The onset of labor alters corticotropin-releasing hormone type 1 receptor variant expression in human myometrium : putative role of interleukin-1ß

CRH targets the human myometrium during pregnancy. The efficiency of CRH actions is determined by expression of functional receptors (CRH-R), which are dynamically regulated. Studies in myometrial tissue biopsies using quantitative RT-PCR demonstrated that the onset of labor, term or preterm, is associated with a significant 2- to 3-fold increase in CRH-R1 mRNA levels. Detailed analysis of myometrial CRH-R1 mRNA variants showed a decline of the pro-CRH-R1 mRNA encoding the CRH-R1ß variant during labor and increased mRNA levels of CRH-R1d mRNA. Studies in myometrial cells identified IL-1ß as an important regulator of myometrial CRH-R1 gene expression because prolonged treatment of myometrial cells with IL-1ß (1 ng/ml) for 18 h induced expression of CRH-R1 mRNA levels by 1.5- to 2-fold but significantly attenuated CRH-R1ß mRNA expression by 70%. In contrast, IL-1ß had no effect on CRH-R1d mRNA expression. Studies using specific inhibitors suggest that ERK1/2, p38 MAPK, and downstream nuclear translocation of nuclear factor-B mediate IL-1ß effects on myometrial CRH-R1 gene. However, the increased CRH-R1 mRNA expression was associated with a dampening of the receptor efficacy to activate the adenylyl cyclase/cAMP signaling cascade. Thus, our findings suggest that IL-1ß is an important regulator of CRH-R1 expression and functional activity, and this interaction might play a role in the transition of the uterus from quiescence to active contractions necessary for the onset of parturition

Performance assessment of urban precinct design: a scoping study

Executive Summary: Significant advances have been made over the past decade in the development of scientifically and industry accepted tools for the performance assessment of buildings in terms of energy, carbon, water, indoor environment quality etc. For resilient, sustainable low carbon urban development to be realised in the 21st century, however, will require several radical transitions in design performance beyond the scale of individual buildings. One of these involves the creation and application of leading edge tools (not widely available to built environment professions and practitioners) capable of being applied to an assessment of performance across all stages of development at a precinct scale (neighbourhood, community and district) in either greenfield, brownfield or greyfield settings. A core aspect here is the development of a new way of modelling precincts, referred to as Precinct Information Modelling (PIM) that provides for transparent sharing and linking of precinct object information across the development life cycle together with consistent, accurate and reliable access to reference data, including that associated with the urban context of the precinct. Neighbourhoods are the ‘building blocks’ of our cities and represent the scale at which urban design needs to make its contribution to city performance: as productive, liveable, environmentally sustainable and socially inclusive places (COAG 2009). Neighbourhood design constitutes a major area for innovation as part of an urban design protocol established by the federal government (Department of Infrastructure and Transport 2011, see Figure 1). The ability to efficiently and effectively assess urban design performance at a neighbourhood level is in its infancy. This study was undertaken by Swinburne University of Technology, University of New South Wales, CSIRO and buildingSMART Australasia on behalf of the CRC for Low Carbon Living

Strategically using public housing assets could transform our middle suburbs

‘Greyfields’ in the Australian context have been defined as those ageing but occupied tracts of inner and middle ring suburbia that are physically, technologically and environmentally failing. The research sought to test the potential of an innovative design based approach to create coordinated precincts in these suburbs involving the coordinated redevelopment of multiple, non-contiguous public housing lots (rather than relying on the ‘default’ option of incremental market based development of in-fill housing and piecemeal selling off of public housing properties). Recent public housing investments (under the Social Housing Initiative) were typically planned with job creation in mind rather than innovative housing outcomes, but innovations were still apparent. Innovations were generally simple such as improvements to parking arrangements and interfaces of private dwellings with common areas and public spaces and arrangements for tenancy mix and social diversity. Innovations were often more apparent when governments partnered with Community Housing Organisations who could access alternative land and funding sources, offer design and delivery expertise and facilitate mixed tenancy outcomes. Innovation also was more likely when there was a ‘champion’ for design quality, relaxation of selected planning controls, and project alignment with existing urban renewal strategies. The Department of Human Services (Victorian Government) was found to have existing housing assets in sufficient number (more than 6500 DHS properties) in well-located areas of Melbourne’s middle suburbs that were clustered in ways broadly suitable for coordinated precinct redevelopment. Preliminary investigations suggest the same in Sydney and Brisbane. The coordinated precinct approach could offer an effective model for redeveloping dispersed public housing assets. Integrated redevelopment can achieve substantial increases in dwelling yield—design scenarios developed in this study delivered two to four times the number of dwellings when compared to business-as-usual dual occupancy outcomes. A precinct design approach is potentially more efficient because it allows for non-uniform, flexible siting of higher density buildings, effective program mixes, efficient parking arrangements and a variety of households and tenure types to be accommodated across a neighbourhood. Preliminary discussions with key stakeholders—municipal authorities, community housing organisations and local community members—showed real interest in the benefits of a coordinated precinct-based development approach. - See more at: http://www.ahuri.edu.au/publications/projects/p52012#sthash.wTtz4itu.dpu

