The dose-effect relationship between 'unopposed' oestrogens and endometrial mitotic rate: its central role in explaining and predicting endometrial cancer risk.

The 'unopposed oestrogen hypothesis' for endometrial cancer maintains that risk is increased by exposure to endogenous or exogenous oestrogen that is not opposed simultaneously by a progestagen, and that this increased risk is due to the induced mitotic activity of the endometrial cells. Investigation of the mitotic rate during the menstrual cycle shows that increases in plasma oestrogen concentration above the relatively low levels of the early follicular phase do not produce any further increase in the mitotic rate of endometrial cells. A modification of the unopposed oestrogen hypothesis which includes this upper limit in the response of endometrial cells to oestrogen is consistent with the known dose-effect relationships between endometrial cancer risk and both oestrogen replacement therapy and postmenopausal obesity; it also suggests that the mechanism by which obesity increases risk in premenopausal women involves progesterone deficiency rather than oestrogen excess, and that the protective effect of cigarette smoking may be greater in postmenopausal than in premenopausal women. Detailed analysis of the age-incidence curve for endometrial cancer in the light of this hypothesis suggests that there will be lifelong effects of even short duration use of exogenous hormones. In particular, 5 years of combination-type oral contraceptive use is likely to reduce a woman's lifetime risk of endometrial cancer by some 60%; whereas 5 years of unopposed oestrogen replacement therapy is likely to increase her subsequent lifetime risk by at least 90%; and even 5 years of 'adequately' opposed therapy is likely to increase subsequent lifetime risk by at least 50%

Rotorcraft handling-qualities design criteria development

Joint NASA/Army efforts at the Ames Research Center to develop rotorcraft handling-qualities design criteria began in earnest in 1975. Notable results were the UH-1H VSTOLAND variable stability helicopter, the VFA-2 camera-and-terrain-board simulator visual system, and the generic helicopter real-time mathematical model, ARMCOP. An initial series of handling-qualities studies was conducted to assess the effects of rotor design parameters, interaxis coupling, and various levels of stability and control augmentation. The ability to conduct in-flight handling-qualities research was enhanced by the development of the NASA/Army CH-47 variable-stability helicopter. Research programs conducted using this vehicle include vertical-response investigations, hover augmentation systems, and the effects of control-force characteristics. The handling-qualities data base was judged to be sufficient to allow an update of the military helicopter handling-qualities specification, MIL-H-8501. These efforts, including not only the in-house experimental work but also contracted research and collaborative programs performed under the auspices of various international agreements. The report concludes by reviewing the topics that are currently most in need of work, and the plans for addressing these topics

Acidosis Is a Key Regulator of Osteoblast Ecto-Nucleotidase Pyrophosphatase/Phosphodiesterase 1 (NPP1) Expression and Activity

Previous work has shown that acidosis prevents bone nodule formation by osteoblasts in vitro by inhibiting mineralisation of the collagenous matrix. The ratio of phosphate (Pi) to pyrophosphate (PPi) in the bone microenvironment is a fundamental regulator of bone mineralisation. Both Pi and PPi, a potent inhibitor of mineralisation, are generated from extracellular nucleotides by the actions of ecto‐nucleotidases. This study investigated the expression and activity of ecto‐nucleotidases by osteoblasts under normal and acid conditions. We found that osteoblasts express mRNA for a number of ecto‐nucleotidases including NTPdase 1–6 (ecto‐nucleoside triphosphate diphosphohydrolase) and NPP1‐3 (ecto‐nucleotide pyrophosphatase/phosphodiesterase). The rank order of mRNA expression in differentiating rat osteoblasts (day 7) was Enpp1 > NTPdase 4 > NTPdase 6 > NTPdase 5 > alkaline phosphatase > ecto‐5‐nucleotidase > Enpp3 > NTPdase 1 > NTPdase 3 > Enpp2 > NTPdase 2. Acidosis (pH 6.9) upregulated NPP1 mRNA (2.8‐fold) and protein expression at all stages of osteoblast differentiation compared to physiological pH (pH 7.4); expression of other ecto‐nucleotidases was unaffected. Furthermore, total NPP activity was increased up to 53% in osteoblasts cultured in acid conditions (P < 0.001). Release of ATP, one of the key substrates for NPP1, from osteoblasts, was unaffected by acidosis. Further studies showed that mineralised bone formation by osteoblasts cultured from NPP1 knockout mice was increased compared with wildtypes (2.5‐fold, P < 0.001) and was partially resistant to the inhibitory effect of acidosis. These results indicate that increased NPP1 expression and activity might contribute to the decreased mineralisation observed when osteoblasts are exposed to acid conditions

