The influence of music liking on episodic memory for rich spatiotemporal contexts.

It is thought that the presence of music influences episodic memory encoding. However, no studies have isolated the influence of music liking - the hedonic value listeners attribute to a musical stimulus - from that of the core affect induced by the presence of that music. In an online survey, participants rated musical excerpts in terms of how much they liked them, as well as in terms of felt valence, felt arousal and familiarity. These ratings were then used to inform the stimuli presented in an online episodic memory task which, across different scenarios, involved dragging cued objects to cued locations and then recalling details of what was moved, where they were moved to and the order of movements made. Our results showed an influence of liking and music-reward sensitivity on memory for what was moved, as well as a detrimental effect of arousing musical stimuli on memory for un-cued scenario details. Taken together, our study showcases the importance of episodic memory paradigms that involve rich spatiotemporal contexts and provides insights into how different aspects of episodic memory may be influenced by the presence of music.

Intimate Partner Violence Against Transgender Women: Prevalence and Correlates in Lima, Peru (2016-2018).

Limited data exists on intimate partner violence (IPV) among transgender women (TW), though global trends suggest IPV is associated with HIV risk in this population. We describe the prevalence of verbal, physical, and/or sexual violence as well as participant- and partner-level correlates of IPV among TW in Lima, Peru. Among 389 respondents, 15.2% reported IPV with one or more of their last three sexual partners: 9.2% verbal, 8.2% physical, and 2.3% sexual violence. Physical and verbal violence were more common with stable partners (aPR 3.46, 95% CI 1.17-10.25, aPR 2.46, 95% CI 1.14-5.28, respectively). Physical violence was associated with condomless receptive anal intercourse (cRAI) (aPR 2.22, 95% CI 1.19-4.13) and partner alcohol use (aPR 4.38, 95% CI 1.56-12.33) while verbal violence correlated with participant inebriation (aPR 4.86, 95% CI 1.63-14.46). Our results link IPV with stable partnerships, alcohol use, and cRAI, suggesting TW in Peru may benefit from multidimensional IPV prevention strategies to foster supportive relationships and reduce HIV transmission.

Retention strategies are routinely communicated to potential trial participants but often differ from what was planned in the trial protocol: an analysis of adult participant information leaflets and their corresponding protocols.

BACKGROUND: Retaining participants in randomised controlled trials (RCTs) is challenging and trial teams are often required to use strategies to ensure retention or improve it. Other than monetary incentives, there is no requirement to disclose the use of retention strategies to the participant. Additionally, not all retention strategies are developed at the planning stage, i.e. post-funding during protocol development, but some protocols include strategies for participant retention as retention is considered and planned for early in the trial planning stage. It is yet unknown if these plans are communicated in the corresponding participant information leaflets (PILs). The purpose of our study was to determine if PILs communicate plans to promote participant retention and, if so, are these outlined in the corresponding trial protocol. METHODS: Ninety-two adult PILs and their 90 corresponding protocols from Clinical Trial Units (CTUs) in the UK were analysed. Directed (deductive) content analysis was used to analyse the participant retention text from the PILs. Data were presented using a narrative summary and frequencies where appropriate. RESULTS: Plans to promote participant retention were communicated in 81.5% (n = 75/92) of PILs. Fifty-seven percent (n = 43/75) of PILs communicated plans to use "combined strategies" to promote participant retention. The most common individual retention strategy was telling the participants that data collection for the trial would be scheduled during routine care visits (16%; n = 12/75 PILs). The importance of retention and the impact that missing or deleted data (deleting data collected prior to withdrawal) has on the ability to answer the research question were explained in 6.5% (n = 6/92) and 5.4% (n = 5/92) of PILs respectively. Out of the 59 PILs and 58 matching protocols that both communicated plans to use strategies to promote participant retention, 18.6% (n = 11/59) communicated the same information, the remaining 81.4% (n = 48/59) of PILs either only partially communicated (45.8%; n = 27/59) the same information or did not communicate the same information (35.6%; n = 21/59) as the protocol with regard to the retention strategy(ies). CONCLUSION: Retention strategies are frequently communicated to potential trial participants in PILs; however, the information provided often differs from the content in the corresponding protocol. Participant retention considerations are best done at the planning stage of the trial and we encourage trial teams to be consistent in the communication of these strategies in both the protocol and PIL.

