Ovarian Cancer Pathogenesis: A Model in Evolution

Ovarian cancer is a deadly disease for which there is no effective means of early detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations, and tumor behaviors. This high degree of heterogeneity presents a major clinical challenge in both diagnosing and treating ovarian cancer. Furthermore, the early events leading to ovarian carcinoma development are poorly understood, thus complicating efforts to develop screening modalities for this disease. Here, we provide an overview of the current models of ovarian cancer pathogenesis, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas. The ovarian cancer model will continue to evolve as we learn more about the genetics and etiology of this disease

The new face of ovarian cancer modeling: better prospects for detection and treatment

Ovarian cancer has a disproportionately high mortality rate because patients typically present with late-stage metastatic disease. The vast majority of these deaths are from high-grade serous carcinoma. Recent studies indicate that many of these tumors arise from the fallopian tube and subsequently metastasize to the ovary. This may explain why such tumors have not been detected at early stage as detection efforts have been focused purely on the ovary. In keeping with this leap in understanding other advances such as the development of ex-vivo models and immortalization of human fallopian tube epithelial cells, and the use of integrated genomic analyses to identify hundreds of novel candidate oncogenes and tumor suppressors potentially involved in tumorigenesis now engender hope that we can begin to truly define the differences in pathogenesis between fallopian tube and ovarian-derived tumors. In doing so, we can hopefully improve early detection, treatment, and outcome

Kinetic study of an on-chip isocyanate derivatization reaction by on-line nano-esi ms

A high-throughput method is presented for the study of reaction kinetics by nano- electrospray ionization mass spectrometry (nano-ESI MS). The reaction of propyl isocyanate (2), benzyl isocyanate (3), and toluene-2,4-diisocyanate (4) with 4-nitro-7- piperazino-2,1,3-benzoxadiazole (NBDPZ) (1) to yield the corresponding urea derivatives (5) was carried out in a continuous flow glass microchip. Real-time monitoring of the reactions was done by nano-ESI MS. Rate constants of 1.6 ␣ 104 M-1 min-1, 5.2 ␣ 104 M-1 min-1, and 2.5 ␣ 104 M-1 min-1 were determined for isocyanate 2, 3 and 4, respectively

Parent and Family Outcomes of PEERS: A Social Skills Intervention for Adolescents with Autism Spectrum Disorder

Raising a child with an Autism Spectrum Disorder (ASD) is associated with increased family chaos and parent distress. Successful long-term treatment outcomes are dependent on healthy systemic functioning, but the family impact of treatment is rarely evaluated. The Program for the Education and Enrichment of Relational Skills (PEERS) is a social skills intervention designed for adolescents with high-functioning ASD. This study assessed the impact of PEERS on family chaos, parenting stress, and parenting self-efficacy via a randomized, controlled trial. Results suggested beneficial effects for the experimental group in the domain of family chaos compared to the waitlist control, while parents in the PEERS experimental group also demonstrated increased parenting self-efficacy. These findings highlight adjunctive family system benefits of PEERS intervention and suggest the need for overall better understanding of parent and family outcomes of ASD interventions

