On the Origins of Phenotypic Parallelism in Benthic and Limnetic Stickleback.

Rapid evolution of similar phenotypes in similar environments, giving rise to in situ parallel adaptation, is an important hallmark of ecological speciation. However, what appears to be in situ adaptation can also arise by dispersal of divergent lineages from elsewhere. We test whether two contrasting phenotypes repeatedly evolved in parallel, or have a single origin, in an archetypal example of ecological adaptive radiation: benthic-limnetic three-spined stickleback (Gasterosteus aculeatus) across species pair and solitary lakes in British Columbia. We identify two genomic clusters across freshwater populations, which differ in benthic-limnetic divergent phenotypic traits and separate benthic from limnetic individuals in species pair lakes. Phylogenetic reconstruction and niche evolution modeling both suggest a single evolutionary origin for each of these clusters. We detected strong phylogenetic signal in benthic-limnetic divergent traits, suggesting that they are ancestrally retained. Accounting for ancestral state retention, we identify local adaptation of body armor due to the presence of an intraguild predator, the sculpin (Cottus asper), and environmental effects of lake depth and pH on body size. Taken together, our results imply a predominant role for retention of ancestral characteristics in driving trait distribution, with further selection imposed on some traits by environmental factors.

Reproductive isolation in a three-way contact zone.

Contact zones between divergent forms within a species provide insight into the role of gene flow in adaptation and speciation. Previous work has focused on contact zones involving only two divergent forms, but in nature, many more than two populations may overlap simultaneously and experience gene flow. Patterns of introgression in wild populations are, therefore, likely much more complicated than is often assumed. We begin to address this gap in current knowledge by investigating patterns of divergence and introgression across a complex natural contact zone. We use phenotypic and genomic data to confirm the existence of a three-way contact zone among divergent freshwater resident, saltwater resident and saltwater migratory three-spined stickleback (Gasterosteus aculeatus) on the island of North Uist, Scottish Western Isles. We find evidence for hybridization, mostly between saltwater resident and saltwater migratory forms. Despite hybridization, genomic analyses reveal pairwise islands of divergence between all forms that are maintained across the contact zone. Genomic cline analyses also provide evidence for selection and/or hybrid incompatibilities in divergent regions. Divergent genomic regions occur across multiple chromosomes and involve many known adaptive loci and several chromosomal inversions. We also identify distinct immune gene expression profiles between forms, but no evidence for transgressive expression in hybrids. Our results suggest that reproductive isolation is maintained in this three-way contact zone, despite some hybridization, and that reduced recombination in chromosomal inversions may play an important role in maintaining this isolation.

Structure-Activity Relationship of Lower Chlorinated Biphenyls and Their Human-Relevant Metabolites for Astrocyte Toxicity.

Exposure to polychlorinated biphenyls (PCBs) is associated with developmental neurotoxicity and neurodegenerative disorders; however, the underlying mechanisms of pathogenesis are unknown. Existing literature has focused mainly on using neurons as a model system to study mechanisms of PCB-mediated neurotoxicity, overlooking the role of glial cells, such as astrocytes. As normal brain function is largely astrocyte-dependent, we hypothesize that astrocytes play an important role in PCB-mediated injury to neurons. We assessed the toxicity of two commercial PCB mixtures, Aroclor 1016 and Aroclor 1254, and a non-Aroclor PCB mixture found in residential air called the Cabinet mixture, all of which contain lower chlorinated PCBs (LC-PCBs) found in indoor and outdoor air. We further assessed the toxicity of five abundant airborne LC-PCBs and their corresponding human-relevant metabolites in vitro models of astrocytes, namely, the C6 cell line and primary astrocytes isolated from Sprague-Dawley rats and C57BL/6 mice. PCB52 and its human-relevant hydroxylated and sulfated metabolites were found to be the most toxic compounds. No significant sex-dependent cell viability differences were observed in rat primary astrocytes. Based on the equilibrium partitioning model, it was predicted that the partitioning of LC-PCBs and their corresponding metabolites in biotic and abiotic compartments of the cell culture system is structure-dependent and that the observed toxicity is consistent with this prediction. This study, for the first time, shows that astrocytes are sensitive targets of LC-PCBs and their human-relevant metabolites and that further research to identify mechanistic targets of PCB exposure in glial cells is necessary.