Registry-based randomised controlled trials: conduct, advantages and challenges-a systematic review.

BACKGROUND: Registry-based randomised controlled trials (rRCTs) have been described as pragmatic studies utilising patient data embedded in large-scale registries to facilitate key clinical trial procedures including recruitment, randomisation and the collection of outcome data. Whilst the practice of utilising registries to support the conduct of randomised trials is increasing, the use of the registries within rRCTs is inconsistent. The purpose of this systematic review is to explore the conduct of rRCTs using a patient registry to facilitate trial recruitment and the collection of outcome data, and to discuss the advantages and challenges of rRCTs. METHODS: A systematic search of the literature was conducted using five databases from inception to June 2020: PubMed, Embase (through Ovid), CINAHL, Scopus and the Cochrane Controlled Register of Trials (CENTRAL). The search strategy comprised of MESH terms and key words related to rRCTs. Study selection was performed independently by two reviewers. A risk of bias for each study was completed. A narrative synthesis was conducted. RESULTS: A total 47,862 titles were screened and 24 rRCTs were included. Eleven rRCTs (45.8%) used more than one registry to facilitate trial conduct. Six rRCTs (25%) randomised participants via a specific randomisation module embedded within a registry. Recruitment ranged between 209 to 106,000 participants. Advantages of rRCTs are recruitment efficiency, shorter trial times, cost effectiveness, outcome data completeness, smaller carbon footprint, lower participant burden and the ability to conduct multiple trials from the same registry. Challenges are data collection/management, quality assurance issues and the timing of informed consent. CONCLUSIONS: Optimising the design of rRCTs is dependent on the capabilities of the registry. New registries should be designed and existing registries reviewed to enable the conduct of rRCTs. At all times, data management and quality assurance of all registry data should be given key consideration. We suggest the inclusion of the term 'registry-based' in the title of all rRCT manuscripts and a clear simple breakdown of the registry-based conduct of the trial in the abstract to facilitate indexing in the major databases.

National Postpartum Permanent Contraception Practices and Perceived Barriers.

Single institution-level studies have demonstrated low postpartum permanent contraception fulfillment rates after vaginal birth. To explore the national scope of the problem, we collected cross-sectional survey data from faculty at 109 U.S. academic medical centers to elicit perceptions about postpartum permanent contraception practices after vaginal birth, including barriers to and changes in practice after the Dobbs v Jackson Women's Health Organization decision, a decision that eliminated the U.S. federal protection of the right to abortion. Of 68 respondent institutions, 65 (95.6%) offered postpartum permanent contraception. A large majority (87.3%) perceived there to be a problem with postpartum permanent contraception fulfillment at their institution. Respondents at institutions with postpartum permanent contraception fulfillment rates in the bottom quartile used main operating rooms (66.7% vs 25.0% respectively, P =.032) and reported institutional culture barriers (86.7% vs 50.0%, respectively, P =.054) more frequently than respondents in the top quartile. Our national data indicate that health care culture changes and the use of labor and delivery operating rooms could increase postpartum permanent contraception fulfillment.

When describing harms and benefits to potential trial participants, participant information leaflets are inadequate.

BACKGROUND: Providing informed consent for trials requires providing trial participants with comprehensive information about the trial, including information about potential risks and benefits. It is required by the ethical principle of respecting patient autonomy. Our study examines the variation in the way information about potential trial benefits and harms is shared in participant information leaflets (PILs). METHODS: A total of 214 PILs and informed consent forms from clinical trials units (CTUs) and Clinical Research Facilities (CRFs) in Ireland and the UK were assessed by two authors independently, to check the extent to which they adhered to seven recently developed principles. Discrepancies were resolved by a third. RESULTS: Usage of the seven principles varied widely between PILs regardless of the intended recipient or trial type. None of the PILs used more than four principles, and some (4%) used none. Twenty-seven per cent of PILs presented information about all known potential harms, whereas 45% presented information on all known potential benefits. Some PILs did not provide any potential harms or potential benefits (8%). There was variation in the information contained in adult and children PILs and across disease areas. CONCLUSION: Significant variation exists in how potential trial benefits and harms are described to potential trial participants in PILs in our sample. Usage of the seven principles of good practice will promote consistency, ensure informed ethical decision-making and invoke trust and transparency. In the long term, a standardised PIL template is needed.

