Regulating Advertisements: The Case of Smoking Cessation Products

In this paper we investigate how direct-to-consumer (DTC) advertising of pharmaceutical products in affected by regulations of the Food and Drug Administration and by market conditions. We focus on a relatively under-studied segment of the pharmaceutical market -- the market for smoking cessation products. Because of their proven effectiveness, these products could be the key to meeting public health goals to reduce smoking. However, in many ways, smoking cessation products have been more heavily regulated than cigarettes. Our empirical analysis uses data on advertising expenditures and data from an archive of print advertisements. The archive includes all smoking cessation product advertisements that appeared in over 13,000 issues of 28 magazines between January 1985 and May 2002. Our study period begins shortly atfer the first nicotine replacement product was introduced, and covers the evolution of the market as new products are introduced while some of the older products move from prescription to over-the-counter (OTC) status. OTC status eases the disclosure requirements imposed on advertisements of prescription pharmaceuticals, substantially reducing the costs of a print advertisement. Our results suggest that OTC status is associated with an increase in advertising expenditures and the number and pages of magazine advertisements. A current proposal to reduce disclosure requirements on all DTC advertisements of prescription drugs could have similar effects. Our results also suggest that advertising increase with the introduction of new products and with market competition.

Automated analysis of lymphocytic infiltration, tumor budding, and their spatial relationship improves prognostic accuracy in colorectal cancer

Funding: Medical Research Scotland, and Indica Labs, Inc. provided in-kind resource.Both immune profiling and tumor budding significantly correlate with colorectal cancer (CRC) patient outcome, but are traditionally reported independently. This study evaluated the association and interaction between lymphocytic infiltration and tumor budding, coregistered on a single slide, in order to determine a more precise prognostic algorithm for patients with stage II CRC. Multiplexed immunofluorescence and automated image analysis were used for the quantification of CD3+CD8+ T cells, and tumor buds (TBs), across whole slide images of three independent cohorts (training cohort: n = 114, validation cohort 1: n = 56, validation cohort 2: n = 62). Machine learning algorithms were used for feature selection and prognostic risk model development. High numbers of TBs (HR = 5.899, 95% CI, 1.875 - 18.55), low CD3+ 11 T cell density (HR = 9.964, 95% CI 3.156 - 31.46), and low mean number of CD3+CD8+ T cells within 50 μm of TBs (HR = 8.907, 95% CI 2.834 - 28.0) were associated with reduced disease-specific survival. A prognostic signature, derived from integrating TBs, lymphocyte infiltration, and their spatial relationship, reported a more significant cohort stratification (HR = 18.75, 95% CI 6.46–54.43), than TBs, Immunoscore, or pT stage. This was confirmed in two independent validation cohorts (HR = 12.27, 95% CI 3.524–42.73, HR = 15.61, 95% CI 4.692-51.91). The investigation of the spatial relationship between lymphocytes and TBs within the tumor microenvironment improves accuracy of prognosis of patients with stage II CRC through an automated image analysis and machine learning workflow.PostprintPeer reviewe

Automated detection and classification of desmoplastic reaction at the colorectal tumour front using deep learning

Funding: This study was funded by Medical Research Scotland, the Japan Society for the Promotion of Science, the British Council and Indica Labs, Inc. who also provided in kind resource.The categorisation of desmoplastic reaction (DR) present at the colorectal cancer (CRC) invasive front into mature, intermediate or immature type has been previously shown to have high prognostic significance. However, the lack of an objective and reproducible assessment methodology for the assessment of DR has been a major hurdle to its clinical translation. In this study, a deep learning algorithm was trained to automatically classify immature DR on haematoxylin and eosin digitised slides of stage II and III CRC cases (n = 41). When assessing the classifier’s performance on a test set of patient samples (n = 40), a Dice score of 0.87 for the segmentation of myxoid stroma was reported. The classifier was then applied to the full cohort of 528 stage II and III CRC cases, which was then divided into a training (n = 396) and a test set (n = 132). Automatically classed DR was shown to have superior prognostic significance over the manually classed DR in both the training and test cohorts. The findings demonstrated that deep learning algorithms could be applied to assist pathologists in the detection and classification of DR in CRC in an objective, standardised and reproducible manner.Publisher PDFPeer reviewe

Are there asymmetries in the effects of training on the conditional male wage distribution?

