental conditions in which feedback was not available. The MFG is a tropisetron region known to be normally involved in working memory and top-down attention control (Awh and Jonides, 2001; Gazzaley and Nobre, 2012; LaBar et al., 1999). Our data shows that in children with ADHD, neural activity in the MFG is affected by the availability of feedback information in VSWM tasks, with little regard to the reward size associated with the feedback. This indicates that the MFG is likely using feedback information primarily as an external error-monitoring signal, rather than processing feedback as a symbolic reward.
Between-groups differences in the MeOFC were significant in the small-reward with feedback condition. This is the experimental condition that required the greatest investment of cognitive resources, yet in which the reward was minimal. In the VSWM tasks with feedback, participants were required to monitor the spatial location of letters and the visual feedback (which further increased the cognitive load). Unlike the large-reward with feedback condition, where the feedback had a significant subjective meaning, here the feedback was with little meaning. In such a scenario, a more adaptive strategy may involve suppressing the feedback information. Minimal MeOFC deactivation in ADHD boys, specifically in the small-reward with feedback condition, may indicate poor capacity in filtering out information with little task relevance, and an unnecessary allocation of cognitive resources for online processing of insignificant reward. In contrast, NC boys showed maximal MeOFC deactivation in this VSWM task, indicating a better capacity in discarding feedback with little subjective relevance (Gottfried and Dolan, 2004a,b; Ströhle et al., 2008; Wilbertz et al., 2012).
Between-groups differences in pattern of activity in the r-AntI were significant when the participants expected large-reward, yet feedback was not available. Low r-AntI activity in ADHD boys may be related to poor risk/gain prediction in ADHD (Preuschoff et al., 2008). Such a relation between poor cognitive control and lower levels of neural activity in the anterior insula in children with ADHD has been reported in the past (Cubillo et al., 2010; Morein-Zamir et al., 2014). Here we show that low r-AntI activity is most likely to be evident when the motivation of children with ADHD is high (expecting large monetary reward), but when there is no external/contextual source of information enabling error monitoring (i.e., there is no trial-by-trial feedback). Such a scenario may be perceived as frustrating by children with ADHD. Frustration has been recently reported to be associated with insula hypersensitivity to expected reward (evident as reduced insula activity) in other young clinical populations that share symptoms with ADHD (Deveney et al., 2013; see also Bebko et al., 2015 for functional connectivity abnormalities in the insula), yet not specifically in ADHD.
Our findings are also consistent with neuroeconomic models of ADHD. These suggest that ADHD is characterized by dysfunctional dorsal frontostriatal network (including the MFG), which is associated with poor autonomous decision selection, and with dysfunctional ventral frontostriatal networks (including the MeOFC), which is associated with poor processing of cues indicating future utility (Sonuga-Barke and Fairchild, 2012). Here we show that trial-by-trial feedback coupled with expectation for large-reward results with a normal-like activation in both networks, in children with ADHD.
Showing that children with ADHD can improve their performances in basic cognitive tasks, when being provided with contextual support, is with significant clinical and educational implications, and it may advance the development of effective behavioral intervention. Here we show that ADHD boys are likely to perform normally in VSWM tasks only when provided with feedback associated with large-reward. However, we note that the reward size manipulation in the current study was only symbolic (a picture of coins in the small-reward conditions versus a picture of dollar bills in the large-reward conditions), where ultimately all participants received the same payment at the end of the experimental session. This suggests that children with ADHD may not require an actual physical reward for behavioral intervention. Furthermore, future studies may also investigate if the reliance on trial-by-trial feedback can be reduced to the point where only partial feedback (feedback provided irregularly rather than in every trial) can be effective in preserving desired behavior (Johansen et al., 2009; Luman et al., 2010).