Trial participants' self-reported understanding of randomisation phrases in participation information leaflets can be high, but acceptability of some descriptions is low, especially those linked to gambling and luck.

BACKGROUND: Evidence indicates that trial participants often struggle to understand participant information leaflets (PILs) for clinical trials, including the concept of randomisation. We analysed the language used to describe randomisation in PILs and determine the most understandable and acceptable description through public and participant feedback. METHODS: We collected 280 PILs/informed consent forms and one video animation from clinical research facilities/clinical trial units in Ireland and the UK. We extracted text on how randomisation was described, plus trial characteristics. We conducted content analysis to group the randomisation phrases inductively. We then excluded phrases that appeared more than once or were very similar to others. The final list of randomisation phrases was then presented to an online panel of participants and the public. Panel members were asked to rate each phrase on a 5-point Likert scale in terms of their understanding of the phrase, confidence in their understanding and acceptability of the phrase. RESULTS: Two hundred and eighty PILs and the transcribed text from one video animation represented 229 ongoing or concluded trials. The pragmatic content analysis generated five inductive categories: (1) explanation of why randomisation is required in trials; (2) synonyms for randomisation; (3) comparative randomisation phrases; (4) elaborative phrases for randomisation (5) and phrases that describe the process of randomisation. We had 48 unique phrases, which were shared with 73 participants and members of the public. Phrases that were well understood were not necessarily acceptable. Participants understood, but disliked, comparative phrases that referenced gambling, e.g. toss of a coin, like a lottery, roll of a die. They also disliked phrases that attributed decision-making to computers or automated systems. Participants liked plain language descriptions of what randomisation is and those that did not use comparative phrases. CONCLUSIONS: Potential trial participants are clear on their likes and dislikes when it comes to describing randomisation in PILs. We make five recommendations for practice.

Staphylococcus aureus manganese transport protein C is a highly conserved cell surface protein that elicits protective immunity against S. aureus and Staphylococcus epidermidis.

Staphylococcus aureus and other staphylococci cause severe human disease, and there are currently no vaccines available. We evaluated whether manganese transport protein C (MntC), which is conserved across the staphylococcal species group, could confer protection against S. aureus and Staphylococcus epidermidis. In vivo analysis of S. aureus MntC expression revealed that expression occurs very early during the infectious cycle. Active immunization with MntC was effective at reducing the bacterial load associated with S. aureus and S. epidermidis infection in an acute murine bacteremia model. Anti-MntC monoclonal antibodies have been identified that can bind S. aureus and S. epidermidis cells and are protective in an infant rat passive protection model and induce neutrophil respiratory burst activity. This is the first description of a protein that has the potential to provide protection across the staphylococcal species group.

How do trial teams plan for retention during the design stage of the trial? A scoping review.

BACKGROUND: Retention to trials is important to ensure the results of the trial are valid and reliable. The SPIRIT guidelines (18b) require "plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols" be included in trial protocols. It is unknown how often protocols report this retention information. The purpose of our scoping review is to establish if, and how, trial teams report plans for retention during the design stage of the trial. MATERIALS AND METHODS: A scoping review with searches in key databases (PubMed, Scopus, EMBASE, CINAHL (EBSCO), and Web of Science from 2014 to 2019 inclusive) to identify randomised controlled trial protocols. We produced descriptive statistics on the characteristics of the trial protocols and also on those adhering to SPIRIT item 18b. A narrative synthesis of the retention strategies was also conducted. RESULTS: Eight-hundred and twenty-four protocols met our inclusion criteria. RCTs (n = 722) and pilot and feasibility trial protocols (n = 102) reported using the SPIRIT guidelines during protocol development 35% and 34.3% of the time respectively. Of these protocols, only 9.5% and 11.4% respectively reported all aspects of SPIRIT item 18b "plans to promote participant retention and to complete follow-up, including list of any outcome data for participants who discontinue or deviate from intervention protocols". Of the RCT protocols, 36.8% included proactive "plans to promote participant retention" regardless of whether they reported using SPIRIT guidelines or not. Most protocols planned "combined strategies" (48.1%). Of these, the joint most commonly reported were "reminders and data collection location and method" and "reminders and monetary incentives". The most popular individual retention strategy was "reminders" (14.7%) followed by "monetary incentives- conditional" (10.2%). Of the pilot and feasibility protocols, 40.2% included proactive "plans to promote participant retention" with the use of "combined strategies" being most frequent (46.3%). The use of "monetary incentives - conditional" (22%) was the most popular individual reported retention strategy. CONCLUSION: There is a lack of reporting of plans to promote participant retention in trial protocols. Proactive planning of retention strategies during the trial design stage is preferable to the reactive implementation of retention strategies. Prospective retention planning and clear communication in protocols may inform more suitable choice, costing and implementation of retention strategies and improve transparency in trial conduct.

