Ab-initio Quantum Enhanced Optical Phase Estimation Using Real-time Feedback Control

Optical phase estimation is a vital measurement primitive that is used to perform accurate measurements of various physical quantities like length, velocity and displacements. The precision of such measurements can be largely enhanced by the use of entangled or squeezed states of light as demonstrated in a variety of different optical systems. Most of these accounts however deal with the measurement of a very small shift of an already known phase, which is in stark contrast to ab-initio phase estimation where the initial phase is unknown. Here we report on the realization of a quantum enhanced and fully deterministic phase estimation protocol based on real-time feedback control. Using robust squeezed states of light combined with a real-time Bayesian estimation feedback algorithm, we demonstrate deterministic phase estimation with a precision beyond the quantum shot noise limit. The demonstrated protocol opens up new opportunities for quantum microscopy, quantum metrology and quantum information processing.Comment: 5 figure

Internal and external cooling methods and their effect on body temperature, thermal perception and dexterity

© 2018 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0191416© 2018 Maley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective The present study aimed to compare a range of cooling methods possibly utilised by occupational workers, focusing on their effect on body temperature, perception and manual dexterity. Methods Ten male participants completed eight trials involving 30 min of seated rest followed by 30 min of cooling or control of no cooling (CON) (34C, 58% relative humidity). The cooling methods utilised were: ice cooling vest (CV0), phase change cooling vest melting at 14C (CV14), evaporative cooling vest (CVEV), arm immersion in 10C water (AI), portable water-perfused suit (WPS), heliox inhalation (HE) and ice slushy ingestion (SL). Immediately before and after cooling, participants were assessed for fine (Purdue pegboard task) and gross (grip and pinch strength) manual dexterity. Rectal and skin temperature, as well as thermal sensation and comfort, were monitored throughout. Results Compared with CON, SL was the only method to reduce rectal temperature (P = 0.012). All externally applied cooling methods reduced skin temperature (P0.05). Conclusion The present study observed that ice ingestion or ice applied to the skin produced the greatest effect on rectal and skin temperature, respectively. AI should not be utilised if workers require subsequent fine manual dexterity. These results will help inform future studies investigating appropriate pre-cooling methods for the occupational worker.This project is financially supported by the US Government through the Technical Support Working Group within the Combating Terrorism Technical Support Office.Published versio

Dairy consumption and ovarian cancer risk in the Netherlands Cohort Study on Diet and Cancer

Ovary cancer risk in relation to consumption of dairy products was investigated using a self-administered questionnaire on dietary habits and other risk factors for cancer, which was completed in 1986 by 62 573 postmenopausal women participating in the Netherlands Cohort Study. Follow-up for cancer was implemented by annual record linkage with the Netherlands Cancer Registry and a nationwide pathology registry. After 11.3 years of follow-up, data of 252 incident epithelial ovarian cancer cases and 2216 subcohort members were available for analysis. No association was seen between consumption of milk, yoghurt, cheese or fermented dairy products and ovarian cancer risk. The multivariable adjusted relative risk of epithelial ovarian cancer for women in the highest compared to the lowest quintile of intake of lactose or dairy fat was 0.93 (95% confidence interval (CI)=0.60–1.45; Ptrend=0.32) and 1.53 (95% CI=1.00–2.36; Ptrend=0.11), respectively. Lactose or dairy fat intakes were not associated with serous ovarian cancer risk. Our results do not support an association between consumption of dairy products or lactose intake and ovarian cancer

A splicing variant of TERT identified by GWAS interacts with menopausal estrogen therapy in risk of ovarian cancer

