Sloth: America\u27s Ironic Structural Vice

Individualism is a popular cultural trope in the United States, often touted for its promotion of industriousness and rejection of laziness. This essay argues that, ironically, America\u27s brand of individualism actually promotes a more fundamental form of the very vice it purports to oppose. To make this case, the essay defines the unique form of individualism in the United States and then retrieves the classical definition of sloth as a vice against charity (not diligence), contrasting Aquinas and Barth with Weber to demonstrate that this peculiarly American individualist impulse undermines civic charity by reaping the benefits of civic relationships while denying any concomitant responsibilities. Identifying this narrative of individualism as a structural vice, the essay proposes structural remedies for reinvigorating civic charity, solidarity, and the common good in the United States

DNA Methylation in Rectal Cancer: Validating Findings of an Epigenome-Wide Association Study

Background: Preliminary studies conducted by our group utilised the Illumina Infinium Human Methylation 450k Beadchip array to perform an epigenome-wide association study (EWAS) of 15 matched rectal tumour (RT) and adjacent mucosa (AM) samples. 176 differentially methylated probes (DMPs) were identified (P<0.00001). RT was also characterised by significantly reduced global methylation in comparison to AM. Aims: This study aimed to validate specific and global DNA methylation differences identified by our preliminary work. We then sought to replicate the findings in additional samples. Finally, we attempted to identify correlations between DNA methylation differences and clinicopathological tumour features. Materials and Methods: Polymerase chain reaction (PCR) and bisulphite pyrosequencing assays were designed and optimised to quantify DNA methylation at nine DMPs nominated by our EWAS. Pearson’s test was used to calculate the correlation between 450k and pyrosequencing methylation values. Replication was performed in an additional cohort of 68 matched colorectal tumour and AM pairs. Global DNA methylation of the discovery cohort was quantified using the luminometric methylation assay (LUMA). Potential relationships between tumour features and differential methylation were investigated using univariate (t-tests or ANOVA) and multivariate analyses (logistic regression). Results: All DMPs selected for validation showed strong correlations between bisulphite pyrosequencing and Illumina 450k methylation values (r= 0.87-0.97). Global hypomethylation was observed in RT (54.6%) when compared to AM (63.5%, P = 0.021). All probes displayed significant levels of differential methylation in the replication cohort (P = <2.2e-16). No significant associations were observed between DNA methylation and clinicopathological tumour features, however this may reflect the relatively small number of samples assessed. Conclusions: Our studies have identified and validated a novel methylomic signature of rectal cancer. Although no clinicopathological correlations were observed with the DMPs investigated, others may represent potential targets in the diagnosis, monitoring and risk stratification of rectal cancer.Northcott Medical FoundationThe Wolfson FoundationThe Royal College of Surgeons of EnglandBowel Cancer Wes

Fundamental Limitations of Cavity-assisted Atom Interferometry

Atom interferometers employing optical cavities to enhance the beam splitter pulses promise significant advances in science and technology, notably for future gravitational wave detectors. Long cavities, on the scale of hundreds of meters, have been proposed in experiments aiming to observe gravitational waves with frequencies below 1 Hz, where laser interferometers, such as LIGO, have poor sensitivity. Alternatively, short cavities have also been proposed for enhancing the sensitivity of more portable atom interferometers. We explore the fundamental limitations of two-mirror cavities for atomic beam splitting, and establish upper bounds on the temperature of the atomic ensemble as a function of cavity length and three design parameters: the cavity g-factor, the bandwidth, and the optical suppression factor of the first and second order spatial modes. A lower bound to the cavity bandwidth is found which avoids elongation of the interaction time and maximizes power enhancement. An upper limit to cavity length is found for symmetric two-mirror cavities, restricting the practicality of long baseline detectors. For shorter cavities, an upper limit on the beam size was derived from the geometrical stability of the cavity. These findings aim to aid the design of current and future cavity-assisted atom interferometers.Comment: 11 pages, 12 figure

Analyzing the Attitudes, Beliefs, and Practices of Breastfeeding Women at Maternity Care Coalition

Introduction: Breastfeeding is essential for health and bonding within the mother-child dyad. Most guidelines, therefore, suggest women continue breastfeeding up to twelve months post-partum. Discrepancies in achieving this exist across zip codes and race in Philadelphia, despite high overall rates of breastfeeding. Our research goal is to understand these discrepancies and the relationship between attitudes and practices of breastfeeding Philadelphian women, in order to target them with breastfeeding resource. Methods: General population data was collected via an online survey taken by residents of Philadelphia and the surrounding counties, whereas the focus group survey was taken in-person by Maternity Care Coalition (MCC) clients. Demographic information was recorded. Both surveys addressed women’s attitudes towards breastfeeding; the focus group survey also included breastfeeding practices and resource preferences. SPSS was used for data analysis. Results: Initial findings from the general population survey show positive to strongly positive attitudes toward breastfeeding. Participants reported a positive attitude toward public breastfeeding. Most participants believed that formula and breastmilk are not equally good. Data analysis is pending regarding significant differences in breastfeeding attitudes by zip code and race, as is focus group survey analysis regarding preferred breastfeeding resources. Conclusion: Because the results of the general population data demonstrate prevailingly positive attitudes toward breastfeeding, the resource developed by the Breastfeeding Taskforce at MCC will likely address disparities in breastfeeding rates among racial groups and zip code by engaging with barriers to initiating and sustaining breastfeeding, as opposed to addressing public perception. Future research includes evaluating the proposed resource’s success