Omission of Pelvic Examination Before Gender-Affirming Hysterectomy and Vaginectomy.

Surgeons may be performing pelvic examinations on transgender patients before gender-affirming pelvic surgery (hysterectomy and vaginectomy) without a clinically significant indication. A retrospective cohort study was conducted at a single-institution academic referral center comparing 30-day perioperative outcomes of all 62 gender-affirming pelvic surgeries, including hysterectomy alone, hysterectomy with vaginectomy, and vaginectomy alone, between April 2018 and March 2022. More than half (53.2%, n=33) of the 62 patients did not have an in-office, preoperative, internal pelvic examination within 1 year of gender-affirming surgery. There were no significant differences in patient characteristics nor 30-day perioperative outcomes between the examined and examination-omitted groups, suggesting that omission of a preoperative pelvic examination is probably safe before gender-affirming hysterectomy and vaginectomy, minimizing barriers to gender-affirming surgical care.

Impaired cognitive and motor function are coincident with L-DOPA-induced dyskinesia in a model of Parkinson's disease.

Dopamine transmission has been implicated in motor and cognitive function. In Parkinson's disease (PD), dopamine replacement using the precursor drug L-DOPA is the predominant treatment approach, but long-term exposure leads to the onset of dyskinesias (LIDs). Chronic L-DOPA exposure has been associated with changes in gene expression and altered cortico-striatal plasticity. The aim of this research was to assess the functional consequence of long-term L-DOPA exposure on cognitive and motor function using a rodent model of PD. Across two independent experiments, we assessed the impact of chronic L-DOPA exposure, or a control D2R agonist, on motor and cognitive function in intact and in hemi parkinsonian rats, in the absence of drug. Abnormal involuntary movements associated with LID were measured and brain tissues were subsequently harvested for immunohistochemical analysis. Exposure to chronic L-DOPA, but not the D2R agonist, impaired motor and cognitive function, when animals were tested in the absence of drug. A meta-analysis of the two experiments allowed further dissociation of L-DOPA -treated rats into those that developed LIDs (dyskinetic) and those that did not develop LIDs (non-dyskinetic). This analysis revealed impaired cognitive and motor performance were evident only in dyskinetic, but not in non-dyskinetic, rats. These data reveal a functional consequence of the altered plasticity associated with LID onset and have implications for understanding symptom progression in the clinic.

Human Papillomavirus Inpatient Postpartum Vaccination: Clinical Guideline Implementation.

OBJECTIVE: The nine-valent human papillomavirus (9vHPV) vaccine is highly effective at preventing cervical cancer, yet U.S. vaccination rates remain low. The objective of this study was to evaluate integration of 9vHPV inpatient vaccination into routine postpartum care. METHODS: Obstetrics professionals at an academic urban referral center received an emailed protocol outlining a novel 9vHPV vaccination program of postpartum inpatients aged 26 years or younger. A retrospective evaluation from March 2021 to March 2022 was conducted to evaluate implementation. Characteristics of patients vaccinated before pregnancy compared with vaccine-eligible patients (none, unknown, or partially vaccinated status) were compared by the use of χ2, analysis of variance, and multivariable logistic regression. Similarly, analyses were performed comparing vaccine-eligible patients who did with those who did not receive an inpatient 9vHPV vaccination. RESULTS: Of 569 postpartum inpatients, 370 (65.0%) were already vaccinated, 70 (34.2%) were never vaccinated, 49 (24.6%) were partially vaccinated, and 80 (14.1%) had unknown status. Of vaccine-eligible patients, 46 (23.1%) received 9vHPV vaccination as an inpatient. In multivariable analysis, race and ethnicity, marital status, and primary language were significant predictors of vaccination before pregnancy. Among vaccine-eligible patients, inpatient vaccination recipients were primarily Hispanic, Spanish speaking, and publicly insured. In multivariable analysis of vaccine-eligible patients, receiving care from the certified nurse midwifery practice was the only independent predictor of vaccination (odds ratio 2.4, 95% CI 1.02-5.74, P=.04). CONCLUSION: Non-Hispanic White, Spanish-speaking, and married patients were disproportionally undervaccinated in our baseline population, but about one quarter of vaccine-eligible patients received 9vHPV vaccination postpartum. Inpatient postpartum 9vHPV vaccination may help narrow disparities in vaccination.

