Perception of first respiratory infection with Pseudomonas aeruginosa by people with cystic fibrosis and those close to them: an online qualitative study

Background: People with cystic fibrosis (CF) are susceptible to respiratory infection with Pseudomonas aeruginosa (PA), which may become chronic if initial eradication fails. Environmental acquisition and person-to-person transmission can occur. Respiratory PA infection is associated with increased mortality and more hospitalisations. This may cause patients and families anxiety and lead them to adopt preventive measures which may be ineffectual and intrusive. It is not possible to hold a conventional focus group to explore these issues because people with CF cannot meet together due to the risk of cross-infection. Objective: To explore the perceptions of first respiratory infection with PA in people with CF and those close to them. Design: We designed an online survey, to maximise accessibility and avoid the risk of cross-infection. This established the respondent's relationship with CF, asked 3 open questions about perceptions of PA and a final question about the prioritisation of research. Responses were analysed using a structured, iterative process. We identified keywords, analysed these incontext and derived key themes. Setting: Promotion through social media allowed respondents from any country to participate. Participants: People with CF and those close to them. Results: Responses were received from 393 people, including 266 parents and 97 people with CF. The key themes were the emotional burden of PA (fear in particular); the burden of treatment PA entails and the need for accurate knowledge about PA. Conclusions: Lack of knowledge and the health beliefs of individuals may promote fear of infection and inappropriate avoidance measures. Uncertainty about the implications of PA infection and the treatment required may cause anxiety. Healthcare professionals should provide clear information about how PA might be acquired and the treatment necessary, making clear the limitations of current understanding and acknowledging health beliefs

Maker Movements, Do-It-Yourself Cultures and Participatory Design: Implications for HCI Research

Falling costs and the wider availability of computational components, platforms and ecosystems have enabled the expansion of maker movements and DIY cultures. This can be considered as a form of democratization of technology systems design, in alignment with the aims of Participatory Design approaches. However, this landscape is constantly evolving, and long-term implications for the HCI community are far from clear. The organizers of this one-day workshop invite participants to present their case studies, experiences and perspectives on the topic with the goal of increasing understanding within this area of research. The outcomes of the workshop will include the articulation of future research directions with the purpose of informing a research agenda, as well as the establishment of new collaborations and networks

Supersymmetric D-branes and calibrations on general N=1 backgrounds

We study the conditions to have supersymmetric D-branes on general {\cal N}=1 backgrounds with Ramond-Ramond fluxes. These conditions can be written in terms of the two pure spinors associated to the SU(3)\times SU(3) structure on T_M\oplus T^\star_M, and can be split into two parts each involving a different pure spinor. The first involves the integrable pure spinor and requires the D-brane to wrap a generalised complex submanifold with respect to the generalised complex structure associated to it. The second contains the non-integrable pure spinor and is related to the stability of the brane. The two conditions can be rephrased as a generalised calibration condition for the brane. The results preserve the generalised mirror symmetry relating the type IIA and IIB backgrounds considered, giving further evidence for this duality.Comment: 23 pages. Some improvements and clarifications, typos corrected and references added. v3: Version published in JHE

Lake-size dependency of wind shear and convection as controls on gas exchange

High-frequency physical observations from 40 temperate lakes were used to examine the relative contributions of wind shear (u*) and convection (w*) to turbulence in the surface mixed layer. Seasonal patterns of u* and w* were dissimilar; u* was often highest in the spring, while w * increased throughout the summer to a maximum in early fall. Convection was a larger mixed-layer turbulence source than wind shear (u */w*-1 for lakes* and w* differ in temporal pattern and magnitude across lakes, both convection and wind shear should be considered in future formulations of lake-air gas exchange, especially for small lakes. © 2012 by the American Geophysical Union.Jordan S. Read, David P. Hamilton, Ankur R. Desai, Kevin C. Rose, Sally MacIntyre, John D. Lenters, Robyn L. Smyth, Paul C. Hanson, Jonathan J. Cole, Peter A. Staehr, James A. Rusak, Donald C. Pierson, Justin D. Brookes, Alo Laas, and Chin H. W

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews

How do Zimbabweans value health states?

