Milton Keynes Park Revisited: changes in internal temperatures

27-30 April 2006 The Carbon Reduction in Buildings project has undertaken a pilot longitudinal survey based on a study of 160 ‘low-energy’ homes in 1989 in Milton Keynes Energy Park. In that study, a sub-sample of 29 dwellings was monitored on an hourly basis for internal temperature for the living room and main bedroom over 2 years. The follow up study has been in progress since 2005 and consists of 15 dwellings from the original detailed survey. Findings include that under an average daily external temperature of 5 ºC, internal temperatures were predicted from regression analysis to be 20.1ºC (95%CI:19.7, 20.5) for the living room in 2005 and 19.5 ºC (95 %CI:19.1, 19.9) for the bedroom. This was not significantly different from the 1990 baseline study, except for main bedroom evening temperatures (6pm-11pm) which were found to have decreased by -1.3°C (95%CI -2.4, 0.08; p-value 0.04). This may be indicative of higher ventilation rates since almost all participants in 2005 reported opening bedroom windows through winter

Long-term interleukin-6 levels and subsequent risk of coronary heart disease: Two new prospective studies and a systematic review

Background The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context. Methods and Findings Measurements were made in samples obtained at baseline from 2,138 patients who had a first-ever nonfatal MI or died of CHD during follow-up, and from 4,267 controls in two cohorts comprising 24,230 participants. Correction for within-person variability was made using data from repeat measurements taken several years apart in several hundred participants. The year-to-year variability of IL-6 values within individuals was relatively high (regression dilution ratios of 0.41, 95% confidence interval [CI] 0.28-0.53, over 4 y, and 0.35, 95% CI 0.23-0.48, over 12 y). Ignoring this variability, we found an odds ratio for CHD, adjusted for several established risk factors, of 1.46 (95% CI 1.29-1.65) per 2 standard deviation (SD) increase of baseline IL-6 values, similar to that for baseline C-reactive protein. After correction for within-person variability, the odds ratio for CHD was 2.14 (95% CI 1.45-3.15) with long-term average ("usual'') IL-6, similar to those for some established risk factors. Increasing IL-6 levels were associated with progressively increasing CHD risk. An updated systematic review of electronic databases and other sources identified 15 relevant previous population-based prospective studies of IL-6 and clinical coronary outcomes (i.e., MI or coronary death). Including the two current studies, the 17 available prospective studies gave a combined odds ratio of 1.61 (95% CI 1.42-1.83) per 2 SD increase in baseline IL-6 (corresponding to an odds ratio of 3.34 [95% CI 2.45-4.56] per 2 SD increase in usual [long-term average] IL-6 levels). Conclusions Long-term IL-6 levels are associated with CHD risk about as strongly as are some major established risk factors, but causality remains uncertain. These findings highlight the potential relevance of IL-6-mediated pathways to CH

Triphasic nature of polymers of intrinsic microporosity (PIM-1 and PIM-PY) induces storage and catalysis effects in hydrogen and oxygen reactivity at electrode surfaces

Hydrogen oxidation and oxygen reduction are two crucial energy conversion reactions, which are shown to be both strongly affected by the presence of intrinsically microporous polymer coatings on electrodes. Polymers of intrinsic microporosity (PIMs) are known to possess extremely high internal surface area and ability to bind gases under dry conditions. It is shown here that both, hydrogen‐ and oxygen gas binding into PIMs, also occurs under wet or “triphasic” conditions in aqueous electrolyte environments (when immersed in 0.01 M phosphate buffer at pH 7). For two known PIM materials (PIM‐1 and PIM‐PY), nanoparticles are formed by an anti‐solvent precipitation protocol and then cast as a film onto platinum or glassy carbon electrodes. Voltammetry experiments reveal evidence for hydrogen and oxygen binding. Both, PIM‐1 and PIM‐PY, locally store hydrogen or oxygen gas at the electrode surface and thereby significantly affect electrocatalytic reactivity. The onset of oxygen reduction on glassy carbon is shifted by 0.15 V in the positive direction

Oxidative stress, lysosomal damage and dysfunctional autophagy in molluscan hepatopancreas (digestive gland) induced by chemical contaminants

