Biotechnology for detecting oxidative modifications to fibrinogen

Systemic inflammation has been recognized as a risk factor for a number of diseases, including type 2 diabetes. There is a growing awareness that inflammatory diseases have an oxidative pathology, which can result in specific oxidation of amino acids within proteins. Patients with inflammatory disease have higher levels of plasma protein 3-nitrotyrosine than healthy controls. Fibrinogen is an abundant plasma protein, and has been shown to be highly susceptible to such oxidative modifications, and is therefore a potential marker. Oxidative damage and modifications to fibrinogen offer potential as biomarkers of disease, and for diagnosis and a greater understanding of the pathology. The aim of this study was to map the in-vitro locations of oxidatively-modified fibrinogen, and test the possibility of producing antibodies that show increased binding to protein-specific modification sites. Fibrinogen was nitrated using the peroxynitrite generator SIN-1, and analyzed by liquid chromatography tandem mass spectrometry. Several modified peptides that consistently occurred were identified with the Mascot© search engine and manually validated. Based on literature or mass spectrometry results, peptides with the core amino acid sequence STSYGTGC or DYEDDQQKQLC, either unmodified, or containing 3-chlorotyrosine or 3-nitrotyrosine were synthesized and subsequently antibodies were produced. Each subsequently produced sheep anti-serum was tested against various native and modified peptides containing a variety of different amino acid sequences. Anti-STSY-(NO2)-GTGC serum showed modification site specificity, whereas anti-DY-(Cl)-EDDQQKQLC serum showed sequence specificity but was unable to distinguish between 3-chlorotyrosine and 3-nitrotyrosine. This cross-reactivity between chlorinated and nitrated modification sites might allow broader detection of modified fibrinogen in inflammation. The anti-STSY-(NO2)-GTGC serum was also tested against plasma from healthy control volunteers and type 2 diabetic patients, but showed limited binding and ability to discriminate the disease state. In conclusion, it has been shown that antibodies can be produced to differentiate between native and modified proteins; however, further work is required to understand sequence-specificity better and monoclonal antibodies might be better suited to achieving sequence-specificity

Acoustic characterization of crack damage evolution in sandstone deformed under conventional and true triaxial loading

We thank the Associate Editor, Michelle Cooke, and the reviewers, Ze'ev Reches and Yves Guéguen, for useful comments which helped to improve the manuscript. We thank J.G. Van Munster for providing access to the true triaxial apparatus at KSEPL and for technical support during the experimental program. We thank R. Pricci for assistance with technical drawings of the apparatus. This work was partly funded by NERC award NE/N002938/1 and by a NERC Doctoral Studentship, which we gratefully acknowledge. Supporting data are included in a supporting information file; any additional data may be obtained from J.B. (e-mail: [email protected]).Peer reviewedPublisher PD

A Significant Threat to Neuropsychological Test Validity

Objective: Neuropsychological test security is vital to the validity of assessment. Previous research in our lab has shown that 71% of participants use the Internet to prepare for neuropsychological evaluations (Kimpton, 2015). We investigated the availability of information related to neuropsychological tests on the Internet, a topic that has received little attention in the research literature. Participants and Methods: First, we decided a priori that we would not reveal the terms used in this Internet search, as to not contribute to the problem of threatened test security. We used the Internet search engine “Google” to begin a search using a general question that a person with no neuropsychological expertise would use to access initial results. We obtained 899,000 results for this question. We decided that of these results, we would select from the first five results. One link provided us with a list of 52 commonly used neuropsychological tests. This list also included information about the type of cognitive information that the test was meant to assess. Lastly, we searched for these tests on Google Images and YouTube in order to investigate the extent of the information available. Results: The protocols for 43% of the 52 tests were available on Google Images. At least partial administration demonstrations were available on YouTube for 54% of the 52 neuropsychological tests. These demonstrations revealed the test protocols and basic strategy of the tests. Conclusions: A substantial amount of information regarding neuropsychological tests is available on Google Images and YouTube, threatening the validity of these tests. It is recommended that professional neuropsychological associations begin to develop guidelines regarding appropriate content for websites and identify and continuously monitor websites that contain threatening information

Management Innovations for Resilient Public Rangelands: Adoption Constraints and Considerations for Interagency Diffusion

Maintaining healthy rangeland ecosystems requires adaptive co-management at the landscape scale. Because the majority of western rangelands are publicly owned, it is critical that federal land management agencies work together in generating and sharing information. Promotion and communication of rangeland management innovations among agencies is one means of sharing information. Two rangeland management innovations, the Weather-Centric Restoration Tool and Interpreting Indicators of Rangeland Health, were studied in order to better understand agency adoption decisions and barriers to diffusion of the innovations across agencies. Using a mixed qualitative methodology, we interviewed land managers across the floristic Great Basin and in southeastern Utah responsible for making or advising rangeland management decisions. Using thematic analysis of participant interviews and land managers’ social networks in southeastern Utah, we were able to identify variables at the innovation, individual, organization, and external system levels that affect innovation adoption and diffusion across agencies. In line with previous research, desirable innovation traits were related to five constructs: complexity, relative advantage, compatibility, trialability, and observability. Interagency siloing was found to be the biggest factor affecting individual and organization-level adoption decisions. External sociopolitical factors were also found to create organization-level barriers including funding streams, legal considerations, and differing institutional cultures between agencies. While management innovations are hindered by these hurdles, innovations also serve as promoters of institutional change that reshape these constraints. However, overcoming barriers to innovation requires the presence of innovation champions who can influence both incremental bottom-up and top-down processes

