Clinical biological and genetic heterogeneity of the inborn errors of pulmonary surfactant metabolism

Pulmonary surfactant is a multimolecular complex located at the air-water interface within the alveolus to which a range of physical (surface-active properties) and immune functions has been assigned. This complex consists of a surface-active lipid layer (consisting mainly of phospholipids), and of an aqueous subphase. From discrete surfactant sub-fractions one can isolate strongly hydrophobic surf acta nt proteins B (SP-B) and C (SP-C) as well as collectins SP-A and SP-D, which were shown to have specific structural, metabolic, or immune properties. Inborn or acquired abnormalities of the surfactant, qualitative or quantitative in nature, account for a number of human diseases. Beside hyaline membrane disease of the preterm neonate, a cluster of hereditary or acquired lung diseases has been characterized by periodic acid-Schiff-positive material filling the alveoli. From this heterogeneous nosologic group, at least two discrete entities presently emerge. The first is the SP-B deficiency, in which an essentially proteinaceous material is stored within the alveoli, and which represents an autosomal recessive Mendelian entity linked to the SFTPB gene (MIM 1786640). The disease usually generally entails neonatal respiratory distress with rapid fatal outcome, although partial or transient deficiencies have also been observed. The second is alveolar proteinosis, characterized by the storage of a mixed protein and lipid material, which constitutes a relatively heterogeneous clinical and biological syndrome, especially with regard to age at onset (from the neonate through to adulthood) as well as the severity of associated signs. Murine models, with a targeted mutation of the gene encoding granulocyte macrophage colony-stimulating factor (GM-CSF) (Csfgm) or the beta subunit of its receptor (II3rb1) support the hypothesis of an abnormality of surfactant turnover in which the alveolar macrophage is a key player. Apart from SP-B deficiency, in which a near-consensus diagnostic chart can be designed, the ascertainment of other abnormalities of surfactant metabolism is not straightforward. The disentanglement of this disease cluster is however essential to propose specific therapeutic procedures: repeated broncho-alveolar ravages, GM-CSF replacement, bone marrow grafting or lung transplantation

East London’s Homeless: a retrospective review of an eye clinic for homeless people

Background There is very little published work on the visual needs of homeless people. This paper is the first study to investigate the visual needs of homeless people in the UK. Although similar work has been done in other countries, this study is unique because the United Kingdom is the only country with a National Health Service which provides free healthcare at the point of access. This study analysed the refractive status of the sample used, determined the demographics of homeless people seeking eye care and established if there is a need for community eye health with access to free spectacle correction in East London. Methods This retrospective case study analysed the clinical records of 1,141 homeless people using the Vision Care for Homeless People services at one of their clinics in East London. All eye examinations were carried out by qualified optometrists and, where appropriate, spectacles were dispensed to patients. Data captured included age, gender, ethnicity and refractive error. Results were analysed using two-sample t-tests with Excel and Minitab. Results Demographics of age, gender and ethnicity are described. Spherical equivalents (SE) were calculated from prescription data available for 841 clinic users. Emmetropia was defined as SE–0.50DS to +1DS, myopia as SE  +1DS. The majority of clinic users were male (79.2 %, n = 923). Approximately 80 % (n = 583) of clinic users were white, 10 % (n = 72) were ‘black’, 4 % (n = 29) ‘Asian’ and the remaining 5.6 % (n = 40) were of ‘mixed ethnicity’ and ‘other’ groups. The mean age of females attending the clinic was significantly lower than that of males (45.9 years, SD = 13.8 vs’ 48.4 years, SD = 11.8) when analysed using a two-sample t-test (t (317) = 2.44, p = 0.02). One third of service users were aged between 50–59 years. Myopia and hyperopia prevalence rates were 37.0 % and 21.0 % respectively. A total of 34.8 % of homeless people were found to have uncorrected refractive error, and required spectacle correction. Conclusions This study has identified a high proportion of uncorrected refractive error in this sample and therefore a need for regular eye examinations and provision of refractive correction for homeless people

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Attention or instruction: do sustained attentional abilities really differ between high and low hypnotisable persons?