Autophagy is a highly conserved evolutionary survival or defence process that enables cells and organisms to survive periods of environmental stress by breaking down cellular organelles and macromolecules in autolysosomes to provide a supply of nutrients for cell maintenance. However, autophagy is also a part of normal cellular physiology that facilitates the turnover of cellular constituents under normal conditions: it can be readily augmented by mild environmental stress; but becomes dysfunctional with severe oxidative stress leading to cellular pathology. The molluscan hepatopancreas or digestive gland provides a versatile and environmentally relevant model to investigate lysosomal autophagy and stress-induced dysfunctional autophagy. This latter process has been implicated in many animal and human disease conditions, including degenerative and neurodegenerative diseases, as well as obesity related conditions. Many environmental pollutants have also been found to induce dysfunctional autophagy in molluscan hepatopancreatic digestive cells, and in this study, the marine blue mussel Mytilus galloprovincialis was exposed for 7 days to: 0.1 μM, 1 μM and 10 μM concentrations of fluoranthene and phenanthrene (PAHs); chlorpyrifos and malathion (organophosphorus compounds); atrazine (triazine herbicide); copper (transition metal) and dodecylbenzene sulphonic acid (LAS, surfactant). The marine snail or periwinkle, Littorina littorea, was also exposed to phenanthrene, chlorpyrifos and copper. Indices of oxidative stress, cell injury and dysfunctional autophagy were measured (i.e., lysosomal membrane stability, protein carbonyls, lipofuscin, and lysosomal accumulation of lipid or lipidosis). Evidence of oxidative stress, based on the elevation of lipofuscin and protein carbonyls, was found for all compounds tested; with chlorpyrifos being the most toxic to both species. Dysfunctional autophagy was induced by all of the compounds tested in both species, except for atrazine in mussels. This failure of normal autophagy was consistently associated with oxidative stress. Autophagic dysfunction is an important emerging feature in the aetiology of many disease conditions in animals and humans; and an explanatory conceptual mechanistic model has been developed for dysregulation of autophagy in response to oxidative stress

Multidrug resistance proteins preferentially regulate natriuretic peptide-driven cGMP signalling in the heart & vasculature.

BACKGROUND & PURPOSE: Cyclic-3',5'-guanosine monophosphate (cGMP) underpins the bioactivity of nitric oxide (NO) and natriuretic peptides and is key to cardiovascular homeostasis. Cyclic GMP-driven responses are terminated primarily by phosphodiesterases but cellular efflux via multidrug resistance proteins (MRPs) might contribute. Herein, the effect of pharmacological blockade of MRPs on cGMP signalling in the heart and vasculature was investigated in vitro and in vivo. EXPERIMENTAL APPROACHES: Proliferation of human coronary artery smooth muscle cells (hCASMC), vasorelaxation of murine aorta and reductions in mean arterial blood pressure (MABP) in response to NO-donors or natriuretic peptides was determined in the absence and presence of the MRP inhibitor MK571. The ability of MRP inhibition to reverse morphological and contractile deficits in a murine model of pressure overload-induced HF was also explored. KEY RESULTS: MK571 attenuated hCASMC growth and enhanced the anti-proliferative effects of NO and ANP. MRP blockade caused concentration-dependent relaxations of murine aorta and augmented responses to ANP (and to a lesser extent NO). MK571 did not decrease MABP, but enhanced the hypotensive actions of ANP and improved structural and functional indices of disease severity in experimental HF. These beneficial actions of MRP inhibition were associated with a greater intra:extra -cellular cGMP ratio in vitro and in vivo. CONCLUSIONS & IMPLICATIONS: MRP blockade promotes the cardiovascular functions of natriuretic peptides in vitro and in vivo, with more modest effects on NO. MRP inhibition may have therapeutic utility in cardiovascular diseases triggered by dysfunctional cGMP signalling, particularly those associated with altered natriuretic peptide bioactivity

Rapid bidirectional reorganization of cortical microcircuits.

Mature neocortex adapts to altered sensory input by changing neural activity in cortical circuits. The underlying cellular mechanisms remain unclear. We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to show reorganization in somatosensory cortex elicited by altered whisker sensory input. We found that there was rapid expansion followed by retraction of whisker cortical maps. The cellular basis for the reorganization in primary somatosensory cortex was investigated with paired electrophysiological recordings in the periphery of the expanded whisker representation. During map expansion, the chance of finding a monosynaptic connection between pairs of pyramidal neurons increased 3-fold. Despite the rapid increase in local excitatory connectivity, the average strength and synaptic dynamics did not change, which suggests that new excitatory connections rapidly acquire the properties of established excitatory connections. During map retraction, entire excitatory connections between pyramidal neurons were lost. In contrast, connectivity between pyramidal neurons and fast spiking interneurons was unchanged. Hence, the changes in local excitatory connectivity did not occur in all circuits involving pyramidal neurons. Our data show that pyramidal neurons are recruited to and eliminated from local excitatory networks over days. These findings suggest that the local excitatory connectome is dynamic in mature neocortex

UK survey of occupational therapist’s and physiotherapist’s experiences and attitudes towards hip replacement precautions and equipment

