Use of poxvirus display to select antibodies specific for complex membrane antigens.

Antibody discovery against complex antigens is limited by the availability of a reproducible pure source of concentrated properly folded antigen. We have developed a technology to enable direct incorporation of membrane proteins such as GPCRs and into the membrane of poxvirus. The protein of interest is correctly folded and expressed in the cell-derived viral membrane and does not require any detergents or refolding before downstream use. The poxvirus is selective in which proteins are incorporated into the viral membrane, making the antigen poxvirus an antigenically cleaner target for in vitro panning. Antigen-expressing virus can be readily purified at scale and used for antibody selection using any in vitro display platform.

Rethinking referral pathways: qualitative evaluation of general practice networks to increase access to intrauterine contraception.

BACKGROUND: Long-acting reversible contraceptives are recommended first-line contraception; however, intrauterine device (IUD) uptake remains low in Australia. OBJECTIVES: To describe the outcomes of an independent evaluation of the General Practitioner IUD Insertion Network (GPIIN), a project designed to address access barriers through formalized referral pathways between general practitioners (GPs) inserting IUDs and noninserters. METHODS: An independent qualitative pragmatic inductive evaluation, involving 14 in-depth interviews with GPIIN members, was conducted 18 months post-GPIIN implementation in 2 Australian jurisdictions to identify and explore critical success factors and limitations of the model. RESULTS: Local GP-to-GP IUD referral networks were considered a useful model to assist affordable and timely IUD access, improve noninserters' IUD knowledge and inserters' reflection on best practice. However, pathway simplification is needed to determine optimal integration of the concept into pragmatic GP-to-GP referral arrangements. CONCLUSIONS: GPIIN provides an opportunity to improve IUD access in Primary Health Care. Further consideration of organizations best positioned and resourced to facilitate sustainable delivery and coordination is necessary.

The Dark Side of Humanity Scale: A reconstruction of the Dark Tetrad constructs.

There has been an absence of consideration regarding measurement invariance across males and females in the widely available Dark Tetrad (DT) scales which measure psychopathy, Machiavellianism, narcissism and everyday sadism. This has resulted in criticisms of the measures, suggesting that the assessed constructs are not wholly relatable between the groups. This article documents the construction and validation of the Dark Side of Humanity Scale (DSHS), which measures dark personalities from an alternative viewpoint, determined by the constructs as they emerged from the male and female data, whilst aligning with theory and attaining invariance between sex. Across four samples (n = 2409), using a diverse range of statistical methods, including exploratory graph analysis, item response theory and confirmatory factor analysis, a divergence from the widely available DT measures emerged, whereby primary psychopathy and Machiavellianism were unified. This corroborated past research which had discussed the two constructs as being parallel. It further supported the DSHS with a shift away from the traditional DT conceptualisation. The resulting scale encompasses four factors which are sex invariant across samples and time. The first factor represents the successful psychopath, factor two addresses the grandiose form of entitlement, factor three taps into everyday sadism whilst the fourth factor pertains to narcissistic entitlement rage. Construct and external validity of the DSHS across two samples (n = 1338), as well as test-retest reliability (n = 413), was achieved. The DSHS provides an alternative approach to investigating the dark side of human nature, whilst also being sex invariant, thus making it highly suitable for use with mixed sex samples.

Community-Based Sexual and Reproductive Health Promotion and Services for First Nations People in Urban Australia.

