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In Europe, we had consolidated net sales of 12, 134 million in 2005, representing 44.4% of total consolidated net sales, compared to 48.9% in 2004. In the United States, our consolidated net sales reached 9, 566 million in 2005, representing 35.0% of total consolidated net sales, compared to 31.3% in 2004, reflecting the greater relative presence of Aventis in the United States compared to sanofi-aventis prior to the acquisition. In other countries, our consolidated net sales reached 5, 611 million in 2005, representing 20.6% of total consolidated net sales, compared to 19.8% in 2004. Trends in net sales in 2005 relative to 2004 are discussed below in "-- Year Ended December 31, 2005 compared with Pro Forma Year Ended 2004 Unaudited ; -- Net sales." Other Revenues Other revenues, which mainly comprise royalty income under licensing agreements contracted in connection with ongoing operations, totaled 1, 202 million, compared with 862 million in 2004. The increase was mainly due to higher royalties from the worldwide alliance with BMS on Plavix and Aprovel. Consolidated Gross Profit Our consolidated gross profit was 20, 947 million in 2005, compared to 11, 294 million in 2004. The gross margin ratio was 76.7% in 2005, against 75.9% in 2004. The improvement in the ratio was due to stronger sales, a more favorable product mix, productivity gains, and our purchasing policy. These positive effects were slightly offset by an increase in cost of sales due to the workdown over the period of some of the acquired inventories remeasured at fair value at the time of the Aventis acquisition. Research and Development Expenses Research and development expenses totaled 4, 044 million in 2005, compared to 2, 389 million in 2004, mainly as a result of the consolidation of Aventis. For additional information regarding our R&D activities, please see "Item 4. Information on the Company -- B. Business Overview -- Research and Development." Selling and General Expenses Selling and general expenses were 8, 250 million in 2005 compared to 4, 600 million in 2004, mainly as a result of the consolidation of Aventis. Other Operating Income and Expenses Other operating income and expenses represented net income of 137 million in 2005, compared to net income of 176 million in 2004. Other operating income mainly includes the share of profits from the alliances with P&G Pharmaceuticals to which we are entitled. The year-on-year change mainly reflects the inclusion over 12 months in 2005 compared to four months and 10 days in 2004 ; of our share of profits from the alliance with P&G on the worldwide development and marketing of Actonel excluding Japan ; and from other Aventis alliances. 90.
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Said the abnormal protein may promote metabolic efficiency and storage of body fat when food is abundant. This could have provided a survival advantage to American Indians in the past when food was scarce. The discovery can be used to identify those who are at risk for diabetes and to guide diet and lifestyle choices to prevent diabetes. Apolipoprotein C1 is a component of high density lipoprotein HDL ; and low density lipoprotein LDL ; . HDL cholesterol is often referred to as good cholesterol, while LDL is called bad cholesterol. The common form of C1 tends to be found in the high-density protein complexes HDL ; that ferry cholesterol to storage depots in the body and are linked to lower cardiovascular disease risk. But the variant form of C1 tends to become part of low density protein complexes LDL ; , which transport cholesterol to arterial walls and are associated with higher cardiovascular disease risk. Thus, having the variant could tip the balance of cholesterol carriers and lead toward depletion of HDL-also a risk factor for heart disease.
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Counter-regulatory responses to exercise. This new knowledge allows clinicians to modulate insulin dosage reduce ; and carbohydrate intake increase ; to prevent exercise-associated hypoglycemia. Additionally, the role sleep plays in hypoglycemic counter-regulatory failure has recently been elucidated. Type 1 DM patients are less likely to be awakened by hypoglycemia and have reduced levels of epinephrine when hypoglycemic during sleep. Even though precise mechanisms of HAAF are still under investigation, this concept needs to be incorporated into clinical approaches when addressing recurrent episodes of hypoglycemia. Type 2 DM has an array of phenotypes that can respond differently to hypoglycemia. The UKDPS clearly indicated that type 2 DM patients receiving insulin therapy have increased hypoglycemic events compared with those on oral antidiabetic agents OADs ; . The study also established the progressive nature of the disease with subjects requiring increasing numbers of oral agents and insulin with time. Insight into how hypoglycemia effects type 2 diabetics at different stages of the disease has been the focus of a few recent studies. Levy et al. reported that the glucagon response to hypoglycemia is preserved in non-insulin-requiring type 2 DM. The glycemic threshold for epinephrine and norepinephrine release and ventolin.
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That FDA initiate rulemaking to amend paragraph e ; of this section to remove an essential use. FDA may initiate notice-and-comment rulemaking to remove an essential use on its own initiative or in response to a petition, if granted. If the petition is to remove an essential use from paragraph e ; of this section, the petitioner must submit compelling evidence of any one of the following criteria: 1 ; The product using an ODS is no longer being marketed; or 2 ; After January 1, 2005, FDA determines that the product using an ODS no longer meets the criteria in paragraph f ; of this section after consultation with a relevant advisory committee s ; and after an open public meeting; or 3 ; For individual active moieties marketed as ODS products and represented by one new drug application NDA ; : i ; At least one non-ODS product with the same active moiety is marketed with the same route of administration, for the same indication, and with approximately the same level of convenience of use as the ODS product containing that active moiety; ii ; Supplies and production capacity for the non-ODS product s ; exist or will exist at levels sufficient to meet patient need; iii ; Adequate U.S. postmarketing use data is available for the non-ODS product s and iv ; Patients who medically required the ODS product are adequately served by the non-ODS product s ; containing that active moiety and other available products; or 4 ; For individual active moieties marketed as ODS products and represented by two or more NDAs: i ; At least two non-ODS products that contain the same active moiety are being marketed with the same route of delivery, for the same indication, and with approximately the same level of convenience of use as the ODS products; and ii ; The requirements of paragraphs g ; 3 ; ii ; , iii ; , and g ; 3 ; iv ; this section are met.
