Meanings, Policies, and Medicine: On the Bioethical Enterprise and History

History of Scienc

Eloge: Owsei Temkin, 6 October 1902–18 July 2002

History of Scienc

Long distance decoy state quantum key distribution in optical fiber

The theoretical existence of photon-number-splitting attacks creates a security loophole for most quantum key distribution (QKD) demonstrations that use a highly attenuated laser source. Using ultra-low-noise, high-efficiency transition-edge sensor photodetectors, we have implemented the first version of a decoy-state protocol that incorporates finite statistics without the use of Gaussian approximations in a one-way QKD system, enabling the creation of secure keys immune to photon-number-splitting attacks and highly resistant to Trojan horse attacks over 107 km of optical fiber.Comment: 4 pages, 3 figure

How many etiological subtypes of breast cancer: two, three, four, or more?

Breast cancer is a heterogeneous disease, divisible into a variable number of clinical subtypes. A fundamental question is how many etiological classes underlie the clinical spectrum of breast cancer? An etiological subtype reflects a grouping with a common set of causes, whereas a clinical subtype represents a grouping with similar prognosis and/or prediction. Herein, we review the evidence for breast cancer etiological heterogeneity. We then evaluate the etiological evidence with mRNA profiling data. A bimodal age distribution at diagnosis with peak frequencies near ages 50 and 70 years is a fundamental characteristic of breast cancer for important tumor features, clinical characteristics, risk factor profiles, and molecular subtypes. The bimodal peak frequencies at diagnosis divide breast cancer overall into a 'mixture' of two main components in varying proportions in different cancer populations. The first breast cancer tends to arise early in life with modal age-at-diagnosis near 50 years and generally behaves aggressively. The second breast cancer occurs later in life with modal age near 70 years and usually portends a more indolent clinical course. These epidemiological and molecular data are consistent with a two-component mixture model and compatible with a hierarchal view of breast cancers arising from two main cell types of origin. Notwithstanding the potential added value of more detailed categorizations for personalized breast cancer treatment, we suggest that the development of better criteria to identify the two proposed etiologic classes would advance breast cancer research and prevention

Incident HIV among pregnant and breast-feeding women in sub-Saharan Africa: a systematic review and meta-analysis

OBJECTIVES: A previous meta-analysis reported high HIV incidence among pregnant and breast-feeding women in sub-Saharan Africa (SSA), but limited evidence of elevated risk of HIV acquisition during pregnancy or breast-feeding when compared with nonpregnant periods. The rapidly evolving HIV prevention and treatment landscape since publication of this review may have important implications for maternal HIV incidence. DESIGN: Systematic review and meta-analysis. METHODS: We searched four databases and abstracts from relevant conferences through 1 December 2018, for literature on maternal HIV incidence in SSA. We used random-effects meta-analysis to summarize incidence rates and ratios, and to estimate 95% prediction intervals. We evaluated potential sources of heterogeneity with random-effects meta-regression. RESULTS: Thirty-seven publications contributed 100 758 person-years of follow-up. The estimated average HIV incidence rate among pregnant and breast-feeding women was 3.6 per 100 person-years (95% prediction interval: 1.2--11.1), while the estimated average associations between pregnancy and risk of HIV acquisition, and breast-feeding and risk of HIV acquisition, were close to the null. Wide 95% prediction intervals around summary estimates highlighted the variability of HIV incidence across populations of pregnant and breast-feeding women in SSA. Average HIV incidence appeared associated with age, partner HIV status, and calendar time. Average incidence was highest among studies conducted pre-2010 (4.1/100 person-years, 95% prediction interval: 1.1--12.2) and lowest among studies conducted post-2014 (2.1/100 person-years, 95% prediction interval: 0.7--6.5). CONCLUSION: Substantial HIV incidence among pregnant and breast-feeding women in SSA, even in the current era of combination HIV prevention and treatment, underscores the need for prevention tailored to high-risk pregnant and breast-feeding women

Assessing bowel preparation quality using the mean number of adenomas per colonoscopy