CONTEXT: Little is known about sexual and reproductive health (SRH) access and health promotion for First Nations peoples in Australia. This study aimed to better understand community preferences, knowledge and access to contraception and SRH services, and use this understanding to make recommendations which support approaches led by local Aboriginal community-controlled health organisations (ACCHOs). METHODS: Qualitative First Nations-led yarning circles were conducted with 55 community members and health service providers using and/or working at ACCHOs in urban South East Queensland. Cultural protocols ensured women's and men's interviews were separately collected and analysed. Thematic analysis was conducted by multiple coders, privileging interpretations by First Nations researchers. RESULTS: Family, kin and friends were described as key knowledge holders and ACCHOs as knowledge spaces for sharing information about maintaining positive SRH and wellbeing for First Nations people. Interviewees wanted accurate and timely information in an accessible, culturally appropriate way. Making informed choices about family planning was described as an important process of agency and self-determination for First Nations people, and contextualized within broader aspirations for growing strong families and healthy relationships. CONCLUSION: Understanding SRH through the concept of "knowledge spaces" and "knowledge holders" highlights the collective importance of community relationality to support individual agency and informed SRH decision-making. ACCHOs appear to be acceptable knowledge spaces for SRH information; and evidence-based recommendations may increase their reach. Health services should consider upskilling community SRH knowledge holders to share consistent, accurate and accessible SRH information.

Medical abortion in primary care.

Early medical abortion is a safe, cost effective and acceptable alternative to surgical abortion. It offers privacy and autonomy and can be provided by general practitioners who have completed an online training module. Abortion can be induced with mifepristone and misoprostol up to nine weeks of gestation. Apart from anticoagulation and severe anaemia, there are few contraindications and precautions for medical abortion. Obtaining informed consent requires the provision of information on expected effects, adverse effects and complications. The woman must know when to present to an emergency department. Follow-up must be arranged to ensure the abortion is complete. A serum human chorionic gonadotropin concentration or a low-sensitivity urine pregnancy test is used to confirm completion. Most contraceptive methods can be started immediately following medical abortion. If an intrauterine device is preferred, it should be inserted after confirming the abortion is complete.

Non-uniform in vivo Expansion of Epstein-Barr Virus-Specific T-Cells Following Donor Lymphocyte Infusion for Post-transplant Lymphoproliferative Disease.

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of T-lymphocyte deplete allogeneic hematopoietic stem cell transplantation (allo-HSCT). For patients with PTLD refractory to Rituximab, donor lymphocyte infusion (DLI) is established as a successful option for salvage therapy. However, although in vivo lymphocyte expansion has been correlated with good clinical outcome following DLI, the specificity and functional characteristics of EBV-specific T-cell responses remain poorly characterized. Here we describe two patients with Rituximab-refractory PTLD complicating T-cell deplete allo-HSCT, both of whom were successfully rescued with 1 × 106/Kg unselected stem cell donor-derived DLI. Prospective analyses revealed that complete clinical and radiological responses were associated with in vivo expansion of T and NK cells. Furthermore, EBV MHC tetramer, and interferon gamma analyses revealed a marked increase in EBV-specific T-cell frequency from 4 weeks after DLI. Reactivity was demonstrated against a range of EBV latent and lytic antigens, including those detected in tumor biopsy material. The immunodominant EBV-specific T cell response expanding in vivo following infusion matched the dominant response present in the DLI preparations prior to administration. Furthermore, differences in the repertoire of subdominant antigen-specific T-cells were also detected, suggesting that antigen-encounter in vivo can shape the immune response. These results demonstrate the value of prospectively studying in vivo T-cell responses, by facilitating the identification of important specificities required for clinical efficacy. Applying this approach on a larger scale promises to yield data which may be essential for the optimization of future adoptive immunotherapeutic strategies for PTLD.

Review of 5.5 Years' Experience Using E-mail-Based Telemedicine to Deliver Orthopedic Care to Remote Communities.

