Cities of culture and the regeneration game

Capital of Culture (ECoC) programme exactly a year on from its inauguration. This event also saw the transition from Liverpool's "Year of Culture 08‟ to "Year of Environment 09" and a simultaneous event in the Austrian city of Linz to which the Capital of Culture mantle passed, along with Vilnius, Lithuania. An estimated 60,000 people congregated at the Pier Head as well as at the Albert Dock and Wirral bank, for a celebration that included sing-a-longs, firework displays, street artists on illuminated bikes and light projections onto a famous refurbished new museum building making up this World Heritage city. This "Light Night" celebration also kick-started similar events held in cities in England and Scotland, with extended opening of venues. The Light Night theme chosen for Liverpool 08's swansong emulates the Nuit Blanche festival celebrated in dozens of cities such as Paris, Rome, Montreal and Toronto - the largest of which attract 1 to 3 million participants over "late night" weekend extravaganzas (Jiwa et al., 2009). These "eventful cities" (Richards and Palmer 2010) reflect a global trend and network that spreads virtually and geographically (Evans, 2011)

Finding the balance in complex regional pain syndrome. Expertise, optimism, and evidence

Complex regional pain syndrome (CRPS), perhaps more than any other chronic pain disorder, is perplexing. It is highly disabling, particularly once it has “set in,” and it has a tendency to polarize the community—some view it as a quasidiagnosis to obscure malingering or conceal substandard clinical skills,1 and others as a multiple system overprotective response.2 What is agreed is that its pathophysiology is not completely understood and that it is difficult to treat. In light of this rather murky backdrop, we welcome the new perspectives article in this issue of Neurology® by Birklein et al.3 They describe their own clinical approach to the problem and their impressions of what works, what does not, and where the field might be heading. The lead author is the most prolific and arguably the most important researcher in this field, and the article clearly draws on a wealth of expertise and clinical experience probably unmatched globally. The article reminds us of the remaining substantial challenges that we face: for example, the need for prospective studies, higher quality clinical trials and audits, and a putative model that accounts for the transition from acute CRPS to chronic CRPS, which is arguably characterized by distinct pathophysiology. Anyone who treats a good number of CRPS patients will recognize the clinical patterns to which the authors allude and be comforted by the realization that even this group, at the top of the field, share the same substantial treatment challenges.G.L.M. is supported by a Principal Research Fellowship from the National Health & Medical Research Council of Australia ID 1061279

Ca2+-dependent changes in cyclic GMP levels are not correlated with opening and closing of the light-dependent permeability of toad photoreceptors.

We have measured the levels of 3',5'-guanosine monophosphate (cyclic GMP) in isolated retinas from toad to investigate their correlation to the opening and closing of the light-dependent permeability of photoreceptors. When Ca2+-induced changes in cyclic GMP concentration are compared with the Ca2+-induced changes in the permeability of photoreceptor light-dependent channel, four quantitative dissimilarities are noted. First, when extracellular Ca2+ ([Ca2+]o) is reduced from normal physiological levels to between 10(-6) and 10(-7) M, the light-dependent permeability is increased, but cyclic GMP levels are not significantly changed. Second, when [Ca2+]o is increased from 1.8 to 20 mM, the light-dependent permeability is suppressed, but cyclic GMP levels are decreased by only 10-15%, about one-quarter the decrease that can be obtained with bright illumination. Third, when [Ca2+]o is increased from 10(-8) M to 20 mM, the light-dependent permeability is closed rapidly, but the cyclic GMP decrease is slow. Fourth, when [Ca2+]o is lowered to 10(-8) M, the sensitivity of the light-dependent permeability to steady illumination is decreased by three to four orders of magnitude, but the sensitivity of the light-dependent decrease in cyclic GMP is not significantly affected. These observations indicate that there is no simple correlation between cyclic GMP levels and the permeability of the light-dependent channels and that Ca2+ can affect the conductance in the absence of changes in cyclic GMP content

The use of diatom records to establish reference conditions for UK lakes subject to eutrophication

