Long-Term Ethanol Consumption Promotes Hepatic Tumorigenesis but Impairs Normal Hepatocyte Proliferation in Rats

Chronic and excessive alcohol consumption has been related to an increased risk of several cancers, including that of the liver; however, studies in animal models have yet to conclusively determine whether ethanol acts as a tumor promoter in hepatic tumorigenesis. We examined whether prolonged alcohol consumption could act as a hepatic tumor promoter after initiation by diethylnitrosamine (DEN) in a rat model. Male Sprague-Dawley rats were injected with 20 mg DEN/kg body weight 1 wk before introduction of either an ethanol liquid diet or an isoenergic control liquid diet. Hepatic pathological lesions, hepatocyte proliferation, apoptosis, PPAR alpha and PPAR gamma, and plasma insulin-like growth factor 1 IGF-1) levels were assessed after 6 and 10 mo. Mean body and liver weights, plasma IGF-1 concentration, hepatic expressions of proliferating cellular nuclear antigen and Ki-67, and cyclin D1 in ethanol-fed rats were all significantly lower after 10 mo of treatment compared with control rats. In addition, levels of hepatic PPAR gamma protein, not PPAR alpha, were significantly higher in the ethanol-fed rats after prolonged treatment. Although ethanol feeding also resulted in significantly fewer altered hepatic foci, hepatocellular adenoma was detected in ethanol-fed rats at 10 mo, but not in control rats given the same dose of DEN. Together, these results indicate that chronic, excessive ethanol consumption impairs normal hepatocyte proliferation, which is associated with reduced IGF-1 levels, but promotes hepatic carcinogenesis. J. Nutr. 141: 1049-1055, 2011.

Comment la crainte de sous-protection engendrera la catastrophe de la surprotection:examen constitutionnel du Digital Millenium Copyright Act

Chaque apparition d’une nouvelle technologie remet inévitablement en cause le cadre législatif établi pour protéger les droits de propriété. Cependant, avec la numérisation de l’information et l’avènement d’Internet, il est de plus en plus facile de reproduire et de distribuer librement des œuvres protégées. Toutefois, depuis le 20 décembre 1996, l’Organisation Mondiale de la Propriété Intellectuelle (OMPI) a adopté deux traités ayant pour objectif principal d’adapter le cadre juridique du droit d’auteur aux nouvelles technologies. C’est pour se conformer à ces traités que l’administration Clinton a adopté le Digital Millenium Copyright Act (DMCA) en 1998. Cet article examine d’abord les dimensions constitutionnelle du Copyright américain, et plus spécifiquement certaines limites qui viennent tempérer les prérogatives exclusives des titulaires de droits, notamment le domaine public et les usages équitables possibles d’ une œuvre. Sont ensuite examinés le DMCA et sa conformité aux principes énoncés à la clause constitutionnelle, source du pouvoir législatif du Congrès américain en matière de Copyright. De plus, comme le DMCA interdit non seulement le contournement de technologies protégeant une œuvre en format numérique, mais également la fabrication et la diffusion de technologies permettant d’arriver à cette fin, cet article analyse les répercussions de cette loi sur la liberté d’expression.

Axially symmetric soliton solutions in a Skyrme-Faddeev-type model with Gies`s extension

We construct static soliton solutions with non-zero Hopf topological charges to a theory which is the extended Skyrme-Faddeev model with a further quartic term in derivatives. We use an axially symmetric ansatz based on toroidal coordinates, and solve the resulting two coupled nonlinear partial differential equations in two variables by a successive over-relaxation method. We construct numerical solutions with the Hopf charge up to 4. The solutions present an interesting behavior under the changes of a special combination of the coupling constants of the quartic terms.