Background: Total hip replacement (THR) is one of the most common orthopaedic procedures in the United Kingdom (UK). Historically, people following THR have been provided with hip precautions and equipment such as: raised toilet seats and furniture rises, in order to reduce the risks of dislocation post-operation. The purpose of this study was to determine current practices in the provision of these interventions in the UK for people following primary THR. Methods: A 27-question, self-administered online survey was developed and distributed to UK physiotherapists and occupational therapists involved in the management of people following primary THR (target respondents). The survey included questions regarding the current practices in the provision of equipment and hip precautions for THR patients, and physiotherapist’s and occupational therapist’s attitudes towards these practices. The survey was disseminated through print and web-based/social media channels. Results: 170 health professionals (87 physiotherapists and 83 occupational therapists), responded to the survey. Commonly prescribed equipment in respondent’s health trusts were raised toilet seats (95%), toilet frames and rails (88%), furniture raises (79%), helping hands/grabbers (77%), perching stools (75%) and long-handled shoe horns (75%). Hip precautions were routinely prescribed by 97% of respondents. Hip precautions were most frequently taught in a pre-operative group (52% of respondents). Similarly equipment was most frequently provided pre-operatively (61% respondents), and most commonly by occupational therapists (74% respondents). There was variability in the advice provided on the duration of hip precautions and equipment from up to six weeks post-operatively to life-time usage. Conclusions: Current practice on hip precautions and provision of equipment is not full representative of clinician’s perceptions of best care after THR. Future research is warranted to determine whether and to whom hip precautions and equipment should be prescribed post-THR as opposed to the current ‘blanket’ provision of equipment and movement restriction provided in UK practice

Marine macroalgae as food for earthworms: Growth and selection experiments across ecotypes

Historically, subsistence farmers around the Atlantic coast of NW Europe utilised marine algae as a fertiliser in agroecosystems, a practice that continued in small areas and is now considered to have real potential for re-establishing sustainable food production systems on marginal soils. Earthworms form a significant component of soil fauna and their ecosystem services are well documented. Therefore, palatability of marine organic amendments to faunal detritivores of terrestrial systems is of interest. This work aimed to assess the potential for growth of Aporrectodea caliginosa, Lumbricus rubellus and Aporrectodea longa fed with two common macroalgae (seaweeds), Laminaria digitata and Fucus serratus. In addition, choice chambers were constructed to permit earthworm selection of these macroalgae with more conventional organic materials, horse manure (HM) and birch leaves (BL). Over a period of two months, earthworm species showed significantly greater mass gain with conventional food (p<0.05). Laminaria outperformed Fucus, which in turn was superior to soil alone. Similarly, when given a choice, a significant preference (p<0.001) was shown for the more nitrogen-rich HM and BL over the seaweeds. No removal was recorded for A. caliginosa when offered seaweeds only. By contrast, L. rubellus and A. longa showed significant preferences (p<0.001) for Laminaria over Fucus and fresh material over degraded. These results underline an interest to profit from natural resources (seaweeds) to maintain or improve soil biological quality in marginal coastal areas

Energy efficiency uptake and energy savings in English houses: A cohort study

The UK Government estimates that approximately 22 TWh of energy can be saved from English dwellings by 2020 from a range of fabric and heating energy efficiency retrofits. Yet the rate of retrofit uptake has been less than is needed to meet government targets and the retrofits impact on energy demand has been less than predicted. Two questions that must be addressed are: who have (and have not) taken up retrofits and what household factors affect this; and, what impact have these retrofits had on energy use and how does this differ among households. The purpose of this study is to provide a better understanding of the uptake of energy efficiency retrofits and the resulting change in energy demand. A cohort of 168,998 dwellings gas-heated English dwellings was used to examine retrofit uptake from 2002 to 2007 and the change in gas use from 2005 to 2007. The findings show that retrofits do have an attributable impact on reducing energy demand and that combining retrofits displays a dose-response like effect, after controlling for household and dwelling factors. Energy savings play a central role in meeting UK climate change mitigation targets and therefore understanding the take up of energy efficiency retrofits and their impact on energy demand and variations in these retrofits across the population is vital to understand their potential

Artificial membrane-binding proteins stimulate oxygenation of stem cells during engineering of large cartilage tissue

Restricted oxygen diffusion can result in central cell necrosis in engineered tissue, a problem that is exacerbated when engineering large tissue constructs for clinical application. Here we show that pre-treating human mesenchymal stem cells (hMSCs) with synthetic membrane-active myoglobin-polymer–surfactant complexes can provide a reservoir of oxygen capable of alleviating necrosis at the centre of hyaline cartilage. This is achieved through the development of a new cell functionalization methodology based on polymer–surfactant conjugation, which allows the delivery of functional proteins to the hMSC membrane. This new approach circumvents the need for cell surface engineering using protein chimerization or genetic transfection, and we demonstrate that the surface-modified hMSCs retain their ability to proliferate and to undergo multilineage differentiation. The functionalization technology is facile, versatile and non-disruptive, and in addition to tissue oxygenation, it should have far-reaching application in a host of tissue engineering and cell-based therapies