Explicating the role of partnerships in changing the health and well-being of local communities: a profile of neighbourhood renewal activity focused on promoting health and well-being in Salford and the north west region and the north east of England

This scoping and mapping report is one of three outputs from a project: Explicating the role of partnerships in changing the health and well-being of local communities, one of a number of projects in a larger Higher Education Funding Council Strategic Development Fund project ( HEFCE ) entitled: Urban Regeneration: Making a Difference. This was a collaborative venture between Manchester Metropolitan University, Northumbria University, University of Salford and University of Central Lancashire. Bradford University was an affiliated partner

Pharmacological analysis and structure determination of 7-methylcyanopindolol–bound b1-adrenergic receptor

Comparisons between structures of the b1-adrenergic receptor (AR) bound to either agonists, partial agonists, or weak partial agonists led to the proposal that rotamer changes of Ser5.46, coupled to a contraction of the binding pocket, are sufficient to increase the probability of receptor activation. (RS)-4-[3 (tertbutylamino)-2-hydroxypropoxy]-1H-indole-2 carbonitrile (cyanopindolol) is a weak partial agonist of b1AR and, based on the hypothesis above, we predicted that the addition of a methyl group to form 4-[(2S)-3 (tert-butylamino)-2-hydroxypropoxy]-7-methyl-1H-indole-2 carbonitrile (7-methylcyanopindolol) would dramatically reduce its efficacy. An eight-step synthesis of 7- methylcyanopindolol was developed and its pharmacology was analyzed. 7-Methylcyanopindolol bound with similar affinity to cyanopindolol to both b1AR and b2AR. As predicted, the efficacy of 7-methylcyanopindolol was reduced significantly compared with cyanopindolol, acting as a very weak partial agonist of turkey b1AR and an inverse agonist of human b2AR. The structure of 7-methylcyanopindolol–bound b1AR was determined to 2.4-Å resolution and found to be virtually identical to the structure of cyanopindolol-bound b1AR. The major differences in the orthosteric binding pocket are that it has expanded by 0.3 Å in 7-methylcyanopindolol–bound b1AR and the hydroxyl group of Ser5.46 is positioned 0.8 Å further from the ligand, with respect to the position of the Ser5.46 side chain in cyanopindololbound b1AR. Thus, the molecular basis for the reduction in efficacy of 7 methylcyanopindolol compared with cyanopindolol may be regarded as the opposite of the mechanism proposed for the increase in efficacy of agonists compared with antagonists

Irrigated greywater in an urban sub-division as a potential source of metals to soil, groundwater and surface water

Increased water demands in dry countries such as Australia, have led to increased adoption of various water reuse practices. Irrigation of greywater (all water discharged from the bathrooms, laundry and kitchen apart from toilet waste) is seen as a potential means of easing water demands; however, there is limited knowledge of how greywater irrigation impacts terrestrial and aquatic environments. This study compared four greywater irrigated residential lots to adjacent non-irrigated lots that acted as controls. Accumulation and potential impacts of metals in soil, groundwater and surface water, as a result of greywater irrigation, were assessed by comparing measured concentrations to national and international guidelines. Greywater increased concentrations of some metals in irrigated soil and resulted in As, B, Cr and Cu exceeding guidelines after only four years of irrigation. Movement of metals from the irrigation areas resulted in metal concentrations in groundwater (Al, As, Cr, Cu, Fe, Mn, Ni and Zn) and surface water (Cu, Fe and Zn) exceeding environmental quality guidelines again within four years. These results are unlikely to be universally applicable but indicate the need to consider metals in greywater in order to minimize potential adverse environmental effects from greywater irrigation

Insight into partial agonism by observing multiple equilibria for ligand-bound and Gs-mimetic nanobody-bound β1-adrenergic receptor.