Operator- and software-related post-experimental variability and source of error in 2-DE analysis.

In the field of proteomics, several approaches have been developed for separating proteins and analyzing their differential relative abundance. One of the oldest, yet still widely used, is 2-DE. Despite the continuous advance of new methods, which are less demanding from a technical standpoint, 2-DE is still compelling and has a lot of potential for improvement. The overall variability which affects 2-DE includes biological, experimental, and post-experimental (software-related) variance. It is important to highlight how much of the total variability of this technique is due to post-experimental variability, which, so far, has been largely neglected. In this short review, we have focused on this topic and explained that post-experimental variability and source of error can be further divided into those which are software-dependent and those which are operator-dependent. We discuss these issues in detail, offering suggestions for reducing errors that may affect the quality of results, summarizing the advantages and drawbacks of each approach.

How much is the lack of retention evidence costing trial teams in Ireland and the UK?

BACKGROUND: Evidence to support the use of many retention strategies in clinical trials is lacking. Despite this, trial teams still need to have some form of retention strategy in their trials to try and avoid high attrition rates. This study aimed to estimate how much this lack of retention evidence might be costing trials in Ireland and the UK. METHODS: We selected the top ten most routinely used retention strategies by Clinical Trial Units in the UK and made assumptions as to how each of these strategies was most likely to be implemented and the costs involved in doing this. We applied our costing model to a hypothetical trial scenario in both Ireland and the UK as well as to three published trial protocols. We developed the costing model and calculated the costs in Microsoft Excel. RESULTS: Retention strategies were often poorly specified, meaning we had to make assumptions about implementation and in some cases about the strategy itself. Based on our assumptions, some retention strategies can be extremely expensive; some of the costliest strategies included "data collection scheduled with routine care" (€900-€32,503.25), "a timeline of participant visits for sites"-with integrated participant reminder (€304.74-€14,803.70), and "routine site visits by CTU staff" and "investigator meetings face to face", both costing (€777.67-€14,753.48). Others such as "telephone reminders for questionnaire response" (€34.58-€568.62), "a timeline of participant visits for sites"-site reminder alone (€79.18-€112.23), and "targeted recruitment of sites/GPs" (€30-€1620) were less costly compared to the other strategies. DISCUSSION: The resources invested in the use of some retention strategies may outweigh known or imagined benefits on retention. Where benefits are currently unknown, evaluation should be a priority. CONCLUSION: More evaluation of the effectiveness and cost of trial retention strategies is needed to avoid widespread use of strategies that are both expensive and ineffective.

How do trial teams plan for retention during the design stage of the trial? A scoping review protocol.

BACKGROUND: Retention remains a major challenge for many clinical trials. The SPIRIT guidelines state the following information on retention should be included in the trial protocol "Plans to promote participant retention and complete follow-up, including list of any outcome data to be collected for participants who discontinue or deviate from intervention protocols". This guidance shows the importance of planning retention methods and handling missing data as this can impact how the results of the trial are interpreted. The most recent Cochrane review of strategies to improve retention in clinical trials highlighted that some trials implemented multiple retention strategies and we questioned whether the use of multiple strategies was planned at the design stage and included in the protocol or are strategies implemented when retention becomes an issue within the trial. The purpose of our scoping review is to establish if and how trial teams prepare for retention at the design phase of clinical trials. METHODS AND ANALYSIS: We will follow the methodological framework and guidelines for scoping reviews outlined by the Joanna Briggs Institute. We will search MEDLINE/PubMed, Scopus, EMBASE, CINAHL (EBSCO), and Web of Science. A comprehensive search strategy for PubMed was developed in collaboration with an experienced research librarian. We will include protocols for phase 2, 3, and 4 RCTs as well as pilot and feasibility studies. The screening process will involve two reviewers. EM will independently screen all titles and abstracts. FS will screen 10% of the overall search output, and where necessary full protocol texts will be screened to determine eligibility. We will randomly sample eligible protocols to ensure the protocols represent a variety of trial and intervention types. Data will be extracted from each protocol and the results will be synthesised. The analysis will be qualitative using a narrative summary and descriptive statistics where appropriate. DISCUSSION: The scoping review will help trial methodologists better understand if retention strategies are planned for during the design stage of the trial contributing to the PRioRiTy II unanswered question "How should people who run trials plan for retention during their funding application and creation of the trial (protocol development)?".

