John Wesley and Methodist music in the eighteenth century : principles and practice

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A pivotal role for interleuking-4 in Atorvastatin-associated neuroprotection in rat brain.

noInflammatory changes, characterized by an increase in pro-inflammatory cytokine production and up-regulation of the corresponding signaling pathways, have been described in the brains of aged rats and rats treated with the potent immune modulatory molecule lipopolysaccharide (LPS). These changes have been coupled with a deficit in long-term potentiation (LTP) in hippocampus. The evidence suggests that anti-inflammatory agents, which attenuate the LPS-induced and age-associated increase in hippocampal interleukin-1ß (IL-1ß) concentration, lead to restoration of LTP. Here we report that atorvastatin, a member of the family of agents that act as inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, exerts powerful anti-inflammatory effects in brain and that these effects are mediated by IL-4 and independent of its cholesterol-lowering actions. Treatment of rats with atorvastatin increased IL-4 concentration in hippocampal tissue prepared from LPS-treated and aged rats and abrogated the age-related and LPS-induced increases in pro-inflammatory cytokines, interferon-¿ (IFN¿) and IL-1ß, and the accompanying deficit in LTP. The effect of atorvastatin on the LPS-induced increases in IFN¿ and IL-1ß was absent in tissue prepared from IL-4¿/¿ mice. The increase in IL-1ß in LPS-treated and aged rats is associated with increased microglial activation, assessed by analysis of major histocompatibility complex II expression, and the evidence suggests that IFN¿ may trigger this activation. We propose that the primary effect of atorvastatin is to increase IL-4, which antagonizes the effects of IFN¿, the associated increase in microglial activation, and the subsequent cascade of events

Opal (Zn/Si) ratios as a nearshore geochemical proxy in coastal Antarctica

Author Posting. © American Geophysical Union, 2008. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 23 (2008): PA2218, doi:10.1029/2007PA001576.During the last 50 years, the Antarctic Peninsula has experienced rapid warming with associated retreat of 87% of marine and tidewater glacier fronts. Accelerated glacial retreat and iceberg calving may have a significant impact on the freshwater and nutrient supply to the phytoplankton communities of the highly productive coastal regions. However, commonly used biogenic carbonate proxies for nutrient and salinity conditions are not preserved in sediments from coastal Antarctica. Here we describe a method for the measurement of zinc to silicon ratios in diatom opal, (Zn/Si)opal, which is a potential archive in Antarctic marine sediments. A core top calibration from the West Antarctic Peninsula shows (Zn/Si)opal is a proxy for mixed layer salinity. We present down-core (Zn/Si)opal paleosalinity records from two rapidly accumulating sites taken from nearshore environments off the West Antarctic Peninsula which show an increase in meltwater input in recent decades. Our records show that the recent melting in this region is unprecedented for over 120 years.The work was funded as part of NERC Antarctic Funding Initiative AFI4– 02. K.R.H. is funded by NERC grant NER/S/A/2004/12390

An ethnographic study of knowledge sharing across the boundaries between care processes, services and organisations: the contributions to ‘safe’ hospital discharge

Background Hospital discharge is a vulnerable stage in the patient pathway. Research highlights communication failures and the problems of co-ordination as resulting in delayed, poorly timed and unsafe discharges. The complexity of hospital discharge exemplifies the threats to patient safety found ‘between’ care processes and organisations. In developing this perspective, safe discharge is seen as relying upon enhanced knowledge sharing and collaboration between stakeholders, which can mitigate system complexity and promote safety. Aim To identify interventions and practices that support knowledge sharing and collaboration in the processes of discharge planning and care transition. Setting The study was undertaken between 2011 and 2013 in two English health-care systems, each comprising an acute health-care provider, community and primary care providers, local authority social services and social care agencies. The study sites were selected to reflect known variations in local population demographics as well as in the size and composition of the care systems. The study compared the experiences of stroke and hip fracture patients as exemplars of acute care with complex discharge pathways. Design The study involved in-depth ethnographic research in the two sites. This combined (a) over 180 hours of observations of discharge processes and knowledge-sharing activities in various care settings; (b) focused ‘patient tracking’ to trace and understand discharge activities across the entire patient journey; and (c) qualitative interviews with 169 individuals working in health, social and voluntary care sectors. Findings The study reinforces the view of hospital discharge as a complex system involving dynamic and multidirectional patterns of knowledge sharing between multiple groups. The study shows that discharge planning and care transitions develop through a series of linked ‘situations’ or opportunities for knowledge sharing. It also shows variations in these situations, in terms of the range of actors, forms of knowledge shared, and media and resources used, and the wider culture and organisation of discharge. The study also describes the threats to patient safety associated with hospital discharge, as perceived by participants and stakeholders. These related to falls, medicines, infection, clinical procedures, equipment, timing and scheduling of discharge, and communication. Each of these identified risks are analysed and explained with reference to the observed patterns of knowledge sharing to elaborate how variations in knowledge sharing can hinder or promote safe discharge. Conclusions The study supports the view of hospital discharge as a complex system involving tightly coupled and interdependent patterns of interaction between multiple health and social care agencies. Knowledge sharing can help to mitigate system complexity through supporting collaboration and co-ordination. The study suggests four areas of change that might enhance knowledge sharing, reduce system complexity and promote safety. First, knowledge brokers in the form of discharge co-ordinators can facilitate knowledge sharing and co-ordination; second, colocation and functional proximity of stakeholders can support knowledge sharing and mutual appreciation and alignment of divergent practices; third, local cultures should prioritise and value collaboration; and finally, organisational resources, procedures and leadership should be aligned to fostering knowledge sharing and collaborative working. These learning points provide insight for future interventions to enhance discharge planning and care transition. Future research might consider the implementation of interviews to mediate system complexity through fostering enhanced knowledge sharing across occupational and organisational boundaries. Research might also consider in more detail the underlying complexity of both health and social care systems and how opportunities for knowledge sharing might be engendered to promote patient safety in other areas

