Stage 1 Development of a Patient Reported Experience Measure (PREM) for Chronic Obstructive Pulmonary Disease (COPD)

The study aimed to explore patients’ experience of living with COPD and their perspective of their community health care for COPD to extract affective responses in order to develop potential items for a patient reported experience measure (PREM) for Chronic Obstructive Pulmonary Disease (COPD). Qualitative face-face interviews were conducted, in the community, with 64 patients with COPD recruited from General Practices and Breath-Easy community groups in the Outer North East, East and City, London and Essex, UK. A two phase analysis of the qualitative data was conducted to identify themes arising from patients’ description of living with COPD and their perceptions of their community health care and subsequently the affective responses underlying the themes raised by patients, which gave emotional colour to the themes, bringing the thematic analysis closer to the subjective patient experience. Five themes were identified from the interview data: ‘Journey to diagnosis’; ‘Smoking’; ‘Usual care’; ‘My everyday life’; and ‘Exacerbations’. Twenty affective responses were identified and categorised as either ‘negative’, ‘positive’ or ‘bivalent’. ‘Frustration’, a negative affective response was prevalent in four themes. ‘Gratitude’, ‘hope’ and ‘happiness/enjoyment’ were among the more positive responses more prevalent across several themes. By conducting a novel two-way analysis (thematic and affective) it was possible to identify themes and affective responses that were aligned to those themes. This enabled the development of 38 COPD specific experience items to take forward for further testing including item reduction and validity and reliability in the next stage of the PREM development

Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans

The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease

World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [-13910*T (rs4988235), -13907*G (rs41525747), -13915*G (rs41380347), -14009*G (rs869051967) and -14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the 'Old World' and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection

Re-examining the Unified Theory of Acceptance and Use of Technology (UTAUT): Towards a Revised Theoretical Model

YesBased on a critical review of the Unified Theory of Acceptance and Use of Technology (UTAUT), this study first formalized an alternative theoretical model for explaining the acceptance and use of information system (IS) and information technology (IT) innovations. The revised theoretical model was then empirically examined using a combination of meta-analysis and structural equation modelling (MASEM) techniques. The meta-analysis was based on 1600 observations on 21 relationships coded from 162 prior studies on IS/IT acceptance and use. The SEM analysis showed that attitude: was central to behavioural intentions and usage behaviours, partially mediated the effects of exogenous constructs on behavioural intentions, and had a direct influence on usage behaviours. A number of implications for theory and practice are derived based on the findings

Is no news good news? Inconclusive genetic test results in BRCA1 and BRCA2 from patients and professionals' perspectives

<p>Abstract</p> <p>Background</p> <p>Women from families with a high risk of breast or ovarian cancer in which genetic testing for mutations in the <it>BRCA1/2 </it>genes is inconclusive are a vulnerable and understudied group. Furthermore, there are no studies of the professional specialists who treat them - geneticists, genetic counsellors/nurses, oncologists, gynaecologists and breast surgeons.</p> <p>Methods</p> <p>We conducted a small qualitative study that investigated women who had developed breast cancer under the age of 45 and who had an inconclusive <it>BRCA1/2 </it>genetic diagnostic test (where no mutations or unclassified variants were identified). We arranged three focus groups for affected women and their close female relatives - 13 women took part. We also interviewed 12 health professionals who were involved in the care of these women.</p> <p>Results</p> <p>The majority of the women had a good grasp of the meaning of their own or a family member's inconclusive result, but a few indicated some misunderstanding. Most of the women in this study underwent the test for the benefit of others in the family and none mentioned that they were having the test purely for themselves. A difficult issue for sisters of affected women was whether or not to undertake prophylactic breast surgery. The professionals were sensitive to the difficulties in explaining an inconclusive result. Some felt frustrated that technology had not as yet provided them with a better tool for prediction of risk.</p> <p>Conclusions</p> <p>Some of the women were left with the dilemma of what decision to make regarding medical management of their cancer risk. For the most part, the professionals believed that the women should be supported in whatever management decisions they considered best, provided these decisions were based on a complete and accurate understanding of the genetic test that had taken place in the family.</p

Doing narrative research? Thinking through the narrative process

Across social science disciplines there has been a growth in narrative research—the so called ‘narrative turn’. This turn echoes broader shifts associated with more complex social worlds, epistemological challenges and feminist responses. Narrative research typically involves exploring individual, subjective experiences through interview-based research, but can also range across researching group and organisational dynamics to document-based analysis. In this chapter the question of what constitutes narrative research is explored and illuminated using data from a qualitative longitudinal study on transition to first-time motherhood. The importance of developing a theoretical rationale when choosing a narrative research approach, together with suggested ways of analysing data once collected, is noted. Researching individual accounts of subjective experience and transitions as a feminist researcher provides opportunities, but challenges too

Pharmacological Analysis of Ionotropic Glutamate Receptor Function in Neuronal Circuits of the Zebrafish Olfactory Bulb

