Escherichia coli expressing chloroplast chaperones as a proxy to test heterologous Rubisco production in leaves.

Rubisco is a fundamental enzyme in photosynthesis and therefore for life. Efforts to improve plant Rubisco performance have been hindered by the enzymes' complex chloroplast biogenesis requirements. New Synbio approaches, however, now allow the production of some plant Rubisco isoforms in Escherichia coli. While this enhances opportunities for catalytic improvement, there remain limitations in the utility of the expression system. Here we generate, optimize, and test a robust Golden Gate cloning E. coli expression system incorporating the protein folding machinery of tobacco chloroplasts. By comparing the expression of different plant Rubiscos in both E. coli and plastome-transformed tobacco, we show that the E. coli expression system can accurately predict high level Rubisco production in chloroplasts but poorly forecasts the biogenesis potential of isoforms with impaired production in planta. We reveal that heterologous Rubisco production in E. coli and tobacco plastids poorly correlates with Rubisco large subunit phylogeny. Our findings highlight the need to fully understand the factors governing Rubisco biogenesis if we are to deliver an efficient, low-cost screening tool that can accurately emulate chloroplast expression.

Dosing practices made mundane: Enacting HIV pre-exposure prophylaxis adherence in domestic routines.

Maintaining routines of medication dosing requires effort amidst the variabilities of everyday life. This article offers a sociomaterial analysis of how the oral HIV prevention regimen, pre-exposure prophylaxis (PrEP), is put to use and made to work, including in situations which disrupt or complicate dosing regimes. Other than a daily pill, PrEP can be taken less frequently based on anticipated sexual activity and HIV risk, including 'on-demand' and 'periodic' dosing. Drawing on 40 interviews with PrEP users in Australia in 2022, we explore PrEP and its dosing as features of assemblages in which bodies, routines, desires, material objects and the home environment interact. Dosing emerges as a practice of coordination involving dosette boxes, blister packs, alarms, partners, pets, planning sex, routines and domestic space, and as an effect of experimentations with timing to suit life circumstances and manage side effects. Dosing is materialised in the mundane; a practice that is made to work, as well as domesticated, in its situations. Although there are no 'simple' solutions to adherence, our analysis offers practical insights into how routine, planning and experimentation come together to capacitate PrEP to work in people's lives, in sometimes unexpected ways, including through adaptations of PrEP dosing.

Uncomfortable science: How mathematical models, and consensus, come to be in public policy.

We explore messy translations of evidence in policy as a site of 'uncomfortable science'. Drawing on the work of John Law, we follow evidence as a 'fluid object' of its situation, also enacted in relation to a hinterland of practices. Working with the qualitative interview accounts of mathematical modellers and other scientists engaged in the UK COVID-19 response, we trace how models perform as evidence. Our point of departure is a moment of controversy in the public announcement of second national lockdown in the UK, and specifically, the projected daily deaths from COVID-19 presented in support of this policy decision. We reflect on this event to trace the messy translations of "scientific consensus" in the face of uncertainty. Efforts among scientists to realise evidence-based expectation and to manage the troubled translations of models in policy, including via "scientific consensus", can extend the dis-ease of uncomfortable science rather than clean it up or close it down. We argue that the project of evidence-based policy is not so much in need of technical management or repair, but that we need to be thinking altogether differently.

Excitable models: Projections, targets, and the making of futures without disease.

In efforts to control disease, mathematical models and numerical targets play a key role. We take the elimination of a viral infection as a case for exploring mathematical models as 'evidence-making interventions'. Using interviews with mathematical modellers and implementation scientists, and focusing on the emergence of models of 'treatment-as-prevention' in hepatitis C control, we trace how projections detach from their calculative origins as social and policy practices. Drawing on the work of Michel Callon and others, we show that modelled projections of viral elimination circulate as 'qualculations', taking flight via their affects, including as anticipation. Modelled numerical targets do not need 'actual numbers' or precise measurements to perform their authority as evidence of viral elimination or as situated matters-of-concern. Modellers grapple with the ways that their models transform in policy and social practices, apparently beyond reasonable calculus. We highlight how practices of 'holding-on' to projections in relation to imaginaries of 'evidence-based' science entangle with the 'letting-go' of models beyond calculus. We conclude that the 'virtual precision' of models affords them fluid evidence-making potential. We imagine a different mode of modelling science in health, one more attuned to treating projections as qualculative, affective and relational, as excitable matter.

