Multiplexed femtomolar quantitation of human cytokines in a fluoropolymer microcapillary film

Sensitive quantitation of multiple cytokines can provide important diagnostic information during infection, inflammation and immunopathology. In this study sensitive immunoassay detection of human cytokines IL-1β, IL-6, IL-12p70 and TNFα is shown for singleplex and multiplex formats using a novel miniaturized ELISA platform. The platform uses a disposable plastic multi-syringe aspirator (MSA) integrating 8 disposable fluoropolymer microfluidic test strips, each containing an array of ten 200 mean i.d. microcapillaries coated with a set of monoclonal antibodies. Each MSA device thus performs 10 tests on 8 samples, delivering 80 measurements. Unprecedented levels of sensitivity were obtained with the novel fluoropolymer microfluidic material and simple colorimetric detection in a flatbed scanner. The limit of detection for singleplex detection ranged from 2.0 to 15.0 pg/ml, i.e. 35 and 713 femtomolar for singleplex cytokine detection, and the intra- and inter-assay coefficient of variation (CV) remained within 10%. In addition, a triplex immunoassay was developed for measuring IL-1β, IL-12p70 and TNFα simultaneously from a given sample in the pg/ml range. These assays permit high sensitivity measurement with rapid <15 min assay or detection from undiluted blood serum. The portability, speed and low-cost of this system are highly suited to point-of-care testing and field diagnostics applications.

Infant Attachment Security and the Timing of Puberty: Testing an Evolutionary Hypothesis

Life-history theories of the early programming of human reproductive strategy stipulate that early rearing experience, including that reflected in infant-parent attachment security, regulates psychological, behavioral, and reproductive development. We tested the hypothesis that infant attachment insecurity, compared with infant attachment security, at the age of 15 months predicts earlier pubertal maturation. Focusing on 373 White females enrolled in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, we gathered data from annual physical exams from the ages of 9½ years to 15½ years and from self-reported age of menarche. Results revealed that individuals who had been insecure infants initiated and completed pubertal development earlier and had an earlier age of menarche compared with individuals who had been secure infants, even after accounting for age of menarche in the infants’ mothers. These results support a conditional-adaptational view of individual differences in attachment security and raise questions about the biological mechanisms responsible for the attachment effects we discerned.

Emotional interactions and an ethic of care: caring relations in families affected by HIV and AIDS

In the context of global processes of economic restructuring, the HIV and AIDS epidemic and socio-cultural constructions of care, many women and young people in low-income households have been drawn into caring roles within the family. Drawing on the literature on an ethics of care, emotional geographies and embodiment, this paper examines the emotional dynamics of the caring process in families affected by HIV and AIDS. Based on the perspectives of both ‘caregivers’ and ‘care-receivers’ from research undertaken in Namibia, Tanzania and the UK, we examine the everyday practices of care that women and young people are engaged in and explore how emotions are performed and managed in caring relationships. Our research suggests caregivers play a crucial role in providing emotional support and reassurance to people with HIV, which in turn often affects caregivers' emotional and physical wellbeing. Within environments where emotional expression is restricted and HIV is heavily stigmatised, caregivers and care-receivers seek to regulate their emotions in order to protect family members from the emotional impacts of a chronic, life-limiting illness. However, whilst caregiving and receiving may lead to close emotional connections and a high level of responsiveness, the intensity of intimate caring relationships, isolation and lack of access to adequate resources can cause tensions and contradictory feelings that may be difficult to manage. These conflicts can severely constrain carers' ability to provide the ‘good care’ that integrates the key ethical phases in Tronto's (1993) ideal of the caring process.