INTRODUCTION: The use of e-mail-based telemedicine has been demonstrated as an effective and low-cost way of delivering healthcare to patients in remote areas who have limited access to medical services. We established a novel teleorthopedic service for a catchment area encompassing 972,000 km2 using a commercial off-the-shelf e-mail application. Before the implementation of this program, patients with acute orthopedic injuries were required to travel by air up to 1,900 km for evaluation by an orthopedic surgeon. In the present study, we examined the patient demographics and consultation characteristics and calculated the cost savings associated with patient travel for this teleorthopedic service. METHODS: We retrospectively reviewed 1,000 consecutive e-mail-based consults and radiographic images received for new patients with acute orthopedic injuries from January 2008 to June 2013. Seventy-nine consults were excluded due to incomplete documentation, leaving 921 available for analysis. The service records were examined to identify patient demographics, orthopedic diagnosis, the percentage of patients managed locally, and the medical indications for patients requiring transfer. As the travel costs for patients requiring transport to the university hospital center are borne by governmental health agencies, the savings accrued from treating patients in their home communities were also calculated. RESULTS: For the 921 consultations, the mean age of patients was 27 years (range, 3 months-88 years), with 40.7% of all patients being younger than 18 years. The most common diagnoses were ankle fractures (15.2%), clavicle fractures (11.2%), distal radius fractures (11.2%), and fractures of the foot (10.2%). One hundred ninety patients (20.6%) required transfer, whereas 731 patients (79.4%) were treated in their home communities. Of the patients who were transferred, 123 (64.7%) required surgery, 55 (28.9%) required clinical evaluation by an orthopedic surgeon, and 12 (6.4%) required CT or MRI. Cost savings related to return trip travel expenses were calculated to be $5,538,120 Canadian (CAD) for the review period. SUMMARY: Using an e-mail-based teleorthopedic service to manage acutely injured patients in remote communities allowed 79% of patients to be treated locally, with travel-related cost savings of $5,538,120 CAD.

User characteristics, experiences and continuation rates of copper intrauterine device use in a cohort of Australian women.

BACKGROUND: Copper intrauterine device (Cu-IUD) use in Australia is low despite being a highly effective, cost effective non-hormonal contraceptive with reported 12-month continuation rates of 85% compared to 59% for oral contraception. AIMS: To describe the characteristics of Cu-IUD users in the Australian context, their experiences of side effects, continuation rates and reasons for discontinuation. METHODS: Between August 2009 and January 2012 we undertook a prospective cohort study of consecutive women presenting for Cu-IUD insertion to three family planning clinics in Queensland and New South Wales. We used survival analysis for continuation rates and univariate and multivariable analyses to characterise users, their experiences up to three years and reasons for discontinuation. RESULTS: Of the 211 enrolled women, a third (36.0%) were aged under 30 and a third were nulliparous (36.5%). Efficacy and lack of hormones were the most frequently cited reasons to choose the method. Four women were lost to follow-up. Overall continuation rates were 79.1% at one year and 61.3% at three years. Early discontinuation was reduced in those with two or more children (adjusted hazards ratio 0.22, 95% CI 0.09-0.50). Heavy menstrual bleeding was the commonest reason for removal in 28 of 59 (47.5%) discontinuations due to complications or side effects. One uterine perforation and one method failure resulting in an ectopic pregnancy occurred. CONCLUSIONS: Cu-IUDs were chosen for their efficacy and lack of hormones by a range of Australian women, including young and nulliparous women. While bleeding-related side effects were relatively common, overall continuation rates were high. Serious complications and failures were rare.

Evaluation of Chlamydia Partner Notification Practices and Use of the "Let Them Know" Website by Family Planning Clinicians in Australia: Cross-Sectional Study.

BACKGROUND: Chlamydia, caused by Chlamydia trachomatis, is the most common reportable infection in many developed countries. Testing, treatment, and partner notification (PN) are key strategies for chlamydia control. In 2008 the Let Them Know (LTK) PN website was established, which provided means for people to send anonymous PN messages by text messaging (short message service, SMS), email, or letter. OBJECTIVE: We evaluated PN practices among Australian family planning clinicians following chlamydia diagnosis and assessed how often clinicians refer their patients to the LTK website. METHODS: A mixed methods approach included a Web-based cross-sectional survey of Australian family planning clinicians to examine PN attitudes and practices and focus groups to explore the context of LTK website use. RESULTS: Between May 2012 and June 2012, all clinicians from 29 different family planning services (n=212) were invited to complete the survey, and 164 participated (response rate=77.4%); of the clinicians, 96.3% (158/164) were females, 56.1% (92/164) nurses, and 43.9% (72/164) doctors. More than half (62.2%, 92/148) agreed that PN was primarily the client's responsibility; however, 93.2% (138/148) agreed it was the clinician's responsibility to support the client in informing their partners by providing information or access to resources. Almost half (49.4%, 76/154) of the clinicians said that they always or usually referred clients to the LTK website, with variation across clinics in Australian states and territories (0%-77%). Eleven focus groups among 70 clinicians at 11 family planning services found that the LTK website had been integrated into routine practice; that it was particularly useful for clients who found it difficult to contact partners; and that the LTK letters and fact sheets were useful. However, many clinicians were not aware of the website and noted a lack of internal clinic training about LTK. CONCLUSIONS: The LTK website has become an important PN tool for family planning clinicians. The variation in referral of patients to the LTK website and lack of awareness among some clinicians suggest further promotion of the website, PN training, and clinic protocols are warranted.