Temporal controls on silicic acid utilisation along the West Antarctic Peninsula

The impact of climatic change along the Antarctica Peninsula has been widely debated in light of atmospheric/oceanic warming and increases in glacial melt over the past half century. Particular concern exists over the impact of these changes on marine ecosystems, not only on primary producers but also on higher trophic levels. Here we present a record detailing the historical controls on the biogeochemical cycling of silicic acid [Si(OH)4] on the west Antarctica Peninsula margin, a region in which the modern phytoplankton environment is constrained by seasonal sea-ice. We demonstrate that Si(OH)4 cycling through the Holocene alternates between being primarily regulated by sea-ice or glacial discharge from the surrounding grounded ice-sheet. With further climate-driven change and melting forecast for the 21st Century, our findings document the potential for biogeochemical cycling and multi-trophic interactions along the peninsula to be increasingly regulated by glacial discharge, altering food-web interactions

Comparative roles of upwelling and glacial iron sources in Ryder Bay, coastal western Antarctic Peninsula

Iron (Fe) is an essential micronutrient for phytoplankton, and is scarce in many regions including the open Southern Ocean. The western Antarctic Peninsula (WAP), an important source region of Fe to the wider Southern Ocean, is also the fastest warming region of the southern hemisphere. The relative importance of glacial versus marine Fe sources is currently poorly constrained, hindering projections of how changing oceanic circulation, productivity, and glacial dynamics may affect the balance of Fe sources in this region.Dissolved and total dissolvable Fe concentrations were measured throughout the summer bloom period at a coastal site on the WAP. Iron inputs to the surface mixed layer in early summer were strongly correlated with meteoric meltwater from glaciers and precipitation. A significant source of Fe from underlying waters was also identified, with dissolved Fe concentrations of up to 9.5 nM at 200 m depth. These two primary Fe sources act on different timescales, with glacial sources supplying Fe during the warm summer growing period, and deep water replenishing Fe over annual periods via deep winter mixing.Iron supply from deep water is sufficient to meet biological demand relative to macronutrient supply, making Fe limitation unlikely in this area even without additional summer Fe inputs from glacial sources. Both glacial and deep-water Fe sources may increase with continued climate warming, potentially enhancing the role of the WAP as an Fe source to offshore waters

State owned enterprises as bribe payers: the role of institutional environment

Our paper draws attention to a neglected channel of corruption—the bribe payments by state-owned enterprises (SOEs). This is an important phenomenon as bribe payments by SOEs fruitlessly waste national resources, compromising public welfare and national prosperity. Using a large dataset of 30,249 firms from 50 countries, we show that, in general, SOEs are less likely to pay bribes for achieving organizational objectives owing to their political connectivity. However, in deteriorated institutional environments, SOEs may be subjected to potential managerial rent-seeking behaviors, which disproportionately increase SOE bribe propensity relative to privately owned enterprises. Specifically, our findings highlight the importance of fostering democracy and rule of law, reducing prevalence of corruption and shortening power distance in reducing the incidence of SOE bribery

The evolution of the upright posture and gait—a review and a new synthesis

During the last century, approximately 30 hypotheses have been constructed to explain the evolution of the human upright posture and locomotion. The most important and recent ones are discussed here. Meanwhile, it has been established that all main hypotheses published until the last decade of the past century are outdated, at least with respect to some of their main ideas: Firstly, they were focused on only one cause for the evolution of bipedality, whereas the evolutionary process was much more complex. Secondly, they were all placed into a savannah scenario. During the 1990s, the fossil record allowed the reconstruction of emerging bipedalism more precisely in a forested habitat (e.g., as reported by Clarke and Tobias (Science 269:521–524, 1995) and WoldeGabriel et al. (Nature 412:175–178, 2001)). Moreover, the fossil remains revealed increasing evidence that this part of human evolution took place in a more humid environment than previously assumed. The Amphibian Generalist Theory, presented first in the year 2000, suggests that bipedalism began in a wooded habitat. The forests were not far from a shore, where our early ancestor, along with its arboreal habits, walked and waded in shallow water finding rich food with little investment. In contrast to all other theories, wading behaviour not only triggers an upright posture, but also forces the individual to maintain this position and to walk bipedally. So far, this is the only scenario suitable to overcome the considerable anatomical and functional threshold from quadrupedalism to bipedalism. This is consistent with paleoanthropological findings and with functional anatomy as well as with energetic calculations, and not least, with evolutionary psychology. The new synthesis presented here is able to harmonise many of the hitherto competing theories

Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe