Do differences in medical comorbidities and treatment impact racial disparities in epithelial ovarian cancer?

BACKGROUND: Population-based studies of women with epithelial ovarian cancer suggest that black women have worse survival compared to white women. The primary objective of this study was to determine if, at a National Cancer Institute (NCI)-Designated Comprehensive Cancer Center (CCC) serving a diverse racial and socioeconomic population, race is independently associated with differences in survival. METHODS: A retrospective review of women with EOC diagnosed between 2004-2009 undergoing treatment with follow-up at our institution was performed. Records were reviewed for demographics, comorbidities (as defined by the Charlson Comorbidity Index (CCI)), tumor characteristics, treatment, progression-free (PFS), and overall survival (OS). Survival was calculated using the Kaplan-Meier method and compared with the log-rank test. Multivariate survival analysis was performed with Cox (proportional hazards) model. RESULTS: 367 patients met inclusion criteria. 54 (15%) were black and 308 (84%) were white. Compared to white women, black women had higher BMI, lower rates of optimal surgical cytoreduction, lower rates of intraperitoneal chemotherapy, and higher CCI scores. The median PFS for black and white women were 9.7 and 14.6months, respectively (p=0.033). The median overall survival was 21.7months for black women and 42.6months for white women (p<0.001). On multivariate analysis, black race independently correlated with a worse overall survival (HR 1.61, 95% CI 1.06-2.43). CONCLUSION: In this cohort, racial disparities may be due to higher medical comorbidities and lower rates of optimal surgical cytoreduction. After accounting for these differences, race remained an independent predictor of worse overall survival.

New self-sexing Aedes aegypti strain eliminates barriers to scalable and sustainable vector control for governments and communities in dengue-prone environments.

For more than 60 years, efforts to develop mating-based mosquito control technologies have largely failed to produce solutions that are both effective and scalable, keeping them out of reach of most governments and communities in disease-impacted regions globally. High pest suppression levels in trials have yet to fully translate into broad and effective Aedes aegypti control solutions. Two primary challenges to date-the need for complex sex-sorting to prevent female releases, and cumbersome processes for rearing and releasing male adult mosquitoes-present significant barriers for existing methods. As the host range of Aedes aegypti continues to advance into new geographies due to increasing globalisation and climate change, traditional chemical-based approaches are under mounting pressure from both more stringent regulatory processes and the ongoing development of insecticide resistance. It is no exaggeration to state that new tools, which are equal parts effective and scalable, are needed now more than ever. This paper describes the development and field evaluation of a new self-sexing strain of Aedes aegypti that has been designed to combine targeted vector suppression, operational simplicity, and cost-effectiveness for use in disease-prone regions. This conditional, self-limiting trait uses the sex-determination gene doublesex linked to the tetracycline-off genetic switch to cause complete female lethality in early larval development. With no female progeny survival, sex sorting is no longer required, eliminating the need for large-scale mosquito production facilities or physical sex-separation. In deployment operations, this translates to the ability to generate multiple generations of suppression for each mosquito released, while being entirely self-limiting. To evaluate these potential benefits, a field trial was carried out in densely-populated urban, dengue-prone neighbourhoods in Brazil, wherein the strain was able to suppress wild mosquito populations by up to 96%, demonstrating the utility of this self-sexing approach for biological vector control. In doing so, it has shown that such strains offer the critical components necessary to make these tools highly accessible, and thus they harbour the potential to transition mating-based approaches to effective and sustainable vector control tools that are within reach of governments and at-risk communities who may have only limited resources.

Transposon-free insertions for insect genetic engineering.

Methods involving the release of transgenic insects in the field hold great promise for controlling vector-borne diseases and agricultural pests. Insect transformation depends on nonautonomous transposable elements as gene vectors. The resulting insertions are stable in the absence of suitable transposase, however, such absence cannot always be guaranteed. We describe a method for post-integration elimination of all transposon sequences in the pest insect Medfly, Ceratitis capitata. The resulting insertions lack transposon sequences and are therefore impervious to transposase activity.

Genetic sexing through the use of Y-linked transgenes.

Sterile insect technique (SIT)-based pest control programs rely on the mass release of sterile insects to reduce the wild target population. In many cases, it is desirable to release only males. Sterile females may cause damage, e.g., disease transmission by mosquitoes or crop damage via oviposition by the Mediterranean fruit fly (Medfly). Also, sterile females may decrease the effectiveness of released males by distracting them from seeking out wild females. To eliminate females from the release population, a suitable sexual dimorphism is required. For several pest species, genetic sexing strains have been constructed in which such a dimorphism has been induced by genetics. Classical strains were based on the translocation to the Y chromosome of a selectable marker, which is therefore expressed only in males. Recently, several prototype strains have been constructed using sex-specific expression of markers or conditional lethal genes from autosomal insertions of transgenes. Here, we describe a novel genetic sexing strategy based on the use of Y-linked transgenes expressing fluorescent proteins. We demonstrate the feasibility of this strategy in a major pest species, Ceratitis capitata (Wiedemann), and discuss the advantages and disadvantages relative to other genetic sexing methods and potential applicability to other species.