A complex conformational energy landscape determines G-protein-coupled receptor (GPCR) signalling via intracellular binding partners (IBPs), e.g., Gs and β-arrestin. Using 13C methyl methionine NMR for the β1-adrenergic receptor, we identify ligand efficacy-dependent equilibria between an inactive and pre-active state and, in complex with Gs-mimetic nanobody, between more and less active ternary complexes. Formation of a basal activity complex through ligand-free nanobody-receptor interaction reveals structural differences on the cytoplasmic receptor side compared to the full agonist-bound nanobody-coupled form, suggesting that ligand-induced variations in G-protein interaction underpin partial agonism. Significant differences in receptor dynamics are observed ranging from rigid nanobody-coupled states to extensive μs-to-ms timescale dynamics when bound to a full agonist. We suggest that the mobility of the full agonist-bound form primes the GPCR to couple to IBPs. On formation of the ternary complex, ligand efficacy determines the quality of the interaction between the rigidified receptor and an IBP and consequently the signalling level

Clinical and Epidemiological Implications of 24-Hour Ambulatory Blood Pressure Monitoring for the Diagnosis of Hypertension in Kenyan Adults: A Population-Based Study.

BACKGROUND: The clinical and epidemiological implications of using ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension have not been studied at a population level in sub-Saharan Africa. We examined the impact of ABPM use among Kenyan adults. METHODS AND RESULTS: We performed a nested case-control study of diagnostic accuracy. We selected an age-stratified random sample of 1248 adults from the list of residents of the Kilifi Health and Demographic Surveillance System in Kenya. All participants underwent a screening blood pressure (BP) measurement. All those with screening BP ≥140/90 mm Hg and a random subset of those with screening BP <140/90 mm Hg were invited to undergo ABPM. Based on the 2 tests, participants were categorized as sustained hypertensive, masked hypertensive, "white coat" hypertensive, or normotensive. Analyses were weighted by the probability of undergoing ABPM. Screening BP ≥140/90 mm Hg was present in 359 of 986 participants, translating to a crude population prevalence of 23.1% (95% CI 16.5-31.5%). Age standardized prevalence of screening BP ≥140/90 mm Hg was 26.5% (95% CI 19.3-35.6%). On ABPM, 186 of 415 participants were confirmed to be hypertensive, with crude prevalence of 15.6% (95% CI 9.4-23.1%) and age-standardized prevalence of 17.1% (95% CI 11.0-24.4%). Age-standardized prevalence of masked and white coat hypertension were 7.6% (95% CI 2.8-13.7%) and 3.8% (95% CI 1.7-6.1%), respectively. The sensitivity and specificity of screening BP measurements were 80% (95% CI 73-86%) and 84% (95% CI 79-88%), respectively. BP indices and validity measures showed strong age-related trends. CONCLUSIONS: Screening BP measurement significantly overestimated hypertension prevalence while failing to identify ≈50% of true hypertension diagnosed by ABPM. Our findings suggest significant clinical and epidemiological benefits of ABPM use for diagnosing hypertension in Kenyan adults

Modelling the toxicity of copper and zinc to wheat and other crops and incorporation of the results into a proposed framework to derive biosolids guidelines

The application of biosolids to land can have both beneficial and detrimental environmentaleffects. The positive effects can arise from nutrients and organic carbon in the biosolids whilethe negative effects generally arise because of the contamination associated with biosolids(e.g. Broos et al., 2006; Heemsbergen et al., 2006; McLaughlin et al., 2006) but can also arisedue to excessive ammonia (Whatmuff et al., 2006). Therefore, any regulatory guidelinesdeveloped to manage the land application of biosolids must be able to enhance the beneficialeffects and minimise the deleterious effects

Benefits of using biosolid nutrients in Australian agriculture - a national perspective.

