Integrating critical realist and feminist methodologies: ethical and analytical dilemmas

This paper reflects on research carried out with a group of women receiving intensive family support aimed at addressing the cause of their family’s ‘anti-social behaviour’. The methodological approach to the research was underpinned by the philosophical principles of critical realism. It was also informed by the ethical and political concerns of feminist scholarship. The paper reports on the potential points of tension that arise between feminism and critical realism in empirical research. In particular, attention is centred on the process of trying to marry approaches which stress the central role of participants’ knowledge, particularly those who are ‘labelled’ and whose voices are not readily heard, with the principle that some accounts of ‘reality’ are better than others

Patterns and Perceptions of Climate Change in a Biodiversity Conservation Hotspot

Quantifying local people's perceptions to climate change, and their assessments of which changes matter, is fundamental to addressing the dual challenge of land conservation and poverty alleviation in densely populated tropical regions To develop appropriate policies and responses, it will be important not only to anticipate the nature of expected changes, but also how they are perceived, interpreted and adapted to by local residents. The Albertine Rift region in East Africa is one of the world's most threatened biodiversity hotspots due to dense smallholder agriculture, high levels of land and resource pressures, and habitat loss and conversion. Results of three separate household surveys conducted in the vicinity of Kibale National Park during the late 2000s indicate that farmers are concerned with variable precipitation. Many survey respondents reported that conditions are drier and rainfall timing is becoming less predictable. Analysis of daily rainfall data for the climate normal period 1981 to 2010 indicates that total rainfall both within and across seasons has not changed significantly, although the timing and transitions of seasons has been highly variable. Results of rainfall data analysis also indicate significant changes in the intra-seasonal rainfall distribution, including longer dry periods within rainy seasons, which may contribute to the perceived decrease in rainfall and can compromise food security. Our results highlight the need for fine-scale climate information to assist agro-ecological communities in developing effective adaptive management

Acute otitis externa: Consensus definition, diagnostic criteria and core outcome set development.

OBJECTIVE: Evidence for the management of acute otitis externa (AOE) is limited, with unclear diagnostic criteria and variably reported outcome measures that may not reflect key stakeholder priorities. We aimed to develop 1) a definition, 2) diagnostic criteria and 3) a core outcome set (COS) for AOE. STUDY DESIGN: COS development according to Core Outcome Measures in Effectiveness Trials (COMET) methodology and parallel consensus selection of diagnostic criteria/definition. SETTING: Stakeholders from the United Kingdom. SUBJECTS AND METHODS: Comprehensive literature review identified candidate items for the COS, definition and diagnostic criteria. Nine individuals with past AOE generated further patient-centred candidate items. Candidate items were rated for importance by patient and professional (ENT doctors, general practitioners, microbiologists, nurses, audiologists) stakeholders in a three-round online Delphi exercise. Consensus items were grouped to form the COS, diagnostic criteria, and definition. RESULTS: Candidate COS items from patients (n = 28) and literature (n = 25) were deduplicated and amalgamated to a final candidate list (n = 46). Patients emphasised quality-of-life and the impact on daily activities/work. Via the Delphi process, stakeholders agreed on 31 candidate items. The final COS covered six outcomes: pain; disease severity; impact on quality-of-life and daily activities; patient satisfaction; treatment-related outcome; and microbiology. 14 candidate diagnostic criteria were identified, 8 reaching inclusion consensus. The final definition for AOE was 'diffuse inflammation of the ear canal skin of less than 6 weeks duration'. CONCLUSION: The development and adoption of a consensus definition, diagnostic criteria and a COS will help to standardise future research in AOE, facilitating meta-analysis. Consulting former patients throughout development highlighted deficiencies in the outcomes adopted previously, in particular concerning the impact of AOE on daily life

Molecular signatures for CCN1, p21 and p27 in progressive mantle cell lymphoma

Mantle cell lymphoma (MCL) is a comparatively rare non-Hodgkin’s lymphoma characterised by overexpression of cyclin D1.Many patients present with or progress to advanced stage disease within 3 years. MCL is considered an incurable disease withmedian survival between 3 and 4 years. We have investigated the role(s) of CCN1 (CYR61) and cell cycle regulators inprogressive MCL. We have used the human MCL cell lines REC1 G519 > JVM2 cells by RQ-PCR, depicting a decrease in CCN1expression with disease progression. Investigation of CCN1 isoform expression by western blotting showed that whilst expres-sion of full-length CCN1 was barely altered in the cell lines, expression of truncated forms (18–20 and 28–30 kDa) decreasedwith disease progression. We have then demonstrated that cyclin D1 and cyclin dependent kinase inhibitors (p21CIP1and p27KIP1)are also involved in disease progression. Cyclin D1 was highly expressed in REC1 cells (OD: 1.0), reduced to one fifth in G519cells (OD: 0.2) and not detected by western blotting in JVM2 cells. p27KIP1followed a similar profile of expression as cyclin D1.Conversely, p21CIP1was absent in the REC1 cells and showed increasing expression in G519 and JVM2 cells. Subcellularlocalization detected p21CIP1/p27KIP1primarily within the cytoplasm and absent from the nucleus, consistent with altered roles in treatment resistance. Dysregulation of the CCN1 truncated forms are associated with MCL progression. In conjunction withreduced expression of cyclin D1 and increased expression of p21, this molecular signature may depict aggressive disease andtreatment resistance