Increasing access to sexual health care for rural and regional young people: Similarities and differences in the views of young people and service providers.

OBJECTIVE: This study aims to describe the views of sexual health service providers on access issues for young people and consider them together with the views of young people themselves. DESIGN: A cross-sectional mixed-methods study design involving semi-structured interviews with health service providers and an electronic survey with young people. SETTING: Four towns in rural and regional Queensland, Australia. PARTICIPANTS: A total of 32 service providers: 9 sexual health nurses, 8 general practitioners, 6 school-based youth health nurses, 5 sexual health educators, 2 Australian Aboriginal health workers and 2 youth workers. There were 391 young people who participated in the Young People's Survey. MAIN OUTCOME MEASURES: Themes generated from interviews with service providers and quantitative data from young people addressing access to sexual and reproductive health (SRH) services for rural and regional young people. RESULTS: Service providers frequently identified structural barriers, confidentiality and lack of awareness of SRH services as barriers for young people seeking SRH care. Young people also reported that structural factors such as transport, cost and service operating hours were important; however, they placed greater value on personal attributes of service providers, particularly welcoming and non-judgemental attitudes. CONCLUSION: Health service policy and training focused on attitudinal qualities of individual service providers may improve access to SRH services for young people. Selective staff recruitment and professional development are important to increase sensitivity to youth issues. Promotion of non-judgemental and confidential care may also improve access for youth.

Young people's perceptions of sexual and reproductive health in regional and rural Queensland: capturing the views of adolescents through reference groups and a user-friendly electronic survey.

UNLABELLED: Background Young people in regional and rural Queensland have difficulty accessing sexual and reproductive health (SRH) services. Young people's views regarding barriers and enablers for accessing SRH services and markers of quality are largely unknown. METHODS: Young people's perceptions regarding SRH services are explored through a cross-sectional study via eight reference group meetings and an electronic survey in four sites: Atherton Tablelands, Rockhampton, Toowoomba and Townsville. The survey, developed in consultation with young people, was administered online and face to face using tablet computers. Data from 391 rural and regional participants was precoded for bivariate comparisons involving χ(2) and confidence interval (CI) tests. RESULTS: The most valued markers of quality in SRH services defined by young people all related to staff characteristics. Young people preferred services where staff were friendly (87.3%; 95% CI: 83.8-90.8%), easy to talk to (91.4%; 95% CI: 88.5-94.3%), good listeners (95.4%; 95% CI: 93.2-97.6%) and did not judge them (90.5%; 95% CI: 87.4-93.6%). A model of SRH service delivery encompassed within general health services was highly valued by 58.9% (95% CI 53.7-64.1%). However, 36.2% (95% CI: 31.4-41.0%) preferred to seek care from SRH specialist services. CONCLUSIONS: Service provision can be improved by training, and retaining friendly, attentive and non-judgemental staff. A model of service provision that includes general health care and provides sexual health services may increase the acceptability and accessibility of SRH services among youth. Additionally, our study highlights the need for choice between general and specialist SRH services.

What can we learn about immediate memory from the development of children's free recall?