Background Quality of life weights based on valuations of health states are often used in cost utility analysis and population health measures. This paper reports on an attempt to develop quality of life weights within the Zimbabwe context. Methods 2,384 residents in randomly selected small residential plots of land in a high-density suburb of Harare valued descriptors of 38 health states based on different combinations of the five domains of the EQ-5D (mobility, self-care, usual activities, pain or discomfort and anxiety or depression). The English version of the EQ-5D was used. The time trade-off method was used to determine the values, and 19,020 individual preferences for health states were analysed. A residual maximum likelihood linear mixed model was used to estimate a function for predicting the values of all possible combinations of levels on the five domains. The model was fit to a random subset of two-thirds of the observations, with the remaining observations reserved for analysis of predictive validity. The results were compared to a similar study undertaken in the United Kingdom. Results A credible model was developed to predict the values of states that were not valued directly. In the subset of observations reserved for validation, the mean absolute difference between predicted and observed values was 0.045. All domains of the EQ-5D were found to contribute significantly to the model, both at the moderate and severe levels. Severe pain was found to have the largest negative coefficient, followed by the inability to wash and dress oneself. Conclusion Despite a generally lower education level than their European counterparts, urban Zimbabweans appear to value health states in a consistent manner, and the determination of a global method of establishing quality of life weights may be feasible and valid. However, as the relative weightings of the different domains, although correlated, differed from the standard set of weights recommended by the EuroQol Group, the locally determined coefficients should be used within the Zimbabwean context

Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

Suppression of cancer stemness p21-regulating mRNA and microRNA signatures in recurrent ovarian cancer patient samples

<p>Abstract</p> <p>Background</p> <p>Malignant ovarian disease is characterised by high rates of mortality due to high rates of recurrent chemoresistant disease. Anecdotal evidence indicates this may be due to chemoresistant properties of cancer stem cells (CSCs). However, our understanding of the role of CSCs in recurrent ovarian disease remains sparse. In this study we used gene microarrays and meta-analysis of our previously published microRNA (miRNA) data to assess the involvement of cancer stemness signatures in recurrent ovarian disease.</p> <p>Methods</p> <p>Microarray analysis was used to characterise early regulation events in an embryonal carcinoma (EC) model of cancer stemness. This was then compared to our previously published microarray data from a study of primary versus recurrent ovarian disease. In parallel, meta-analysis was used to identify cancer stemness miRNA signatures in tumor patient samples.</p> <p>Results</p> <p>Microarray analysis demonstrated a 90% difference between gene expression events involved in early regulation of differentiation in murine EC (mEC) and embryonic stem (mES) cells. This contrasts the known parallels between mEC and mES cells in the undifferentiated and well-differentiated states. Genelist comparisons identified a cancer stemness signature set of genes in primary versus recurrent data, a subset of which are known p53-p21 regulators. This signature is present in primary and recurrent or in primary alone but essentially never in recurrent tumors specifically. Meta-analysis of miRNA expression showed a much stronger cancer stemness signature within tumor samples. This miRNA signature again related to p53-p21 regulation and was expressed prominently in recurrent tumors. Our data indicate that the regulation of p53-p21 in ovarian cancer involves, at least partially, a cancer stemness component.</p> <p>Conclusion</p> <p>We present a p53-p21 cancer stemness signature model for ovarian cancer. We propose that this may, at least partially, differentially regulate the p53-p21 mechanism in ovarian disease. Targeting CSCs within ovarian cancer represents a potential therapeutic avenue.</p

The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers

There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on 10 research priorities which will be attractive to funders

A novel synonymous KMT2B variant in a patient with dystonia causes aberrant splicing

BACKGROUND: Heterozygous KMT2B variants are a common cause of dystonia. A novel synonymous KMT2B variant, c.5073C>T (p.Gly1691=) was identified in an individual with childhood-onset progressive dystonia. METHODS: The splicing impact of c.5073C>T was assessed using an in vitro exon-trapping assay. The genomic region of KMT2B exons 23-26 was cloned into the pSpliceExpress plasmid between exon 2 and 3 of the rat Ins2 gene. The c.5073C>T variant was then introduced through site-directed mutagenesis. The KMT2B wild-type and c.5073C>T plasmids were transfected separately into HeLa cells and RNA was extracted 48 hours after transfection. The RNA was reverse transcribed to produce cDNA, which was PCR amplified using primers annealing to the flanking rat Ins2 sequences. RESULTS: Sanger sequencing of the PCR products revealed that c.5073C>T caused a novel splice donor site and therefore a 5-bp deletion of KMT2B exon 23 in mature mRNA, leading to a coding frameshift and premature stop codon (p.Lys1692AsnfsTer7). CONCLUSION: To our knowledge, this is the first report of a KMT2B synonymous variant associated with dystonia. Reassessment of synonymous variants may increase diagnostic yield for inherited disorders including monogenic dystonia. This is of clinical importance, given the generally favourable response to deep brain stimulation for KMT2B-related dystonia