Exploring the challenges and opportunities of public engagement with fundamental biology.

The Human Developmental Biology Initiative (HDBI) is a Wellcome-funded research consortium involving scientists based in institutions across the UK and Europe. It aims to pioneer new technologies and techniques to answer fundamental questions about human development and could, therefore, eventually improve treatments for fertility, birth defects and developmental diseases, as well as aiding regenerative medicine. HDBI research relies on human fetal and embryonic tissues donated following pregnancy terminations or fertility treatment. The situations in which these tissues are donated, their use in research and the potential healthcare impacts of this work all present complex ethical and moral questions that are of interest not only to scientists but also to the public. As such, HDBI's public engagement programme 'What makes us human?' aspires to test new ways of engaging the public with fundamental biology. In this brief Perspective, we provide an overview of this public engagement approach, exploring its challenges and opportunities, and outline our longer-term plans. We hope that by sharing our experiences we will encourage and enable others to organise similarly experimental public engagement, even if their research is very fundamental or potentially controversial.

Enhanced 129 Xe T1 relaxation in whole blood and in the presence of SPIONs at low magnetic field strengths.

PURPOSE: To compare the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on the T1 of 129 Xe and 1 H and to measure the relaxation of 129 Xe in blood at low and high magnetic field strengths. METHODS: 129 Xe and 1 H T1 relaxometry was performed at low- and high-field strengths in samples containing different SPION concentrations, while imaging was used to compare the contrast obtainable in these two field regimes. In vivo experiments at variable field strengths were performed to determine the depolarization of 129 Xe in blood and the feasibility of in vivo dissolved-phase spectroscopy and imaging at low field. RESULTS: The SPION relaxivity was substantially greater at low field for 1 H, increasing from 0.92 ± 0.06 mM s-1 at 11.7T to 31.5 ± 1.8 mM s-1 at 0.6 mT, and for 129 Xe, which increased from 0.13 ± 0.03 mM s-1 at 11.7T to 7.32 ± 0.71 mM s-1 at 2.1 mT. The additional MR signal loss increased from 0.7% at 9.4T to 20.6 ± 4.2% at 0.6 mT for 1 H and from -0.7 ± 3.4% at 9.4T to 12.7 ± 3.5% at 2.1 mT for 129 Xe. Blood was found to depolarize 129 Xe below 3T in a manner inversely proportional to the field strength. In vitro studies at 2.1 mT suggest 129 Xe relaxation times below 5 s in blood dilutions as low as 0.4% volume. CONCLUSION: SPIONs longitudinal relaxivity increases at low field both for 1 H and 129 Xe. The depolarization of xenon in blood, which is found to increase below 3T, effectively prevents in vivo dissolved-phase spectroscopy and imaging at low-field strengths.

Integrating safer conception services into primary care: providers' perspectives.

BACKGROUND: In 2012, South Africa adopted the Contraception and Fertility Planning guidelines to incorporate safer conception services into care for HIV-affected couples trying to conceive. These guidelines lacked clear implementation and training recommendations. The objective of this study was to investigate factors influencing integration of safer conception services in a clinical setting. METHODS: Twenty in-depth interviews were conducted between October-November 2017 with providers and staff at Witkoppen Clinic in Johannesburg, where the Sakh'umndeni safer conception demonstration project had enrolled patients from July 2013-July 2017. Semi-structured interview guides engaged providers on their perspectives following the Sakh'umndeni project and possible integration plans to inform the translation of the stand-alone Sakh'umndeni services into a routine service. A grounded theory approach was used to code interviews and an adaptation of the Atun et al. (2010) 'Integration of Targeted Interventions into Health Systems' conceptual framework was applied as an analysis tool. RESULTS: Five themes emerged: (1) The need for safer conception training; (2) The importance of messaging and demand generation; (3) A spectrum of views around the extent of integration of safer conception services; (4) Limitations of family planning services as an integration focal point; and (5) Benefits and challenges of a "couples-based" intervention. In-depth interviews suggested that counselors, as the first point of contact, should inform patients about safer conceptions services, followed by targeted reinforcement of safer conception messaging by all clinicians, and referral to more intensively trained safer conception providers. CONCLUSION: A safer conception counseling guide would facilitate consultations. While many providers felt that the services belonged in family planning, lack of HIV management skills, men and women trying to conceive within family planning may pose barriers.

