Ultrasonic measurement of core material temperature Final report

Ultrasonic measurement of core material temperature in nuclear rocket engine

Plant Sterols as Dietary Adjuvants in the Reduction of Cardiovascular Risk: Theory and Evidence

Plant sterol-enriched foods are an effective dietary adjuvant in reducing cardiovascular risk by lowering total cholesterol and low density lipoprotein-cholesterol (LDL-C) in serum by up to ∼15%. The mechanism of action of plant sterols is different from those of 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) and thus their effect is additive. Combining plant sterols with other dietary components known to reduce cholesterol in a portfolio approach has proven to be most effective for reduction of hypercholesterolemia and provide an alternative treatment option for clinicians. Plant sterol-enriched foods provides clinicians with a relatively cheap, safe, and effective way to help patients manage their cardiovascular risk

Young people's understanding, attitudes and involvement in decision-making about genome sequencing for rare diseases: A qualitative study with participants in the UK 100,000 genomes project

Genome sequencing (GS) will have a profound impact on the diagnosis of rare and inherited diseases in children and young people. We conducted 27 semi-structured interviews with young people aged 11-19 having GS through the UK 100,000 Genomes Project. Participants demonstrated an understanding of the role and function of genes and DNA, however the terms 'genome' and 'genome sequencing' were less well understood. Participants were primarily motivated to take part to get a diagnosis or identify the gene causing their condition. The majority of participants understood they might not receive a diagnostic result. Most were unconcerned about data security or access, however anxieties existed around what the results might show and the potential for disappointment if the result was negative. Signing an assent form empowered young people, formalised the process and instilled a sense of responsibility for their choice to participate. Most young people (≥16 years) had consented to receive secondary findings and had come to that decision without parental influence. Our research suggests that at least some young people are capable of making informed decisions about taking part in GS, and that involving them in discussions about testing can empower them to take responsibility over healthcare decisions that affect them

Delivering genome sequencing in clinical practice: an interview study with healthcare professionals involved in the 100 000 Genomes Project

Objectives: Genome sequencing is poised to be incorporated into clinical care for diagnoses of rare diseases and some cancers in many parts of the world. Healthcare professionals are key stakeholders in the clinical delivery of genome sequencing-based services. Our aim was to explore views of healthcare professionals with experience of offering genome sequencing via the 100 000 Genomes Project. Design: Interview study using thematic analysis. Setting: Four National Health Service hospitals in London. Participants: Twenty-three healthcare professionals (five genetic clinicians and eight non-genetic clinicians (all consultants), and 10 ‘consenters’ from a range of backgrounds) involved in identifying or consenting patients for the 100 000 Genomes Project. Results: Most participants expressed positive attitudes towards genome sequencing in terms of improved ability to diagnose rare diseases, but many also expressed concerns, with some believing its superiority over exome sequencing had not yet been demonstrated, or worrying that non-genetic clinicians are inadequately prepared to discuss genome sequencing results with patients. Several emphasised additional evidence about utility of genome sequencing in terms of both main and secondary findings is needed. Most felt non-genetic clinicians could support patients during consent, as long as they have appropriate training and support from genetic teams. Many stated genetics experts will play a vital role in training and supporting non-genetic clinicians in variant interpretation and results delivery, particularly for more complex cases. Conclusions: Healthcare professionals responsible for delivering clinical genome sequencing have largely positive views about the potential for genome sequencing to improve diagnostic yield, but also significant concerns about practical aspects of offering these tests. Non-genetic clinicians delivering genome sequencing require guidance and support. Additional empirical evidence is needed to inform policy and practice, including how genome compares to exome sequencing; utility of secondary findings; training, in particular of non-genetic health professionals; and mechanisms whereby genetics teams can offer appropriate support to their non-genetics colleagues

Quantitative analysis of Nipah virus proteins released as virus-like particles reveals central role for the matrix protein

BACKGROUND: Nipah virus (NiV) is an emerging paramyxovirus distinguished by its ability to cause fatal disease in both animal and human hosts. Together with Hendra virus (HeV), they comprise the genus Henipavirus in the Paramyxoviridae family. NiV and HeV are also restricted to Biosafety Level-4 containment and this has hampered progress towards examining details of their replication and morphogenesis. Here, we have established recombinant expression systems to study NiV particle assembly and budding through the formation of virus-like particles (VLPs). RESULTS: When expressed by recombinant Modified Vaccinia virus Ankara (rMVA) or plasmid transfection, individual NiV matrix (M), fusion (F) and attachment (G) proteins were all released into culture supernatants in a membrane-associated state as determined by sucrose density gradient flotation and immunoprecipitation. However, co-expression of F and G along with M revealed a shift in their distribution across the gradient, indicating association with M in VLPs. Protein release was also altered depending on the context of viral proteins being expressed, with F, G and nucleocapsid (N) protein reducing M release, and N release dependent on the co-expression of M. Immunoelectron microscopy and density analysis revealed VLPs that were similar to authentic virus. Differences in the budding dynamics of NiV proteins were also noted between rMVA and plasmid based strategies, suggesting that over-expression by poxvirus may not be appropriate for studying the details of recombinant virus particle assembly and release. CONCLUSION: Taken together, the results indicate that NiV M, F, and G each possess some ability to bud from expressing cells, and that co-expression of these viral proteins results in a more organized budding process with M playing a central role. These findings will aid our understanding of paramyxovirus particle assembly in general and could help facilitate the development of a novel vaccine approach for henipaviruses