A knowledge of pre-disturbance conditions is important for setting realistic restoration targets for lakes. For European waters this is now a requirement of the European Council Water Framework Directive where ecological status must be assessed based on the degree to which present day conditions deviate from reference conditions. Here, we employ palaeolimnological techniques, principally inferences of total phosphorus from diatom assemblages (DI-TP) and classification of diatom composition data from the time slice in sediment cores dated to similar to 1850 AD, to define chemical and ecological reference conditions, respectively, for a range of UK lake types. The DI-TP results from 169 sites indicate that reference TP values for low alkalinity lakes are typically 3 m mean depth) generally had lower reference TP concentrations than the shallow sites. A small group of shallow marl lakes had concentrations of similar to 30 mu g L-1. Cluster analysis of diatom composition data from 106 lakes where the key pressure of interest was eutrophication identified three clusters, each associated with particular lake types, suggesting that the typology has ecological relevance, although poor cross matching of the diatom groups and the lake typology at type boundaries highlights the value of a site-specific approach to defining reference conditions. Finally the floristic difference between the reference and present day (surface sample) diatom assemblages of each site was estimated using the squared chord distance dissimilarity coefficient. Only 25 of the 106 lakes experienced insignificant change and the findings indicate that eutrophication has impacted all lake types with > 50% of sites exhibiting significant floristic change. The study illustrates the role of the sediment record in determining both chemical and ecological reference conditions, and assessing deviation from the latter. Whilst restoration targets may require modification in the future to account for climate induced alterations, the long temporal perspective offered by palaeolimnology ensures that such changes are assessed against a sound baseline

Impacts of river engineering on river channel behaviour : implications for managing downstream flood risk

Although knowledge of sediment transport has improved over the last 25 years, our understanding of bedload transfer and sediment delivery is still based on a limited set of observations or on models that make assumptions on hydraulic and sediment transport processes. This study utilises repeat lidar survey data of the River Caldew above the City of Carlisle in the UK to investigate the balance of erosion and deposition associated with channel switching from an engineered and managed single thread channel to a naturalising incipient wandering system. Over the 11-year survey period (four bankfull flood events) around 271,000 m3 of sediment were delivered to the river and floodplain and 197,000 m3 eroded suggesting that storage rates of around 7000 m3/annum occurred. The balance of erosion and deposition is influenced by channelisation with very restricted overbank sedimentation and only limited local and transient in-channel bar deposition along the engineered reach (8000 m3 eroded). This contrasts with the activity of the naturalising reach downstream where a developing wandering channel system is acting to store coarse sediment in-stream as large bar complexes and the associated upstream aggrading plane bed reaches and overbank as splay deposits (87,000 m3 stored). Such behavior suggests that naturalisation of channelised systems upstream of flood vulnerable urban areas can have a significant impact on sediment induced flooding downstream. This conclusion must, however, be moderated in the light of the relatively small volumes of material needed to instigate local aggradation in over-capacity urban channels

The refolding activity of the yeast heat shock proteins Ssa1 and Ssa2 defines their role in protein translocation.

Ssa1/2p, members of one of the yeast cytosolic hsp70 subfamilies, have been implicated in the translocation of secretory proteins into the lumen of the ER. The involvement of these hsp70s in translocation was tested directly by examining the effect of immunodepleting Ssa1/2p from yeast cytosol and subsequently testing the cytosol for its ability to support co- and post-translational translocation of prepro-alpha-factor. Depletion of Ssa1/2p had no effect on the efficiency of translocation in this in vitro assay. The system was used to examine the effect of the absence of Ssa1/2p on two other putative hsp70 functions: cotranslational folding of nascent luciferase and refolding of denatured luciferase. Depletion of Ssa1/2p had no effect on the ability of the yeast lysate to synthesize enzymatically active luciferase, but had a dramatic effect on the ability of the lysate to refold chemically denatured luciferase. These results demonstrate, for the first time, the refolding activity of Ssa1/2p in the context of the yeast cytosol, and define refolding activity as a chaperone function specific to Ssa1/2p, aprt from other cytosolic hsp70s. They also suggest that Ssa1/2p do not play a significant role in chaperoning the folding of nascent polypeptides. The implications of these findings for Ssa1/2p activity on their proposed role in the process of translocation are discussed

Affective coherence: Affect as embodied evidence in attitude, advertising and art

For the first time, this volume brings together these varied developments under one umbrella and furnishes a comprehensive overview of this intellectual ..