Mortality mitigation of a translocated rare New Zealand frog Leiopelma pakeka

A small population (n=58) of Maud Island frogs, Leiopelma pakeka, was translocated to the Zealandia wildlife sanctuary in Wellington, New Zealand in 2006/2007. The 29 frogs that were released into a predator-proof enclosure, along with some of their progeny, are currently spread over three separate predator-proof enclosures. However, their status has not been assessed since 2011. With the aim of establishing a viable, freeranging population, the remaining 29 frogs were released into forested habitat around the original enclosure. In 2010, the translocation of the free-ranging population was assessed as a failure, citing too few founding individuals, inadequate habitat, predation by little spotted kiwi (LSK), Apteryx owenii, and predation by house mice, Mus musculus, as potential factors. This thesis re-addresses the status of L. pakeka in the three enclosures, as well as the potential predation of these threatened endemic frogs by LSK and mice. Survival of L. pakeka in the three enclosures was estimated by nocturnal emergence over 11 ve-night capture periods from October 2012 - August 2013. Identi cation of individuals was via photography utilizing distinguishable skin patterns and iris vessel (eye venation) patterns. The relocation of six adults after a 2011 census, including one inadvertently missed frog found during this study, left 19 adult frogs in the original enclosure, which continued to survive well, with 18 adults recaptured. In addition, juveniles of varying ages were seen throughout this study. In total, 34 recently metamorphosed froglets were released into a second enclosure over the years of 2008, 2009 and 2011. Night monitoring indicated only 8 individuals had survived, but a full enclosure census on 8 May 2013 revealed 12 of the 34 individuals (35%) had survived. Three of these frogs were then relocated to the Te Mahanga, publicly viewed enclosure. Emergence during the 11-month period indicated that the six frogs relocated to this enclosure from the original enclosure in October 2011 had survived; however, only two out of the three frogs that were relocated there after the May census had emerged. Additionally, two juveniles of unknown age were also seen in this enclosure. Potential predation by LSK was assessed by a ve-night video analysis (23-28 June 2013) of foraging behavior in the presence of mesh-protected L. pakeka. Out of the 668 videos reviewed, only three videos provided foraging behavior that helped ascertain whether LSK exhibited a potential interest in L. pakeka as a prey item. These videos showed that LSK failed to indicate a strong response to the presence of the frog, suggesting that the LSK in Zealandia do not have a strong predatory interest in L. pakeka. To investigate the potential causes of the free-range translocation failure, the habitat was enhanced with more rocks, a kiwi-exclusion fence was erected, and a further 101 L. pakeka were translocated from Maud Island to Zealandia on 2 December 2012. The frogs' survival as well as mouse activity levels (indicated by the presence of mouse prints in tracking tunnels) were monitored over nine ve-night capture periods from 17 December 2012 - 2 August 2013. Eighty-six out of the 101 translocated frogs were recaptured. Identi cation of individuals was via photography utilizing distinguishable skin patterns and iris vessel (eye venation) patterns, or by unique toe-clip combinations. Despite previous assessments, four surviving adults from the 2006/2007 translocation were recaptured as well as 12 of their progeny, resulting in a total of 117 Maud Island frogs for this study. Jolly-Seber analysis indicated high overall survival (0.914, 0.87/0.94, 95%CI), but temporally the population estimates indicated a negative regression starting at the second capture period (slope= -4.69, -6.70/- 2.68, 95%CI). With overall frog emergence, a negative binomial generalized linear model did not show signi cance in mouse activity levels, precipitation during sampling nor precipitation in the previous 24 hours (p>0.05). However, temperature did show a positive correlation to overall frog emergence (p<0.001) while relative humidity approached signi cance (p=0.0517) and indicated a potential positive trend. This study could not conclusively indicate whether A. owenii or M. musculus prey upon L. pakeka. However, it does suggest that the protected predator-proof enclosures may provide appropriate conditions for the ongoing survival and successful breeding of the endemic anuran. The study also suggests that LSK do not have a strong predatory response to the presence of Maud Island frogs, nor did increased levels of mouse activity have a signi cant e ect on the emergence of the 117 Maud Island frogs. Additionally, the discovery of the four survivors and 12 of their o spring indicates that the original translocation did not entirely fail. This newly acquired knowledge suggests that with the current mammal eradication program, Zealandia may continue with the establishment of a viable, free-ranging population of L. pakeka. Continued monitoring of all Maud Island frogs in the Zealandia sanctuary is recommended as a conservation measure, especially as mice have now established on its original island habitat

A methodological framework to conduct joint zone-based analysis of traffic safety and accessibility

Increasing accessibility and improving cycling safety are the primary objectives of cities and policymakers. In the literature, there are several studies examining cycling safety and few studies examining cycling accessibility. However, few studies conduct a joint examination of these two topics to understand the relationship between them. This paper aims to develop and apply a methodological framework to conduct a joint zone-based analysis of traffic safety and accessibility. The developed framework integrates route choice modelling and four-step modelling into traffic safety and accessibility analysis and the outcome is a novel zone-based crash risk estimation incorporating traffic crashes with trip characteristics (including, trip purpose, origin-destination, and alternative routes). The proposed framework was applied in a case study to examine the injury crash risk imposed on commuting cyclists and job accessibility in the city of Utrecht, the Netherlands. The results illustrate the need to embed trip characteristics into zone-based traffic safety estimation to be able to compare the spatial distribution of traffic safety with other mobility and transport-related indicators. Moreover, the findings reflect on significance of taking route choice features into account in accessibility analysis to avoid overestimating accessibility levels. They show that safety and accessibility levels are not equally distributed in the city of Utrecht. For example, low-income areas generally have lower job accessibility levels and higher cycling crash risks which imply the spatial and social inequalities in the transport system's effects.</p