Impacts of Leisure Activity Noise Levels A Revised Case Study

An article originally published in the International Journal of Industrial Ergonomics in 1991 discussed the effects of damaging noise levels exposed during the leisure time of industrial workers. With a noise level change preferences, this study was designed to work in collaboration with a 2013 study (Claire Drummond, 2013) which began the groundwork of measuring and examining the consistency of the data collected in 1990. Attributed to an increase in popularity of electronic music and improved digital sound equipment, indoor leisure environment sound levels have increased since the original study. The purpose of this study is to expand the collection of data on exposure levels in current leisure activities reported in the 2012 study to enhance the statistical significance that levels are indeed higher than the noise level preferences and tolerances specified by the Occupational Health and Safety Administration (OSHA) and International Standards Organization (ISO) guidelines. With strenuous legal standards, industries have taken substantial steps to follow the OSHA and ISO recommended guidelines; however, places of leisure such as bars, movie theaters, churches, and sporting events are not required to adhere to the same standards. The noise data was collected using a Quest SPL (2800) calibrated dosimeter. This device is a great improvement from the GenRad Sound Level Meter originally used in the 1990 study for the fact that the Quest SPL (2800) gives a complete printout at the end of a data run that takes in account the duration and average dose of noise exposure run as well as average and peak noise levels. The GenRad device was limited to measuring low and high noise level readings. Average leisure noise levels by category were as follows: peak levels in a sample of thirty-nine leisure activities: churches and concerts (118.06 dB (σ = 2.62 dB)), bars (117.48 dB (σ = 9.32 dB)), and sporting events (122.99 dB (σ = 10.97 dB)). Following the OSHA and ISO standards, any exposure noise level over 115.00dB exceeds the recommended allowance. Adult industrial workers exposing themselves to these levels after an eight hour workday in an OSHA-controlled environment are exceeding the allowable exposure. Industrial business are spending large sums of money to make sure they are in compliance with OSHA standards yet their employees are potentially permanently damaging hearing due to their choice of leisure activity. These individuals are thus increasing their risk of a permanent threshold shift. As a side observation to the adult exposures, many parents had their children under the age of 4 in attendance at the high level peak level leisure activities. Hearing is fully developed at birth, but extended exposure times to high peak noise levels can cause an earlier permanent threshold shift in children or permanent hearing loss at a younger age

Development and mixed-methods evaluation of an online animation for young people about genome sequencing

Abstract: Children and young people with rare and inherited diseases will be significant beneficiaries of genome sequencing. However, most educational resources are developed for adults. To address this gap in informational resources, we have co-designed, developed and evaluated an educational resource about genome sequencing for young people. The first animation explains what a genome is, genomic variation and genome sequencing (“My Genome Sequence”: http://bit.ly/mygenomesequence), the second focuses on the limitations and uncertainties of genome sequencing (“My Genome Sequence part 2”: http://bit.ly/mygenomesequence2). In total, 554 school pupils (11–15 years) took part in the quantitative evaluation. Mean objective knowledge increased from before to after watching one or both animations (4.24 vs 7.60 respectively; t = 32.16, p < 0.001). Self-rated awareness and understanding of the words ‘genome’ and ‘genome sequencing’ increased significantly after watching the animation. Most pupils felt they understood the benefits of sequencing after watching one (75.4%) or both animations (76.6%). Only 17.3% felt they understood the limitations and uncertainties after watching the first, however this was higher among those watching both (58.5%, p < 0.001). Twelve young people, 14 parents and 3 health professionals consenting in the 100,000 Genomes Project reported that the animation was clear and engaging, eased concerns about the process and empowered young people to take an active role in decision-making. To increase accessibility, subtitles in other languages could be added, and the script could be made available in a leaflet format for those that do not have internet access. Future research could focus on formally evaluating the animations in a clinical setting

The YPLGVG sequence of the Nipah virus matrix protein is required for budding

<p>Abstract</p> <p>Background</p> <p><it>Nipah virus </it>(NiV) is a recently emerged paramyxovirus capable of causing fatal disease in a broad range of mammalian hosts, including humans. Together with <it>Hendra virus </it>(HeV), they comprise the genus <it>Henipavirus </it>in the family <it>Paramyxoviridae</it>. Recombinant expression systems have played a crucial role in studying the cell biology of these Biosafety Level-4 restricted viruses. <it>Henipavirus </it>assembly and budding occurs at the plasma membrane, although the details of this process remain poorly understood. Multivesicular body (MVB) proteins have been found to play a role in the budding of several enveloped viruses, including some paramyxoviruses, and the recruitment of MVB proteins by viral proteins possessing late budding domains (L-domains) has become an important concept in the viral budding process. Previously we developed a system for producing NiV virus-like particles (VLPs) and demonstrated that the matrix (M) protein possessed an intrinsic budding ability and played a major role in assembly. Here, we have used this system to further explore the budding process by analyzing elements within the M protein that are critical for particle release.</p> <p>Results</p> <p>Using rationally targeted site-directed mutagenesis we show that a NiV M sequence YPLGVG is required for M budding and that mutation or deletion of the sequence abrogates budding ability. Replacement of the native and overlapping Ebola VP40 L-domains with the NiV sequence failed to rescue VP40 budding; however, it did induce the cellular morphology of extensive filamentous projection consistent with wild-type VP40-expressing cells. Cells expressing wild-type NiV M also displayed this morphology, which was dependent on the YPLGVG sequence, and deletion of the sequence also resulted in nuclear localization of M. Dominant-negative VPS4 proteins had no effect on NiV M budding, suggesting that unlike other viruses such as Ebola, NiV M accomplishes budding independent of MVB cellular proteins.</p> <p>Conclusion</p> <p>These data indicate that the YPLGVG motif within the NiV M protein plays an important role in M budding; however, involvement of any specific components of the cellular MVB sorting pathway in henipavirus budding remains to be demonstrated. Further investigation of henipavirus assembly and budding may yet reveal a novel mechanism(s) of viral assembly and release that could be applicable to other enveloped viruses or have therapeutic implications.</p