Increased nutrient levels in inland waterways have led to algal blooms and eutrophication in many agricultural regions. To ensure fertiliser inputs are managed more effectively, the source of contamination needs to be tracked and identified. Point sources could include inorganic fertilisers, livestock excreta, or more recently biosolids. The presence of faecal indicator microorganisms has been widely used to identify the presence of faeces, however, these methods cannot distinguish between human and animals samples. This study investigated PCR amplification as a molecular method to distinguish biosolids from livestock faeces of biosolids, cattle, sheep, poultry and kangaroo. This was achieved using published priming sequences and restriction site profiling of amplified DNA across the 16S rRNA gene of anaerobic gastrointestinal bacteria Bacteroides spp and Bifidobacteria spp. Preliminary investigation showed that of the three Bacteroides spp primer pairs investigated, two were useful for cow faecal material; though at lower annealing temperatures were also applicable to biosolids and sheep faecal material. The third primer pair was specific only for biosolids. All three primer pairs were unable to PCR-amplify Bacteroides spp sequences in faecal material of kangaroo. Of the three Bifidobacteria spp primer pairs, one was useful for sheep faecal material; though at lower annealing temperature was also applicable to biosolids and cow and kangaroo faecal material. The Bifidobacterium angulatum specific primer pair enabled the PCR detection of anaerobes only in biosolids and faecal material of kangaroo. The third, a Bifidobacterium catenulatum specific primer pair was suitable for faecal material of cow and at lower annealing temperatures was also applicable to the sample from sheep. Varying degrees of success were observed in faecal material from other animals. Generally, biosolids tested positive for Bacteroides and Bfidobacteria with all primers except for those specific for B. angulatum. For some primer sets, PCR amplification alone could not differentiate biosolids from other faecal samples. The serial dilution of water contaminated by a range of livestock excreta and biosolids is being examined further to enable the sensitivity of this method to be applied in the field.Soil acidification is an increasing problem throughout many agricultural regions in Australia typically on lighter-textured soils that have a low buffering capacity to changes in soil pH and/or that may be naturally acidic. Crops and pastures grown on acidic soils are subject to problems such as aluminium toxicity (particularly in the subsoil), nodulation failure in legumes and a reduced availability of some nutrients. Lime and dolomite are products that are commonly applied to neutralise soil acidity and improve plant productivity with application rates often determined by their neutralising value and particle size of the product, and the pH buffering capacity (lime requirement) of the soil. To investigate the effect of lime amended biosolids (LAB) as a product for neutralising soil acidity and for improving crop growth, four rates of LAB (0, 5, 10 and 15 t DS/ha) and four equivalent rates of lime product (0, 2.3, 4.6 and 6.7 t/ha) were applied to an acidic red/brown sandy loam in the central wheatbelt of Western Australia. In addition, one rate of dewatered biosolids cake (DBC) at 7 t DS/ha was included to enable comparison to be made to this product. The experiment was conducted over three years and sown to wheat (Triticum aestivum), canola (Brassica napus) and then wheat in 2005, 2006 and 2007, respectively. Plants were sampled at 8 weeks and at harvest to determine the effect of LAB, lime and DBC on crop growth, nutrient uptake and grain yield. Samples of surface soil (0-10 cm) were collected and analysed at harvest for pH and major nutrients. Soil pH increased significantly with increasing rates of LAB or lime at the end of the first year, with similar values recorded between equivalent values of lime product. There was no significant change in soil pH following the addition of the DBC treatment. No further changes in soil pH had occurred by the end of the second year. The growth of both wheat and canola in the first two years was affected to a greater extent by nutrients (typically nitrogen) in the LAB than by the reduction in soil acidity. Measurements on wheat yield in the third year of the experiment and changes in soil pH in the surface (0-10 cm) and subsoil (10-20 cm) will provide further information as to the long term effects of LAB in agriculture and allow recommendations to be made regarding best practise land application rates

Effects of biosolids application on pasture and grape vines in south-eastern Australia

Biosolids were applied to a pasture and a vineyard in south-eastern Australia. At both sites, soil Cd, Cu, and Zn concentrations linearly increased with biosolids application rates although not to the extent of exceeding soil quality guidelines. Biosolids marginally increased soil C and N concentrations at the pasture site but significantly increased P concentrations. With lower overall soil fertility at the vineyard, biosolids increased C, N, and P concentrations. At neither site did biosolids application affect soil microbial endpoints. Biosolids increased pasture production compared to the unfertilised control but had little effect on grape production or quality. Interestingly, over the 3-year trial, there was no difference in pasture production between the biosolids treated plots and plots receiving inorganic fertiliser. These results suggest that biosolids could be used as a fertiliser to stimulate pasture production and as a soil conditioner to improve vineyard soils in this regio