Situating adherence to medicines: The embodied practices and hinterlands of HIV antiretrovirals.

Adherence to medicines tends to be envisaged as a matter of actors' reasoned actions, though there is increasing emphasis on situating adherence as a practice materialised in everyday routines. Drawing on the qualitative interview accounts of Black African women living with HIV in London, UK, we treat adherence to HIV medicines as not only situated in the practices of the immediate and everyday but also relating to a hinterland of historical and social relations. We move from accounts which situate adherence as an embodied matter of affect in the present, to accounts which locate adherence as a condition of precarity, which also trace to enactments of time and place in the past. Adherence is therefore envisaged as a multiple and fluid effect which is made-up in-the-now and in relation to a hinterland of practices which locate elsewhere.

Qualitative Analysis of Community Support to Methadone Access in Kenya.

BACKGROUND: Methadone, as part of Medically Assisted Therapy (MAT) for treatment of opioid dependence and supporting HIV prevention and treatment, has been recently introduced in Kenya. Few low income settings have implemented methadone, so there is little evidence to guide ongoing scale-up across the region. We specifically consider the role of community level access barriers and support. OBJECTIVES: To inform ongoing MAT implementation we implemented a qualitative study to understand access barriers and enablers at a community level. METHODS: We conducted 30 semi-structured interviews with people who use drugs accessing MAT, supplemented by interviews with 2 stakeholders, linked to participant observation in a community drop in center within one urban area in Kenya. We used thematic analysis. RESULTS: We developed five themes to express experiences of factors enabling and disabling MAT access and how community support can address these: 1) time, travel and economic hardship; 2) managing methadone and contingencies of life, 3) peer support among MAT clients as treatment ambassadors, 4) family relations, and 5)outreach project contributions. Crosscutting themes address managing socioeconomic constraints and gender inequities. CONCLUSIONS: People who use drugs experience and manage socio-economic constraints and gender inequities in accessing MAT with the support of local communities. We discuss how these access barriers could be addressed through strengthening the participation of networks of people who use drugs in drug treatment and supporting community projects working with people who use drugs. We also explore potential for how socio-economic constraints could be managed within an integrated health and social care response.

What prevents health policy being 'evidence-based'? New ways to think about evidence, policy and interventions in health.

BACKGROUND: Evidence-based policy decision-making is a dominant paradigm in health but realizing this ideal has proven challenging. SOURCES OF DATA: This paper conceptually maps health policy, policy studies and social science literature critically engaged with evidence and decision-making. No new data were generated or analysed in support of this review. AREAS OF AGREEMENT: Barriers to evidence-based policy have been documented, with efforts made to increase the uptake of evidence. AREAS OF CONTROVERSY: Evident complexities have been regarded as a problem of translation. However, this assumes that policy-making is a process of authoritative choice, and that 'evidence' is inherently valuable policy knowledge, which has been critiqued. GROWING POINTS: Alternative accounts urge consideration of how evidence comes to bear on decisions made within complex systems, and what counts as evidence. AREAS TIMELY FOR DEVELOPING RESEARCH: An 'evidence-making intervention' approach offers a framework for conceptualizing how evidence and interventions are made relationally in practices, thus working with the politics and contingencies of implementation and policy-making.

A qualitative study of diphenhydramine injection in Kyrgyz prisons and implications for harm reduction.

BACKGROUND: To reduce opioid dependence and HIV transmission, Kyrgyzstan has introduced methadone maintenance therapy and needle/syringe programs into prisons. Illicit injection of diphenhydramine, an antihistamine branded as Dimedrol®, has been anecdotally reported as a potential challenge to harm reduction efforts in prisons but has not been studied systematically. METHODS: We conducted qualitative interviews in Kyrgyz or Russian with prisoners (n = 49), former prisoners (n = 19), and stakeholders (n = 18), including prison administrators and prisoner advocates near Bishkek, Kyrgyzstan from October 2016 to September 2018. Interviews explored social-contextual factors influencing methadone utilization in prisons. Transcripts were coded by five researchers using content analysis. Dimedrol injection emerged as an important topic, prompting a dedicated analysis. RESULTS: After drinking methadone, some people in prison inject crushed Dimedrol tablets, a non-prescription antihistamine that is banned but obtainable in prison, to achieve a state of euphoria. From the perspectives of the study participants, Dimedrol injection was associated with devastating physical and mental health consequences, including psychosis and skin infections. Moreover, the visible wounds of Dimedrol injecting contributed to the perception of methadone as a harmful drug and supporting preference for heroin over methadone. CONCLUSION: Dimedrol injecting is a potentially serious threat to harm reduction and HIV prevention efforts in Kyrgyzstan and elsewhere in the Eastern European and Central Asian region and requires further investigation.