Menopausal estrogen-alone therapy (ET) is a well-established risk factor for serous and endometrioid ovarian cancer. Genetics also plays a role in ovarian cancer, which is partly attributable to 18 confirmed ovarian cancer susceptibility loci identified by genome-wide association studies. The interplay among these loci, ET use and ovarian cancer risk has yet to be evaluated. We analyzed data from 1,414 serous cases, 337 endometrioid cases and 4,051 controls across 10 case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Conditional logistic regression was used to determine the association between the confirmed susceptibility variants and risk of serous and endometrioid ovarian cancer among ET users and non-users separately and to test for statistical interaction. A splicing variant in TERT, rs10069690, showed a statistically significant interaction with ET use for risk of serous ovarian cancer (pint  = 0.013). ET users carrying the T allele had a 51% increased risk of disease (OR = 1.51, 95% CI 1.19-1.91), which was stronger for long-term ET users of 10+ years (OR = 1.85, 95% CI 1.28-2.66, pint  = 0.034). Non-users showed essentially no association (OR = 1.08, 95% CI 0.96-1.21). Two additional genomic regions harboring rs7207826 (C allele) and rs56318008 (T allele) also had significant interactions with ET use for the endometrioid histotype (pint  = 0.021 and pint  = 0.037, respectively). Hence, three confirmed susceptibility variants were identified whose associations with ovarian cancer risk are modified by ET exposure; follow-up is warranted given that these interactions are not adjusted for multiple comparisons. These findings, if validated, may elucidate the mechanism of action of these loci

Association Between Menopausal Estrogen-Only Therapy and Ovarian Carcinoma Risk

OBJECTIVE: To describe the association between postmenopausal estrogen-only therapy use and risk of ovarian carcinoma, specifically with regard to disease histotype and duration and timing of use. METHODS: We conducted a pooled analysis of 906 women with ovarian carcinoma and 1,220 women in a control group; all 2,126 women included reported having had a hysterectomy. Ten population-based case-control studies participating in the Ovarian Cancer Association Consortium, an international consortium whose goal is to combine data from many studies with similar methods so reliable assessments of risk factors can be determined, were included. Self-reported questionnaire data from each study were harmonized and conditional logistic regression was used to examine estrogen-only therapy's histotype-specific and duration and recency of use associations. RESULTS: Forty-three and a half percent of the women in the control group reported previous use of estrogen-only therapy. Compared with them, current or recent estrogen-only therapy use was associated with an increased risk for the serous (51.4%, odds ratio [OR] 1.63, 95% confidence interval [CI] 1.27-2.09) and endometrioid (48.6%, OR 2.00, 95% CI 1.17-3.41) histotypes. In addition, statistically significant trends in risk according to duration of use were seen among current or recent postmenopausal estrogen-only therapy users for both ovarian carcinoma histotypes (Ptrend<.001 for serous and endometrioid). Compared with women in the control group, current or recent users for 10 years or more had increased risks of serous ovarian carcinoma (36.8%, OR 1.73, 95% CI 1.26-2.38) and endometrioid ovarian carcinoma (34.9%, OR 4.03, 95% CI 1.91-8.49). CONCLUSION: We found evidence of an increased risk of serous and endometrioid ovarian carcinoma associated with postmenopausal estrogen-only therapy use, particularly of long duration. These findings emphasize that risk may be associated with extended estrogen-only therapy use

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer

BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer. METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients. RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid (p = 0.082) and clear cell (p = 0.083), with the most significant gene level association seen with TGFBR2 (p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 (p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA (p = 0.035, endometrioid and mucinous), LGALS1 (p = 0.03, mucinous), STAT5B (p = 0.022, clear cell), TGFBR1 (p = 0.021 endometrioid) and TGFBR2 (p = 0.017 and p = 0.025, endometrioid and mucinous, respectively). CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients

The ‘Biophilic Organization’: An Integrative Metaphor for Corporate Sustainability