Previous research has suggested that highly hypnotisable participants (‘highs’) are more sensitive to the bistability of ambiguous figures—as evidenced by reporting more perspective changes of a Necker cube—than low hypnotisable participants (‘lows’). This finding has been interpreted as supporting the hypothesis that highs have more efficient sustained attentional abilities than lows. However, the higher report of perspective changes in highs in comparison to lows may reflect the implementation of different expectation-based strategies as a result of differently constructed demand characteristics according to one’s level of hypnotisability. Highs, but not lows, might interpret an instruction to report perspective changes as an instruction to report many changes. Using a Necker cube as our bistable stimulus, we manipulated demand characteristics by giving specific information to participants of different hypnotisability levels. Participants were told that previous research has shown that people with similar hypnotisability as theirs were either very good at switching or maintaining perspective versus no information. Our results show that highs, but neither lows nor mediums, were strongly influenced by the given information. However, highs were not better at maintaining the same perspective than participants with lower hypnotisability. Taken together, these findings favour the view that the higher sensitivity of highs in comparison to lows to the bistability of ambiguous figures reflect the implementation of different strategies

Volunteer Bias in Recruitment, Retention, and Blood Sample Donation in a Randomised Controlled Trial Involving Mothers and Their Children at Six Months and Two Years: A Longitudinal Analysis

BACKGROUND: The vulnerability of clinical trials to volunteer bias is under-reported. Volunteer bias is systematic error due to differences between those who choose to participate in studies and those who do not. METHODS AND RESULTS: This paper extends the applications of the concept of volunteer bias by using data from a trial of probiotic supplementation for childhood atopy in healthy dyads to explore 1) differences between a) trial participants and aggregated data from publicly available databases b) participants and non-participants as the trial progressed 2) impact on trial findings of weighting data according to deprivation (Townsend) fifths in the sample and target populations. 1) a) Recruits (n = 454) were less deprived than the target population, matched for area of residence and delivery dates (n = 6,893) (mean [SD] deprivation scores 0.09[4.21] and 0.79[4.08], t = 3.44, df = 511, p<0.001). b) i) As the trial progressed, representation of the most deprived decreased. These participants and smokers were less likely to be retained at 6 months (n = 430[95%]) (OR 0.29,0.13-0.67 and 0.20,0.09-0.46), and 2 years (n = 380[84%]) (aOR 0.68,0.50-0.93 and 0.55,0.28-1.09), and consent to infant blood sample donation (n = 220[48%]) (aOR 0.72,0.57-0.92 and 0.43,0.22-0.83). ii) Mothers interested in probiotics or research or reporting infants' adverse events or rashes were more likely to attend research clinics and consent to skin-prick testing. Mothers participating to help children were more likely to consent to infant blood sample donation. 2) In one trial outcome, atopic eczema, the intervention had a positive effect only in the over-represented, least deprived group. Here, data weighting attenuated risk reduction from 6.9%(0.9-13.1%) to 4.6%(-1.4-+10.5%), and OR from 0.40(0.18-0.91) to 0.56(0.26-1.21). Other findings were unchanged. CONCLUSIONS: Potential for volunteer bias intensified during the trial, due to non-participation of the most deprived and smokers. However, these were not the only predictors of non-participation. Data weighting quantified volunteer bias and modified one important trial outcome. TRIAL REGISTRATION: This randomised, double blind, parallel group, placebo controlled trial is registered with the International Standard Randomised Controlled Trials Register, Number (ISRCTN) 26287422. Registered title: Probiotics in the prevention of atopy in infants and children

The effect of a supplementary ('Gist-based') information leaflet on colorectal cancer knowledge and screening intention: a randomized controlled trial.

Guided by Fuzzy Trace Theory, this study examined the impact of a 'Gist-based' leaflet on colorectal cancer screening knowledge and intentions; and tested the interaction with participants' numerical ability. Adults aged 45-59 years from four UK general practices were randomly assigned to receive standard information ('The Facts', n = 2,216) versus standard information plus 'The Gist' leaflet (Gist + Facts, n = 2,236). Questionnaires were returned by 964/4,452 individuals (22 %). 82 % of respondents reported having read the information, but those with poor numeracy were less likely (74 vs. 88 %, p < .001). The 'Gist + Facts' group were more likely to reach the criterion for adequate knowledge (95 vs. 91 %; p < .01), but this was not moderated by numeracy. Most respondents (98 %) intended to participate in screening, with no group differences and no interaction with numeracy. The improved levels of knowledge and self-reported reading suggest 'The Gist' leaflet may increase engagement with colorectal cancer screening, but ceiling effects reduced the likelihood that screening intentions would be affected