Oestradiol and sex hormone-binding globulin in premenopausal and post-menopausal meat-eaters, vegetarians and vegans

Endogenous oestradiol is strongly associated with breast cancer risk but its determinants are poorly understood. To test the hypothesis that vegetarians have lower plasma oestradiol and higher sex hormone-binding globulin (SHBG) than meat-eaters we assayed samples from 640 premenopausal women (153 meat-eaters, 382 vegetarians, 105 vegans) and 457 post-menopausal women (223 meat-eaters, 196 vegetarians, 38 vegans). Vegetarians and vegans had lower mean body mass indices (BMI) and lower plasma cholesterol concentrations than meat-eaters, but there were no statistically significant differences between meat-eaters, vegetarians and vegans in pre- or post-menopausal plasma concentrations of oestradiol or SHBG. Before adjusting for BMI there were small differences in the direction expected, with the vegetarians and vegans having higher SHBG and lower oestradiol (more noticeable amongst post-menopausal women) than the meat-eaters. These small differences were essentially eliminated by adjusting for BMI. Thus this study implies that the relatively low BMI of vegetarians and vegans does cause small changes in SHBG and in post-menopausal oestradiol, but that the composition of vegetarian diets may not have any additional effects on these hormones

On the Validation of Satellite-Derived Sea Ice Surface Temperature

The surface temperature of sea ice controls the rate of ice growth and heat exchange between the ocean and the atmosphere. An algorithm for the satellite retrieval of ice surface temperature has recently been published, but due to the lack of validation data has not been extensively tested. In this paper, data from a recent Arctic field experiment is used in an attempt to validate that algorithm. While the procedure is, in principle, straightforward, we demonstrate that validation is complicated by a variety of factors, including incorrectly assumed atmospheric conditions, undetected clouds in the satellite data, spatial and temporal variability in the surface temperature field, and surface and satellite measurement errors. Comparisons between surface temperatures determined from upwelling broadband longwave radiation, spatial measurements of narrow-band radiation, thermocouples buried just below the snow surface, and narrow-band satellite data show differences of 1 to 13 degrees C. The range in these independent measurements indicates the need for specially designed validation experiments utilizing narrow-band radiometers on aircraft to obtain broad spatial coverage.Key words: ice surface temperature, Arctic climate, sea ice, AVHRRLa temp&eacute;rature de la surface de la glace de mer contr&ocirc;le le taux de croissance de la glace et les &eacute;changes thermiques entre l'oc&eacute;an et l'atmosph&egrave;re. Un algorithme d'extraction par satellite de la temp&eacute;rature de la surface de la glace a r&eacute;cemment &eacute;t&eacute; publi&eacute;, mais n'a pu &ecirc;tre mis &agrave; l'essai sur une grande &eacute;chelle, en raison du manque de donn&eacute;es de validation. On tente, dans cet article, de valider cet algorithme &agrave; l'aide de donn&eacute;es provenant d'une exp&eacute;rience de terrain men&eacute;e r&eacute;cemment dans l'Arctique. Si la proc&eacute;dure est, en principe, simple, on d&eacute;montre que divers facteurs viennent compliquer cette validation, dont une &eacute;valuation incorrecte des conditions atmosph&eacute;riques, la pr&eacute;sence de nuages non d&eacute;tect&eacute;s dans les donn&eacute;es obtenues par satellite, une variabilit&eacute; spatiale et temporelle dans la temp&eacute;rature de surface de l'aire exp&eacute;rimentale, et des erreurs dans les mesures prises sur le terrain m&ecirc;me et par satellite. Des comparaisons entre les temp&eacute;ratures de surface d&eacute;termin&eacute;es &agrave; partir du rayonnement ascendant des ondes longues &agrave; large bande, des mesures spatiales du rayonnement &agrave; bande &eacute;troite, des thermocouples plac&eacute;s juste sous la surface de la neige et des donn&eacute;es de satellite dans la bande &eacute;troite r&eacute;v&egrave;lent des diff&eacute;rences allant de 1 &agrave; 3 &deg;C. La diff&eacute;rence qui existe dans ces mesures prises ind&eacute;pendamment montre bien la n&eacute;cessit&eacute; de mettre sur pied des exp&eacute;riences de validation con&ccedil;ues &agrave; des fins sp&eacute;cifiques, qui utilisent des radiom&egrave;tres &agrave; bande &eacute;troite sur les avions en vue d'obtenir une grande couverture spatiale.Mots cl&eacute;s: temp&eacute;rature de la surface de la glace, climat de l&rsquo;Arctique, glace de mer, radiom&egrave;tre perfectionn&eacute; &agrave; tr&egrave;s haute r&eacute;solutio

