Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX® Colon Cancer Assay

<p>Abstract</p> <p>Background</p> <p>The Onco<it>type </it>DX^®Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Onco<it>type </it>DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Onco<it>type </it>DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation.</p> <p>Results</p> <p>All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log₂concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 C_Ts), gene groups (≤0.05 normalized/aggregate C_Ts) and RS (≤1.38 RS units).</p> <p>Conclusions</p> <p>Analytical performance characteristics shown here for both individual genes and gene groups in the Onco<it>type </it>DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Onco<it>type </it>DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.</p

Neglected bodily senses in women living with vertebral fracture: a focus group study

ObjectiveOlder women are at particular risk of osteoporosis. Among women with osteoporosis, fractures of the vertebra (vertebral fracture) are common, hard to detect and associated with risk of further fracture. Identifying vertebral fracture in a timely manner allows instigation of preventive measures to reduce the risk of further fracture. Although detection of vertebral fracture requires spinal radiograph, many women do not receive referral. To begin development of a screening tool to identify women in need of referral we undertook a qualitative study to characterize women’s experiences of vertebral fracture, using Eccleston’s ‘Ten Neglected Bodily Senses’.MethodsFour qualitative focus groups were conducted with women who had been diagnosed with vertebral fracture (n = 19, age 60–91 years). Data were audio-recorded, transcribed and analysed thematically using the ‘Ten Neglected Bodily Senses’.ResultsWomen’s experiences of vertebral fractures related to seven senses: pain, movement, fatigue, balance, pressure, appetite and breathing. Pain was the dominant sense and all participants explained how pain increased with activity, reaching a crescendo, and described strategies to minimize this disruption. Most participants had become physically shorter, making some feel ‘squashed’, putting pressure on other body parts. Some described appetite loss or a sense of restricted breathing. Participants experienced a sense of being ‘pulled’ forwards, impacting on balance and exacerbating fear of falling.ConclusionThe study found senses that have not been previously described in the experiences of women with vertebral fracture. These will be used to inform the design of a new screening tool for use in primary care

Do program practices matter for mentors?: How implementation of empirically supported program practices is associated with youth mentoring relationship quality

This study investigates how the implementation of program-level practices by formal youth mentoring programs is associated with the quality of youth mentoring relationships as contexts for youth development and also examines whether this connection is mediated by the mentor-staff working alliance. Using data from mentors (n = 542) participating in multiple programs (n = 55), multilevel path models examined hypothesized direct and mediated effects. Parallel analyses were conducted with assessments of program practices from staff (n = 219). Greater exposure to program practices was associated with higher ratings of mentoring relationship satisfaction, commitment, and security and lower mentor-youth relationship negativity. The mentor-staff working alliance either partially or fully mediated these associations. Staff-reported practices predicted mentoring relationship satisfaction and commitment without mediation by the working alliance. This study suggests program practices contribute to stronger youth mentoring relationships. The findings also highlight the mentor-staff working alliance in supporting the development of positive mentoring relationships

Long-term drought sensitivity of trees in second-growth forests in a humid region

Classical field methods of reconstructing drought using tree rings in humid, temperate regions typically target old trees from drought-prone sites. This approach limits investigators to a handful of species and excludes large amounts of data that might be useful, especially for coverage gaps in large-scale networks. By sampling in more “typical” forests, network density and species diversity would increase in ways that could potentially improve reconstructions. Ten nonclassical tree-ring chronologies derived from randomly selected trees, trees from logged forests, or both were compared to more classical chronologies and an independent regional drought reconstruction to determine their usefulness for dendrohydroclimatic research. We find that nonclassical chronologies are significantly correlated to classical chronologies and reconstructed drought over the last 2–3 centuries. While nonclassical chronologies have spectral properties similar to those from classical dendroclimatic collections, they do lack spectral power at lower frequencies that are present in the drought reconstruction. Importantly, our results show that tree growth is strongly dependent on moisture availability, even for small, randomly selected trees in cut forests. These results indicate that there could be more data available in areas with few current tree-ring collections for studying climate history and that drought plays an important role in humid forests