Illness patterns prior to diagnosis of lymphoma : Analysis of UK medical records

Background: Increased understanding of the relationship between lymphomas and co-morbidities is likely to provide valuable insights into the natural history of these disorders. Methods: 761 cases with lymphoma (310 diffuse large B-cell [DLBCL]; 226 follicular [FL]; and 225 Hodgkin [HL]) and 761 unaffected age and sex matched controls were recruited and their histories of infection and non-infection diagnoses in primary care records were compared using negative binomial regression. Results: No differences were observed between the infectious illness patterns of DLBCL and FL cases and their matched controls over the 15 years preceding lymphoma diagnosis. A marked excess of infectious illness episodes was recorded for HL cases compared to their controls; evident at least a decade prior to HL diagnosis. For non-infectious consultations an excess of case over control visits emerged 4-6 years before DLBCL and FL diagnosis; no specific co-morbidity associations were found. No case-control differences for non-infectious conditions were apparent for HL. Conclusion: There are substantial variations in patterns of illness prior to diagnosis of the three lymphoma subtypes examined. The excess of infectious diagnoses prior to HL may point to underlying immune abnormality, but there was no suggestion of this for DLBCL and FL where a generalized excess of non-infectious conditions was evident. (C) 2010 Elsevier Ltd. All rights reserved

Adverse pregnancy outcomes in rural Uganda (1996-2013): trends and associated factors from serial cross sectional surveys.

OBJECTIVE: Community based evidence on pregnancy outcomes in rural Africa is lacking yet it is needed to guide maternal and child health interventions. We estimated and compared adverse pregnancy outcomes and associated factors in rural south-western Uganda using two survey methods. METHODS: Within a general population cohort, between 1996 and 2013, women aged 15-49 years were interviewed on their pregnancy outcome in the past 12 months (method 1). During 2012-13, women in the same cohort were interviewed on their lifetime experience of pregnancy outcomes (method 2). Adverse pregnancy outcome was defined as abortions or stillbirths. We used random effects logistic regression for method 1 and negative binomial regression with robust clustered standard errors for method 2 to explore factors associated with adverse outcome. RESULTS: One third of women reported an adverse pregnancy outcome; 10.8% (abortion = 8.4%, stillbirth = 2.4%) by method 1 and 8.5% (abortion = 7.2%, stillbirth = 1.3%) by method 2. Abortion rates were similar (10.8 vs 10.5) per 1000 women and stillbirth rates differed (26.2 vs 13.8) per 1000 births by methods 1 and 2 respectively. Abortion risk increased with age of mother, non-attendance of antenatal care and proximity to the road. Lifetime stillbirth risk increased with age. Abortion and stillbirth risk reduced with increasing parity. DISCUSSION: Both methods had a high level of agreement in estimating abortion rate but were markedly below national estimates. Stillbirth rate estimated by method 1 was double that estimated by method 2 but method 1 estimate was more consistent with the national estimates. CONCLUSION: Strategies to improve prospective community level data collection to reduce reporting biases are needed to guide maternal health interventions

Development and initial application of δ18Op to understand phosphorus cycling in river, lake and groundwater ecosystems.