Sex hormones in women in rural China and in Britain.

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group

Cancer incidence in British vegetarians

Background: Few prospective studies have examined cancer incidence among vegetarians. Methods: We studied 61 566 British men and women, comprising 32 403 meat eaters, 8562 non-meat eaters who did eat fish ('fish eaters') and 20 601 vegetarians. After an average follow-up of 12.2 years, there were 3350 incident cancers of which 2204 were among meat eaters, 317 among fish eaters and 829 among vegetarians. Relative risks (RRs) were estimated by Cox regression, stratified by sex and recruitment protocol and adjusted for age, smoking, alcohol, body mass index, physical activity level and, for women only, parity and oral contraceptive use. Results: There was significant heterogeneity in cancer risk between groups for the following four cancer sites: stomach cancer, RRs (compared with meat eaters) of 0.29 (95% CI: 0.07–1.20) in fish eaters and 0.36 (0.16–0.78) in vegetarians, P for heterogeneity=0.007; ovarian cancer, RRs of 0.37 (0.18–0.77) in fish eaters and 0.69 (0.45–1.07) in vegetarians, P for heterogeneity=0.007; bladder cancer, RRs of 0.81 (0.36–1.81) in fish eaters and 0.47 (0.25–0.89) in vegetarians, P for heterogeneity=0.05; and cancers of the lymphatic and haematopoietic tissues, RRs of 0.85 (0.56–1.29) in fish eaters and 0.55 (0.39–0.78) in vegetarians, P for heterogeneity=0.002. The RRs for all malignant neoplasms were 0.82 (0.73–0.93) in fish eaters and 0.88 (0.81–0.96) in vegetarians (P for heterogeneity=0.001). Conclusion: The incidence of some cancers may be lower in fish eaters and vegetarians than in meat eaters

Novel Ferromagnetic Atom Waveguide with in situ loading

Magneto-optic and magnetostatic trapping is realized near a surface using current carrying coils wrapped around magnetizable cores. A cloud of 10^7 Cesium atoms is created with currents less than 50 mA. Ramping up the current while maintaining optical dissipation leads to tightly confined atom clouds with an aspect ratio of 1:1000. We study the 3D character of the magnetic potential and characterize atom number and density as a function of the applied current. The field gradient in the transverse dimension has been varied from < 10 G/cm to > 1 kG/cm. By loading and cooling atoms in-situ, we have eliminated the problem of coupling from a MOT into a smaller phase space.Comment: 4 pages, 4 figure