24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats

Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25 (OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25 (OH)2D3] accumulates in articular cartilage following injection of [3 H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 to prevent degenerative changes in articular cartilage in an OAlike environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH)2D3 or vehicle (t = 0, 7, 14, 21 days). Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis

The Labour Government, the Treasury and the £6 pay policy of July 1975

The 1974-79 Labour Government was elected in a climate of opinion that was fiercely opposed to government intervention in the wage determination process, and was committed to the principles of free collective bargaining in its manifestoes. However, by December 1974 the Treasury was advocating a formal incomes policy, and by July 1975 the government had introduced a £6 flat rate pay norm. With reference to archival sources, the paper demonstrates that TUC and Labour Party opposition to incomes policy was reconciled with the Treasury's advocacy by limiting the Bank of England‟s intervention in the foreign exchange market when sterling came under pressure. This both helped to achieve the Treasury's objective of improving the competitiveness of British industry, and acted as a catalyst for the introduction of incomes policy because the slide could be attributed to a lack of market confidence in British counter-inflation policy

Competitiveness and sustainability: can ‘smart city regionalism’ square the circle?

Increasingly, the widely established, globalisation-driven agenda of economic competitiveness meets a growing concern with sustainability. Yet, the practical and conceptual co-existence—or fusion—of these two agendas is not always easy. This includes finding and operationalising the ‘right’ scale of governance, an important question for the pursuit of the distinctly transscalar nature of these two policy fields. ‘New regionalism’ has increasingly been discussed as a pragmatic way of tackling the variable spatialities associated with these policy fields and their changing articulation. This paper introduces ‘smart (new) city-regionalism’, derived from the principles of smart growth and new regionalism, as a policy-shaping mechanism and analytical framework. It brings together the rationales, agreed principles and legitimacies of publicly negotiated polity with collaborative, network-based and policy-driven spatiality. The notion of ‘smartness’, as suggested here as central feature, goes beyond the implicit meaning of ‘smart’ as in ‘smart growth’. When introduced in the later 1990s the term embraced a focus on planning and transport. Since then, the adjective ‘smart’ has become used ever more widely, advocating innovativeness, participation, collaboration and co-ordination. The resulting ‘smart city regionalism’ is circumscribed by the interface between the sectorality and territoriality of policy-making processes. Using the examples of Vancouver and Seattle, the paper looks at the effects of the resulting specific local conditions on adopting ‘smartness’ in the scalar positioning of policy-making

Subchondral bone of the human knee joint in aging and osteoarthritis

AbstractObjective Although most research investigating the pathogenesis of osteoarthritis (OA) has focused on cartilage, it has been suggested that the subchondral bone (SCB) plays an important role in the development of OA. The relationships between aging, severity of OA change and the SCB thickness and density in the human knee joint specimens from a wide range of ages were examined.Methods One hundred forty knee joints from 72 individuals (25 females, 45 males and 2 unknowns; average age 54.8 years, range 17 to 91 years) were obtained. The surface of the articular cartilage of both the femur and tibia was evaluated for gross morphological changes with a 4-point grading scale. The lateral and medial femoral condyles were cut along a sagittal plane and the tibia along a coronal plane to make bone and cartilage strip specimens. The strips were X-rayed onto mammography film and then scanned into a computer for assessment of SCB thickness and density using image analysis software.Results Medial tibial SCB thickness was significantly lower among the elderly (age>69 years) than among the young (age<40) or the middle-aged (40 to 69) (P< 0.001 via ANOVA). Lateral tibial SCB thickness also showed the same trend of decreasing thickness with increasing age, but differences between age groups were not statistically significant. Tibial SCB thicknesses were significantly lower in arthritic grades compared to normal grades (P=0.008 in lateral and 0.017 in medial via ANOVA); in contrast, no significant differences between normal and arthritic were found in femoral SCB thicknesses. The arthritic group tended to have lower SCB densities than the normal group, but this was statistically significant in only the lateral femoral condyle.Conclusions The results obtained in the present study are not consistent with generally accepted notions of the relationship between subchondral bone thickness or density and OA. Subchondral bone changes are not etiologic for OA but, more likely, are secondary to loss of articular cartilage which precedes the appearance of subchondral sclerosis. Copyright 2002 Published by Elsevier Science Ltd on behalf of OsteoArthritis Research Society International

Quantized Scaling of Growing Surfaces

The Kardar-Parisi-Zhang universality class of stochastic surface growth is studied by exact field-theoretic methods. From previous numerical results, a few qualitative assumptions are inferred. In particular, height correlations should satisfy an operator product expansion and, unlike the correlations in a turbulent fluid, exhibit no multiscaling. These properties impose a quantization condition on the roughness exponent $\chi$ and the dynamic exponent $z$. Hence the exact values $\chi = 2/5, z = 8/5$ for two-dimensional and $\chi = 2/7, z = 12/7$ for three-dimensional surfaces are derived.Comment: 4 pages, revtex, no figure

Impact of long-term daylight deprivation on retinal light sensitivity, circadian rhythms and sleep during the Antarctic winter.

Long-term daylight deprivation such as during the Antarctic winter has been shown to lead to delayed sleep timing and sleep fragmentation. We aimed at testing whether retinal sensitivity, sleep and circadian rest-activity will change during long-term daylight deprivation on two Antarctic bases (Concordia and Halley VI) in a total of 25 healthy crew members (mean age: 34 ± 11y; 7f). The pupil responses to different light stimuli were used to assess retinal sensitivity changes. Rest-activity cycles were continuously monitored by activity watches. Overall, our data showed increased pupil responses under scotopic (mainly rod-dependent), photopic (mainly L-/M-cone dependent) as well as bright-blue light (mainly melanopsin-dependent) conditions during the time without direct sunlight. Circadian rhythm analysis revealed a significant decay of intra-daily stability, indicating more fragmented rest-activity rhythms during the dark period. Sleep and wake times (as assessed from rest-activity recordings) were significantly delayed after the first month without sunlight (p &lt; 0.05). Our results suggest that during long-term daylight deprivation, retinal sensitivity to blue light increases, whereas circadian rhythm stability decreases and sleep-wake timing is delayed

Mixed income housing (MIH)

Mixed Income Housing (MIH) is the outcome of a deliberate effort to build a mixed-income development, usually including a variety of housing typologies, sometime combined with the goal of creating a mixed-tenure development. International consensus on a more specific definition of MIH does not exist; instead, multiple expressions can be equally used, with similar meaning. The expression MIH is mainly used within the USA context where it is sometime replaced by mixed-income neighborhood. In Europe, MIH tend to fall within initiatives on (sustainable) urban regeneration, neighborhood restructuring, urban renewal, while the UK legislation often refers to “pepper-potting” with respect to different tenures in the same neighborhood aimed to achieve MIH. Non-English-speaking countries tend to use different terms. The MIH policies are challenged by a specific connotation, i.e., in the United States it is the combination between urban poverty and black or Latinos ghettoes; hence, spatial segregation is combined with racial considerations which are less present in other countries, except for South Africa. In the USA, desegregation in public housing estates became a legal obligation following the famous 1969 Gautreaux case, because of the application of the 1964 Civil Rights Act prohibiting racial discrimination in federally funded activities