We ask the question: Which aspects of immediate memory performance improve with age? In two studies, we reexamine the widely held view that primary memory capacity estimates derived from children's immediate free recall are age invariant. This was done by assessing children's immediate free-recall accuracy while also measuring the order in which they elected to recall items (Experiment 1) and by encouraging children to begin free recall with items from towards the end of the presented list (Experiment 2). Across samples aged between 5 and 8 years we replicated the previously reported age-related changes in free-recall serial position functions when aggregated across all trials of the standard task, including an absence of age differences in the recency portion of this curve. However, we also show that this does not reflect the fact that primary memory capacity is constant across age. Instead, when we incorporate order of report information, clear age differences are evident in the recall of list-final items that are output at the start of a participant's response. In addition, the total amount that individuals recalled varied little across different types of free-recall tasks. These findings have clear implications for the use of immediate free recall as a means of providing potential indices of primary memory capacity and in the study of the development of immediate memory.

Factors affecting the relative age effect in NHL athletes.

BACKGROUND: The relative age effect (RAE) has been reported for a number of different activities. The RAE is the phenomena whereby players born in the first few months of a competition year are advantaged for selection to elite sports. Much of the literature has identified elite male athletics, such as the National Hockey League (NHL), as having consistently large RAEs. We propose that RAE may be lessened in the NHL since the last examination. METHODS: We examined demographic and selection factors to understand current NHL selection biases. RESULTS: We found that RAE was weak and was only evident when birth dates were broken into year halves. Players born in the first half of the year were relatively advantaged for entry into the NHL. We found that the RAE is smaller than reported in previous studies. Intraplayer comparisons for multiple factors, including place of birth, country of play, type of hockey played, height and weight, revealed no differences. Players who were not drafted (e.g., free agents) or who played university hockey in North America had no apparent RAE. CONCLUSION: We found little evidence of an RAE in the current NHL player rosters. A larger study of all Canadian minor hockey intercity teams could help determine the existence of an RAE.

CONTEXTE: L'effet de l'âge relatif (EAR) entre en ligne de compte dans plusieurs types d'activités. Dans le contexte des sports d'élite, par exemple, l'EAR est le phénomène qui fait que les joueurs nés au cours des premiers mois d'une année de compétition ont un avantage sur les autres au moment de la sélection. La littérature a abondamment fait mention de la persistance d'un EAR important dans les sports d'élite masculins, entre autres, au sein de la Ligue nationale de hockey (LNH). Selon notre hypothèse, l'EAR peut avoir diminué au sein de la LNH depuis la dernière étude. MÉTHODES: Nous avons analysé les facteurs démographiques et les facteurs de sélection afin de comprendre les biais de sélection actuels au sein de la LNH. RÉSULTATS: Nous avons observé que l'EAR était faible et qu'il ne se manifestait que lorsque les dates de naissance étaient scindées en demi-années. Les joueurs nés durant la première demie de l'année étaient relativement avantagés au moment de la sélection pour la LNH. Nous avons constaté que l'EAR était plus faible qu'on ne l'avait rapporté lors des études antérieures. Les comparaisons entre les joueurs selon différents facteurs, dont le lieu de naissance, le pays où le sport a été pratiqué, le type de hockey pratiqué, la taille et le poids, n'ont révélé aucune différence. Les joueurs qui étaient sans contrats (c.-à-d., agents libres) ou qui ont joué dans des ligues de hockey universitaires nord-américaines ne semblaient pas soumis à un quelconque EAR. CONCLUSION: Nous avons trouvé peu de preuves d'un EAR dans les listes actuelles des joueurs de la LNH. Une étude de plus grande envergure sur les équipes de hockey mineures intercités au Canada permettrait de vérifier l'existence d'un EAR.

Bone marrow trephine biopsy involvement by lymphoma: review of histopathological features in 511 specimens and correlation with diagnostic biopsy, aspirate and peripheral blood findings.