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The North Atlantic is believed to represent the largest ocean sink for atmospheric carbon dioxide in the Northern Hemisphere, yet little is known about its temporal variability. We report an 18-year time series of upper-ocean inorganic carbon observations from the northwestern subtropical North Atlantic near Bermuda that indicates substantial variability in this sink. We deduce that the carbon variability at this site is largely driven by variations in winter mixed-layer depths and by sea surface temperature anomalies. Because these variations tend to occur in a basinwide coordinated pattern associated with the North Atlantic Oscillation, it is plausible that the entire North Atlantic Ocean may vary in concert, resulting in a variability of the strength of the North Atlantic carbon sink of about 0.3 petagrams of carbon per year 1 petagram 1015 grams ; or nearly 50%. This extrapolation is supported by basin-wide estimates from atmospheric carbon dioxide inversions. The ocean's contribution to the observed interannual variability of atmospheric carbon dioxide CO2 ; is poorly established. Estimates based on atmospheric measurements of CO2, oxygen, and stable carbon isotopes indicate that the variability contributed by the oceanic carbon cycle is more than 1 Pg C year 1 14 ; . contrast, estimates based on direct observations of the partial pressure of CO2 pCO2 ; in surface waters 5, 6 ; and on modeling studies 7, 8 ; indicate a contribution of less than 0.5 Pg C year 1, mainly associated with tropical Pacific ocean variability caused by El Nino and La Nina 9 ; . How~ ~ ever, many uncertainties are associated.
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The failure was due to the sudden escape of brake fluid from a hole in a pipe in the hydraulic braking system resulting from corrosion of that pipe. The widow of the deceased claimed damages, alleging that the defendants had been negligent in failing to keep the braking system in efficient repair. The defendants pleaded that the accident had been caused by a latent defect in the braking system. The defence of latent defect applies only where all reasonable care has been taken. The defendants established that they had carried out routine maintenance, but failed to show that there were no special circumstances in the past use of the vehicle to indicate that the lorry might have been subjected to a corrosive agent resulting in the corrosion of the pipe. The House of Lords held, by a majority of three to two, that the burden of proving that all reasonable care had been taken rested on the defendant and that the plaintiff was therefore entitled to succeed.42 As a matter of policy this decision also would seem correct. Since in most cases where injury is caused as a result of mechanical failure, the explanation is likely to be failure to keep the items in a sufficient state of good repair rather than the presence of a latent defect not discoverable by taking all reasonable steps, it follows that the percentage of correct results will be maximised by placing the burden of proof on the defendant rather than the plaintiff. iii ; Agreement Between the Parties In cases of disputes arising under agreements between the parties, the form of the agreement may affect the onus of proof. In Stateliner Pty Ltd v Legal and General Assurance Society Ltd 43 a policy of insurance on a passenger bus provided that the policy did not cover damage caused while the vehicle was being used `in an unsafe or unroadworthy condition, unless such condition could not reasonably have been detected by the Insured'.44 The Supreme Court of South Australia held that this agreement obliged the insurer to prove the bus had been used while in an unsafe or unroadworthy condition, but placed the obligation of establishing that such defective condition could not reasonably have been detected by the insured on the insured.45 iv ; Measure of Damages in Tort Cases The issue of burden of proof in relation to damages in tort cases is of particular significance because of the difficulties involved in measuring damages. The plaintiff must, of course, prove the extent of her or his damages.46 Where the.
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ISO, TAC or ETH were incubated at 37C in 500 l of 50 Tris HCl pH7.4 containing 100 mM KCl, 200 g ml bovine serum albumin, 4 mM NADPH and 8 g of EthA for 1 hr. Samples were analysed by HPLC on a Genesis reverse phase column C18-300, 250 mm x 7 internal diameter, 4 m particle size ; . Reactions were diluted with an equal volume of water and filtered before loading. Elution was achieved using a linear gradient from 0.05% formic acid in water to 0.05% formic acid in acetonitrile and monitored by measuring absorbance at A254nm. The amount of residual drug was calculated through integration of peak areas. Samples were also analysed by TLC. Reactions as above were thoroughly mixed with 600 l ethyl acetate in microcentrifuge tubes and centrifuged at 18, 000 x g for 1 minute. The upper organic phase was removed and the solvent evaporated. The sample was resuspended in 20 l ethyl acetate, loaded onto aluminium-backed plates of silica gel 60 F254 Merck ; and developed using toluene ethyl acetate 7: 3 v Drugs were visualized by careful charring with molybdophosphoric acid. -9.
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