“We definitely need an audience”: experiences of Twitter, Twitter networks and tweet content in adults with severe communication disabilities who use augmentative and alternative communication (AAC)

Purpose: The aim of this study was to investigate the Twitter experiences of adults with severe communication disabilities who use augmentative and alternative communication (AAC) to inform Twitter training and further research on the use of Twitter in populations with communication disabilities. Method: This mixed methods research included five adults with severe communication disabilities who use AAC. It combined (a) quantitative analysis of Twitter networks and (b) manual coding of tweets with (c) narrative interviews with participants on their Twitter experiences and results. Results: The five participants who used AAC and Twitter were diverse in their patterns and experiences of using Twitter. Twitter networks reflected interaction with a close-knit network of people rather than with the broader publics on Twitter. Conversational, Broadcast and Pass Along tweets featured most prominently, with limited use of News or Social Presence tweets. Tweets appeared mostly within each participant's micro- or meso-structural layers of Twitter. Conclusions: People who use AAC report positive experiences in using Twitter. Obtaining help in Twitter, and engaging in hashtag communities facilitated higher frequency of tweets and establishment of Twitter networks. Results reflected an inter-connection of participant Twitter networks that might form part of a larger as yet unexplored emergent community of people who use AAC in Twitter.Implications for RehabilitationTwitter can be used as an important vehicle for conversation and a forum for people with communication disabilities to exchange information and participate socially in online communities.It is important that information and resources relating to the effective use of Twitter for a range of purposes are made available to people with communication disabilities who wish to take up or maintain use of Twitter.People with communication disabilities might benefit from support in using Twitter to meet their goals relating to participation in online forums and information exchange. Practitioners need to consider how their own social media skills might impact on service delivery and supporting these goals

Broadening community engagement in clinical research: Designing and assessing a pilot crowdsourcing project to obtain community feedback on an HIV clinical trial.

BACKGROUND/AIMS:Community engagement is widely acknowledged as an important step in clinical trials. One underexplored method for engagement in clinical trials is crowdsourcing. Crowdsourcing involves having community members attempt to solve a problem and then publicly sharing innovative solutions. We designed and conducted a pilot using a crowdsourcing approach to obtain community feedback on an HIV clinical trial, called the Acceptability of Combined Community Engagement Strategies Study. In this work, we describe and assess the Acceptability of Combined Community Engagement Strategies Study's crowdsourcing activities in order to examine the opportunities of crowdsourcing as a clinical trial community engagement strategy. METHODS:The crowdsourcing engagement activities involved in the Acceptability of Combined Community Engagement Strategies Study were conducted in the context of a phase 1 HIV antibody trial (ClinicalTrials.gov identifier: NCT03803605). We designed a series of crowdsourcing activities to collect feedback on three aspects of this clinical trial: the informed consent process, the experience of participating in the trial, and fairness/reciprocity in HIV clinical trials. All crowdsourcing activities were open to members of the general public 18 years of age or older, and participation was solicited from the local community. A group discussion was held with representatives of the clinical trial team to obtain feedback on the utility of crowdsourcing as a community engagement strategy for informing future clinical trials. RESULTS:Crowdsourcing activities made use of innovative tools and a combination of in-person and online participation opportunities to engage community members in the clinical trial feedback process. Community feedback on informed consent was collected by transforming the clinical trial's informed consent form into a series of interactive video modules, which were screened at an open public discussion. Feedback on the experience of trial participation involved designing three fictional vignettes which were then transformed into animated videos and screened at an open public discussion. Finally, feedback on fairness/reciprocity in HIV clinical trials was collected using a crowdsourcing idea contest with online and in-person submission opportunities. Our public discussion events were attended by 38 participants in total; our idea contest received 43 submissions (27 in-person, 16 online). Facebook and Twitter metrics demonstrated substantial engagement in the project. The clinical team found crowdsourcing primarily useful for enhancing informed consent and trial recruitment. CONCLUSION:There is sufficient lay community interest in open calls for feedback on the design and conduct of clinical trials, making crowdsourcing both a novel and feasible engagement strategy. Clinical trial researchers are encouraged to consider the opportunities of implementing crowdsourcing to inform trial processes from a community perspective

On the static and dynamic properties of flax and Cordenka epoxy composites

Fibre reinforced composites have excellent specific properties and are widely sought after by engineers seeking to reduce mass. However, end of life disposal is a significant problem and so research into more sustainable natural fibre composites is extremely topical. This paper examines the applicability of natural fibre composites for high performance structural applications. Woven flax and regenerated cellulose (Cordenka) textiles were pre-impregnated with commercially available epoxy resins and consolidated into test laminates in an autoclave to determine their static (compressive, tensile, flexural) and dynamic (energy absorption) properties. The range of compressive strengths was 77.5–299.6 MPa. Tensile strengths ranged from 63 to 92.6 MPa and interlaminar shear strength (ILSS) from 10.7 to 23.3 MPa. Specific energy absorption (SEA) varied between 21.2–34.2 kJ/kg. Biotex flax combined with MTM49 resin matched the SEA of T300 carbon fibre using the same resin system and layup. This work has demonstrated that natural fibre composites have significant scope for use in structural applications but additional work is required on fibre to matrix bonding in order to maximise their properties whilst remaining an environmentally credible option