This paper proposes a new organizational metaphor, the ‘Biophilic Organization’, which aims to counter the bio-cultural disconnection of many organizations despite their espoused commitment to sustainability. This conceptual research draws on multiple disciplines such as evolutionary psychology and architecture to not only develop a diverse bio-cultural connection but to show how this connection tackles sustainability, in a holistic and systemic sense. Moreover, the paper takes an integrative view of sustainability, which effectively means that it embraces the different emergent tensions. Three specific tensions are explored: efficiency versus resilience, organizational versus personal agendas and isomorphism versus institutional change. In order to illustrate how the Biophilic Organization could potentially provide a synthesis strategy for such tensions, healthcare examples are drawn from the emerging fields of Biophilic Design in Singapore and Generative Design in the U.S.A. Finally, an example is provided which highlights how a Taoist cultural context has impacted on a business leader in China, to illustrative the significance of a transcendent belief system to such a bio-cultural narrative

Cigarette Smoking and Effects on Hormone Function in Premenopausal Women

Cigarette smoke contains compounds that are suspected to cause reproductive damage and possibly affect hormone activity; therefore, we examined hormone metabolite patterns in relation to validated smoking status. We previously conducted a prospective study of women of reproductive age (n = 403) recruited from a large health maintenance organization, who collected urine daily during an average of three to four menstrual cycles. Data on covariates and daily smoking habits were obtained from a baseline interview and daily diary, and smoking status was validated by cotinine assay. Urinary metabolite levels of estrogen and progesterone were measured daily throughout the cycles. For the present study, we measured urinary levels of the pituitary hormone follicle-stimulating hormone (FSH) in a subset of about 300 menstrual cycles, selected by smoking status, with the time of transition between two cycles being of primary interest. Compared with nonsmokers, moderate to heavy smokers (≥ 10 cigarettes/day) had baseline levels (e.g., early follicular phase) of both steroid metabolites that were 25–35% higher, and heavy smokers (≥ 20 cigarettes/day) had lower luteal-phase progesterone metabolite levels. The mean daily urinary FSH levels around the cycle transition were increased at least 30–35% with moderate smoking, even after adjustment. These patterns suggest that chemicals in tobacco smoke alter endocrine function, perhaps at the level of the ovary, which in turn effects release of the pituitary hormones. This endocrine disruption likely contributes to the reported associations of smoking with adverse reproductive outcomes, including menstrual dysfunction, infertility, and earlier menopause

Exome genotyping arrays to identify rare and low frequency variants associated with epithelial ovarian cancer risk

Rare and low frequency variants are not well covered in most germline genotyping arrays and are understudied in relation to epithelial ovarian cancer (EOC) risk. To address this gap, we used genotyping arrays targeting rarer protein-coding variation in 8,165 EOC cases and 11,619 controls from the international Ovarian Cancer Association Consortium (OCAC). Pooled association analyses were conducted at the variant and gene level for 98,543 variants directly genotyped through two exome genotyping projects. Only common variants that represent or are in strong linkage disequilibrium (LD) with previously-identified signals at established loci reached traditional thresholds for exome-wide significance (P ( )P≥5.0 ×10 (-)  (7)) were detected for rare and low-frequency variants at 16 novel loci. Four rare missense variants were identified (ACTBL2 rs73757391 (5q11.2), BTD rs200337373 (3p25.1), KRT13 rs150321809 (17q21.2) and MC2R rs104894658 (18p11.21)), but only MC2R rs104894668 had a large effect size (OR = 9.66). Genes most strongly associated with EOC risk included ACTBL2 (PAML = 3.23 × 10 (-)  (5); PSKAT-o = 9.23 × 10 (-)  (4)) and KRT13 (PAML = 1.67 × 10 (-)  (4); PSKAT-o = 1.07 × 10 (-)  (5)), reaffirming variant-level analysis. In summary, this large study identified several rare and low-frequency variants and genes that may contribute to EOC susceptibility, albeit with possible small effects. Future studies that integrate epidemiology, sequencing, and functional assays are needed to further unravel the unexplained heritability and biology of this disease

Hormone replacement therapy and risk of epithelial ovarian cancer

It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case–control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32–4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% Cl 1.54–5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours. © 1999 Cancer Research Campaig