Under-five mortality before and after implementation of the Liberia National Community Health Assistant (NCHA) program: A study protocol.

Between 2018 and 2022 the Liberian Government implemented the National Community Health Assistant (NCHA) program to improve provision of maternal and child health care to underserved rural areas of the country. Whereas the contributions of this and similar community health worker (CHW) based healthcare programs have been associated with improved process measures, the impact of a governmental CHW program at scale on child mortality has not been fully established. We will conduct a cluster sampled, community-based survey with landmark event calendars to retrospectively assess child births and deaths among all children born to women in the Grand Bassa District of Liberia. We will use a mixed effects Cox proportional hazards model, taking advantage of the staggered program implementation in Grand Bassa districts over a period of 4 years to compare rates of under-5 child mortality between the pre- and post-NCHA program implementation periods. This study will be the first to estimate the impact of the Liberian NCHA program on under-5 mortality.

In-vivo detection of white adipose tissue browning: a multimodality imaging approach.

Detection and differentiation of brown fat in humans poses several challenges, as this tissue is sparse and often mixed with white adipose tissue. Non-invasive detection of beige fat represents an even greater challenge as this tissue is structurally and functionally more like white fat than brown fat. Here we used positron emission tomography with 18F-fluorodeoxyglucose, computed tomography, xenon-enhanced computed tomography, and dynamic contrast-enhanced ultrasound, to non-invasively detect functional and structural changes associated with the browning process of inguinal white fat, induced in mice by chronic stimulation with the ß3-adrenergic receptor agonist CL-316243. These studies reveal a very heterogeneous increase in baseline tissue radiodensity and xenon-enhanced radiodensity, indicative of both an increase in adipocytes water and protein content as well as tissue perfusion, mostly in regions that showed enhanced norepinephrine-stimulated perfusion before CL-316243 treatment. No statistically significant increase in 18F-fluorodeoxyglucose uptake or norepinephrine-stimulated tissue perfusion were observed in the mice after the CL-316243 treatment. The increase in tissue-water content and perfusion, along with the negligible increase in the tissue glucose uptake and norepinephrine-stimulated perfusion deserve more attention, especially considering the potential metabolic role that this tissue may play in whole body metabolism.

Absolute thermometry of human brown adipose tissue by magnetic resonance with laser polarized 129Xe.

BACKGROUND: Absolute temperature measurements of tissues inside the human body are difficult to perform non-invasively. Yet, for brown adipose tissue (BAT), these measurements would enable direct monitoring of its thermogenic activity and its association with metabolic health. METHODS: Here, we report direct measurement of absolute BAT temperature in humans during cold exposure by magnetic resonance (MR) with laser polarized xenon gas. This methodology, which leverages on the sensitivity of the chemical shift of the 129Xe isotope to temperature-induced changes in fat density, is first calibrated in vitro and then tested in vivo in rodents. Finally, it is used in humans along with positron emission tomography (PET) scans with fluorine-18-fluorodeoxyglucose to detect BAT thermogenic activity during cold exposure. RESULTS: Absolute temperature measurements, obtained in rodents with an experimental error of 0.5 °C, show only a median deviation of 0.12 °C against temperature measurements made using a pre-calibrated optical temperature probe. In humans, enhanced uptake of 129Xe in BAT during cold exposure leads to background-free detection of this tissue by MR. Global measurements of supraclavicular BAT temperature, made over the course of four seconds and with an experimental error ranging from a minimum of 0.4 °C to more than 2 °C, in case of poor shimming, reveal an average BAT temperature of 38.8° ± 0.8 °C, significantly higher (p < 0.02 two-sided t test) than 37.7 °C. Hot BAT is also detected in participants with a PET scan negative for BAT. CONCLUSIONS: Non-invasive, radiation-free measurements of BAT temperature by MRI with hyperpolarized 129Xe may enable longitudinal monitoring of human BAT activity under various stimulatory conditions.

