Enhanced Recovery Pathways in Gynecology and Gynecologic Oncology

Enhanced recovery programs (ERPs) are considered standard of care across a variety of surgical disciplines, but ERPs have not been widely adopted in gynecology

Expression of three forms of melanoma growth stimulating activity (MGSA)/gro in human retinal pigment epithelial cells

PURPOSE: To characterize mRNA expression and protein production of the cytokine MGSA/gro in human retinal pigment epithelial (RPE) cells and to determine whether expression of MGSA/gro is modulated by serum and the cytokines interleukin 1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), or transforming growth factor beta (TGF beta) mediators implicated in proliferative vitreoretinopathy (PVR). METHODS: Reverse-transcription polymerase chain reaction was used to determine the steady-state mRNA expression of three forms of MGSA/gro, alpha, beta, and gamma, by cultured human RPE cells in the presence or absence of recombinant IL-1 beta, TNF alpha, or TGF beta, or when serum-starved cells were re-fed with medium containing serum. Immunocytochemistry was used to characterize RPE cell-associated MGSA/gro protein, and immunoprecipitation of MGSA/gro from cell-conditioned medium was used to demonstrate MGSA/gro secretion. RESULTS: MGSA/gro mRNA was expressed minimally under basal conditions. Expression for all three forms of MGSA/gro mRNA was induced in a dose- and time-dependent manner after exposure to IL-1 beta, to a lesser extent after exposure to TNF alpha, but not after exposure to TGF beta. Serum induced MGSA/gro alpha and gamma transcripts, but not beta transcripts. Cell-associated MGSA/gro was identified on RPE cells grown in the absence of cytokines, but MGSA/gro was not secreted under these conditions. Exposure to IL-1 beta did not consistently cause increased cell-associated MGSA/gro; however, IL-1 beta induced secretion of MGSA/gro in a time-dependent manner. CONCLUSION: MGSA/gro is produced by human RPE in response to mediators implicated in PVR. Because MGSA/gro is a pleiotropic modulator of cell proliferation and inflammation, it may contribute to the intraocular wound healing response that characterizes PVR

Evaluation of Three Adolescent Sexual Health Programs in Ha Noi and Khanh Hoa Province, Vietnam

With an increase in sexual activity among young adults in Vietnam and associated risks, there is a need for evidence-based sexual health interventions. This evaluation of three sexual health programs based on the Protection Motivation Theory (PMT) was conducted in 12 communes in Ha Noi, Nha Trang City, and Ninh Hoa District. Inclusion criteria included unmarried youth 15–20 years residing in selected communes. Communes were randomly allocated to an intervention, and participants were randomly selected within each commune. The intervention programs included Vietnamese Focus on Kids (VFOK), the gender-based program Exploring the World of Adolescents (EWA), and EWA plus parental and health provider education (EWA+). Programs were delivered over a ten-week period in the communities by locally trained facilitators. The gender-based EWA program with parental involvement (EWA+) compared to VFOK showed significantly greater increase in knowledge. EWA+ in comparison to VFOK also showed significant decrease at immediate postintervention for intention to have sex. Sustained changes are observed in all three interventions for self-efficacy condom use, self-efficacy abstinence, response efficacy for condoms, extrinsic rewards, and perceived vulnerability for HIV. These findings suggest that theory-based community programs contribute to sustained changes in knowledge and attitudes regarding sexual risk among Vietnamese adolescents

Novel insights in the regulation of CCL18 secretion by monocytes and dendritic cells via cytokines, Toll-like receptors and rheumatoid synovial fluid

BACKGROUND: The T cell attracting chemokine CCL18 is produced by antigen presenting cells and a role for CCL18 has been suggested in the pathogenesis of a variety of diseases. Rheumatoid arthritis (RA) is one of these conditions, in which abundant CCL18 production is present. Although Th2 cytokines and IL-10 are known to have an effect on CCL18 production, there are several gaps in our knowledge regarding the exact regulation of CCL18 secretion, both in general and in RA. In this study we provide new insights in the regulation of CCL18 secretion by monocytes and dendritic cells. RESULTS: In contrast to a large panel of pro-inflammatory stimuli (IL-1β, TNF-α, IL-10, IL-13, IL-15, IL-17, IL-18, IFN-γ), T cell mimicking molecules (RANKL, CD40L) or TLR driven maturation, the anti-inflammatory IL-10 strongly stimulated DC to secrete CCL18. On freshly isolated monocytes, CCL18 secretion was induced by IL-4 and IL-13, in strong synergy with IL-10. This synergistic effect could already be observed after only 24 hours, indicating that not only macrophages and dendritic cells, but also monocytes secrete CCL18 under these stimulatory conditions. A high CCL18 expression was detected in RA synovial tissue and incubation of monocytes with synovial fluid from RA patients clearly enhanced the effects of IL-4, IL-13 and IL-10. Surprisingly, the effect of synovial fluid was not driven by IL-10 of IL-13, suggesting the presence of another CCL18 inducing factor in synovial fluid. CONCLUSION: In summary, IL-10 synergistically induces CCL18 secretion in combination with IL-4 of IL-13 on monocytes and monocyte derived cells. The effects of IL-14, IL-13 and IL-10 are strongly enhanced by synovial fluid. This synergy may contribute to the high CCL18 expression in RA

A phase II study of paclitaxel for the treatment of ovarian stromal tumors: An NRG Oncology/ Gynecologic Oncology Group Study

To estimate the probability of complete clinical response and toxicity of paclitaxel as second-line chemotherapy in measurable disease patients with malignant tumors of the ovarian stroma, and to evaluate the value of inhibin for predicting response