Understanding how, why, for whom, and under what circumstances opt-out blood-borne virus testing programmes work to increase test engagement and uptake within prison: a rapid-realist review.

BACKGROUND: Prisons represent a unique opportunity to diagnose blood-borne viruses. Opt-out testing is receiving increasing interest, as a result of mounting evidence to suggest that the manner in which a test offer is delivered, affects test uptake. Although the effectiveness of opt-out testing within the prison setting has been established, robust explanations are required for the variation in outcomes reported. METHODS: Rapid-realist review methodology was used to synthesise the literature on prison-based opt-out testing. The review was carried out in three phases. Phase one: An expert panel provided literature relevant to the implementation of opt-out testing within the English prison estate. Unstructured searches were also conducted to identify other social programmes where "opt-out" had been used to increase uptake. Phase two: a systematic search of six peer-review and five grey literature databases was carried out to identify empirical data on opt-out testing within the prison setting. Phase three: Additional non-exhaustive searches were carried out to identify literature that reinforced emergent concepts. The development of programme theory took place with each iteration and was validated in consultation with stakeholders. RESULTS: Programme theory was constructed for two outcomes: the proportion of intake offered a test and the proportion offered that accepted testing. The proportion of intake offered testing was influenced by the timing of the test offer, which was often delayed due to barriers to prisoner access. The decision to accept testing was influenced by concerns about confidentiality, fear of a positive diagnosis, a prisoner's personal interpretation of risk, discomfort with invasive procedures, trust in healthcare, and the fidelity of the opt-out offer. CONCLUSIONS: This review identified important implementation considerations that moderate the effectiveness of opt-out testing programmes. It also highlighted a lack of appreciation for the theoretical underpinnings of opt-out programmes and tension around how to implement testing in a manner that adheres to both default theory and informed consent. It is anticipated that results will be used to inform the design and implementation of subsequent versions of these programmes, as well as catalyse further in-depth analysis into their operation within the unique context of prison. REVIEW REGISTRATION: CRD42017068342 .

The becoming-methadone-body: on the onto-politics of health intervention translations.

In this paper, we reflect on health intervention translations as matters of their implementation practices. Our case is methadone treatment, an intervention promoted globally for treating opioid dependence and preventing HIV among people who inject drugs. Tracing methadone's translations in high-security prisons in the Kyrgyz Republic, we notice the multiple methadones made possible, what these afford, and the onto-political effects they make. We work with the idea of the 'becoming-methadone-body' to trace the making-up of methadone treatment and its effects as an intra-action of human and nonhuman substances and bodies. Methadone's embodied effects flow beyond the mere psycho-activity of substances incorporating individual bodies, to material highs and lows incorporating the governing practices of prisoner society. The methadone-in-practice of prisoner society is altogether different to that imagined as being in translation as an intervention of HIV prevention and opioid treatment, and has material agency as a practice of societal governance. Heroin also emerges as an actor in these relations. Our analysis troubles practices of 'evidence-based' intervention and 'implementation science' in the health field, by arguing for a move towards 'evidence-making' intervention approaches. Noticing the onto-politics of health intervention translations invites speculation on how intervening might be done differently.

A qualitative assessment of the acceptability of hepatitis C remote self-testing and self-sampling amongst people who use drugs in London, UK.