Recent studies have used quantile regression (QR) techniques to estimate the impact of education on the location, scale and shape of the conditional wage distribution. In our paper we investigate the degree to which work-related training – another important form of human capital – affects the location, scale and shape of the conditional wage distribution. Using the first six waves of the European Community Household Panel, we utilise both ordinary least squares and QR techniques to estimate associations between work-related training and wages for private sector men in ten European Union countries. Our results show that, for the majority of countries, there is a fairly uniform association between training and hourly wages across the conditional wage distribution. However, there are considerable differences across countries in mean associations between training and wages

Experimental Investigation of Project Orion Crew Exploration Vehicle Aeroheating in AEDC Tunnel 9

An investigation of the aeroheating environment of the Project Orion Crew Entry Vehicle has been performed in the Arnold Engineering Development Center Tunnel 9. The goals of this test were to measure turbulent heating augmentation levels on the heat shield and to obtain high-fidelity heating data for assessment of computational fluid dynamics methods. Laminar and turbulent predictions were generated for all wind tunnel test conditions and comparisons were performed with the data for the purpose of helping to define uncertainty margins for the computational method. Data from both the wind tunnel test and the computational study are presented herein

Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy

Postpartum depression (PPD) affects up to 19% of women, negatively impacting maternal and infant health. Reductions in plasma oxytocin levels have been associated with PPD and heritability studies have established a genetic contribution. Epigenetic regulation of the oxytocin receptor gene (OXTR) has been demonstrated and we hypothesized that individual epigenetic variability at OXTR may impact the development of PPD and that such variability may be central to predicting risk. This case-control study is nested within the Avon Longitudinal Study of Parents and Children and included 269 cases with PPD and 276 controls matched on age group, parity, and presence or absence of depressive symptoms in pregnancy as assessed by the Edinburgh Postnatal Depression Scale. OXTR DNA methylation (CpG site -934) and genotype (rs53576 and rs2254298) were assayed from DNA extracted from blood collected during pregnancy. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of elevated symptoms of PPD with genotype, methylation, and their interaction adjusted for psychosocial factors (n=500). There was evidence of an interaction between rs53576 and methylation in the OXTR gene amongst women who did not have depression prenatally but developed PPD (p interaction=0.026, adjusted for covariates, n=257). Those women with GG genotype showed 2.63 greater odds of PPD for every 10% increase in methylation level (95% CI: 1.37, 5.03), whereas methylation was unrelated to PPD amongst A carriers (OR=1.00, 95%CI: 0.58, 1.73). There was no such interaction among women with PPD and prenatal depression. These data indicate that epigenetic variation that decreases expression of OXTR in a susceptible genotype may play a contributory role in the etiology of postpartum depression

Making sense of social pretense: The effect of the dyad, sex and language ability in a large observational study of children’s behaviors in a social pretend play context

Pretend play with peers is purportedly an important driver of social development in the preschool period, however, fundamental questions regarding the features of children’s pretend play with a peer, and the effect of the dyad for pretend play, have been overlooked. The current study undertook detailed behavioral coding of social pretend play in 134 pairs of 5-year-old children (54% boys) in order to address three main aims: (i) describe the duration and proportion of children engaging in key social pretend play behaviors, namely, calls for attention, negotiation (comprising role assignment and joint proposals) and enactment of pretend play, (ii) examine the effect of the dyad in influencing the occurrence of different social pretend play behaviors, and (iii) assess the independent and combined effect of individual child characteristics (i.e., language ability and sex) that may influence social pretend play behaviors beyond the influence of the dyad. Results demonstrated the overwhelming effect of the dyad in shaping children’s social pretend play behaviors, with language ability and sex explaining relatively little of the total variability in play behaviors. Results are discussed considering the contribution that this type of study can make to theories of associations between children’s social development and social pretend play.LEGO Foundatio