AIMS: This study aimed to evaluate the key features of bone marrow trephine (BMT) biopsy involvement by lymphoma. METHODS: 511 cases were assessed for percentage of marrow involvement, pattern of involvement (diffuse, nodular, paratrabecular, interstitial or intrasinusoidal), presence/absence of granulomas, stromal fibrosis and necrosis, presence/absence of neoplastic/reactive follicles and discordance with other biopsy sites. Correlation with aspirate and peripheral blood findings was made in a subset of 345 patients (167 aspirates, 178 blood). RESULTS: The most frequent subtype was follicular lymphoma (26.2%) followed by extranodal marginal zone (23.1%), lymphoplasmacytic (19.2%), diffuse large B cell (DLBCL) (12.5%), Hodgkin (HL) (5.7%) and mantle cell lymphomas (4.3%). The predominant pattern in follicular lymphoma was paratrabecular. Marginal zone lymphomas of all types and lymphoplasmacytic lymphoma showed a relatively even distribution between diffuse, interstitial, paratrabecular and nodular patterns. The majority of mantle cell lymphoma cases showed either diffuse or nodular patterns. A diffuse pattern was common in DLBCL and Burkitt lymphomas. An intrasinusoidal pattern was seen only in extranodal and splenic marginal zone lymphomas. Granulomas and fibrosis were uncommon in small cell B cell lymphomas but frequent in DLBCL and HL. Aspirate and trephine results concurred in 73.8% of cases overall, but this varied widely between subtypes. Peripheral blood involvement rates by lymphoma also varied, with a mean of 37.1%. CONCLUSIONS: Different lymphomas often demonstrate reliably characteristic architectural patterns of marrow involvement which can help differentiate them even when cytological features do not permit this, and marrow stromal and other background changes may also be useful pointers towards a particular lymphoma subtype.

Marking the skin for oral surgical procedures: improving the WHO checklist.

We present a system for marking the skin during oral surgical operations. This system identifies teeth to be extracted or exposed under general anaesthesia. Removal of the wrong tooth can cause appreciable morbidity and leaves the surgeon and organisation liable for litigation and scrutiny by regulatory bodies. A recent review of claims to the NHS litigation authority between 1995 and 2010 showed that in the field of oral and maxillofacial surgery, dentoalveolar surgery resulted in the largest number of claims for negligence, of which removal of the wrong tooth was one of the most common. In 2010/2011 the National Reporting and Learning System (NRLS) of the National Patient Safety Agency (NPSA) were notified of 20 incidents when the wrong tooth had been extracted, which accounted for 5% of all incidents reported. We have therefore developed a robust marking system for oral surgical procedures in our hospital, which improves on the World Health Organisation (WHO) checklist. We have audited patients' perceptions and the clinical application of our marking system, and have shown that the system is welcomed by patients, and is simple and effective for clinicians to use.

Chlamydia testing and retesting patterns at family planning clinics in Australia.

INTRODUCTION: National guidelines recommend opportunistic chlamydia screening of sexually active 16- to 29-year-olds and encourage retesting 3-12 months after a diagnosed chlamydia (Chlamydia trachomatis) infection. We assessed chlamydia testing patterns at five Australian family planning clinics (FPCs). METHODS: Using routine clinic data from 16- to 29-year-olds, we calculated chlamydia testing and positivity rates in 2008-2009. Reattendance, retesting and positivity rates at retesting within 1.5-4 and 1.5-12 months of a positive result were calculated. RESULTS: Over 2 years, 13?690 individuals aged 16-29 years attended five FPCs (93% female). In 2008, 3159 females (41.4%,) and 263 males (57.0%) were tested for chlamydia; positivity was 8% and 19%, respectively. In 2009, 3178 females (39.6%) and 295 males (57.2%) were tested; positivity was 8% and 23%, respectively. Of 7637 females attending in 2008, 38% also attended in 2009, of which 20% were tested both years. Within 1.5-4 months of a positive test, 83 (31.1%) females reattended; the retesting rate was 13% and 12% retested positive. Within 1.5-12 months of a positive test, 96 (57.5%) females reattended; the retesting rate was 36% and 13% retested positive. CONCLUSIONS: Approximately 40% of young people attending FPCs were tested for chlamydia but a smaller proportion were tested annually or were retested following chlamydia infection. High positivity rates emphasise that FPCs see a high-risk population. To maximise testing opportunities, clinical prompts, patient reminder systems and non-clinic testing strategies may be needed.