Brown adipose tissue (BAT) is a fat tissue specialized in heat production and considered a potential target for the treatment of obesity and diabetes. Detection of this tissue and its metabolic activity in adult humans is challenging as this tissue is often mixed with white fat, which makes up most of the fat in adult humans. Here we demonstrate that magnetic resonance imaging with laser-polarized xenon gas, a medical imaging technique used to assess lung ventilation function, can detect the presence of this tissue in humans and measure its temperature. These temperature measurements, which show that brown fat becomes significantly hotter than 37 °C when humans are exposed to cold, may be useful in future studies to assess the effects of drugs that aim to target BAT's heat-generating activity to regulate blood sugar level.

Understanding who is and isn't involved and engaged in health research: capturing and analysing demographic data to diversify patient and public involvement and engagement.

BACKGROUND: Patient and public involvement and engagement (PPIE) can improve the relevance, quality, ethics and impact of research thus contributing to high quality research. Currently in the UK, people who get involved in research tend to be aged 61 years or above, White and female. Calls for greater diversity and inclusion in PPIE have become more urgent especially since the COVID-19 pandemic, so that research can better address health inequalities and be relevant for all sectors of society. Yet, there are currently no routine systems or requirements to collect or analyse the demographics of people who get involved in health research in the UK. The aim of this study was to develop to capture and analyse the characteristics of who does and doesn't take part in patient and public involvement and engagement (PPIE) activities. METHODS: As part of its strategic focus on diversity and inclusion, Vocal developed a questionnaire to assess the demographics of people taking part in its PPIE activities. Vocal is a non-profit organisation which supports PPIE in health research across the region of Greater Manchester in England. The questionnaire was implemented across Vocal activities between December 2018 and March 2022. In that time. Vocal was working with approximately 935 public contributors. 329 responses were received: a return rate of 29.3%. Analysis of findings and comparison against local population demographic data, and available national data related to public contributors to health research, was performed. RESULTS: Results show that it is feasible to assess the demographics of people who take part in PPIE activities, through a questionnaire system. Further, our emerging data indicate that Vocal are involving people from a wider range of ages and with a greater diversity of ethnic backgrounds in health research, as compared to available national data. Specifically, Vocal involves more people of Asian, African and Caribbean heritage, and includes a wider range of ages in its PPIE activities. More women than men are involved in Vocal's work. CONCLUSION: Our 'learn by doing' approach to assessing who does and doesn't take part in Vocal's PPIE activities has informed our practice and continues influence our strategic priorities for PPIE. Our system and learning reported here may be applicable and transferable to other similar settings in which PPIE is carried out. We attribute the greater diversity of our public contributors to our strategic priority and activities to promote more inclusive research since 2018.

Patient and public involvement and engagement (PPIE) can improve the relevance, quality, ethics and impact of research thus contributing to high quality research. Currently in the UK, people who get involved in research tend to be aged 61 years or above, White and female. Calls for greater diversity and inclusion in PPIE have become more urgent especially since the COVID-19 pandemic, so that research can better address health inequalities and be relevant for all sectors of society. Yet, there are currently no routine systems or requirements to collect or analyse the demographics of people who get involved in health research in the UK. Vocal is a non-profit organisation which supports PPIE in health research across the region of Greater Manchester in England. Since 2018, one of Vocal's strategic priorities has been to promote inclusive research by diversifying those who are engaged and involved in research, through the development of more inclusive ways of working together, including methods to understand who is (and isn't) currently involved in Vocal's PPIE activities. We find that it's feasible to capture and analyse demographic data related to PPIE. Further, our emerging data indicate that we are involving people from a wider range of ages and with a greater diversity of ethnic backgrounds in PPIE for health research, as compared to available national data. However, similarly to national trends, more women than men are involved in PPIE work.

