Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review and meta-analysis

OBJECTIVE: To compare the effectiveness and safety of intraarticular high-molecular hylan with standard preparations of hyaluronic acids in osteoarthritis of the knee. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials comparing hylan with a hyaluronic acid in patients with knee osteoarthritis. Trials were identified by systematic searches of Central, Medline, EMBase, Cinahl, the Food and Drug Administration, and Science Citation Index supplemented by hand searches of conference proceedings and reference lists (last update November 2006). Literature screening and data extraction were performed in duplicate. Effect sizes were calculated from differences in means of pain-related outcomes between treatment and control groups at the end of the trial, divided by the pooled standard deviation. Trials were combined using random-effects meta-analysis. RESULTS: Thirteen trials with a pooled total of 2,085 patients contributed to the meta-analysis. The pooled effect size was -0.27 (95% confidence interval [95% CI] -0.55, 0.01), favoring hylan, but between-trial heterogeneity was high (I(2) = 88%). Trials with blinded patients, adequate concealment of allocation, and an intent-to-treat analysis had pooled effect sizes near null. The meta-analyses on safety revealed an increased risk associated with hylan for any local adverse events (relative risk [RR] 1.91; 95% CI 1.04, 3.49; I(2) = 28%) and for flares (RR 2.04; 95% CI 1.18, 3.53; I(2) = 0%). CONCLUSION: Given the likely lack of a superior effectiveness of hylan over hyaluronic acids and the increased risk of local adverse events associated with hylan, we discourage the use of intraarticular hylan in patients with knee osteoarthritis in clinical research or practice.

Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation

A key energy-saving adaptation to chronic hypoxia that enables cardiomyocytes to withstand severe ischemic insults is hibernation, i.e., a reversible arrest of contractile function. Whereas hibernating cardiomyocytes represent the critical reserve of dysfunctional cells that can be potentially rescued, a lack of a suitable animal model has hampered insights on this medically important condition. We developed a transgenic mouse system for conditional induction of long-term hibernation and a system to rescue hibernating cardiomyocytes at will. Via myocardium-specific induction (and, in turn, deinduction) of a VEGF-sequestering soluble receptor, we show that VEGF is indispensable for adjusting the coronary vasculature to match increased oxygen consumption and exploit this finding to generate a hypoperfused heart. Importantly, ensuing ischemia is tunable to a level at which large cohorts of cardiomyocytes are driven to enter a hibernation mode, without cardiac cell death. Relieving the VEGF blockade even months later resulted in rapid revascularization and full recovery of contractile function. Furthermore, we show that left ventricular remodeling associated with hibernation is also fully reversible. The unique opportunity to uncouple hibernation from other ischemic heart phenotypes (e.g., infarction) was used to determine the genetic program of hibernation; uncovering hypoxia-inducible factor target genes associated with metabolic adjustments and induced expression of several cardioprotective genes. Autophagy, specifically self-digestion of mitochondria, was identified as a key prosurvival mechanism in hibernating cardiomyocytes. This system may lend itself for examining the potential utility of treatments to rescue dysfunctional cardiomyocytes and reverse maladaptive remodeling.

Enforcement of the GNU GPL in Germany and Europe

GPL enforcement is successful in Europe. In several court decisions and out of court settlements the license conditions of the GPL have been successfully enforced. In particular, embedded systems are the main focus of such compliance activities. The article describes the practice of enforcement activities and the legal prerequisites under the application of German law.

Stable oxygen isotopes of Globigerinoides ruber and biostratigraphic datums at ODP Site 165-1002

Ocean Drilling Program Site 1002 in the Cariaco Basin was drilled in the final two days of Leg 165 with only a short transit remaining to the final port of San Juan, Puerto Rico. Because of severe time constraints, cores from only the first of the three long replicate holes (Hole 1002C) were opened at sea for visual description, and the shipboard sampling was restricted to the biostratigraphic examination of core catchers. The limited sampling and general scarcity of biostratigraphic datums within the late Quaternary interval covered by this greatly expanded hemipelagic sequence resulted in a very poorly defined age model for Site 1002 as reported in the Leg 165 Initial Reports volume of the Proceedings of the Ocean Drilling Program. Here, we present for the first time a new integrated stratigraphy for Site 1002 based on the standard of late Quaternary oxygen-isotope variations linked to a suite of refined biostratigraphic datums. These new data show that the sediment sequence recovered by Leg 165 in the Cariaco Basin is continuous and spans the time interval from 0 to ~580 ka, with a basal age roughly twice as old as initially suspected from the tentative shipboard identification of a single biostratigraphic datum. Lithologic subunits recognized at Site 1002 are here tied into this new stratigraphic framework, and temporal variations in major sediment components are reported. The biogenic carbonate, opal, and organic carbon contents of sediments in the Cariaco Basin tend to be high during interglacials, whereas the terrigenous contents of the sediments increase during glacials. Glacioeustatic variations in sea level are likely to exert a dominant control on these first-order variations in lithology, with glacial surface productivity and the nutrient content of waters in the Cariaco Basin affected by shoaling glacial sill depths, and glacial terrigenous inputs affected by narrowing of the inner shelf and increased proximity of direct riverine sources during sea-level lowstands.

Predominance of heavily calcified coccolithophores at low CaCO3 saturation during winter in the Bay of Biscay

Coccolithophores are an important component of the Earth system, and, as calcifiers, their possible susceptibility to ocean acidification is of major concern. Laboratory studies at enhanced pCO2 levels have produced divergent results without overall consensus. However, it has been predicted from these studies that, although calcification may not be depressed in all species, acidification will produce "a transition in dominance from more to less heavily calcified coccolithophores" [Ridgwell A, et al., (2009) Biogeosciences 6:2611-2623]. A recent observational study [Beaufort L, et al., (2011) Nature 476:80-83] also suggested that coccolithophores are less calcified in more acidic conditions. We present the results of a large observational study of coccolithophore morphology in the Bay of Biscay. Samples were collected once a month for over a year, along a 1,000-km-long transect. Our data clearly show that there is a pronounced seasonality in the morphotypes of Emiliania huxleyi, the most abundant coccolithophore species. Whereas pH and CaCO3 saturation are lowest in winter, the E. huxleyi population shifts from <10% (summer) to >90% (winter) of the heavily calcified form. However, it is unlikely that the shifts in carbonate chemistry alone caused the morphotype shift. Our finding that the most heavily calcified morphotype dominates when conditions are most acidic is contrary to the earlier predictions and raises further questions about the fate of coccolithophores in a high-CO2 world.

Involutivity of the Hamilton-Cartan equations of a second-order Lagrangian admitting a first-order Hamiltonian formalism

Involutivity of the Hamilton-Cartan equations of a second-order Lagrangian admitting a first-order Hamiltonian formalism

Large-scale testing of proficiency in English: Back to multiple choice?

The paper analyses whether that a properly designed multiple choice test can discriminate with a high level of accuracy if a student in our context has reached a B2 level according to the CEFRL.