Comprehension of spatial language terms in Williams syndrome: evidence for an interaction between domains of strength and weakness.

Individuals with Williams syndrome show an unusual neuropsychological profile, with relatively strong language abilities and impoverished visual and spatial abilities. Two studies are reported that examine the interaction between these two domains in Williams syndrome by assessing individuals' comprehension of spoken language with a spatial component. In a first study, the Test for Reception of Grammar (Bishop, 1983) was given to 32 individuals with Williams syndrome and to controls matched individually for total number of errors on the task. Individuals with Williams syndrome had particular problems when asked to comprehend sentences containing spatial prepositions, making significantly more errors on these items than control groups. A second study examined in more detail comprehension of sentences with spatial and non-spatial components, comparing the performance of 15 individuals with Williams syndrome and control groups matched for vocabulary ability. Individuals with Williams syndrome again showed impaired comprehension of spoken spatial terms. In contrast, they were unimpaired in comprehending utterances without a spatial component, with the exception of descriptions testing comprehension of non-spatial comparatives (lighter than and darker than). These results suggest that the spatial difficulties experienced by individuals with Williams syndrome may constrain language comprehension in certain circumstances. They also shed light on the ways in which spatial cognition may interact with language comprehension more generally.

Verbal short-term memory in Down syndrome: a problem of memory, audition, or speech?

The current study explored three possible explanations of poor verbal short-term memory performance among individuals with Down syndrome in an attempt to determine whether the condition is associated with a fundamental verbal short-term memory deficit. The short-term memory performance of a group of 19 children and young adults with Down syndrome was contrasted with that of two control groups matched for level of receptive vocabulary. The specificity of a deficit was assessed by comparing memory for verbal and visuo-spatial information. The effect of auditory problems on performance was examined by contrasting memory for auditorily presented material with that for material presented both auditorily and visually. The influence of speech-motor difficulties was investigated by employing both a traditional recall procedure and a serial recognition procedure that reduced spoken response demands. Results confirmed that individuals with Down syndrome do show impaired verbal short-term memory performance for their level of receptive vocabulary. The findings also indicated that this deficit is specific to memory for verbal information and is not primarily caused by auditory or speech-production difficulties.

Field longevity of a fluorescent protein marker in an engineered strain of the pink bollworm, Pectinophora gossypiella (Saunders).

The cotton pest, pink bollworm (Pectinophora gossypiella (Saunders)), is a significant pest in most cotton-growing areas around the world. In southwestern USA and northern Mexico, pink bollworm is the target of the sterile insect technique (SIT), which relies on the mass-release of sterile pink bollworm adults to over-flood the wild population and thereby reduce it over time. Sterile moths reared for release are currently marked with a dye provided in their larval diet. There are concerns, however, that this marker fails from time to time, leading to sterile moths being misidentified in monitoring traps as wild moths. This can lead to expensive reactionary releases of sterile moths. We have developed a genetically marked strain that is engineered to express a fluorescent protein, DsRed2, which is easily screened under a specialised microscope. In order to test this marker under field conditions, we placed wild-type and genetically marked moths on traps and placed them in field cages. The moths were then screened, in a double-blind fashion, for DsRed2 fluorescence at regular intervals to determine marker reliability over time. The marker was shown to be robust in very high temperatures and generally proved reliable for a week or longer. More importantly, genotyping of moths on traps by PCR screening of the moths was 100% correct. Our findings indicate that this strain--and fluorescent protein markers in general--could make a valuable contribution to SIT.

Field performance of a genetically engineered strain of pink bollworm.

Pest insects harm crops, livestock and human health, either directly or by acting as vectors of disease. The Sterile Insect Technique (SIT)--mass-release of sterile insects to mate with, and thereby control, their wild counterparts--has been used successfully for decades to control several pest species, including pink bollworm, a lepidopteran pest of cotton. Although it has been suggested that genetic engineering of pest insects provides potential improvements, there is uncertainty regarding its impact on their field performance. Discrimination between released and wild moths caught in monitoring traps is essential for estimating wild population levels. To address concerns about the reliability of current marking methods, we developed a genetically engineered strain of pink bollworm with a heritable fluorescent marker, to improve discrimination of sterile from wild moths. Here, we report the results of field trials showing that this engineered strain performed well under field conditions. Our data show that attributes critical to SIT in the field--ability to find a mate and to initiate copulation, as well as dispersal and persistence in the release area--were comparable between the genetically engineered strain and a standard strain. To our knowledge, these represent the first open-field experiments with a genetically engineered insect. The results described here provide encouragement for the genetic control of insect pests.