A new double coronary artery anomaly: The right coronary artery originating above the coronary sinus giving off the circumflex artery

This is the first reported case of a coronary artery anomaly in which the right coronary artery originates above the left sinus of Valsalva and also gives off the circumflex system. Use of the aortogram and careful inspection of the ventriculogram in the right anterior oblique view were most helpful in recognizing the anomaly. The potential pathologic significance of the anomaly and pitfalls of misdiagnosis are discussed

Images of survival, stories of destruction: Nuclear war on British screens from 1945 to the early 1960s

This article discusses a range of depictions and discussions of nuclear war, which appeared on British screens in the first half of the Cold War, in order to understand the changing way nuclear weapons were viewed within British culture. Using such screened images to understand how nuclear war was constructed and represented within British culture, the article argues that the hydrogen bomb, not the atomic bomb, was the true harbinger of the nuclear revolution that transformed cultural understandings of warfare and destruction. Although the atomic bomb created a great deal of anxiety within British popular culture, representations of atomic attack elided atomic destruction with that experienced in 1939-45, emphasising the 'survivability' of atomic war. In the thermonuclear era, the Second World War could not undertake the same symbolic work. The image of the city-destroying bomb was an imaginative as well as technological step-change. Screened representations stressed that a thermonuclear war would literally end the world. As such, they preceded, and indeed provided the cultural climate for, the rise of the Campaign for Nuclear Disarmament (CND). The Campaign exploited and further popularised this idea of the apocalyptic nuclear war as a key aspect of its political and moral standpoint. The article concludes, however, that the cultural hegemony of this vision of nuclear war equally helped underpin notions of nuclear deterrence. The basic assumptions about the nature of nuclear war constructed and circulated on British screens therefore formed part of CND's 'cultural' victory but the article also explains why this did not translate into the political realm. © Edinburgh University Press

Multiplex Cytological Profiling Assay to Measure Diverse Cellular States

Computational methods for image-based profiling are under active development, but their success hinges on assays that can capture a wide range of phenotypes. We have developed a multiplex cytological profiling assay that “paints the cell” with as many fluorescent markers as possible without compromising our ability to extract rich, quantitative profiles in high throughput. The assay detects seven major cellular components. In a pilot screen of bioactive compounds, the assay detected a range of cellular phenotypes and it clustered compounds with similar annotated protein targets or chemical structure based on cytological profiles. The results demonstrate that the assay captures subtle patterns in the combination of morphological labels, thereby detecting the effects of chemical compounds even though their targets are not stained directly. This image-based assay provides an unbiased approach to characterize compound- and disease-associated cell states to support future probe discovery

Atheisms and the purification of faith

Philosophers of religion have distinguished between ‘negative’ and ‘positive’ atheism. This article considers further conceptions of atheism, especially the idea that atheism can facilitate a faith in God purified of idolatrous assumptions. After introducing Bultmann’s contention that a ‘conscious atheist’ can find something transcendent in the world, this contention is interpreted through reflection on Ricoeur’s claim that the atheisms of Nietzsche and Freud serve to mediate a transition to a purified faith – a faith involving heightened receptivity to agapeic love. The troubling question of what differentiates atheism from belief in God is then discussed in the light of Simone Weil’s meditations on God’s secret presence

The Democratic Biopolitics of PrEP

PrEP (Pre-Exposure Prophylaxis) is a relatively new drug-based HIV prevention technique and an important means to lower the HIV risk of gay men who are especially vulnerable to HIV. From the perspective of biopolitics, PrEP inscribes itself in a larger trend of medicalization and the rise of pharmapower. This article reconstructs and evaluates contemporary literature on biopolitical theory as it applies to PrEP, by bringing it in a dialogue with a mapping of the political debate on PrEP. As PrEP changes sexual norms and subjectification, for example condom use and its meaning for gay subjectivity, it is highly contested. The article shows that the debate on PrEP can be best described with the concepts ‘sexual-somatic ethics’ and ‘democratic biopolitics’, which I develop based on the biopolitical approach of Nikolas Rose and Paul Rabinow. In contrast, interpretations of PrEP which are following governmentality studies or Italian Theory amount to either farfetched or trivial positions on PrEP, when seen in light of the political debate. Furthermore, the article is a contribution to the scholarship on gay subjectivity, highlighting how homophobia and homonormativity haunts gay sex even in liberal environments, and how PrEP can serve as an entry point for the destigmatization of gay sexuality and transformation of gay subjectivity. ‘Biopolitical democratization’ entails making explicit how medical technology and health care relates to sexual subjectification and ethics, to strengthen the voice of (potential) PrEP users in health politics, and to renegotiate the profit and power of Big Pharma

Randomized Trial of Letrozole Following Tamoxifen as Extended Adjuvant Therapy in Receptor-Positive Breast Cancer: Updated Findings from NCIC CTG MA.17

Background: Most recurrences in women with breast cancer receiving 5 years of adjuvant tamoxifen occur after 5 years. The MA.17 trial, which was designed to determine whether extended adjuvant therapy with the aromatase inhibitor letrozole after tamoxifen reduces the risk of such late recurrences, was stopped early after an interim analysis showed that letrozole improved disease-free survival. This report presents updated findings from the trial. Methods: Postmenopausal women completing 5 years of tamoxifen treatment were randomly assigned to a planned 5 years of letrozole (n = 2593) or placebo (n = 2594). The primary endpoint was disease-free survival (DFS); secondary endpoints included distant disease-free survival, overall survival, incidence of contralateral tumors, and toxic effects. Survival was examined using Kaplan-Meier analysis and log-rank tests. Planned subgroup analyses included those by axillary lymph node status. All statistical tests were two-sided. Results: After a median follow-up of 30 months (range = 1.5-61.4 months), women in the letrozole arm had statistically significantly better DFS and distant DFS than women in the placebo arm (DFS: hazard ratio [HR] for recurrence or contralateral breast cancer = 0.58, 95% confidence interval [CI] = 0.45 to 0.76; P<.001; distant DFS: HR = 0.60, 95% CI = 0.43 to 0.84; P = .002). Overall survival was the same in both arms (HR for death from any cause = 0.82, 95% CI = 0.57 to 1.19; P = .3). However, among lymph node-positive patients, overall survival was statistically significantly improved with letrozole (HR = 0.61, 95% CI = 0.38 to 0.98; P = .04). The incidence of contralateral breast cancer was lower in women receiving letrozole, but the difference was not statistically significant. Women receiving letrozole experienced more hormonally related side effects than those receiving placebo, but the incidences of bone fractures and cardiovascular events were the same. Conclusion: Letrozole after tamoxifen is well-tolerated and improves both disease-free and distant disease-free survival but not overall survival, except in node-positive patient

Genome-Wide Association Meta-analysis of Neuropathologic Features of Alzheimer's Disease and Related Dementias

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias

Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study

Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer's dementia, while the APOE2 allele is associated with a lower risk of Alzheimer's dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer's dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer's dementia cases and controls. APOE2/2 was associated with a low Alzheimer's dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer's disease could have a major impact on the understanding, treatment and prevention of the disease