Yersinia enterocolitica in wild and peridomestic rodents within Great Britain, a prevalence study.

Yersinia enterocolitica is a human pathogen transmitted via the faecal-oral route among animals and humans and is a major foodborne public health hazard. This study explores the role of Y. enterocolitica transmission at the livestock-wildlife interface and investigates the potential role wild and peridomestic rodents play as a source of this zoonotic pathogen. The total of 342 faecal samples collected from the seven rodent species and one insectivore was examined using an optimized protocol to culture and identify Y. enterocolitica. Positive samples were also bioserotyped for grouping and determination of sample pathogenicity. Wildlife species sampled in this study were separated into two sample groups: randomly sampled (brown rats, house mice, wood mice, bank voles, field voles and the common shrew), as well as targeted sampling (red and grey squirrels). The overall prevalence of Y. enterocolitica in the randomly sampled population was 3.73%. Brown rats were chosen as sentinel species and tested to determine if location (pig farm vs non-pig farm) was a significant factor affecting Y. enterocolitica prevalence. In this study, location was not significant. All positive samples were found to be of biotype 1A, deemed non-pathogenic. Three of the samples were serotype 09, six were serotype 27 and five had an unidentifiable serotype. This study represents the first time Y. enterocolitica has been identified in these species of wildlife within mainland Britain. In addition, this study's findings are entirely novel and overall with regard to field voles and common shrews. However, the role of wild and peridomestic rodents in the transmission of pathogenic Y. enterocolitica remains unknown, as this study was unable to detect the presence of pathogenic Y. enterocolitica strains in these species.

NMR dynamics and antibody recognition of the meningococcal lipidated outer membrane protein LP2086 in micellar solution.

Neisseria meningitidis is a major cause of meningitis. Although protective vaccination is available against some pathogenic serogroups, serogroup B meningococci have been a challenge for vaccinologists. A family of outer membrane lipoproteins, LP2086 (or factor H binding proteins, fHbp), has been shown to elicit bactericidal antibodies and is currently part of a cocktail vaccine candidate. The NMR structure of the variant LP2086-B01 in micellar solution provided insights on the topology of this family of proteins on the biological membrane. Based on flow cytometry experiments on whole meningococcal cells, binding experiments with monoclonal antibodies, and the NMR structure in micellar solution, we previously proposed that LP2086-B01 anchors the outer bacterial membrane through its lipidated N-terminal cysteine, while a flexible 20 residue linker positions the protein above the layer of lipo-oligosaccharides that surrounds the bacteria. This topology was suggested to increase the antigen exposure to the immune system. In the present work, using micellar solution as a membrane mimicking system, we characterized the backbone dynamics of the variant LP2086-B01 in both its lipidated and unlipidated forms. In addition, binding experiments with a Fab fragment derived from the monoclonal MN86-1042-2 were also performed. Our data suggests that due to the length and flexibility of the N-terminal linker, the antigen is not in contact with the micelle, thus making both N- and C-domains highly available to the host immune system. This dynamic model, combined with the binding data obtained with MN86-1042-2, supports our previously proposed arrangement that LP2086-B01 exposes one face to the extracellular space. Binding of MN86-1042-2 antibody shows that the N-domain is the primary target of this monoclonal, providing further indication that this domain is immunologically important for this family of proteins.

Challenges for the evaluation of Staphylococcus aureus protein based vaccines: monitoring antigenic diversity.