Stress-dependent relocalization of translationally primed mRNPs to cytoplasmic granules that are kinetically and spatially distinct from P-bodies.

Cytoplasmic RNA granules serve key functions in the control of messenger RNA (mRNA) fate in eukaryotic cells. For instance, in yeast, severe stress induces mRNA relocalization to sites of degradation or storage called processing bodies (P-bodies). In this study, we show that the translation repression associated with glucose starvation causes the key translational mediators of mRNA recognition, eIF4E, eIF4G, and Pab1p, to resediment away from ribosomal fractions. These mediators then accumulate in P-bodies and in previously unrecognized cytoplasmic bodies, which we define as EGP-bodies. Our kinetic studies highlight the fundamental difference between EGP- and P-bodies and reflect the complex dynamics surrounding reconfiguration of the mRNA pool under stress conditions. An absence of key mRNA decay factors from EGP-bodies points toward an mRNA storage function for these bodies. Overall, this study highlights new potential control points in both the regulation of mRNA fate and the global control of translation initiation.

Adapting Mindfulness-Based Cognitive Therapy for Perinatal Depression to Improve Access and Appeal of Preventive Care.

Existing and emerging evidence indicates that perinatal depression is a key contributor to preventable morbidity and mortality during and after childbearing. Despite this, there are few effective options for prevention and treatment that are readily accessible for and appealing to pregnant people. Aspects of routine health care systems contribute to this situation. Furthermore, societal and health care systems factors create additional barriers for people of color, people living in rural regions, and people living in poverty. Our interprofessional team of perinatal care providers, mental health providers, community partners, health services scientists, health equity scientists, and business leaders developed and are piloting a perinatal mental health preventive intervention designed to increase access and appeal of a program incorporating mindfulness cognitive behavioral therapy with proven efficacy in preventing perinatal depression. In this article, we briefly summarize key systems barriers to delivering preventive care for perinatal depression in standard prenatal care clinics. We then describe Mindfulness-Based Cognitive Therapy for Perinatal Depression and outline our adaptation of this intervention, Center M. Finally, we identify next steps, challenges, and opportunities for this recent innovation.

"We are not hard to reach, but we may find it hard to trust" . Involving and engaging 'seldom listened to' community voices in clinical translational health research: a social innovation approach.

BACKGROUND: Public involvement in clinical translational research is increasingly recognised as essential for relevant and reliable research. Public involvement must be diverse and inclusive to enable research that has the potential to reach those that stand to benefit from it the most, and thus address issues of health equity. Several recent reports, however, indicate that public involvement is exclusive, including in its interactions with ethnic groups. This paper outlines a novel community-led methodology - a community sandpit - to address the inclusion of ethnic groups in public involvement in research, reports on its evaluation, findings, legacy and impact. METHODS: Through detailed planning - thinking through and taking into account all stakeholders perspectives in the planning and design of the sandpit, relationship-building, co-design and co-delivery between the Public Programmes team based at Manchester University NHS Foundation Trust and the Greater Manchester Black and Minority Ethnic Network - the community sandpit was held in July 2018. RESULTS: Fifteen community organisations took part in the two-day event, as well as six researchers, and six creative practitioners. Six community-based partnership projects were seed-funded; four of these received additional funding from other sources also. CONCLUSIONS: Evaluation of the sandpit showed the format to be well-received by all: it levelled power relationships between community organisations, health researchers and research infrastructure; it developed capacity amongst researchers about the accessibility, role and potential of community organisations. Described as "not another community seed fund" by community partners, the sandpit offered community partners, equitable avenues for collaboration within Greater Manchester translational research and led to the formation of the Black, Asian and Minority Ethnic Research Advisory Group (BRAG Vocal Website information, - https://www.wearevocal.org/opportunities/black-asian-and-minority-ethnic-research-advisory-group-brag/ , 2021). The method has the potential to be replicated elsewhere to support inclusive public involvement in research and inclusive research.