The VLT-FLAMES Tarantula Survey XV. VFTS 822: A candidate Herbig B[e] star at low metallicity

We report the discovery of the B[e] star VFTS 822 in the 30 Doradus star-forming region of the Large Magellanic Cloud, classified by optical spectroscopy from the VLT-FLAMES Tarantula Survey and complementary infrared photometry. VFTS 822 is a relatively low-luminosity (log L = 4.04 ± 0.25 L⊙) B8[e] star. In this Letter, we evaluate the evolutionary status of VFTS 822 and discuss its candidacy as a Herbig B[e] star. If the object is indeed in the pre-main sequence phase, it would present an exciting opportunity to spectroscopically measure mass accretion rates at low metallicity, to probe the effect of metallicity on accretion rates

Examining how changes in provincial policy on vape marketing impacted the distribution of vaping advertisements near secondary schools in London, Ontario

Objectives: On January 1, 2020, the Government of Ontario passed a regulation banning vaping advertisements by retailers, apart from specialty shops. A motivation for this ban was to limit youth exposure to vaping advertisements. The primary goal of this research was to evaluate the impact of this ban on the number and density of vaping advertisements surrounding secondary schools. Additionally, we examined whether the number of vaping advertisements varied by school socio-demographic characteristics. Methods: This study used a pre-post design. Audits were conducted December 2019 (pre-ban) and again January to February 2020 (post-ban), to identify vaping advertisements within 800 m surrounding secondary schools (n = 18) in London, Ontario. Results: Prior to the ban, there were 266 vaping advertisements within 800 m of secondary schools. After the ban, this was reduced to 58, a 78.2% reduction. The mean number of vaping advertisements surrounding schools significantly decreased from 18.1 before the ban to 3.6 after the ban (p \u3c 0.001). A significant positive correlation was found, prior to the ban, between the number of vaping advertisements surrounding schools and school-level residential instability (r = 0.42, p = 0.02). After the ban, no significant correlations were found between the number of vaping advertisements and school socio-demographic characteristics. Conclusion: The provincial ban of vaping advertisements in select retail settings significantly reduced the number of vaping advertisements in the areas surrounding secondary schools in London, Ontario. The ban also reduced socio-demographic inequities in youths’ potential exposure to marketing of vaping products. Continued monitoring of the geographic accessibility and promotion of vaping products is warranted

The effects of hibernation on the contractile and biochemical properties of skeletal muscles in the thirteen-lined ground squirrel, Ictidomys tridecemlineatus

Hibernation is a crucial strategy of winter survival used by many mammals. During hibernation, thirteen-lined ground squirrels, Ictidomys tridecemlineatus, cycle through a series of torpor bouts, each lasting more than a week, during which the animals are largely immobile. Previous hibernation studies have demonstrated that such natural models of skeletal muscle disuse cause limited or no change in either skeletal muscle size or contractile performance. However, work loop analysis of skeletal muscle, which provides a realistic assessment of in vivo power output, has not previously been undertaken in mammals that undergo prolonged torpor during hibernation. In the present study, our aim was to assess the effects of 3 months of hibernation on contractile performance (using the work loop technique) and several biochemical properties that may affect performance. There was no significant difference in soleus muscle power output-cycle frequency curves between winter (torpid) and summer (active) animals. Total antioxidant capacity of gastrocnemius muscle was 156% higher in torpid than in summer animals, suggesting one potential mechanism for maintenance of acute muscle performance. Soleus muscle fatigue resistance was significantly lower in torpid than in summer animals. Gastrocnemius muscle glycogen content was unchanged. However, state 3 and state 4 mitochondrial respiration rates were significantly suppressed, by 59% and 44%, respectively, in mixed hindlimb skeletal muscle from torpid animals compared with summer controls. These findings in hindlimb skeletal muscles suggest that, although maximal contractile power output is maintained in torpor, there is both suppression of ATP production capacity and reduced fatigue resistance