The relationships between accessibility and crash risk from social equity perspectives: A case study at the Rotterdam-The Hague metropolitan region

Traflic safety and accessibility have been two important subjects in transportation research. On the one hand traffic crashes bring about high societal costs and serious health risks for urban road users. The cost oftraffic crashes is estimated to be 17 billion euros per year only in the Netherlands while over 600 people were killed in traffic, of whom 229 were cyclists and 195 were car users [l, 2]. Accessibility, on the other band, is regarded as one of the indicators of the quality of the transport system serving the public. There is comprehensive literature investigating the relationship between traffic crashes and factors associated with traffic, roadway design, built environment, and human factors. Similarly, several studies assessed and evaluated accessibility levels of individuals, communities, and regions by utilizing the aforementioned. factors. Nevertheless, there is a scarcity ofliterature investigating the relationships between accessibility and traffic safety. This is especially surprising considering that both subjects are associated with a similar set of factors, including land use and transport systems, as weil as individual and temporal factors [3-7]. The relationships between accessibility and traffic safety can be an adverse one; for example, improved accessibility by increasing the travel speeds (i.e., declining travel time) intensifies the crash risks which also deteriorates equity. Furthermore, levels ofboth accessibility and traffic safety are not homogeneous throughout urban areas and among different population groups. Based on the literature, it is obvious that accessibility is associated with economic equity [8]. lt is revealed that accessibility of lower-income groups is substantially worse than the higher-income groups as these groups have less mobility [9]. Previous studies also showed. that lower-income groups usually suffer from traffic safety problems more than other socio-economic groups [10-12]. Therefore, this research aims to address the aforementioned gap in the literature in understanding the relationships between accessibility levels and traffic safety with a focus on social equity perspecti.ves. For this purpose, a Gravity model and risk exposure evaluation approaches are utilix.ed to analyze traffic safety and accessibility to jobs by bicycle via extending the traditional definition of accessibility based on only travel time or proximity to a location

The Effects of Shoe Traction and Obstacle Height on Lower Extremity Coordination Dynamics During Walking

This study aims to investigate the effects of shoe traction and obstacle height on lower extremity relative phase dynamics (analysis of intralimb coordination) during walking to better understand the mechanisms employed to avoid slippage following obstacle clearance. Ten participants walked at a self-selected pace during eight conditions: four obstacle heights (0%, 10%, 20%, and 40% of limb length) while wearing two pairs of shoes (low and high traction). A coordination analysis was used and phasing relationships between lower extremity segments were examined. The results demonstrated that significant behavioral changes were elicited under varied obstacle heights and frictional conditions. Both decreasing shoe traction and increasing obstacle height resulted in a more in-phase relationship between the interacting lower limb segments. The higher the obstacle and the lower the shoe traction, the more unstable the system became. These changes in phasing relationship and variability are indicators of alterations in coordinative behavior, which if pushed further may have lead to falling

Measuring the Plasticity of Social Approach: A Randomized Controlled Trial of the Effects of the PEERS Intervention on EEG Asymmetry in Adolescents with Autism Spectrum Disorders

This study examined whether the Program for the Education and Enrichment of Relational Skills (PEERS: Social skills for teenagers with developmental and autism spectrum disorders: The PEERS treatment manual, Routledge, New York, 2010a) affected neural function, via EEG asymmetry, in a randomized controlled trial of adolescents with Autism spectrum disorders (ASD) and a group of typically developing adolescents. Adolescents with ASD in PEERS shifted from right-hemisphere gamma-band EEG asymmetry before PEERS to left-hemisphere EEG asymmetry after PEERS, versus a waitlist ASD group. Left-hemisphere EEG asymmetry was associated with more social contacts and knowledge, and fewer symptoms of autism. Adolescents with ASD in PEERS no longer differed from typically developing adolescents in left-dominant EEG asymmetry at post-test. These findings are discussed via the Modifier Model of Autism (Mundy et al. in Res Pract Persons Severe Disabl 32(2):124, 2007), with emphasis on remediating isolation/withdrawal in ASD