Public involvement in "bench to bedside" research (from laboratory-based research to clinical practice) is increasingly recognised as essential for relevant and reliable research. To enable the findings from health research to meet the needs of those who stand to benefit from it the most and to ensure that differences in health and disease are reduced as much as possible, public involvement must be diverse and inclusive. Recent reports, however, indicate that public involvement is exclusive, including in its interactions with racially minoritised groups. This paper outlines a novel community-led methodology ­ a community sandpit ­ to address the inclusion of ethnic groups in public involvement in research, reports on its evaluation, findings, legacy and impact.Through detailed planning ­ thinking through and taking into account all stakeholders perspectives in the planning and design of the sandpit, relationship-building, co-design and co-delivery between the Public Programmes Team (now Vocal) based at Manchester University NHS Foundation Trust worked with the Greater Manchester Black and Minority Ethnic Network - the community sandpit was held in July 2018. Fifteen community organisations took part in the two-day event, as well as six researchers, and six creative practitioners (artists with experience of working with the public on socially engaged projects to engage them in areas such as science). Six community-based partnership projects were seed-funded; four of these received additional funding from other sources. Evaluation of the sandpit showed the format to be well-received by all: it levelled power relationships between community organisations, health researchers and research infrastructure; it increased researchers knowledge and insights about the accessibility of community organisations and of how they might work effectively with them. Described as "not another community seed fund" by community partners, the sandpit began the process of levelling the playing field for collaboration between Greater Manchester translational research and local community organisations and led to the formation of the Black, Asian and Minority Ethnic Research Advisory Group (BRAG) (Vocal Website information, - https://www.wearevocal.org/opportunities/black-asian-and-minority-ethnic-research-advisory-group-brag/ , 2021). The method has the potential to be repeated elsewhere to support inclusive public involvement in research and inclusive research.

Sexual Relationship Types, Partner HIV Self-Testing, and Pre-Exposure Prophylaxis Among South African Adolescent Girls and Young Women: A Latent Class Analysis.

BACKGROUND: Sexual relationships among adolescent girls and young women (AGYW) are influenced by social, economic, and gender dynamics. Understanding AGYW's different relationship types and their implications for HIV risk is important for development of tailored interventions. We sought to identify relationship typologies among AGYW and their impact on uptake of HIV prevention interventions. METHODS: From May 2018 to February 2019, 2200 HIV-negative AGYW (ages 16-24) in Johannesburg, South Africa, participated in an HIV prevention intervention involving distribution of HIV self-test kits to their male partners. AGYW were also offered pre-exposure prophylaxis. At baseline, AGYW completed a questionnaire, and outcomes were assessed for 3 months. We used latent class analysis to identify relationship types and mixture modeling to estimate the impact of relationship type on engagement in prevention interventions. RESULTS: We identified 3 relationship types: "stable, empowered relationships with older partners" (class 1, n = 973); "shorter, empowered relationships with peer partners" (class 2, n = 1067); and "shorter relationships with risky partners" (class 3, n = 160). Compared with AGYW in class 1 relationships, AGYW in class 2 and 3 relationships were less likely to complete partner testing alongside HIV results sharing (class 2 adjusted risk ratio: 0.89, 95% confidence interval: 0.85 to 0.95; class 3 adjusted risk ratio: 0.84, 95% confidence interval: 0.73 to 0.94). Pre-exposure prophylaxis uptake was highest in class 3 (11.2%) compared with class 2 (3.8%) and class 1 (1.0%; P < 0.001). CONCLUSIONS: Relationship type impacts uptake of HIV prevention interventions among South African youth. Intervention effectiveness could be optimized by using tailored approaches to HIV risk mitigation among AGYW.

