922017 research outputs found
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Position Paper: Towards a Hybrid Approach to Protect Against Memory Safety Vulnerabilities
No full textMemory corruption bugs continue to plague lowlevel systems software, generally written in unsafe programming languages. In order to detect and protect against such exploits, many pre- and post-deployment techniques exist. In this position paper, we propose and motivate the need for a hybrid approach for the protection against memory safety vulnerabilities, combining techniques that can identify the presence (and absence) of vulnerabilities pre-deployment with those that can detect and mitigate such vulnerabilities post-deployment. Our proposed hybrid approach involves three layers: hardware runtime protection provided by capability hardware, software runtime protection provided by compiler instrumentation, and static analysis provided by bounded model checking and symbolic execution. The key aspect of the proposed hybrid approach is that the protection offered is greater than the sum of its parts – the expense of postdeployment runtime checks is potentially reduced via information obtained during pre-deployment analysis. During pre-deployment analysis, static checking can be guided by runtime information
SWAT 86 evaluation: Randomised evaluation of pre-notification of trial participants before self-report outcome data collection to improve retention
No full textBackgroundRetention is considered the second highest trial methods priority in the UK after recruitment. There is limited evidence on whether notifying trial participants that a follow-up questionnaire will be sent soon (‘pre-notification’) affects retention. MethodsThis Study Within a Trial (SWAT) evaluated whether sending a pre-notification letter or email around 2 weeks before sending a self-report questionnaire increased retention, in terms of provision of the host trial primary outcome. The SWAT was a randomised, two-arm, parallel-design (1:1 allocation ratio) trial, controlled by ‘no pre-notification letter’. It was embedded within the WORKWELL host trial, which evaluated the impact of job retention vocational rehabilitation on work-related and health-related outcomes of employed people with inflammatory arthritis. The SWAT primary outcome was a valid response for the WORKWELL primary outcome.Results244 trial participants took part in the SWAT. All were included in the analysis. Among those sent a pre-reminder, 100/121 (83%) provided a valid response for the WORKWELL primary outcome, compared to 97/123 (79%) of those not sent a pre-reminder. The estimated adjusted odds ratio was 1.28 (95% confidence interval 0.67 to 2.42), with a risk difference of 3.8% (95%CI -6.1% to 13.6%), favouring the pre-reminder. The estimated intervention cost per additional participant retained was £53.42, and the total cost per additional participant retained was £46.52.ConclusionResearchers may have a small improvement in trial retention by using pre-notification. The cost per additional participant retained is relatively low. However, further evaluations are merited.<br/
Multilevel modelling approach to analysing life course socioeconomic status and understanding missingness
No full textThis paper investigated the extent to which parental socioeconomic status was associated with life course socioeconomic status heterogeneity between adult cohort members of the 1958 National Child Development Study and how this association differed depending on methods used to address longitudinal missing data. We compared three variants of the full information maximum likelihood approach, namely available case, complete case and partially observed case and two methods designed to compensate for missing at random data, namely multilevel multiple imputation and multiple imputation chained equations. Our results highlighted the important contribution of parental socioeconomic status in explaining the divergence in achieved socioeconomic status over the adult life course, how the available case approach increasingly overestimated socioeconomic attainment as age increased and survey sample size decreased, and how the complete case approach downwardly biased the effect of parental socioeconomic status on adult socioeconomic status
Photocatalytic biomass reforming: what role will the technology play in future energy systems
No full textPhotocatalytic biomass reforming has emerged as an area of significant interest within the last decade. The number of papers published in the literature has been steadily increasing with keywords such as ‘hydrogen’ and ‘visible’ becoming prominent research topics. There are likely two primary drivers behind this, the first of which is biomass represents a more sustainable photocatalytic feedstock for reforming to value-added products and energy. The second is the transition towards achieving net zero emission targets, which has increased focus on the development of technologies that could play a role in future energy systems. Therefore, this review provides a perspective on not only the current state of the art of research but also a future outlook on the potential roadmap for photocatalysis biomass reforming. Producing energy via photocatalytic biomass reforming is very desirable due to the ambient operating conditions and potential to utilise renewable energy (e.g. solar) with a wide variety of biomass resources. As both interest and development within this field continues to grow, however, there are challenges being identified that are paramount to further advancement. In reviewing both the literature and trajectory of the field, research priorities can be identified and utilised to facilitate fundamental research alongside whole systems evaluation. Moreover, this would underpin the enhancement of photocatalytic technology with a view towards improving the Technology Readiness Level and promoting engagement between academic and industry