Voices from the aid 'chain': The personal dynamics of care

This paper uses a simplified model of the aid 'chain' to explore some causes and consequences of breakdown in communication. Although the rhetoric of Northern-based donors is awash with words such as 'partnership' and 'inclusion' when dealing with their Southern-based partners, the situation in practice is different. Unequal power relationships sometimes result in donor imposition of Perspectives and values. It is our contention, based on a collective experience of fifty-four years in a Nigerian-based non-governmental development organization (NGDO), the Diocesan Development Services (DDS), that much of the driving force behind the successes and problems faced by the institution was founded on relationships that evolved between individuals. In order to understand why things happened the way they did it is necessary to begin with the human element that cannot be condensed into objects or categories. While injudicious donor interference bad damaging repercussions, our experience suggests that care and consideration flow throughout the aid chain and actions are not malevolent. Breakdowns can be attributed to a number of factors, with the over-riding one being pressures operating at the personal level that emanate from within the institution itself and the larger community. The paper analyses three experiences using institutional ethnography theory and methodologies as a basis. Examples taken address the influence key donor personnel had in the function of DDS, and how these changed with time. The mission, policies and even procedures of the donor did not change markedly over thirty-two years, but each changing desk officer had their own philosophy and approach and a different interpretation of their own institutional policies. Hence while the 'macro' has an influence it is mediated via individual interpretation. In our view, the importance of people-people relationships is particularly understated in development literature where emphasis gravitates towards the aggregate and global.

Getting pupils to 'see the point' of school subjects: history, a case study

This paper examines the factors that influence pupil take up of a subject, in this case history, at GCSE. The research indicates that pupils enjoy history but significant factors prevent many from choosing it for further study; these include factors that are beyond the control of teachers, such as government policy and the way this is interpreted by senior managers in school, and factors that are within the control of teachers. The paper suggests that there are lessons that departments can learn from more successful departments but there are also important side effects of government policy that are having unintended consequences.

Tobit estiamtion with unknown point of censoring with an application to milk market participation in the Ethiopian highlands

Data augmentation is a powerful technique for estimating models with latent or missing data, but applications in agricultural economics have thus far been few. This paper showcases the technique in an application to data on milk market participation in the Ethiopian highlands. There, a key impediment to economic development is an apparently low rate of market participation. Consequently, economic interest centers on the “locations” of nonparticipants in relation to the market and their “reservation values” across covariates. These quantities are of policy interest because they provide measures of the additional inputs necessary in order for nonparticipants to enter the market. One quantity of primary interest is the minimum amount of surplus milk (the “minimum efficient scale of operations”) that the household must acquire before market participation becomes feasible. We estimate this quantity through routine application of data augmentation and Gibbs sampling applied to a random-censored Tobit regression. Incorporating random censoring affects markedly the marketable-surplus requirements of the household, but only slightly the covariates requirements estimates and, generally, leads to more plausible policy estimates than the estimates obtained from the zero-censored formulation

Glycogen synthase kinase 3 (GSK3) in the heart: a point of integration in hypertrophic signalling and a therapeutic target? A critical analysis

Glycogen synthase kinase 3 (GSK3, of which there are two isoforms, GSK3alpha and GSK3beta) was originally characterized in the context of regulation of glycogen metabolism, though it is now known to regulate many other cellular processes. Phosphorylation of GSK3alpha(Ser21) and GSK3beta(Ser9) inhibits their activity. In the heart, emphasis has been placed particularly on GSK3beta, rather than GSK3alpha. Importantly, catalytically-active GSK3 generally restrains gene expression and, in the heart, catalytically-active GSK3 has been implicated in anti-hypertrophic signalling. Inhibition of GSK3 results in changes in the activities of transcription and translation factors in the heart and promotes hypertrophic responses, and it is generally assumed that signal transduction from hypertrophic stimuli to GSK3 passes primarily through protein kinase B/Akt (PKB/Akt). However, recent data suggest that the situation is far more complex. We review evidence pertaining to the role of GSK3 in the myocardium and discuss effects of genetic manipulation of GSK3 activity in vivo. We also discuss the signalling pathways potentially regulating GSK3 activity and propose that, depending on the stimulus, phosphorylation of GSK3 is independent of PKB/Akt. Potential GSK3 substrates studied in relation to myocardial hypertrophy include nuclear factors of activated T cells, beta-catenin, GATA4, myocardin, CREB, and eukaryotic initiation factor 2Bvarepsilon. These and other transcription factor substrates putatively important in the heart are considered. We discuss whether cardiac pathologies could be treated by therapeutic intervention at the GSK3 level but conclude that any intervention would be premature without greater understanding of the precise role of GSK3 in cardiac processes.