BACKGROUND: Hepatitis C (HCV) diagnosis and care is a major challenge for people who use illicit drugs, and is characterised by low rates of testing and treatment engagement globally. New approaches to fostering engagement are needed. We explored the acceptability of remote forms of HCV testing including self-testing and self-sampling among people who use drugs in London, UK. METHODS: A qualitative rapid assessment was undertaken with people who use drugs and stakeholders in London, UK. Focus groups were held with men who have sex with men engaged in drug use, people who currently inject drugs and people who formerly injected drugs (22 participants across the 3 focus groups). Stakeholders participated in semi-structured interviews (n = 5). We used a thematic analysis to report significant themes in participants' responses. RESULTS: We report an overarching theme of 'tension' in how participants responded to the acceptability of remote testing. This tension is evident across four separate sub-themes we explore. First, choice and control, with some valuing the autonomy and privacy remote testing could support. Second, the ease of use of self testing linked to its immediate result and saliva sample was preferred over the delayed result from a self administered blood sample tested in a laboratory. Third, many respondents described the need to embed remote testing within a supportive care pathway. Fourth, were concerns over managing a positive result, and its different meanings, in isolation. CONCLUSIONS: The concept of remote HCV testing is acceptable to some people who use drugs in London, although tensions with lived experience of drug use and health system access limit its relevance. Future development of remote testing must respond to concerns raised in order for acceptable implementation to take place.

"They accept me, because I was one of them": formative qualitative research supporting the feasibility of peer-led outreach for people who use drugs in Dakar, Senegal.

BACKGROUND: Peer outreach harm reduction initiatives are being developed with and for people who use drugs in Dakar, Senegal. This is in response to growing injecting drug use across the West Africa region and linked emerging epidemics of HIV and hepatitis C. We undertook formative qualitative research to explore the feasibility and potential of peer outreach in this context and in particular how outreach could be linked to fostering community-level processes of change. METHODS: We undertook a total of 44 semi-structured qualitative interviews. Thirty-four interviews were with people who used drugs (comprised of 25 participants who had injected at least once in their life) and included 11 peer educators who delivered "awareness-raising" harm reduction activities. We also interviewed 10 service providers involved in the planning and monitoring of peer outreach initiatives. We used thematic analysis to identify key characteristics of how peer-led outreach is being delivered, beneficiary need, and the nature of the social networks in which the awareness-raising activities operate. RESULTS: Through interviews with peer educators, people who use drugs, and service providers, four main overlapping themes are identified as follows: peer educators as a bridge to responsibilization through awareness-raising activities, awareness-raising activities as an enactment of recovery, awareness raising through social network diffusion, and the contexts and constraints of peer outreach engagement through awareness-raising activities. CONCLUSIONS: The study results suggest that peer education is on a trajectory to develop into a central role for harm reduction interventions in Dakar, Senegal. This research shows how peer education is bound in processes of responsibilization and self-change, which link to varying possibilities for risk reduction or recovery. For peer education to achieve a range of significant goals, broader structural and system changes should be implemented in the region. We caution that without such changes, awareness-raising activities and the role of peer educators may instead become part of state- and agency-sponsored processes of seeking to responsibilize individuals for health and harm reduction.

"It's Not Much of a Life": The Benefits and Ethics of Using Life History Methods With People Who Inject Drugs in Qualitative Harm Reduction Research.

A life history approach enables study of how risk or health protection is shaped by critical transitions and turning points in a life trajectory and in the context of social environment and time. We employed visual and narrative life history methods with people who inject drugs to explore how hepatitis C protection was enabled and maintained over the life course. We overview our methodological approach, with a focus on the ethics in practice of using life history timelines and life-grids with 37 participants. The life-grid evoked mixed emotions for participants: pleasure in receiving a personalized visual history and pain elicited by its contents. A minority managed this pain with additional heroin use. The methodological benefits of using life history methods and visual aids have been extensively reported. Crucial to consider are the ethical implications of this process, particularly for people who lack socially ascribed markers of a "successful life."

Integrated opioid substitution therapy and HIV care: a qualitative systematic review and synthesis of client and provider experiences.

People who use drugs in many contexts have limited access to opioid substitution therapy and HIV care. Service integration is one strategy identified to support increased access. We reviewed and synthesized literature exploring client and provider experiences of integrated opioid substitution therapy and HIV care to identify acceptable approaches to care delivery. We systematically reviewed qualitative literature. We searched nine bibliographic databases, supplemented by manual searches of reference lists of articles from the database search, relevant journals, conferences, key organizations and consultation with experts. Thematic synthesis was used to develop descriptive themes in client and provider experiences. The search yielded 11 articles for inclusion, along with 8 expert and policy reports. We identify five descriptive themes: the convenience and comprehensive nature of co-located care, contrasting care philosophies and their role in shaping integration, the limits to disclosure and communication between clients and providers, opioid substitution therapy enabling HIV care access and engagement, and health system challenges to delivering integrated services. The discussion explores how integrated opioid substitution therapy and HIV care needs to adapt to specific social conditions, rather than following universal approaches. We identify priorities for future research. Acceptable integrated opioid substitution therapy and HIV care for people who use drugs and providers is most likely through co-located care and relies upon attention to stigma, supportive relationships and client centred cultures of delivery. Further research is needed to understand experiences of integrated care, particularly delivery in low and middle income settings and models of care focused on community and non-clinic based delivery.

