Consent for the use of human biological samples for biomedical research: a mixed methods study exploring the UK public’s preferences

OBJECTIVE: A mixed-methods study exploring the UK general public's views towards consent for the use of biosamples for biomedical research.<p></p> SETTING: Cross-sectional population-based focus groups followed by an online survey.<p></p> PARTICIPANTS: 12 focus groups (81 participants) selectively sampled to reflect a range of demographic groups; 1110 survey responders recruited through a stratified sampling method with quotas set on sex, age, geographical location, socioeconomic group and ethnicity.<p></p> MAIN OUTCOME MEASURES: (1) Views on the importance of consent when donating residual biosamples for medical research; (2) preferences for opt-in or opt-out consent approaches and (3) preferences for different consent models.<p></p> RESULTS: Participants believed obtaining consent for use of residual biosamples was important as it was 'morally correct' to ask, and enabled people to make an active choice and retain control over their biosamples. Survey responders preferred opt-in consent (55%); the strongest predictor was being from a low socioeconomic group (OR 2.22, 95% CI 1.41 to 3.57, p=0.001) and having a religious affiliation (OR 1.36, 95% CI 1.01 to 1.81, p=0.04). Focus group participants had a slight preference for opt-out consent because by using this approach more biosamples would be available and facilitate research. Concerning preferred models of consent for research use of biosamples, survey responders preferred specific consent with recontact for each study for which their biosamples are eligible. Focus group participants preferred generic consent as it provided 'flexibility for researchers' and reduced the likelihood that biosamples would be wasted. The strongest predictor for preferring specific consent was preferring opt-in consent (OR 4.58, 95% CI 3.30 to 6.35, p=0.015) followed by non-'White' ethnicity (OR 2.94, 95% CI 1.23 to 7.14, p<0.001).<p></p> CONCLUSIONS: There is a preference among the UK public for ongoing choice and control over donated biosamples; however, increased knowledge and opportunity for discussion is associated with acceptance of less restrictive consent models for some people.<p></p&gt

Tunable Ag@SiO2 core-shell nanocomposites for broad spectrum antibacterial applications

Silica encapsulated silver nanoparticle core–shell nanocomposites of tunable dimensions were synthesised via a one-pot reverse microemulsion route to achieve controlled release of Ag+ ions for broad spectrum antibacterial application. Silver release rates and bactericidal efficacy against Gram-positive and Gram-negative bacteria, S. aureus and P. aeruginosa respectively, were inversely proportional to nanoparticle core diameter (3–8 nm) and silica shell (7–14 nm) thickness, and readily tuned through a facile hydrothermal etching protocol employing a PVP stabiliser to introduce mesoporosity

New Experimental Limits on Macroscopic Forces Below 100 Microns

Results of an experimental search for new macroscopic forces with Yukawa range between 5 and 500 microns are presented. The experiment uses 1 kHz mechanical oscillators as test masses with a stiff conducting shield between them to suppress backgrounds. No signal is observed above the instrumental thermal noise after 22 hours of integration time. These results provide the strongest limits to date between 10 and 100 microns, improve on previous limits by as much as three orders of magnitude, and rule out half of the remaining parameter space for predictions of string-inspired models with low-energy supersymmetry breaking. New forces of four times gravitational strength or greater are excluded at the 95% confidence level for interaction ranges between 200 and 500 microns.Comment: 25 Pages, 7 Figures: Minor Correction

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion

Looking backward: From Euler to Riemann

We survey the main ideas in the early history of the subjects on which Riemann worked and that led to some of his most important discoveries. The subjects discussed include the theory of functions of a complex variable, elliptic and Abelian integrals, the hypergeometric series, the zeta function, topology, differential geometry, integration, and the notion of space. We shall see that among Riemann's predecessors in all these fields, one name occupies a prominent place, this is Leonhard Euler. The final version of this paper will appear in the book \emph{From Riemann to differential geometry and relativity} (L. Ji, A. Papadopoulos and S. Yamada, ed.) Berlin: Springer, 2017

Synthesis and crystal structures of 5'-phenylspiro[indoline-3, 2'-pyrrolidin]-2-one derivatives

<p>Abstract</p> <p>Background</p> <p>The spiro- indole-pyrrolidine ring system is a frequently encountered structural motif in many biologically important and pharmacologically relevant alkaloids. The derivatives of spirooxindole ring systems are used as antimicrobial, antitumour agents and as inhibitors of the human NKI receptor besides being found in a number of alkaloids like horsifiline, spirotryprostatin and (+) elacomine. The recently discovered small-molecule MDM2 inhibitor MI-219 and its analogues are in advanced preclinical development as cancer therapeutics.</p> <p>Results</p> <p>In the crystal structures of the two organic compounds, 4'-Nitro-3',5'-diphenylspiro[indoline-3,2'-pyrrolidin]-2-one and 3'-(4-Methoxyphenyl)- 4'-nitro -5'-phenylspiro[indoline-3,2'-pyrrolidin]-2-one, N-H···O hydrogen bonds make the R²₂(8) ring motif. Further, the structures are stabilized by intermolecular hydrogen bonds.</p> <p>Conclusion</p> <p>The crystal structures of 4'-Nitro-3',5'-diphenylspiro[indoline-3,2'-pyrrolidin]-2-one and 3'-(4-Methoxyphenyl)- 4'-nitro -5'-phenylspiro[indoline-3,2'-pyrrolidin]-2-one have been investigated in detail. In both the compounds, the R²₂(8) motif is present. Due to the substitution of methoxyphenyl instead of phenyl ring, the entire configuration is inverted with respect to the 2-oxyindole ring.</p