Introduction: The quality of the bowel preparation directly influences colonoscopy effectiveness. Quality indicators are widely employed to monitor operator performance and to gauge colonoscopy effectiveness. Some have suggested that the enumeration of the mean number of adenomas per colonoscopy (MNA) may be a more useful measure of bowel preparation quality, but evidence of the utility of this metric is limited. The relationship between bowel preparation quality and MNA was assessed. Methods: Records of adult patients, aged 50–74 years, who had undergone a screening colonoscopy in a 6 month period at a hospital-based endoscopy suite in New York City were examined. Excluded were those who were symptomatic or having a colonoscopy for surveillance. Patient and procedural characteristics and clinical findings were abstracted from the endoscopy database. Bowel preparation quality was recorded as excellent, good, fair and poor. Histology and size of polyps removed were gathered from pathology reports. MNA was calculated and incident rate ratios assessing the relationship between bowel preparation quality, MNA, and covariates was calculated using Poisson regression. Results: A total of 2422 colonoscopies were identified; 815 (33.6%) were screening colonoscopies among average risk individuals, 50–74 years; 203 (24.9%) had ≥1 adenomas; and 666 (81.7%) had excellent/good preparation quality. Overall MNA was 0.34 [standard deviation (SD) 0.68] and MNA was greater among those >60 years [incident rate ratio (IRR) 1.89, 95% confidence interval (CI) 1.48–2.42), males (IRR 1.60, 95%CI 1.26–2.04) and those with good bowel preparation (IRR 2.54, 95%CI 1.04–6.16). Among those with ≥1 adenomas, MNA was 1.48 (SD 1.05) for excellent and 1.00 (SD 0.00) for poor quality preparation (p = 0.55). Conclusions: We found that MNA is sensitive to changes in bowel preparation with higher MNA among those with good bowel preparation compared with those with poor preparation. Our evidence suggests MNA was particularly sensitive when restricted to only those in whom adenomas were seen

Products as Affective Modifiers of Identities

© The Author(s) 2015. Are salesclerks seen as better, more powerful, or more active when they drive Mustangs? What about entrepreneurs? What about driving a mid-sized car? Intuitively, we have ideas about these, but much of the research on the affective nature of products is on purchasing, desires, and self-fulfillment. Drawing on symbolic interactionism, we argue that people's association with products has some basis in the impression management of their identity. For this to occur, there must be some cultural consensus about the way that products modify identities. Drawing on affect control theory's (ACT) methodology and equations, we measure the goodness, powerfulness, and activeness of several products, identities, and the associated product-modified identities to explore how products function as affective modifiers of identities. We find consistent effects across several types of technology products, whereby products pull the modified identity in the direction of the products' affective qualities. Support is established for the ACT equations that predict how traits modify identities as also having utility for predicting how products modify identities. This suggests that the opening questions can be answered empirically by measuring cultural-specific sentiments of the identity and the product and by developing equations to predict the identity modification process

Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8(+) T cells

Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy of transferred CD8(+) T cells, but the specific mechanisms that contribute to this enhanced immunity remain poorly defined. Elimination of CD4(+)CD25(+) regulatory T (T reg) cells has been proposed as a key mechanism by which lymphodepletion augments ACT-based immunotherapy. We found that even in the genetic absence of T reg cells, a nonmyeloablative regimen substantially augmented CD8(+) T cell reactivity to self-tissue and tumor. Surprisingly, enhanced antitumor efficacy and autoimmunity was caused by increased function rather than increased numbers of tumor-reactive T cells, as would be expected by homeostatic mechanisms. The γ (C) cytokines IL-7 and IL-15 were required for augmenting T cell functionality and antitumor activity. Removal of γ (C) cytokine–responsive endogenous cells using antibody or genetic means resulted in the enhanced antitumor responses similar to those seen after nonmyeloablative conditioning. These data indicate that lymphodepletion removes endogenous cellular elements that act as sinks for cytokines that are capable of augmenting the activity of self/tumor-reactive CD8(+) T cells. Thus, the restricted availability of homeostatic cytokines can be a contributing factor to peripheral tolerance, as well as a limiting resource for the effectiveness of tumor-specific T cells

Alcohol Intake and Breast Cancer Risk in African American Women from the AMBER Consortium

Alcohol is a recognized risk factor for invasive breast cancer, but few studies involve African American women