MIKE-SHE integrated groundwater and surface water model used to simulate scenario hydrology for input to DRIFT-ARID: the Mokolo River case study

A fully integrated, physically-based MIKE SHE/MIKE11 model was developed for the Mokolo River basin flow system to simulate key hydraulic and hydrologic indicator inputs to the Downstream Response to Imposed Flow Transformation for Arid Rivers (DRIFT-ARID) decision support system (DSS). The DRIFT-ARID tool is used in this study to define environmental water requirements (EWR) for non-perennial river flow systems in South Africa to facilitate ecosystembased management of water resources as required by the National Water Act (Act No. 36 of 1998). Fifty years of distributed daily climate data (1950 to 2000) were used to calibrate the model against decades of daily discharge data at various gauges, measurements of Mokolo Dam stage levels, and one-time groundwater level measurements at hundreds of wells throughout the basin. Though the calibrated model captures much of the seasonal and post-event stream discharge response characteristics, lack of sub-daily climate and stream discharge data limits the ability to calibrate the model to event-level system response (i.e. peak flows). In addition, lack of basic subsurface hydrogeologic characterisation and transient groundwater level data limits the ability to calibrate the groundwater flow model, and therefore baseflow response, to a high level. Despite these limitations, the calibrated model was used to simulate changes in hydrologic and hydraulic indicators at five study sites within the basin for five 50-year land-use change scenarios, including a present-day (with dam), natural conditions (no development/irrigation), and conversion of present-day irrigation to game farm, mine/city expansion, and a combination of the last two. Challenges and recommendations for simulating the range of non-perennial systems are presented.Keywords: hydrology, non-perennial, MIKE SHE, integrated surface and groundwater modellin

DRIFT-ARID: A method for assessing environmental water requirements (EWRs) for non-perennial rivers

Environmental water requirement (EWR) assessment methods, for ascertaining how much water should be retained in rivers to sustain ecological functioning and desired levels of biodiversity, have mostly been developed for perennial rivers. Despite non-perennial rivers comprising about 30–50% of the world’s freshwater systems, data on their hydrology, biota and ecological functioning are sparse. Current EWR assessments require hydrological and other data that may not be available for such rivers and some adaptation in the methods used seems necessary. DRIFT is an EWR method for perennial (or near-perennial) rivers that has been developed in South Africa over the past two decades and is now widely applied nationally and internationally. When applied to the semi-permanent Mokolo River, challenges particular to, or accentuated by, non-perennial rivers included the reliable simulation of hydrological data, the extent of acceptable extrapolation of data, difficulties in predicting surface-water connectivity along the river, and the location and resilience of pools, as well as whether it was possible to identify a reference (natural) condition. DRIFT-ARID, reported on here, is an adaptation of the DRIFT approach to begin addressing these and other issues. It consists of 11 phases containing 29 activities.Keywords: EWR, non-perennial, DRIFT, DS

Perinatal death in a term fetal growth restriction randomized controlled trial:the paradox of prior risk and consent

BACKGROUND: The disproportionate intrauterine growth intervention trial at term was an intention to treat analysis and compared labor induction with expectant monitoring in pregnancies complicated by fetal growth restriction at term and showed equivalence for neonatal outcomes. OBJECTIVE: To evaluate trial participation bias and to examine the generalizability of the results of an obstetrical randomized trial. STUDY DESIGN: We used data from participants and nonparticipants of a randomized controlled trial-the disproportionate intrauterine growth intervention trial at term (n=1116) -to perform a secondary analysis. This study compared induction of labor and expectant management in women with term growth restriction. Data were collected in the same manner for both groups. Baseline characteristics and neonatal and maternal outcomes were compared. The primary outcome was a composite measure of adverse neonatal outcome. Secondary outcomes were delivery by cesarean delivery and instrumental vaginal delivery; length of stay in the neonatal intensive care, neonatal ward, and the maternal hospital; and maternal morbidity. RESULTS: Nonparticipants were older, had a lower body mass index, had a higher level of education, smoked less, and preferred expectant management. The time between study inclusion and labor onset was shorter in participants than in nonparticipants. Notably, 4 perinatal deaths occurred among nonparticipants and none among participants. Among nonparticipants, there were more children born with a birthweight below the third centile. The nonparticipants who had expectant management were monitored less frequently than the participants in both the intervention and the expectant arm. CONCLUSION: We found less favorable outcomes and more perinatal deaths in nonparticipants. Protocol-driven management, differences between participants and nonparticipants, or the fact that nonparticipants had a preference for expectant management might explain the findings

Best Practices for Publishing, Retrieving, and Using Spatial Data on the Web

Data owners are creating an ever richer set of information resources online, and these are being used for more and more applications. With the rapid growth of connected embedded devices, GPS-enabled mobile devices, and various organizations that publish their location-based data (i.e., weather and traffic services), maps and geographical and spatial information (i.e., GIS and open maps), spatial data on the Web is becoming ubiquitous and voluminous. However, the heterogeneity of the available spatial data, as well as some challenges related to spatial data in particular make it difficult for data users, web applications and services to discover, interpret and use the information in large and distributed web systems. This paper summarizes some of the efforts that have been undertaken in the joint W3C/OGC Working Group on Spatial Data on the Web, in particular the effort to describe the best practices for publishing spatial data on the Web. This paper presents the set of principles that guide the selection of these best practices, describes best practices that are employed to enable publishing, discovery and retrieving (querying) this type of data on the Web, and identifies some areas where a best practice has not yet emerged

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283