Qualitative characterizations of relationships among South African adolescent girls and young women and male partners: implications for engagement across HIV self-testing and pre-exposure prophylaxis prevention cascades.

INTRODUCTION: Adolescent girls and young women (AGYW) in sub-Saharan Africa have emerged as a priority population in need of HIV prevention interventions. Secondary distribution of home-based HIV self-test kits by AGYW to male partners (MP) is a novel prevention strategy that complements pre-exposure prophylaxis (PrEP), a female-controlled prevention intervention. The objective of this analysis was to qualitatively operationalize two HIV prevention cascades through the lens of relationship dynamics for secondary distribution of HIV self-tests to MP and PrEP for AGYW. METHODS: From April 2018 to December 2018, 2200 HIV-negative AGYW aged 16-24 years were enrolled into an HIV prevention intervention which involved secondary distribution of self-tests to MP and PrEP for AGYW; of these women, 91 participants or MP were sampled for in-depth interviews based on their degree of completion of the two HIV prevention cascades. A grounded theory approach was used to characterize participants' relationship profiles, which were mapped to participants' engagement with the interventions. RESULTS: In cases where AGYW had a MP with multiple partners, AGYW perceived both interventions as inviting distrust into the relationship and insinuating non-monogamy. Many chose not to accept either intervention, while others accepted and attempted to deliver the self-test kit but received a negative reaction from their MP. In the few cases where AGYW held multiple partnerships, both interventions were viewed as mechanisms for protecting one's health, and these AGYW exhibited confidence in accepting and delivering the self-test kits and initiating PrEP. Women who indicated intimate partner violence experiences chose not to accept either intervention because they feared it would elicit a violent reaction from their MP. For AGYW in relationships described as committed and emotionally open, self-test kit delivery was completed with ease, but PrEP was viewed as unnecessary. MP experience with the cascade corroborated AGYW perspectives and demonstrated how men can perceive female-initiated HIV prevention options as beneficial for AGYW and a threat to MP masculinity. CONCLUSIONS: Screening to identify AGYW relationship dynamics can support tailoring prevention services to relationship-driven barriers and facilitators. HIV prevention counseling for AGYW should address relationship goals or partner's influence, and engage with MP around female-controlled prevention interventions.

Innovating public engagement and patient involvement through strategic collaboration and practice.

BACKGROUND: Patient and public involvement and engagement is an important and expected component of health-related research activity in the UK. Specifically within the health research sphere, public engagement (usually defined as raising awareness of research) and patient involvement (usually defined as actively involving people in research) have traditionally been seen as separate but have much to gain from working together towards a common goal of better health outcomes for all. METHODS: This paper describes a unique approach taken by the Public Programmes Team: a small interdisciplinary team of public engagement specialists, with backgrounds in science, community development, public engagement and involvement, policy, ethics, communications, industry, museums and creative practice, embedded within translational research infrastructure and delivery in Manchester in the North West of England. We propose a new model of professional practice - a 'cycle' of engagement and involvement - innovating across the complementary fields of public engagement and patient involvement, and working inclusively and in partnership with people in health research. Further, our approach capitalises on strategic collaboration offering economies of scale and a joined up way of working. Our ambition is to boldly experiment, learn and reflect, responsibly and based on evidence and partnerships, using methods of engagement that address issues of social justice. RESULTS: Here, we report on preliminary case studies exemplifying the impact of our approach, and data relating to achievements and learning between April 2017 and March 2018. Informed by our findings, we propose that our approach has the potential to be replicated elsewhere. CONCLUSIONS: Our practice and the beginning of its evaluation lead us to believe that our way of working and model of professional practice - the 'cycle' of engagement and involvement - is effective in: addressing our vision of making health research relevant and inclusive for everyone; and embedding and joining up public involvement in a busy and fertile translational health research ecosystem.

Linkage to treatment and supportive services among HIV-positive ex-offenders in Project Bridge.