Impact of Opioid Substitution Therapy on Antiretroviral Therapy Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Human immunodeficiency virus (HIV)-infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID. METHODS: We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I(2) statistic. RESULTS: We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32-2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17-2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41-3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63-.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21-1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65-1.25). CONCLUSIONS: These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID.

Access to HIV treatment and care for people who inject drugs in Kenya: a short report.

People who inject drugs (PWID) experience a range of barriers to HIV treatment and care access. The Kenyan government and community-based organisations have sought to develop HIV care for PWID. A principal approach to delivery in Kenya is to provide care from clinics serving the general population and for this to be linked to support from community-based organisations providing harm reduction outreach. This study explores accounts of PWID accessing care in Kenya to identify care barriers and facilitators. PWID accounts were collected within a qualitative longitudinal study. In-depth interviews with PWID living with HIV (n = 44) are combined with interviews with other PWID, care providers and community observation. Results show that some PWID are able to access care successfully, whilst other PWID report challenges. The results focus on three principal themes to give insights into these experiences: the hardship of addiction and the costs of care, the silencing of HIV in the community and then discrimination and support in the clinic. Some PWID are able to overcome, often with social and outreach support, barriers to clinic access; for others, the challenges of addiction, hardship, stigma and discrimination are too constraining. We discuss how clinics serving the general population could be further adapted to increase access. Clinic-based care, even with community links, may, however, be fundamentally challenging for some PWID to access. Additional strategies to develop stand-alone care for PWID and also decentralise HIV treatment and care to community settings and involve peers in delivery should be considered.

'They won't change it back in their heads that we're trash': the intersection of sex work-related stigma and evolving policing strategies.

In Vancouver, Canada, there has been a continuous shift in the policing of sex work away from arresting sex workers, which led to the implementation of a policing strategy that explicitly prioritised the safety of sex workers and continued to target sex workers' clients. We conducted semi-structured interviews with 26 cisgender and five transgender women street-based sex workers about their working conditions. Data were analysed thematically and by drawing on concepts of structural stigma and vulnerability. Our results indicated that despite police rhetoric of prioritising the safety of sex workers, participants were denied their citizenship rights for police protection by virtue of their 'risky' occupation and were thus responsiblised for sex work related violence. Our findings further suggest that sex workers' interactions with neighbourhood residents were predominantly shaped by a discourse of sex workers as a 'risky' presence in the urban landscape and police took swift action in removing sex workers in the case of complaints. This study highlights that intersecting regimes of stigmatisation and criminalisation continued to undermine sex workers citizenship rights to police protection and legal recourse and perpetuated labour conditions that render sex workers at increased risk for violence and poor health.

What am I 'living' with? Growing up with HIV in Uganda and Zimbabwe.

As paediatric HIV treatment has become increasingly available across the world, the global perinatally infected cohort is ageing. However, we know surprisingly little about what it is like to grow up with HIV in resource-stretched settings. We draw on findings from a prospective, qualitative study with HIV-positive children, their carers and healthcare workers from four clinics in Uganda and Zimbabwe to examine children's experiences of living with HIV on treatment. We consider how the HIV experience is made in a symbiotic relationship between children, carers and healthcare workers and shaped by broader discourses. Despite the radical development in prognosis for children, their experience of HIV is largely constructed in relation to a language of 'sickness' through the promotion of medicalised talk and the recounting of past illness stories. This narrow narrative framework both reflects and reproduces core dimensions of the lived experience of growing up with HIV, which emphasises an absence of resilient healthiness in the face of ongoing vulnerability and risk. The challenges that children encounter in articulating alternative narratives that prioritise the relative buoyancy of their health is indicative of the broader uncertainty that exists around the future for these children at this point in the epidemic.