Green Plants in the Red: A Baseline Global Assessment for the IUCN Sampled Red List Index for Plants

Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question ‘How threatened are plants?’ is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world’s plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed

Primary care nurses' experiences of how the mass media influence frontline healthcare in the UK

Background: Mass media plays an important role in communicating about health research and services to patients, and in shaping public perceptions and decisions about health. Healthcare professionals also play an important role in providing patients with credible, evidence-based and up-to-date information on a wide range of health issues. This study aims to explore primary care nurses' experiences of how mass media influences frontline healthcare.&lt;p&gt;&lt;/p&gt; Methods: In-depth telephone interviews were carried out with 18 primary care nurses (nine health visitors and nine practice nurses) working in the United Kingdom (UK). Interviews were recorded and transcribed. The data was analysed using thematic analysis, with a focus on constant comparative analysis.&lt;p&gt;&lt;/p&gt; Results: Three themes emerged from the data. First, participants reported that their patients were frequently influenced by controversial health stories reported in the media, which affected their perceptions of, and decisions about, care. This, in turn, impinged upon participants' workloads as they had to spend additional time discussing information and reassuring patients. Second, participants also recalled times in their own careers when media reports had contributed to a decline in their confidence in current healthcare practices and treatments. Third, the participants in this study suggested a real need for additional resources to support and expand their own media literacy skills, which could be shared with patients.&lt;p&gt;&lt;/p&gt; Conclusion: In an ever expanding media landscape with greater reporting on health, nurses working in the primary care setting face increasing pressure to effectively manage media stories that dispute current health policies and practices. These primary care nurses were keen to expand their media literacy skills to develop critical autonomy in relation to all media, and to facilitate more meaningful conversations with their patients about their health concerns and choices.&lt;p&gt;&lt;/p&gt

Rationality and the experimental study of reasoning

A survey of the results obtained during the past three decades in some of the most widely used tasks and paradigms in the experimental study of reasoning is presented. It is shown that, at first sight, human performance suffers from serious shortcomings. However, after the problems of communication between experimenter and subject are taken into account, which leads to clarify the subject's representation of the tasks, one observes a better performance, although still far from perfect. Current theories of reasoning, of which the two most prominent are very briefly outlined, agree in identifying the load in working memory as the main source of limitation in performance. Finally, a recent view on human rationality prompted by the foregoing results is described

Epigenetic silencing and deletion of the BRCA1 gene in sporadic breast cancer

INTRODUCTION: BRCA1 or BRCA2 germline mutations increase the risk of developing breast cancer. Tumour cells from germline mutation carriers have frequently lost the wild-type allele. This is predicted to result in genomic instability where cell survival depends upon dysfunctional checkpoint mechanisms. Tumorigenic potential could then be acquired through further genomic alterations. Surprisingly, somatic BRCA mutations are not found in sporadic breast tumours. BRCA1 methylation has been shown to occur in sporadic breast tumours and to be associated with reduced gene expression. We examined the frequency of BRCA1 methylation in 143 primary sporadic breast tumours along with BRCA1 copy number alterations and tumour phenotype. METHODS: Primary sporadic breast tumours were analysed for BRCA1α promoter methylation by methylation specific PCR and for allelic imbalance (AI) at BRCA1 and BRCA2 loci by microsatellite analysis and TP53 (also known as p53) mutations by constant denaturing gel electrophoresis. The BRCA1 methylated tumours were analysed for BRCA1 copy alterations by fluorescence in situ hybridisation and BRCA1 expression by immunostaining. RESULTS: BRCA1 methylation was found in 13/143 (9.1%) sporadic breast tumours. The BRCA1 methylated tumours were significantly associated with estrogen receptor (ER) negativity (P = 0.0475) and displayed a trend for BRCA1 AI (P = 0.0731) as well as young-age at diagnosis (≤ 55; P = 0.0898). BRCA1 methylation was not associated with BRCA2 AI (P = 0.5420), although a significant association was found between BRCA1 AI and BRCA2 AI (P < 0.0001). Absent/markedly reduced BRCA1 expression was observed in 9/13 BRCA1 methylated tumours, most of which had BRCA1 deletion. An elevated TP53 mutation frequency was found among BRCA1 methylated tumours (38.5%) compared with non-methylated tumours (17.2%). The BRCA1 methylated tumours were mainly of tumour grade 3 (7/13) and infiltrating ductal type (12/13). Only one methylated tumour was of grade 1. CONCLUSION: BRCA1 methylation is frequent in primary sporadic breast tumours. We found an indication for BRCA1 methylation to be associated with AI at the BRCA1 locus. Almost all BRCA1 methylated tumours with absent/markedly reduced BRCA1 expression (8/9) displayed BRCA1 deletion. Thus, epigenetic silencing and deletion of the BRCA1 gene might serve as Knudson's two 'hits' in sporadic breast tumorigenesis. We observed phenotypic similarities between BRCA1 methylated and familial BRCA1 tumours, based on BRCA1 deletion, TP53 mutations, ER status, young age at diagnosis and tumour grade