Potential impact of adjustment policies on vulnerability of women and children to HIV/AIDS in sub-Saharan Africa

This paper evaluates the potential impact of adjustment policies of the International Monetary Fund and the World Bank on the vulnerability of women and children to HIV/AIDS in sub-Saharan Africa. A conceptual framework, composed of five different pathways of causation, is used for the evaluation. These five pathways connect changes at the macro level (e.g. removal of food subsidies) with effects at the meso (e.g. higher food prices) and micro levels (e.g. exposure of women and children to commercial sex) that influence the vulnerability of women and children to HIV/AIDS. Published literature on adjustment policies and socioeconomic determinants of HIV/AIDS among women and children in sub-Saharan Africa was reviewed to explore the cause-effect relationships included in the theoretical framework. Evidence suggests that adjustment policies may inadvertently produce conditions facilitating the exposure of women and children to HIV/AIDS. Complex research designs are needed to further investigate this relationship. A shift in emphasis from an individual approach to a socioeconomic approach in the study of HIV infection among women and children in the developing world is suggested. Given the potential for adjustment policies to exacerbate the AIDS pandemic among women and children, a careful examination of the effects of these policies on maternal and child welfare is urgently needed

Interventions to Reduce Spasticity and Improve Function in People With Chronic Incomplete Spinal Cord Injury: Distinctions Revealed by Different Analytical Methods.

Background. Spinal cord injury (SCI) results in impaired function, and ankle joint spasticity is a common secondary complication. Different interventions have been trialed with variable results. Objective. We investigated the effects of pharmacological and physical (locomotor training) interventions on function in people living with incomplete motor function loss caused by SCI and used different analytical techniques to understand whether functional levels affect recovery with different interventions. Methods. Participants with an incomplete SCI were assigned to 3 groups: no intervention, Lokomat, or tizanidine. Outcome measures were the 10-m walk test, 6-minute walk test, and the Timed Up and Go. Participants were classified in 2 ways: (1) based on achieving an improvement above the minimally important difference (MID) and (2) using growth mixture modeling (GMM). Functional levels of participants who achieved the MID were compared and random coefficient regression (RCR) was used to assess recovery in GMM classes. Results. Overall, walking speed and endurance improved, with no difference between interventions. Only a small number of participants achieved the MID. Both MID and GMM-RCR analyses revealed that tizanidine improved endurance in high-functioning participants. GMM-RCR classification also showed that speed and mobility improved after locomotor training. Conclusions. Improvements in function were achieved in a limited number of people with SCI. Using the MID and GMM techniques, differences in responses to interventions between high-and low-functioning participants could be identified. These techniques may, therefore, have potential to be used for characterizing therapeutic effects resulting from different interventions

Single-channel recordings from cultured human retinal pigment epithelial cells.

We have applied patch-clamp techniques to on-cell and excised-membrane patches from human retinal pigment epithelial cells in tissue culture. Single-channel currents from at least four ion channel types were observed: three or more potassium-selective channels with single-channel slope conductances near 100, 45, and 25 pS as measured in on-cell patches with physiological saline in the pipette, and a relatively nonselective channel with subconductance states, which has a main-state conductance of approximately 300 pS at physiological ion concentrations. The permeability ratios, PK/PNa, measured in excised patches were 21 for the 100-pS channels, 3 for the 25-pS channels, and 0.8 for the 300-pS nonselective channel. The 45-pS channels appeared to be of at least two types, with PK/PNa's of approximately 41 for one type and 3 for the other. The potassium-selective channels were spontaneously active at all potentials examined. The average open time for these channels ranged from a few milliseconds to many tens of milliseconds. No consistent trend relating potassium-selective channel kinetics to membrane potential was apparent, which suggests that channel activity was not regulated by the membrane potential. In contrast to the potassium-selective channels, the activity of the nonselective channel was voltage dependent: the open probability of this channel declined to low values at large positive or negative membrane potentials and was maximal near zero. Single-channel conductances observed at several symmetrical KCl concentrations have been fitted with Michaelis-Menten curves in order to estimate maximum channel conductances and ion-binding constants for the different channel types. The channels we have recorded are probably responsible for the previously observed potassium permeability of the retinal pigment epithelium apical membrane