Variation in the stable isotope composition of oxygen within dissolved phosphate (δ18Op) represents a novel and potentially powerful environmental tracer. In freshwater, marine and terrestrial ecosystems, δ18Op can act as an inherent label for the sources of phosphorus and the extent to which phosphorus from different sources is metabolised. This paper focuses on the methodological development and initial application of δ18Op across a range of freshwater ecosystems. Initially, we report modifications to the analytical protocol for δ18Op that are designed to minimise incorporation of contaminant oxygen in the final silver phosphate precipitate prior to pyrolysis. This is critical given the range of possible sources of contaminant oxygen within freshwater matrices. Subsequently, we consider the potential utility of δ18Op through application of the technique within a range of freshwater ecosystems in England, UK. Firstly, we characterise δ18Op in river water and effluents from Sewage Treatment Works (STW), and examine the opportunity to use the 18Op of STW effluents to trace the entry and downstream fate of phosphorus from these point sources in rivers. Secondly, we analyse δ18Op to gain insights into variations in the sources and biological cycling of phosphorus in a seasonally stratified lake ecosystem. Thirdly, we characterise δ18Op in shallow and deep groundwater samples, considering whether δ18Op might provide evidence for variation in source and extent of metabolism for phosphorus in groundwater ecosystems. Taken together, these data extend the catalogue of δ18Op in freshwater ecosystems, and further the scope of δ18Op as a tool to better understand phosphorus biogeochemistry

Risk factors for high anti-HHV-8 antibody titers (≥1:51,200) in black, HIV-1 negative South African cancer patients: a case control study

Background: Infection with human herpesvirus 8 (HHV-8) is the necessary causal agent in the development of Kaposi's sarcoma (KS). Infection with HIV-1, male gender and older age all increase risk for KS. However, the geographic distribution of HHV-8 and KS both prior to the HIV/AIDS epidemic and with HIV/AIDS suggest the presence of an additional co-factor in the development of KS. Methods: Between January 1994 and October 1997, we interviewed 2576 black in-patients with cancer in Johannesburg and Soweto, South Africa. Blood was tested for antibodies against HIV-1 and HHV-8 and the study was restricted to 2191 HIV-1 negative patients. Antibodies against the latent nuclear antigen of HHV-8 encoded by orf73 were detected with an indirect immunofluorescence assay. We examined the relationship between high anti-HHV-8 antibody titers (≥1:51,200) and sociodemographic and behavioral factors using unconditional logistic regression models. Variables that were significant at p = 0.10 were included in multivariate analysis. Results: Of the 2191 HIV-1 negative patients who did not have Kaposi's sarcoma, 854 (39.0%) were positive for antibodies against HHV-8 according to the immunofluorescent assay. Among those seropositive for HHV-8, 530 (62.1%) had low titers (1:200), 227 (26.6%) had medium titers (1:51,200) and 97 (11.4%) had highest titers (1:204,800). Among the 2191 HIV-1 negative patients, the prevalence of high anti-HHV-8 antibody titers (≥1:51,200) was independently associated with increasing age (ptrend = 0.04), having a marital status of separated or divorced (p = 0.003), using wood, coal or charcoal as fuel for cooking 20 years ago instead of electricity (p = 0.02) and consuming traditional maize beer more than one time a week (p = 0.02; p-trend for increasing consumption = 0.05) although this may be due to chance given the large number of predictors considered in this analysis. Conclusions: Among HIV-negative subjects, patients with high anti-HHV-8 antibody titers are characterized by older age. Other associations that may be factors in the development of high anti- HHV-8 titers include exposure to poverty or a low socioeconomic status environment and consumption of traditional maize beer. The relationship between these variables and high anti- HHV-8 titers requires further, prospective study

Kaposi sarcoma in South African children

This article has been published as part of Infectious Agents and Cancer Volume 5 Supplement 1, 2010: Proceedings of the 12th International Conference on Malignancies in AIDS and Other Acquired Immunodeficiencies (ICMAOI).The AIDS epidemic has contributed to an abrupt increase of the incidence of Kaposi sarcoma, especially in Sub-Saharan Africa, to values tens of times higher than in the pre-epidemic era. There is, however, very little literature concerning the clinical features of this disease and its management and outcome in HIV-positive children in Africa.Peer Reviewe

A synthesis is emerging between biodiversity–ecosystem function and ecological resilience research: reply to Mori

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