Continuity of care for people with psychotic illness: its relationship to clinical and social functioning.

Background: The relationship between continuity of care and user characteristics or outcomes has rarely been explored. The ECHO study operationalized and tested a multi-axial definition of continuity of care, producing a seven-factor model used here. Aims: To assess the relationship between user characteristics and established components of continuity of care, and the impact of continuity on clinical and social functioning. Methods: The sample comprised 180 community mental health team users with psychotic disorders who were interviewed at three annual time-points, to assess their experiences of continuity of care and clinical and social functioning. Scores on seven continuity factors were tested for association with user-level variables. Results: Improvement in quality of life was associated with better Experience & Relationship continuity scores (better user-rated continuity and therapeutic relationship) and with lower Meeting Needs continuity factor scores. Higher Meeting Needs scores were associated with a decrease in symptoms. Conclusion: Continuity is a dynamic process, influenced significantly by care structures and organizational change.

Continuity of care for carers of people with severe mental illness: results of a longitudinal study

Introduction: Continuity of care has been demonstrated to be important for service users and carer groups have voiced major concerns over disruptions of care. We aimed to assess the experienced continuity of care in carers of patients with both psychotic and non-psychotic disorders and explore its association with carer characteristics and psychological well-being. Methods: Friends and relatives caring for two groups of service users in the care of community mental health teams (CMHTs), 69 with psychotic and 38 with non-psychotic disorders, were assessed annually at three and two time points, respectively. CONTINUES, a measure specifically designed to assess continuity of care for carers themselves, was utilized along with assessments of psychological well-being and caregiving. Results: One hundred and seven carers participated. They reported moderately low continuity of care. Only 22 had had a carer’s assessment and just under a third recorded psychological distress on the GHQ. For those caring for people with psychotic disorders, reported continuity was higher if the carer was male, employed, lived with the user and had had a carer’s assessment; for those caring for people with non-psychotic disorders, it was higher if the carer was from the service user’s immediate family, lived with them and had had a carer’s assessment. Conclusion: The vast majority of the carers had not had a carer’s assessment provided by the CMHT despite this being a clear national priority and being an intervention with obvious potential to increase carers’ reported low levels of continuity of care. Improving continuity of contact with carers may have an important part to play in the overall improvement of care in this patient group and deserves greater attention.

Wall materials and techniques available for low cost housing in Khartoum from a sustainability point of view

Khartoum like many cities in least developing countries (LDCs) still witnesses huge influx of people. Accommodation of the new comers leads to encroachment on the cultivation land leads to sprawl expansion of Greater Khartoum. The city expanded in diameter from 16.8 km in 1955 to 802.5 km in 1998. Most of this horizontal expansion was residential. In 2008 Khartoum accommodated 29% of the urban population of Sudan. Today Khartoum is considered as one of 43 major cities in Africa that accommodates more than 1 million inhabitants. Most of new comers live in the outskirts of the city e.g. Dar El-Salam and Mayo neighbourhoods. The majority of those new comers built their houses especially the walls from mud, wood, straw and sacks. Selection of building materials usually depends on its price regardless of the environmental impact, quality, thermal performance and life of the material. Most of the time, this results in increasing the cost with variables of impacts over the environment during the life of the building. Therefore, consideration of the environmental impacts, social impacts and economic impacts is crucial in the selection of any building material. Decreasing such impacts could lead to more sustainable housing. Comparing the sustainability of the available wall building materials for low cost housing in Khartoum is carried out through the life cycle assessment (LCA) technique. The purpose of this paper is to compare the most available local building materials for walls for the urban poor of Khartoum from a sustainability point of view by going through the manufacturing of the materials, the use of these materials and then the disposal of the materials after their life comes to an end. Findings reveal that traditional red bricks couldn’t be considered as a sustainable wall building material that will draw the future of the low cost housing in Greater Khartoum. On the other hand, results of the comparison lead to draw attention to the wide range of the soil techniques and to its potentials to be a promising sustainable wall material for urban low cost housing in Khartoum.