Readily accessible sp3-rich cyclic hydrazine frameworks exploiting nitrogen fluxionality

Increased molecular complexity correlates with improved chances of success in the drug development process. Here, a strategy for the creation of sp3-rich, non-planar heterocyclic scaffolds suitable for drug discovery is described that obviates the need to generate multiple stereogenic centers with independent control. Asymmetric transfer hydrogenation using a tethered Ru-catalyst is used to efficiently produce a range of enantiopure cyclic hydrazine building blocks (up to 99% ee). Iterative C–N functionalization at the two nitrogen atoms of these compounds produces novel hydrazine and hydrazide based chemical libraries. Wide chemical diversification is possible through variation in the hydrazine structure, use of different functionalization chemistries and coupling partners, and controlled engagement of each nitrogen of the hydrazine in turn. Principal Moment of Inertia (PMI) analysis of this small hydrazine library reveals excellent shape diversity and three-dimensionality. NMR and crystallographic studies confirm these frameworks prefer to orient their substituents in three-dimensional space under the control of a single stereogenic center through exploitation of the fluxional behavior of the two nitrogen atoms

Program Management Versus Portfolio Management in Defense Acquisition

Excerpt from the Proceedings of the Nineteenth Annual Acquisition Research SymposiumThis research performed a gap analysis on the existing Department of Defense (DoD) program management competency standards to determine if changes are required to fully adopt product portfolio management (PPM) strategies in defense acquisition. Current DoD program management standards are compared to the Project Management Institute’s Portfolio Management Professional certification standards to analyze alignment and gaps between the standards. Barrier to Implementation (BTI) scores are assigned to address the identified gaps in the DoD standard. The study found that the DoD program management competencies are on average 41% aligned with portfolio management industry standards. The DoD program management competencies are least aligned with the portfolio management domains of governance and strategic alignment. The composite BTI score indicates low to medium level of implementation barriers for most of the gaps. Results indicate that the DoD is capable of conducting PPM, and further research is needed to fully align the current competency standards with industry best practices. Defense acquisition senior leaders should consider formulating DoD portfolio management career field functional competencies to address congressional mandates for portfolio management implementation within the DoD.Approved for public release; distribution is unlimited

Program Management versus Portfolio Management in Defense Acquisition

Symposium PresentationApproved for public release; distribution is unlimited

Development of an evidence-based regimen of prednisolone to treat giant cell arteritis - the Norwich regimen

We have reviewed the literature to form a bespoke regimen for daily oral prednisolone (DP) in GCA. Initial DP in clinical trials is 40-60 mg daily, but relapse rates are 67-92%. Cumulative prednisolone (CP) of 3.2 and 3.9 g (at 6 months) resulted in a relapse rate of 83 and 67%, respectively; and 3 and 3.9 g (at 12 months) resulted in 92 and 82% relapse, respectively. CP was 6.2-7.1 g in the first year. Mean DP was 18.8 mg at 3 months and 6.6-7.4 mg at 12 months. The duration of treatment with prednisolone for GCA was 22-26 months. The CP to achieve discontinuation was 6.5-12.1 g. Using these data, the Norwich regimen starts DP at 1 mg/kg/day of lean body mass, discontinuing over 100 weeks. For the average UK woman, initial DP is 45 mg daily, reaching 21 mg daily by 12 weeks and 6 mg daily by 52 weeks. The CP for the average UK woman would be 6.5 g at 52 weeks and 7.4 g to discontinuation

Program Management versus Portfolio Management in Defense Acquisition

Program Management / Faculty ReportAcquisition Research Program Sponsored Report SeriesSponsored Acquisition Research & Technical ReportsThis research performed a gap analysis on the existing Department of Defense (DoD) program management competency standards to determine if changes are required to fully adopt product portfolio management (PPM) strategies in defense acquisition. Current DoD program management standards are compared to the Project Management Institute's Portfolio Management Professional certification standards to analyze alignment and gaps between the standards. Barrier to Implementation (BTI) scores are assigned to address the identified gaps in the DoD standard. The study found that the DoD program management competencies are on average 41% aligned with portfolio management industry standards. The DoD program management competencies are least aligned with the portfolio management domains of governance and strategic alignment. The composite BTI score indicates low to medium level of implementation barriers for most of the gaps. Results indicate that the DoD is capable of conducting PPM, and further research is needed to fully align the current competency standards with industry best practices. Defense acquisition senior leaders should consider formulating DoD portfolio management career field functional competencies to address congressional mandates for portfolio management implementation within the DoD.Approved for public release; distribution is unlimited