Clumping factors A (ClfA) and B (ClfB) are Staphylococcus aureus virulence proteins that are displayed on the cell surface of the organism and have potential as vaccine antigens for the prevention of S. aureus disease. Here we evaluate the phylogeny of S. aureus in the context of antigenic variation of these two surface proteins. ClfA and ClfB gene sequences, along with epidemiological markers (MLST, spa and capsule genotype) were obtained for 224 S. aureus isolates including both historical strains and a collection representative of current MRSA isolates from the United States. Variation within ClfA and ClfB was consistent with the established population biology of S. aureus, namely, that S. aureus strains belong to a relatively small number of clonal lineages, with evolution proceeding mainly by mutation and with little to no recombination between clades. Thus most variation in ClfA and ClfB occurs between but not within lineages, and particular groups of ClfA and ClfB variants are closely linked. This has important implications for vaccine development and assessment as it suggests that a relatively small survey of strains will be representative of the total population variation, whereas for species that evolve mainly by recombination, such as Neisseria meningitidis, analysis of a much larger number of strains is needed to accomplish the same purpose. Our study also revealed evidence for the de-evolution of ClfB and therefore its reduced suitability as a target for vaccine development compared to ClfA.

Preclinical evidence for the potential of a bivalent fHBP vaccine to prevent Neisseria meningitidis Serogroup C Disease.

A bivalent factor H binding protein (fHBP) vaccine for the prevention of disease caused by Neisseria meningitidis serogroup B is currently in clinical development. Since fHBP is also expressed by other meningococcal serogroups, anti-fHBP antibodies may have bactericidal activity against meningococci independent of serogroup. To begin examining the susceptibility of other meningococcal serogroups to anti-fHBP antibodies, meningococcal serogroup C invasive isolates (n = 116) were collected from the Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs) sites during 2000-2001. These isolates were analyzed for the presence of the fhbp gene. All serogroup C isolates contained the gene, and sequence analysis grouped the proteins into two subfamilies, A and B. Flow cytometry analysis demonstrated that fHBP was expressed on the surface of ~70% of isolates in vitro with varying levels of expression. fHBP was accessible to antibodies on the cell surface even in the presence of the polysaccharide capsule. Nine isolates from different geographic regions were identified which harboured an identical single nucleotide deletion that could result in a truncated subfamily B fHBP. Analysis by flow cytometry using a polyclonal fHBP antibody preparation revealed that a subpopulation of each of these isolates expressed fHBP. Rabbit and non-human primate immune sera generated with bivalent fHBP vaccine were tested for bactericidal activity against a panel of diverse serogroup C clinical isolates using human complement. Sera from both species demonstrated serum bactericidal antibody activity against the serogroup C isolates tested. These promising findings suggest that a bivalent fHBP vaccine may be capable of providing protection against meningococcal disease caused by both serogroup C and B.

Patient perceptions of the challenges of recruitment to a renal randomised trial registry: a pilot questionnaire-based study.

BACKGROUND: Randomised controlled trials (RCTs) are the gold standard for demonstrating the efficacy of new therapies. However, issues of external validity often affect result application to real-world settings. Using registries to conduct RCTs is a reasonably new practice, but is appealing because it combines the benefits of both observational studies and RCTs. There is limited literature on patient motivators, barriers, and consent to registries for conducting RCTs. The purpose of our study was to establish the factors that motivate and/or inhibit patients from joining a registry for RCTs and to determine what information matters to patients when making an enrolment decision to participate in such a registry. METHODS: We conducted a cross-sectional questionnaire-based study at a dialysis centre in Southwest Ireland representing a catchment patient population of approximately 430,000. Quantitative data were coded and analysed in SPSS (v16). Descriptive statistics were produced, and open-ended questions were analysed by thematic analysis. RESULTS: Eighty-seven patients completed the questionnaire. Reasons for participation in a registry included personal and altruistic benefits. Barriers to participation were time and travel requirements associated with registry participation, data safety concerns, risks, side effects, and concerns that registry participation would impact current treatment. Although 29.8% of patients expressed concern regarding their data being stored in a registry, 79.3% were still willing to consent to have their data uploaded and stored in a registry for conducting RCTs. It was important to patients to have their GP (general practitioner) involved in the decision to participate, despite little day-to-day contact with their GP for renal dialysis management. CONCLUSION: Challenges to recruitment to registries for RCTs exist, but addressing the identified concerns of potential participants may aid patients in making a more informed enrolment decision and may improve recruitment to registries, and by extension, to RCTs conducted using the registry.