Comparison of multiple gene expression platforms for measuring a bladder cancer hypoxia signature
No full textTumour hypoxia status provides prognostic information and predicts response to hypoxia-modifying treatments. We previously derived a 24-gene signature to assess hypoxia in bladder cancer. The objectives here were to: compare platforms for generating signature scores, identify cut-off values for prospective studies, assess intra-tumour heterogeneity and confirm hypoxia relevance. RNA was extracted from prospectively-collected diagnostic biopsies of muscle invasive bladder cancer (51 patients) and gene expression measured using customised Taqman Low Density Array (TLDA) cards, NanoString and Clariom S arrays. Cross-platform transferability of the gene signature was assessed using regression and concordance analysis. Cut-off values were the cohort median expression values. Intra- and inter-tumour variability were determined in a retrospective patient cohort (n=51) with multiple blocks (2-18) from the same tumour. To demonstrate relevance, bladder cancer cell lines were exposed to hypoxia (0.1% oxygen, 24 h), and extracted RNA run on custom TLDA cards. Hypoxia scores showed good agreement between platforms: Clariom S vs TLDA (r=0.72, p<0.0001; concordance 73%); Clariom S vs NanoString (r=0.84, p<0.0001; 78%); TLDA vs NanoString (r=0.80, p<0.0001; 78%). Cut-off values were 0.047 (TLDA), 7.328 (NanoString) and 6.667 (Clariom S). Intra-tumour heterogeneity in gene expression and HS (coefficient of variation 3.9%) was less than inter-tumour (7.9%) variability. Hypoxia scores were higher in bladder cancer cells exposed to hypoxia vs normoxia (p<0.02). Application of the 24-gene bladder cancer hypoxia signature is platform agnostic, cut-off values determined prospectively can be used in a clinical trial, intra-tumour heterogeneity is low and the signature is sensitive to changes in oxygen levels in vitro
Depression and anxiety in a real-world psoriatic arthritis longitudinal study. Should we focus more on patients’ perception?
No full textObjectives: Longitudinal studies using validated tools to evaluate depression and anxiety in psoriatic arthritis (PsA) are lacking. We aimed to estimate their course in PsA and to examine possible associations with disease-related parameters and patient-reported outcomes (PROs).Methods: PsA patients attending two outpatient rheumatology clinics were consecutively enrolled (January 2019-June 2021, n=128). The hospital anxiety and depression scale (HADS) was used at two sequential visits (mean±SD: 10±6 months) to prospectively assess depression (HADS-Depression) and anxiety (HADS-Anxiety) (cut-off scores≥11). Associations with demographic, clinical, laboratory features and PROs for quality of life (QoL) (EQ-5D), functional status (HAQ-DI) and nocebo-behaviour (Q-No) were examined. ‘Change’ was the difference between values at the first and second visit.Results: Prevalence of depression and anxiety at the first visit was 19.5% and 21.1%, respectively. Depression was associated with EQ-5D [OR (95% CI): 1.70 (1.02-2.59), p=0.019] and anxiety with EQ-5D [1.81 (1.20 to 2.72), p=0.005], nocebo-behaviour [1.19 (1.01-1.40), p=0.04] and current corticosteroid use [6.95 (1.75-27.59), p=0.006]. At the second visit, HADS-Depression and HADS-Anxiety scores were improved in 40.9% and 41.9% of patients, respectively. While no associations were found for HADS-Anxiety score change, changes in HADS-Depression score correlated with changes in subjective (tender joint count, r= 0.204, p=0.049; PtG, r= 0.236, p=0.023; patient pain assessment, r= 0.266, p=0.01) but not objective (swollen joint count, ESR, CRP) parameters of disease activity.Conclusion: In PsA, depression and anxiety are associated with worse PROs, including QoL. Subjective parameters of disease activity parallel course of depression.<br/
Second coordination sphere effects on the mechanistic pathways for dioxygen activation by a ferritin: involvement of a Tyr radical and the identification of a cation binding site
No full textFerritins are ubiquitous diiron enzymes involved in iron(II) detoxification and oxidative stress responses and can act as metabolic iron stores. The overall reaction mechanisms of ferritin enzymes are still unclear, particularly concerning the role of the conserved, near catalytic center Tyr residue. Thus, we carried out a computational study of a ferritin using a large cluster model of well over 300 atoms including its first- and second-coordination sphere. The calculations reveal important insight into the structure and reactivity of ferritins. Specifically, the active site Tyr residue delivers a proton and electron in the catalytic cycle prior to iron(II) oxidation. In addition, the calculations highlight a likely cation binding site at Asp65, which through long-range electrostatic interactions, influences the electronic configuration and charge distributions of the metal center. The results are consistent with experimental observations but reveal novel detail of early mechanistic steps that lead to an unusual mixedvalent iron(III)-iron(II) center
