A Framework for Clinical Validation of Automatic Contour Propagation: Standardizing Geometric and Dosimetric Evaluation

PurposeThe objective of this work was to outline and demonstrate a standardized framework for evaluating automatically propagated contour quality against expert contours. A 2-pronged approach is used to evaluate contour quality: a geometric evaluation to identify geometric and spatial discrepancies between propagated and expert contours, and a comprehensive dosimetric comparison to provide clinical context for the results.Methods and MaterialsThe standardized framework requires a primary image, with reference contours and a radiation therapy treatment plan, and a secondary image. Reference contours are automatically propagated onto the secondary image anatomy and compared with expert contours obtained in an interobserver study. The standardized framework outlines geometric and dosimetric evaluation methodologies for determining indistinguishability between propagated and expert contours in a cohort analysis. Propagated contours are geometrically compared with expert contours in terms of the Dice similarity coefficient and the mean distance to agreement. Statistical analysis is performed on the central tendency and variability of Dice similarity coefficient and mean distance to agreement values over the patient cohort. Dosimetric evaluation involves computing the mean and 95% confidence intervals for the differences in cumulative dose-volume histograms for propagated and expert contours. A case study in accelerated partial breast irradiation was shown to demonstrate the framework.ResultsThe standardized framework was applied to a case study of 24 patient data sets with 3 radiation oncologists providing the expert contours. Cohort analysis indicated that propagated contours were geometrically indistinguishable and dosimetrically distinguishable from expert contours.ConclusionsThe recommended framework standardizes the comparison of geometric and dosimetric parameters to demonstrate indistinguishability of propagated contours from expert contours. Adoption of this framework is vital for consistent and comprehensive validation of automatic contour propagation for use in large-scale cohort analyses.     

Smoking-attributable mortality in Bangladesh: proportional mortality study

Objective

To directly estimate how much smoking contributes to cause-specific mortality in Bangladesh.

Methods

A case–control study was conducted with surveillance data from Matlab, a rural subdistrict. Cases (n = 2213) and controls (n = 261) were men aged 25 to 69 years who had died between 2003 and 2010 from smoking-related and non-smoking-related causes, respectively. Cause-specific odds ratios (ORs) were calculated for “ever-smokers” versus “never-smokers”, with adjustment for education, tobacco chewing status and age. Smoking-attributable deaths among cases, national attributable fractions and cumulative probability of surviving from 25 to 69 years of age among ever-smokers and never-smokers were also calculated.

Findings

The fraction of ever-smokers was about 84% among cases and 73% among controls (OR: 1.7; 99% confidence interval, CI: 1.1–2.5). ORs were highest for cancers and lower for respiratory, vascular and other diseases. A dose–response relationship was noted between age at smoking initiation and daily number of cigarettes or bidis smoked and the risk of death. Among 25-year-old Bangladeshi men, 32% of ever-smokers will die before reaching 70 years of age, compared with 19% of never-smokers. In 2010, about 25% of all deaths observed in Bangladeshi men aged 25 to 69 years (i.e. 42 000 deaths) were attributable to smoking.

Conclusion

Smoking causes about 25% of all deaths in Bangladeshi men aged 25 to 69 years and an average loss of seven years of life per smoker. Without a substantial increase in smoking cessation rates, which are low among Bangladeshi men, smoking-attributable deaths in Bangladesh are likely to increase.     

Effect of omega-3 fatty acid supplementation on resolvin (RvE1)-mediated suppression of inflammation in a mouse model of asthma

Objective: ResolvinE1 (RvE1), an endogenous lipid mediator derived from omega 3 fatty acids contributes to resolution of allergic inflammatory responses. We investigated effects of RvE1 (R) and omega 3 fatty acids (O) on airway reactivity and inflammation using allergic mice.

Methods: Mice were divided into control (nonasthmatic; CON) and allergen sensitized-challenged (asthmatic; SEN) groups, and were sensitized i.p. on days 1, 6 with 0.2?μg ovalbumin (OVA) followed by 5% OVA aerosol challenges on days 11–13. RvE1 was administered i.p. postallergen challenge, while omega 3 fatty acids (fish oil) were administered via oral gavage once daily (days 1–13). Whole body plethysmography and bronchoalveolar lavage (BAL) studies were performed on day 14.