A manifesto for an e-lending limitation in copyright

In the European Union, lending is an exclusive right for copyright and related rights, but Member States can transform public lending to a right of remuneration and even exempt some establishments from any payment. The making available of works online is not covered by the public lending right regime of the Rental and Lending Directive but is considered as an act of making available governed by the InfoSoc Directive. As a consequence, libraries are currently not allowed to digitally transmit works to their patrons as lending, but have entered into licenses with publishers to develop an offer of lending of e-books, also called e-lending, with the intermediation of dedicated platforms operated by commercial actors. Compared to physical lending, e-lending is not based on ownership of the book by libraries but on its provision by this intermediary. This paper discusses how the objective of enabling libraries to engage in e-lending should be achieved, and what is the proper dividing line between a market-based solution, as developing today, and a limitation to exclusive rights. The impact of an extension of the public lending right to e-lending should be assessed, but not based on a criterion of direct substitution of a book on loan at the library to a book bought at a retailer. By definition, libraries are substitutes to normal trade. Instead, the overall effect of lending to the commercialisation of books and other works should be verified. Particular conditions for a limitation in favour of lending are also addressed, and notably the modalities of lending (a limited duration, one simultaneous user per title, …), not to make e-lending through libraries easier and preferable to the normal acquisition of an e-book. This paper argues in favour of some and controlled extension of the public lending right to cover the lending of e-books and other digital content. For the role of libraries is essential in providing access to works and culture to readers who would or could not rely only on normal acquisition of books or other items on the market, to works that are not provided by the market, and to material for research. Libraries are a third sector providing access to works, aside the market and non-market exchanges between individuals. This role should not lose its relevance in the digital context, or it would culturally impoverish future generations of readers.

The Effect of 6 versus 9 Years of Zoledronic Acid Treatment in Osteoporosis: A Randomized Second Extension to the HORIZON-Pivotal Fracture Trial (PFT).

While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n=95) and Z6P3 (n=95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was -0.54% in Z9 vs. -1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: -0.37%, 1.93%; p=0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. This article is protected by copyright. All rights reserved.

Further reductions in nonvertebral fracture rate with long-term denosumab treatment in the FREEDOM open-label extension and influence of hip bone mineral density after 3 years

Limited data exist on the efficacy of long-term therapies for osteoporosis. In osteoporotic postmenopausal women receiving denosumab for 7 years, nonvertebral fracture rates significantly decreased in years 4-7 versus years 1-3. This is the first demonstration of a further benefit on fracture outcomes with long-term therapy for osteoporosis. INTRODUCTION This study aimed to evaluate whether denosumab treatment continued beyond 3 years is associated with a further reduction in nonvertebral fracture rates. METHODS Participants who completed the 3-year placebo-controlled Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) study were invited to participate in an open-label extension. The present analysis includes 4,074 postmenopausal women with osteoporosis (n = 2,343 long-term; n = 1,731 cross-over) who enrolled in the extension, missed ≤1 dose during their first 3 years of denosumab treatment, and continued into the fourth year of treatment. Comparison of nonvertebral fracture rates during years 1-3 of denosumab with that of the fourth year and with the rate during years 4-7 was evaluated. RESULTS For the combined group, the nonvertebral fracture rate per 100 participant-years was 2.15 for the first 3 years of denosumab treatment (referent) and 1.36 in the fourth year (rate ratio [RR] = 0.64; 95 % confidence interval (CI) = 0.48 to 0.85, p = 0.003). Comparable findings were observed in the groups separately and when nonvertebral fracture rates during years 1-3 were compared to years 4-7 in the long-term group (RR = 0.79; 95 % CI = 0.62 to 1.00, p = 0.046). Fracture rate reductions in year 4 were most prominent in subjects with persisting low hip bone mineral density (BMD). CONCLUSIONS Denosumab treatment beyond 3 years was associated with a further reduction in nonvertebral fracture rate that persisted through 7 years of continuous denosumab administration. The degree to which denosumab further reduces nonvertebral fracture risk appears influenced by the hip bone density achieved with initial therapy.

The first copyright statute; an essay on An act for the encouragement of learning, 1710.

Includes text of the act.

An act to provide for the management and control, and for the extension of the usefulness of the state library.

Mode of access: Internet.

Long-Term Care Assistance Act of 1988 [microform] : hearings before the Subcommittee on Health of the Committee on Finance, United States Senate, One Hundredth Congress, second session, on S. 2305, May 27, and June 17, 1988.

CIS Microfiche Accession Numbers: CIS 89 S361-23

Extension of the Public works and economic development act of 1965 [microform] : hearings before the Subcommittee on Regional and Community Development of the Committee on Environment and Public Works, United States Senate, Ninety-sixth Congress, first session, on S. 914 ... S. 971 ... April 10, 24, and 25, 1979.

Reuse of record except for individual research requires license from Congressional Information Service, Inc.