Studies on urinary oestrogens

For many years,ovariectomy has been known to cause cessation of oestrus and modification of secondary sex characteristics in animals# In 1913, Fellner observed that transient oestrous symptoms could he produced by injecting an ovariectomized animal with extracts of ovaries. These oestrous symptoms could be followed in the rat by observing histological changes in the vaginal epithelium and in 1923 this keratinization of the vaginal wall was used in the development by Allen and Doisy (1923) of a quantitative test for oestrogenic substances. Four years later, using this method of bioassay, Ascheim and Zondek (1927) discovered that extracts of human pregnancy urine possessed much greater oestrogenic activity than did ovarian extracts. This observation led to a closer examination of pregnancy urine and within two years the first crystalline oestrogenic substance, oestrone (oestra-1:3:5-triene-5-ol-17*-one), was isolated from urine independently by two groups of workers - Doisy, Veler and Thayer (1929) and Butenandt (1929). In the following year, oestriol (oestra-1:3:5-triene-3:16a:17p-triol) was isolated from the same source first by Marrian (1930) and soon after by Doisy, Thayer, Levin and Curtis (1930), In 1933, Schwenk and Hildebrandt succeeded in reducing oestrone to an oestradiol (later shown to be oestradiol~17p (oestra-1:5:5- triene-3:17p-di.ol)) which was found to possess higher oestrogenic activity than either oestrone or oestriol. As a result of this finding, oestradiol-17P was adopted as the probable active principle secreted by the ovaries. Although this oestrogen was isolated from pregnant mares * urine (Wintersteiner, Schwehk and Whitman, 1935) and sows1 ovaries (Mac Corquodale, Thayer and Doisy, 1936) it was not until 1939 that Smith, Smith, Huffman, MacCorquodale» Thayer and Doisy isolated it from human pregnancy urine. Between 1939 and 1953 no further metabolites of oestrogen metabolism were isolated from urine although a number of investigators reported the presence in various urine extracts of unknown substances whose chemical and physical properties suggested that they might prove to be derivatives of known oestrogens (Pincus and Pearlman, 1943; Serchi, 1952; Zondek and Finkelstein, 1952; Migeon, 1953; Braunsberg, Stern and Swyer, 1954), Only one of these led to the actual isolation of an oestrogen metabolite, viz. 16-oxo-oostrone (oestra-1:3:5~triene-3-ol-16:17-dione) which Serchi (1953) obtained in crystalline form from the urine of nonpregnant women

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Inflation and Dark Energy from Spectroscopy at z>2z > 2

The expansion of the Universe is understood to have accelerated during two epochs: in its very first moments during a period of Inflation and much more recently, at $z < 1$, when Dark Energy is hypothesized to drive cosmic acceleration. The undiscovered mechanisms behind these two epochs represent some of the most important open problems in fundamental physics. The large cosmological volume at $2 < z < 5$, together with the ability to efficiently target high-$z$ galaxies with known techniques, enables large gains in the study of Inflation and Dark Energy. A future spectroscopic survey can test the Gaussianity of the initial conditions up to a factor of ~50 better than our current bounds, crossing the crucial theoretical threshold of $\sigma(f_{NL}^{\rm local})$ of order unity that separates single field and multi-field models. Simultaneously, it can measure the fraction of Dark Energy at the percent level up to $z = 5$, thus serving as an unprecedented test of the standard model and opening up a tremendous discovery space

Inflation and Dark Energy from Spectroscopy at z>2z > 2

The expansion of the Universe is understood to have accelerated during two epochs: in its very first moments during a period of Inflation and much more recently, at $z < 1$, when Dark Energy is hypothesized to drive cosmic acceleration. The undiscovered mechanisms behind these two epochs represent some of the most important open problems in fundamental physics. The large cosmological volume at $2 < z < 5$, together with the ability to efficiently target high-$z$ galaxies with known techniques, enables large gains in the study of Inflation and Dark Energy. A future spectroscopic survey can test the Gaussianity of the initial conditions up to a factor of ~50 better than our current bounds, crossing the crucial theoretical threshold of $\sigma(f_{NL}^{\rm local})$ of order unity that separates single field and multi-field models. Simultaneously, it can measure the fraction of Dark Energy at the percent level up to $z = 5$, thus serving as an unprecedented test of the standard model and opening up a tremendous discovery space

Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between Mar