A development study and randomised feasibility trial of a tailored intervention to improve activity and reduce falls in older adults with mild cognitive impairment and mild dementia

Background: People with dementia progressively lose abilities and are prone to falling. Exercise- and activity-based interventions hold the prospect of increasing abilities, reducing falls, and slowing decline in cognition. Current falls prevention approaches are poorly suited to people with dementia, however, and are of uncertain effectiveness. We used multiple sources, and a co-production approach, to develop a new intervention, which we will evaluate in a feasibility randomised controlled trial (RCT), with embedded adherence, process and economic analyses. Methods: We will recruit people with mild cognitive impairment or mild dementia from memory assessment clinics, and a family member or carer. We will randomise participants between a therapy programme with high intensity supervision over 12 months, a therapy programme with moderate intensity supervision over 3 months, and brief falls assessment and advice as a control intervention. The therapy programmes will be delivered at home by mental health specialist therapists and therapy assistants. We will measure activities of daily living, falls and a battery of intermediate and distal health status outcomes, including activity, balance, cognition, mood and quality of life. The main aim is to test recruitment and retention, intervention delivery, data collection and other trial processes in advance of a planned definitive RCT. We will also study motivation and adherence, and conduct a process evaluation to help understand why results occurred using mixed methods, including a qualitative interview study and scales measuring psychological, motivation and communication variables. We will undertake an economic study, including modelling of future impact and cost to end-of-life, and a social return on investment analysis. Discussion: In this study, we aim to better understand the practicalities of both intervention and research delivery, and to generate substantial new knowledge on motivation, adherence and the approach to economic analysis. This will enable us to refine a novel intervention to promote activity and safety after a diagnosis of dementia, which will be evaluated in a definitive randomised controlled trial.\ud Trial registration: ClinicalTrials.gov: NCT02874300; ISRCTN 10550694

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Large Differences in Publicly Visible Health Behaviours across Two Neighbourhoods of the Same City

Background: There are socioeconomic disparities in the likelihood of adopting unhealthy behaviours, and success at giving them up. This may be in part because people living in deprived areas are exposed to greater rates of unhealthy behaviour amongst those living around them. Conventional self-report surveys do not capture these differences in exposure, and more ethological methods are required in order to do so. Methodology/Principal Findings: We performed 12 hours of direct behavioural observation in the streets of two neighbourhoods of the same city which were similar in most regards, except that one was much more socioeconomically deprived than the other. There were large differences in the publicly visible health behaviours observed. In the deprived neighbourhood, we observed 266 more adults smoking (rate ratio 3.44), 53 more adults drinking alcohol (rate ratio not calculable), and 38 fewer adults running (rate ratio 0.23), than in the affluent neighbourhood. We used data from the Health Survey for England to calculate the differences we ought to expect to have seen given the individual-level socioeconomic characteristics of the residents. The observed disparities between the two neighbourhoods were considerably greater than this null model predicted. There were also different patterns of smoking in proximity to children in the two neighbourhoods. Conclusions/Significance: The differences in observed smoking, drinking alcohol, and physical activity between these tw

A survey study of women's responses to information about overdiagnosis in breast cancer screening in Britain

Background: There is concern about public understanding of overdiagnosis in breast cancer screening, and uncertainty about the likely impact on screening participation. Methods: In a population-based survey of 2272 women, we assessed understanding of overdiagnosis and screening intentions before and after exposure to an explanation of overdiagnosis, and one of the three information formats providing an estimate of the rate of overdiagnosis based on the findings of the UK Independent Review. Results: Subjective and objective comprehension of overdiagnosis was moderate across information formats (64% and 57%, respectively). Following overdiagnosis information, 7% of women showed a decrease in screening intention, with a stronger effect among women below screening age (<47 years), and receiving the estimate of the rate of overdiagnosis in a simple ratio format (one life saved to three overdiagnoses). Conclusions: Brief written information on overdiagnosis was incompletely understood, but reduced breast screening intentions in a proportion of women, regardless of comprehension. Subjective comprehension was lower among women who had not yet reached screening age but the deterrent effect was higher