Combined statistical decision limits based on two GH-2000 scores for the detection of growth hormone misuse
No full textThe GH-2000 biomarker method, based on the measurements of insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP), has been developed as a powerful technique for the detection of growth hormone (GH) misuse by athletes. IGF-I and P-III-NP are combined in gender specific formulas to create the GH-2000 score, which is used to determine whether GH has been administered. To comply with World Anti-Doping Agency regulations, each analyte must be measured by two methods. IGF-I and P-III-NP can be measured by a number of approved methods, each leading to its own GH-2000 score. Single decision limits for each GH-2000 score have been introduced and developed by Bassett, Erotokritou-Mulligan, Holt, Boehning and their co-authors in a series of papers. These have been incorporated into the guidelines of the World Anti-Doping Agency. A joint decision limit was constructed based on the sample correlation between the two GH-2000 scores generated from an available sample in order to increase the sensitivity of the biomarker method. This paper takes this idea further into a fully developed statistical approach. It constructs combined decision limits when two GH-2000 scores from different assay combinations are used to decide whether an athlete has been misusing GH. The combined decision limits are directly related to tolerance regions and constructed using a Bayesian approach. It is also shown to have highly satisfactory frequentist properties. The new approach meets the required false-positive rate with a pre-specified level of certainty
Students’ views about alternates to traditional dissertation for Master in Public Health: results of a virtual focus group
No full textA traditional dissertation remains a component of most Master in Public Health programmes, but there is increasing interest and use of alternatives. A virtual focus group of six students studying an online distance Master in Public Health explored their perceptions about dissertations and preferences for alternatives. Students value the dissertation as a means of consolidating learning and focusing in-depth on chosen topics. Alternatives were viewed as attractive but not always practical. Participants felt that additional options need to be accompanied by guidance to ensure students make the most appropriate choice for their future. Three types of students with different needs emerged; students aspiring to progress to a PhD should do a traditional dissertation, students already employed in a relevant role may choose a work-based dissertation or replace the dissertation with taught units, and students doing the master to increase their employability could choose a placement-based dissertation or replace the dissertation with work experience reflection. Innovations that introduce alternatives to the traditional dissertation would be welcomed by MPH students studying online, but they would need to be accompanied by suitable career advice to ensure students choose the most appropriate route for their future aspirations
Self-report measures of secure attachment in adulthood: A systematic review:Self-report adult secure attachment measures
No full textBackground: Secure attachment in adulthood is associated with many markers of adaptive functioning. Valid and reliable self-report measures of attachment security could provide a practical tool to help advance strengths-based research and clinical work. Previous reviews have not specifically examined the psychometric properties of self-report instruments with respects to secure attachment, or systematically appraised the methodological quality of relevant validation studies. Method: A systematic review was completed in accordance with the COSMIN guidelines for reviews of patient-reported outcome measures. The methodological quality of individual studies was evaluated, and results were rated against criteria for good measurement properties. Results: 40 studies were included in the review, which collectively reported on 24 self-report instruments. The methodological quality of individual studies was variable, and no single instrument was identified as having sufficient evidence of a range of psychometric properties. However, the Attachment Style Questionnaire – Short Form (ASQ-SF), the Cartes-Modèles Individuels de Relations (CAMIR), Cartes-Modèles Individuels de Relations-Reduced (CAMIR-R), and the Psychological Treatment Inventory – Attachment Style Scales (PTI-ASS) had the most robust evidence for the properties assessed.Conclusion: Existing self-report measures assessing adult secure attachment have limited psychometric support. More methodologically robust studies of content validity, reliability, measurement invariance, and construct validity in particular are needed. <br/