Although synaptic functions of ionotropic glutamate receptors in the olfactory bulb have been studied in vitro, their roles in pattern processing in the intact system remain controversial. We therefore examined the functions of ionotropic glutamate receptors during odor processing in the intact olfactory bulb of zebrafish using pharmacological manipulations. Odor responses of mitral cells and interneurons were recorded by electrophysiology and 2-photon Ca2+ imaging. The combined blockade of AMPA/kainate and NMDA receptors abolished odor-evoked excitation of mitral cells. The blockade of AMPA/kainate receptors alone, in contrast, increased the mean response of mitral cells and decreased the mean response of interneurons. The blockade of NMDA receptors caused little or no change in the mean responses of mitral cells and interneurons. However, antagonists of both receptor types had diverse effects on the magnitude and time course of individual mitral cell and interneuron responses and, thus, changed spatio-temporal activity patterns across neuronal populations. Oscillatory synchronization was abolished or reduced by AMPA/kainate and NMDA receptor antagonists, respectively. These results indicate that (1) interneuron responses depend mainly on AMPA/kainate receptor input during an odor response, (2) interactions among mitral cells and interneurons regulate the total olfactory bulb output activity, (3) AMPA/kainate receptors participate in the synchronization of odor-dependent neuronal ensembles, and (4) ionotropic glutamate receptor-containing synaptic circuits shape odor-specific patterns of olfactory bulb output activity. These mechanisms are likely to be important for the processing of odor-encoding activity patterns in the olfactory bulb

Development of a cDNA microarray for the measurement of gene expression in the sheep scab mite Psoroptes ovis

Background: Sheep scab is caused by the ectoparasitic mite Psoroptes ovis which initiates a profound cutaneous inflammatory response, leading to the development of the skin lesions which are characteristic of the disease. Existing control strategies rely upon injectable endectocides and acaricidal dips but concerns over residues, eco-toxicity and the development of acaricide resistance limit the sustainability of this approach. In order to identify alternative means of disease control, a deeper understanding of both the parasite and its interaction with the host are required. Methods: Herein we describe the development and utilisation of an annotated P. ovis cDNA microarray containing 3,456 elements for the measurement of gene expression in this economically important ectoparasite. The array consists of 981 P. ovis EST sequences printed in triplicate along with 513 control elements. Array performance was validated through the analysis of gene expression differences between fed and starved P. ovis mites. Results: Sequences represented on the array include homologues of major house dust mite allergens and tick salivary proteins, along with factors potentially involved in mite reproduction and xenobiotic metabolism. In order to validate the performance of this unique resource under biological conditions we used the array to analyse gene expression differences between fed and starved P. ovis mites. These analyses identified a number of house dust mite allergen homologues up-regulated in fed mites and P. ovis transcripts involved in stress responses, autophagy and chemosensory perception up-regulated in starved mites. Conclusion: The P. ovis cDNA microarray described here has been shown to be both robust and reproducible and will enable future studies to analyse gene expression in this important ectoparasite

Proteomic Identification of IPSE/alpha-1 as a Major Hepatotoxin Secreted by Schistosoma mansoni Eggs

The flatworm disease, schistosomiasis, is a major public health problem in sub-Saharan Africa, South America and East Asia. A hallmark of infection with Schistosoma mansoni is the immune response to parasite eggs trapped in the liver and other organs. This response involves an infiltration of cells that surround the parasite egg forming a “granuloma.” In mice deprived of T-cells, this granulomatous response is lacking, and toxic products released by eggs quickly cause liver damage and death. Thus the granulomata protect the host from toxic egg products. Only one hepatotoxic molecule, omega-1, has been described to date. We set out to identify other S. mansoni egg hepatotoxins using liver cells grown in culture. We first showed that live eggs, their secretions, and pure omega-1 are toxic. Using a physical separation technique to prepare fractions from whole egg secretions, we identified the presence of IPSE/alpha-1, a protein that is known to strongly influence the immune system. We showed that IPSE/alpha-1 is also hepatotoxic, and that toxicity of both omega-1 and IPSE/alpha-1 can be prevented by first mixing the proteins with specific neutralizing antibodies. Both proteins constitute the majority of hepatotoxicity released by eggs

Distribution and determinants of patient satisfaction in oncology with a focus on health related quality of life

<p>Abstract</p> <p>Background</p> <p>Cancer patients usually undergo extensive and debilitating treatments, which make quality of life (QoL) and patient satisfaction important health care assessment measures. However, very few studies have evaluated the relationship between QoL and patient satisfaction in oncology. We investigated the clinical, demographic and QoL factors associated with patient satisfaction in a large heterogeneous sample of cancer patients.</p> <p>Methods</p> <p>A cohort of 538 cancer patients treated at Cancer Treatment Centers of America^®(CTCA) was assessed. A patient satisfaction questionnaire developed in-house by CTCA was used. It covered the following dimensions of patient satisfaction: hospital operations and services, physicians and staff, and patient endorsements for themselves and others. QoL was assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30). The clinical, demographic and QoL factors were evaluated for predictive significance using univariate and multivariate logistic regression.</p> <p>Results</p> <p>The mean age of our patient population was 54.1 years (SD = 10.5, range 17-86), with a slight preponderance of females (57.2%). Breast cancer (n = 124) and lung cancer (n = 101) were the most frequent cancer types. 481 (89.4%) patients were "very satisfied" with their overall experience. Age and several QoL function and symptom scales were predictive of overall patient satisfaction upon univariate analysis. In the multivariate modeling, only those with a score above the median on the fatigue measure (i.e. worse fatigue) had reduced odds of 0.28 of being very satisfied (p = 0.03).</p> <p>Conclusion</p> <p>Patient fatigue, as reported by the QoL fatigue scale, was an independent significant predictor of overall patient satisfaction. This finding argues for special attention and programs for cancer patients who report higher levels of fatigue given that fatigue is the most frequently reported symptom in cancer patients.</p