UNLABELLED: HIV-positive inmates often have histories of substance use, mental illness, and homelessness. Access to supportive services is important for members of this population upon their release from prison to improve continuity of medical care in the community. This paper briefly reviews Project Bridge, a federally funded demonstration project that provided intensive case management for HIV positive ex-offenders. METHODS: Ex-offenders received 18 months of intensive case management by teams of a professional social worker and an outreach worker between May 2003 and December 2005. Client contacts were weekly for 12 weeks and, at a minimum, monthly thereafter. RESULTS: Most clients (95%) received medical care throughout their enrollment. Of all clients in Project Bridge, 45.8% secured housing, 71% were linked to mental health care, and 51% were linked to addiction services. CONCLUSION: Despite high levels of addiction (97%) and mental health disorders (34% on medication), ex-offenders were retained in health care for a year after being released from incarceration.

Working with public contributors to improve the patient experience at the Manchester Clinical Research Facility: an evaluation of the Experience Based Design approach.

PLAIN ENGLISH SUMMARY: The Experience Based Design (EBD) approach involves patients, staff and members of the public working together to improve a service. This paper evaluates the methods that are used to involve patients and members of the public in a project that aimed to improve the patient experience at Manchester Clinical Research Facility (MCRF). The aim was to explore what helps staff and members of the public to work well together. An evaluation questionnaire was used to get feedback from staff and public contributors. Questions included whether each person felt that they were able to shape the project; if they received enough training; whether they had enough time to complete each task; how well they thought the group worked together; and what could be improved. The findings showed that both staff and public contributors felt valued and that they were able to shape the project from the beginning. Training in EBD and research methodology, and providing enough time to complete each task helped to build relationships and increase confidence when contributing to the project. Personal benefits included a feeling of ownership over a worthwhile and rewarding project, increased awareness of public involvement and gaining new skills. The recommendations for successful involvement of patients and the public in EBD projects will hopefully be helpful for similar projects in the future. ABSTRACT: Background The Experience Based Design (EBD) approach promotes the effective involvement of patients and public contributors by enabling patients, public contributors and staff to co-design projects that aim to improve the patient experience. This approach allows patients and members of the public to have a role in shaping and improving current services. This paper aims to evaluate the EBD process from a public involvement perspective, exploring the barriers and facilitators to building successful working relationships. Methods An open-ended evaluation questionnaire was developed to gain feedback from staff and public contributors who co-produced an EBD project that aimed to improve the patient experience at Manchester CRF. Questions explored what worked well, how the project could be improved, and the benefits of being involved. Results Our findings highlight the importance of providing opportunities for staff, patients and members of the public to build relationships in order to feel confident in voicing their opinions. This can be achieved by training both staff and public contributors in EBD methodology to reduce any power imbalance that may exist. Negotiating adequate time to complete tasks and debate the best way forward also allows everyone to fully contribute to the project. Each individual felt that their contribution was valued and that they shaped the final action plan. Both public contributors and staff listed a number of personal benefits from their involvement in the project. This included a feeling of ownership over a worthwhile and rewarding project, increased awareness of public involvement in EBD projects and gaining new skills. Conclusion This evaluation provides recommendations for best practice for effectively involving public contributors in an EBD methodology. These findings aim to encourage a more consistent approach to EBD across organisations.

Glucose depletion inhibits translation initiation via eIF4A loss and subsequent 48S preinitiation complex accumulation, while the pentose phosphate pathway is coordinately up-regulated.