Aeroheating Testing and Predictions for Project Orion CEV at Turbulent Conditions

An investigation of the aeroheating environment of the Project Orion Crew Exploration Vehicle was performed in the Arnold Engineering Development Center Hypervelocity Wind Tunnel No. 9 Mach 8 and Mach 10 nozzles and in the NASA Langley Research Center 20 - Inch Mach 6 Air Tunnel. Heating data were obtained using a thermocouple-instrumented approx.0.035-scale model (0.1778-m/7-inch diameter) of the flight vehicle. Runs were performed in the Tunnel 9 Mach 10 nozzle at free stream unit Reynolds numbers of 1x10(exp 6)/ft to 20x10(exp 6)/ft, in the Tunnel 9 Mach 8 nozzle at free stream unit Reynolds numbers of 8 x 10(exp 6)/ft to 48x10(exp 6)/ft, and in the 20-Inch Mach 6 Air Tunnel at free stream unit Reynolds numbers of 1x10(exp 6)/ft to 7x10(exp 6)/ft. In both facilities, enthalpy levels were low and the test gas (N2 in Tunnel 9 and air in the 20-Inch Mach 6) behaved as a perfect-gas. These test conditions produced laminar, transitional and turbulent data in the Tunnel 9 Mach 10 nozzle, transitional and turbulent data in the Tunnel 9 Mach 8 nozzle, and laminar and transitional data in the 20- Inch Mach 6 Air Tunnel. Laminar and turbulent predictions were generated for all wind tunnel test conditions and comparisons were performed with the experimental data to help define the accuracy of computational method. In general, it was found that both laminar data and predictions, and turbulent data and predictions, agreed to within less than the estimated 12% experimental uncertainty estimate. Laminar heating distributions from all three data sets were shown to correlate well and demonstrated Reynolds numbers independence when expressed in terms of the Stanton number based on adiabatic wall-recovery enthalpy. Transition onset locations on the leeside centerline were determined from the data and correlated in terms of boundary-layer parameters. Finally turbulent heating augmentation ratios were determined for several body-point locations and correlated in terms of the boundary-layer momentum Reynolds number

Diamond-like carbon produced by plasma source ion implantation as a corrosion barrier

There currently exists a broad range of applications for which the ability to produce an adherent, hard, wear and, corrosion-resistant coating plays a vital role. These applications include engine components, orthopedic devices, textile manufacturing components, hard disk media, optical coatings, and cutting and machining tools (e.g., punches, taps, scoring dies, and extrusion dies). Ion beam processing can play an important role in all of these technologies. Plasma source ion implantation (PSII) is an emerging technology which has the potential to overcome the limitations of conventional ion implantation by: (1) reducing the time and expense for implanting onto complex shapes and large areas and (2) extending the thickness of the modification zone through ion beam enhanced plasma growth of surface coatings. In PSII, targets are placed directly in a plasma source and then pulse biased to produce a non-line-of-sight process for complex-shaped targets without complex fixturing. If the pulse bias is a relatively high negative potential (20 to 100 kV) ion implantation will result. If however, a low voltage (50--1,200 eV) high duty cycle pulse bias is applied, film deposition from the chamber gas will result, thereby increasing the extent of the surface modification into the 1--10 micron regime. To evaluate the potential for DLC to be used as a corrosion barrier, Electrochemical Impedance Spectroscopy (EIS) and traditional electrochemistry techniques were used to investigate the breakdown mechanism in chloride and nonchloride containing environments. The effect of surface preparation on coating breakdown was also evaluated