Results: RvE1 attenuated airway responsiveness to methacholine (48?mg/ml) in treated asthmatic mice vs. nontreated (150?±?27.88% in SEN vs. 54?±?7.52% in SEN?+?R, p?<?.05). No difference was observed with omega-3 supplementation (115?±?19.28% in SEN?+?O) or treatment with both RvE1 and omega 3 fatty acids (39?±?12.37% in SEN?+?R?+?O vs. 54?±?7.52% in SEN?+?R). Differential BAL cell analysis showed that RvE1 decreased eosinophils and neutrophils in SEN mice (p?<?.005) while no difference was observed with omega-3 fatty acids. SEN?+?R?+?O group had similar results as RvE1 treated mice, suggesting that only RvE1 attenuated inflammation.

Conclusions: RvE1 attenuated airway responsiveness and inflammation in asthmatic mice. Omega-3 fatty acids, although a precursor for RvE1 formation, had no additive effects on RvE1 decreases in airway inflammation and airway reactivity. Our data suggests that omega-3 supplementation has little effect on airway inflammation and reactivity in our model of asthma.     

What impact does antenatal and postnatal care have on neonatal deaths in low- and lower-middle-income countries? Evidence from Bangladesh

We investigated the contribution of antenatal and postnatal care in reducing the risk of neonatal deaths in Bangladesh. The effects of these services were examined using adjusted Cox regression models and secondary data with 7,314 live-born infants. We observed that neonatal mortality was significantly decreased for newborns whose mothers' attended antenatal care services but postnatal care did not show any effect. Health promotion programs offering antenatal care in Bangladesh and other low- and lower-middle-income countries may build awareness about these practices. Further research is required to examine the reasons for the lack of impact of postnatal care on mortality.     

Prevalence of CSOM among rural school going children

A prospective study was carried out from January 2001 to December 2002 to find the prevalence of CSOM among rural school going children. Altogether 225 students aged 4-13 years from five primary schools and junior high schools of Magura district were interviewed and examined. 28 (12.44%) children were found to have CSOM. Out of these 28 cases, 25 came from lower and 3 from middle income group families. No case of CSOM was found in higher income group family. In this study 73.33% mothers were not aware of CSOM. 60% mothers had no knowledge about treatment and sequelae of CSOM. Only (5.78%) people use cotton bud to clean ear while majority use unhygienic materials like matchstick, cloth with stick and chicken feathers. Treatment seeking pattern was observed in our study. 10.71% cases did not receive any treatment and remaining 89.29% received treatment of which 25% from MBBS doctor or Hospital and 7.14%, 35.71%, 10.71%, 10.71% received it from Kabiraj, Quack, Homeopathy doctor, and salesman of pharmacy respectively.     

Biscoumarin–pyrimidine conjugates as potent anticancer agents and binding mechanism of hit candidate with human serum albumin

In our continuing efforts to develop therapeutically active coumarin‐based compounds, a series of new C4–C4′ biscoumarin–pyrimidine conjugates ( 1a–l ) was synthesized via S_N2 reaction of substituted 4‐bromomethyl coumarin with thymine. All compounds were characterized using spectroscopic techniques, that is, attenuated total reflection infrared (ATR‐IR), CHN elemental analysis, and ¹H and ¹³C NMR (nuclear magnetic resonance). In addition, the structure of compound 1d (1,3‐bis[(7‐chloro‐2‐oxo‐2H‐chromen‐4‐yl)methyl]‐5‐methylpyrimidine‐2,4(1H,3H)‐dione) was established through X‐ray crystallography. Compounds 1a–l were screened for in vitro anticancer activity against C6 rat glioma cells. Among the screened compounds, 1,3‐bis[(6‐chloro‐2‐oxo‐2H‐chromen‐4‐yl)methyl]‐5‐methylpyrimidine‐2,4(1H,3H)‐dione ( 1c ) was identified as the best antiproliferative candidate, exhibiting an IC₅₀ value of 4.85 μM. All the compounds ( 1a – l ) were found to be nontoxic toward healthy human embryonic kidney cells (HEK293), indicating their selective nature. In addition, the most active compound ( 1c ) displayed strong binding interactions with the drug carrier protein, human serum albumin, and exhibited good solution stability at biological pH conditions. Fluorescence, UV–visible spectrophotometry and molecular modeling methodologies were employed for studying the interaction mechanism of compound 1c with protein.