Cellular stress can globally inhibit translation initiation, and glucose removal from yeast causes one of the most dramatic effects in terms of rapidity and scale. Here we show that the same rapid inhibition occurs during yeast growth as glucose levels diminish. We characterize this novel regulation showing that it involves alterations within the 48S preinitiation complex. In particular, the interaction between eIF4A and eIF4G is destabilized, leading to a temporary stabilization of the eIF3-eIF4G interaction on the 48S complex. Under such conditions, specific mRNAs that are important for the adaptation to the new conditions must continue to be translated. We have determined which mRNAs remain translated early after glucose starvation. These experiments enable us to provide a physiological context for this translational regulation by ascribing defined functions that are translationally maintained or up-regulated. Overrepresented in this class of mRNA are those involved in carbohydrate metabolism, including several mRNAs from the pentose phosphate pathway. Our data support a hypothesis that a concerted preemptive activation of the pentose phosphate pathway, which targets both mRNA transcription and translation, is important for the transition from fermentative to respiratory growth in yeast.

Is the UK public ready for genetic medicine?

While discussion about the potential for personalized medicine persists, in the UK embedding pharmacogenetics in mainstream clinical practice will also depend on high levels of confidence and trust of citizens in the motives of stakeholders. The role of Government, regulators and the guidance offered by health practitioners will contribute to its acceptance or otherwise. Nowgen, a center for genetics in healthcare, is dedicated to exploring how health service research, practice and innovation, in relation to genetic medicine, are informed and perceived by the public. In 2006, Nowgen commissioned a national polling organization, ICM, to carry out a representative survey of UK public attitudes to key questions related to genetic medicine, in order to help inform its future activity. The survey indicated that the UK public is relatively well informed about the contribution made by genes to common and complex disease and that it is fairly optimistic about the role of genetics in the treatment of a range of medical conditions. A significant proportion of the population seem reticent to subscribe to genetic testing in order to personalize drug prescription, although the rationale for resistance is, as yet, unclear.

Health literacy of HIV-positive individuals enrolled in an outreach intervention: results of a cross-site analysis.

This article examines health literacy among a group a HIV-positive persons at risk for receiving suboptimal health care due to histories of substance abuse, mental illness, incarceration, and unstable housing or homelessness. Participants receiving services from three outreach programs funded as part of a multisite demonstration project were screened for health literacy using the Test of Functional Health Literacy in Adults (TOFHLA) at program enrollment. The goal of this analysis was to identify demographics, risk factors, and health indicators associated with different levels of health literacy. Results indicated that although fewer than 30% of the sample scored in the marginal or inadequate range for health literacy, participants with these lower levels of health literacy were more likely to be African American or Latino/a, heterosexual, speak Spanish as their primary language, and have less than a high school education. The disparities in health literacy found in this study point to a need to assess level of health literacy and provide culturally sensitive health literacy interventions for persons with chronic diseases such as HIV. In addition to offering these services within HIV health care settings, health professionals can use other potential venues for health literacy assessment and intervention including substance abuse treatment and community-based social service, education, and training programs. Health care and support service providers also must become aware of the importance of health literacy when caring for all patients with HIV, particularly those most likely to have low health literacy.

Regulation of translation initiation by the yeast eIF4E binding proteins is required for the pseudohyphal response.

The eukaryotic translation initiation factor eIF4E is responsible for the recognition of the mRNA cap structure and, as such, plays a key role in the selection of mRNAs for translation. The interaction of eIF4E with the 'multi-adaptor' eIF4G (and thus recruitment of ribosomes to mRNA) can be regulated via competitive binding of 4E-binding proteins (4E-BPs). 4E-BPs have broad functions in cell growth, proliferation and development. We have found that disruption of the genes for either of the yeast 4E-BPs (Eap1p or Caf20p) leads to an inhibition of pseudohyphal growth in the resulting diploid yeast strain following nitrogen limitation. Specific 4E-binding domain mutations destroy the capacity of each 4E-BP gene to complement the non-pseudohyphal phenotype, suggesting that a translational function for the 4E-BPs is important for pseudohyphal growth. In addition, neither of the 4E-BP deletion strains is deficient in global or stress-regulated protein synthesis. However, our evidence reveals that the two 4E-BPs are functionally distinct with regard to pseudohyphal growth. Therefore, this work supports a model where the yeast 4E-BPs are acting on specific mRNAs to facilitate a defined proliferative response to environmental stress in yeast.