Inorganic Semiconductor Quantum Dots as a Saturated Excitation (SAX) Probe for Sub‐Diffraction Imaging

The photoluminescence (PL) saturation of CdSe/ZnS core/shell inorganic semiconductor quantum dots (QDs) and its utility as a probe for saturated excitation (SAX) microscopy are reported. Under saturating excitation power densities, the PL signal was demodulated and recorded at harmonics of the fundamental frequency. For commercially available Qdot® 655 ITK™ QDs, the power density required to achieve saturation was dependent upon the local environment of the QDs. For QDs deposited and dried on a glass substrate, the excitation power density required for PL saturation was less than 1 kW/cm2. Compared to this, saturation of PL for QDs dispersed in water required an excitation power density greater than 200 kW/cm2. This observation is manifested as a limitation in the imaging of hydrated samples, as demonstrated for HeLa cells labelled with biotinylated‐phalloidin followed by labelling with streptavidin‐coated QDs. As saturation affects the obtained spatial resolution in several imaging formats, including confocal imaging, the provided data will aid in obtaining the optimal spatial resolution when using QD probes to image biological samples

Cellular and behavioral effects of lipopolysaccharide treatment are dependent upon neurokinin-1 receptor activation

Abstract Background Several psychiatric conditions are affected by neuroinflammation and neuroimmune activation. The transcription factor nuclear factor kappa light-chain-enhancer of activated B cells (NFkB) plays a major role in inflammation and innate immunity. The neurokinin-1 receptor (NK1R) is the primary endogenous target of the neuroactive peptide substance P, and some data suggests that NK1R stimulation may influence NFkB activity. Both NK1R and NFkB have been shown to play a functional role in complex behaviors including stress responsivity, depression, and addiction. In this study, we test whether NFkB activity in the brain (stimulated by lipopolysaccharide administration) is dependent upon the NK1R. Methods Adult male Wistar rats were treated systemically with the NK1R antagonist L822429 followed by administration of systemic lipopolysaccharide (LPS, a strong activator of NFkB). Hippocampal extracts were used to assess expression of proinflammatory cytokines and NFkB-DNA-binding potential. For behavioral studies, rats were trained to consume 1% (w/v) sucrose solution in a continuous access two-bottle choice model. After establishment of baseline, animals were treated with L822429 and LPS and sucrose preference was measured 12 h post-treatment. Results Systemic LPS treatment causes a significant increase in proinflammatory cytokine expression and NFkB-DNA-binding activity within the hippocampus. These increases are attenuated by systemic pretreatment with the NK1R antagonist L822429. Systemic LPS treatment also led to the development of anhedonic-like behavior, evidenced by decreased sucrose intake in the sucrose preference test. This behavior was significantly attenuated by systemic pretreatment with the NK1R antagonist L822429. Conclusions Systemic LPS treatment induced significant increases in NFkB activity, evidenced by increased NFkB-DNA binding and by increased proinflammatory cytokine expression in the hippocampus. LPS also induced anhedonic-like behavior. Both the molecular and behavioral effects of LPS treatment were significantly attenuated by systemic NK1R antagonism, suggesting that NK1R stimulation lies upstream of NFkB activation following systemic LPS administration and is at least in part responsible for NFkB activation

Incongruent HIV and tuberculosis co-dynamics in Kenya: interacting epidemics monitor each other

Kenya is heralded as an example of declining HIV in Africa, while its tuberculosis (TB) numbers continue rising. We conducted a comparative investigation of TB-HIV co-dynamics in Africa to determine the likelihood of reported trends. Our mathematical modeling analysis exposes the notable incongruence of reported trends in Kenya because TB-HIV co-dynamics, tightly knit worldwide and most dramatically in sub-Saharan Africa, suggest that declining HIV trends should trigger reductions in TB trends. Moreover, a continental-scale analysis of TB-HIV trends places Kenya as an outlier in eastern and southern Africa, and shows TB outpacing HIV in western central Africa. We further investigate which TB processes across HIV stages have greater potential to reduce TB incidence via a sensitivity analysis. There are two parsimonious explanations: an unaccounted improvement in TB case detection has occurred, or HIV is not declining as reported. The TB-HIV mismatch could be compounded by surveillance biases due to spatial heterogeneity in disease dynamics. Results highlight the need to re-evaluate trends of both diseases in Kenya, and identify the most critical epidemiological factors at play. Substantial demographic changes have occurred in Kenya, including rapid urbanization accompanied by poor living conditions, which could disproportionately increase TB incidence. Other possible contributors include immune reconstitution due to the recent delivery of antiretrovirals, and an increased presence of the virulent Beijing/W TB genotype. Results support the importance of integrating information from closely interacting epidemics, because this approach provides critical insights unobtainable when components of generalized epidemics are considered individuall