Si en los a os tanto las militantes del MLF

Si en los años 70, tanto las militantes del MLF como las de la UFA (algunas de ellas ligadas por fuertes simpatías con partidos de izquierda) estuvieron de acuerdo en no contaminar al feminismo con otras militancias, en una lucha por conseguir cierta escucha específica, en los años 80, y de la mano de las atemas, esto fue revisado. Así, muchas exmilitantes de la ufa pasaron tropisetron participar con más intensidad en las actividades de atem que en las de ofa (organización formada en los primeros años de la década de los 80 que nucleaba a feministas destacadas de los 70 y que reeditaba la revista Persona).
Sin embargo, por su parte, desde Persona (años 80) se insistió sobre aquel punto aprendido del feminismo radical, en un contexto que marcaba otras demandas: “La Organización Feminista Argentina es una institución sin fines de lucro, ni partidismo político, que nos nuclea a las mujeres sin discriminación alguna con el fin de trabajar para el mejoramiento de nuestra condición en lo social, jurídico y económico” (Persona, abril 1980, folleto abrochado a la revista, sin paginación).
Persona, en marzo de 1982, en su editorial redoblaba la apuesta y sostenía:
El contrapunto hace evidente que las diferencias entre ambas escrituras se volvieron insoslayables. Las atemas enunciaron y enfatizaron un aspecto del feminismo que estuvo ausente en las definiciones de las militantes de los 70 y fue rechazado por ciertas estelas de aquel feminismo: una contextualización de la lucha feminista y un posicionamiento político. Desde Brujas, afirmaron que: “Contextualizar el movimiento feminista es una necesidad que marca su crecimiento. El feminismo debe contextuar (sic.) sus objetivos y sus luchas en el lugar en que actúa. En Argentina, el feminismo debe tomar posiciones antiimperialistas, a favor de los derechos humanos y de la lucha de clases” (Brujas, año 1, núm. 3, p. 7; las cursivas son nuestras). En distintos números de Brujas se insistió en remarcar el carácter anticapitalista y tercermun- dista latinoamericano en contexto posdictatorial del feminismo que ellas proponían. Brujas afirmó que el movimiento feminista, “como movimiento político y transformador, plantea objetivos y propuestas que se relacionan con el conjunto de la sociedad [pues] es necesario construir una sociedad sin relaciones jerárquicas. Tal pretensión lleva al feminismo a cuestionar la propiedad privada, las opresiones nacionales, de clase, de raza, de etnia” (Brujas, año 1, núm. 3, p. 7; las cursivas son nuestras).
María Elena Oddone cuenta en su autobiografía algunos de los desencuentros que se produjeron con las militantes feministas en los albores de los 80. Bajo el título El feminismo y las izquierdas, escribió una crítica acre a bladder la participación de las feministas en la política nacional que experimentaba la alegría y la esperanza del retorno a la democracia. En aquel escenario político, el reclamo incansable de las Madres de Plaza de Mayo por la aparición de los detenidos/as o desaparecidos/as de la dictadura militar marcaba el escenario político local. Oddone denunció lo que entendía como un embelesamiento de las nuevas militantes feministas por las Madres, y propuso entonces apoyar a las madres de los soldados muertos por la subversión. Así, tras la huella de sus posiciones políticas, nunca asumidas plenamente como tales, María Elena Oddone fue expulsada de varios espacios de militancia feminista a raíz no sólo de esta propuesta, sino de otras de similar talante (Oddone 2001). Por su parte, las atemas, después de estos primeros momentos de confrotación, desde las páginas de Brujas, guardaron un silencio casi sepulcral respecto del feminismo anterior. Se hacía evidente que las hebras con las cuales tejer la genealogía del feminismo argentino no eran del todo firmes o deseables a la mirada de las atemas.

Es un lugar común del discurso académico, pero también del discurso político, afirmar o sugerir que el principal obstáculo para la constitución del movimiento feminista en la Argentina fue otro movimiento, el peronista. Dicha operación de pensamiento, por otra parte, no sólo se aplica a las relaciones históricas del peronismo con el feminismo, sino que resulta cara a múltiples interpretaciones de las consecuencias que produjo la irrupción del fenómeno peronista. El peronismo, para la intelectualidad progresista, sigue siendo, a su manera, objeto de preguntas que, si recaen en la figura del fenómeno —algo más que una fenomenología entendida como las condiciones de aparición—, dan cuenta de que se entiende poco o nada. En cambio, si abonan la cuestión peronista, puede decirse que se está frente a verdaderas preguntas. En ambos casos, el peronismo —parodiando a Vovelle— sigue siendo una cantera abierta que no deja de suscitar inquietudes políticas e intelectuales. Ahora, si bien esa conexión entre el menos (-) del feminismo y el más (+) del peronismo no asume hoy la forma cruda o bienpensante que adquirió en los años 70 y 80, o el estilo amable y sutil presente en alguna ensayística de los 70 —como la Eva Perón ¿aventurera o militante? de Sebreli—, sigue siendo un presupuesto, en alto grado inexpugnable para el saber académico, que la política del peronismo hacia y con las mujeres afectó el ideal de una condición femenina volcada hacia una práctica militante feminista.

br Conclusion br Bladder exstrophy is a

Conclusion

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.

Discussion
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

Introduction

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: http://www.ispor.org/TaskForces/Simulation-ModelingApps-HCDelivery.asp. The task force report and Webpage may also be accessed from the ISPOR homepage (www.ispor.org) 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).

Results

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###http://www.apexbt.com//media/diy/images/structpng/B4795.png#### 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.