Unpacking the impact of integrating the neglected tropical disease supply chain into the national supply chain system: illustrative evidence from Liberia.

Effective supply chain management is a critical pillar of well-functioning health systems ensuring that medical commodities reach those in need. In Liberia, the national neglected tropical disease (NTD) programme supports health systems strengthening for case management of NTDs. Integration of NTD commodities into the national health system supply chain is central to the integrated approach; however, there is minimal evidence on enablers and barriers. Drawing on qualitative evaluation data, we illustrate that perceived benefits and strengths to integrating NTD commodities into the supply chain include leveraged storage and management capacities capitalized at lower system levels; the political will to integrate based on cost-saving and capacity strengthening potential and positive progress integrating paper-based reporting tools. Challenges remain, specifically the risk of reliance on donor funding; difficulty in accessing commodities due to bureaucratic bottlenecks; lack of inclusion of NTD commodities within electronic data tools and poor coordination leading to an inability to meet demand. Collectively, the negative consequences of ineffective integration of NTD commodities into the supply chain has a detrimental impact on health workers (including community health workers) unable to deliver the quality of care to patients. Trust between affected populations and the health system is compromised when treatments are unavailable.

Perceived impacts of COVID-19 responses on routine health service delivery in Liberia and UK: cross-country lessons for resilient health systems for equitable service delivery during pandemics.

BACKGROUND: COVID-19 has caused significant public health problems globally, with catastrophic impacts on health systems. This study explored the adaptations to health services in Liberia and Merseyside UK at the beginning of the COVID-19 pandemic (January-May 2020) and their perceived impact on routine service delivery. During this period, transmission routes and treatment pathways were as yet unknown, public fear and health care worker fear was high and death rates among vulnerable hospitalised patients were high. We aimed to identify cross-context lessons for building more resilient health systems during a pandemic response. METHODS: The study employed a cross-sectional qualitative design with a collective case study approach involving simultaneous comparison of COVID-19 response experiences in Liberia and Merseyside. Between June and September 2020, we conducted semi-structured interviews with 66 health system actors purposively selected across different levels of the health system. Participants included national and county decision-makers in Liberia, frontline health workers and regional and hospital decision-makers in Merseyside UK. Data were analysed thematically in NVivo 12 software. RESULTS: There were mixed impacts on routine services in both settings. Major adverse impacts included diminished availability and utilisation of critical health services for socially vulnerable populations, linked with reallocation of health service resources for COVID-19 care, and use of virtual medical consultation in Merseyside. Routine service delivery during the pandemic was hampered by a lack of clear communication, centralised planning, and limited local autonomy. Across both settings, cross-sectoral collaboration, community-based service delivery, virtual consultations, community engagement, culturally sensitive messaging, and local autonomy in response planning facilitated delivery of essential services. CONCLUSION: Our findings can inform response planning to assure optimal delivery of essential routine health services during the early phases of public health emergencies. Pandemic responses should prioritise early preparedness, with investment in the health systems building blocks including staff training and PPE stocks, address both pre-existing and pandemic-related structural barriers to care, inclusive and participatory decision-making, strong community engagement, and effective and sensitive communication. Multisectoral collaboration and inclusive leadership are essential.

A health-systems journey towards more people-centred care: lessons from neglected tropical disease programme integration in Liberia.

BACKGROUND: Neglected tropical diseases (NTDs) are associated with high levels of morbidity and disability as a result of stigma and social exclusion. To date, the management of NTDs has been largely biomedical. Consequently, ongoing policy and programme reform within the NTD community is demanding the development of more holistic disease management, disability and inclusion (DMDI) approaches. Simultaneously, integrated, people-centred health systems are increasingly viewed as essential to ensure the efficient, effective and sustainable attainment of Universal Health Coverage. Currently, there has been minimal consideration of the extent to which the development of holistic DMDI strategies are aligned to and can support the development of people-centred health systems. The Liberian NTD programme is at the forefront of trying to establish a more integrated, person-centred approach to the management of NTDs and provides a unique learning site for health systems decision makers to consider how shifts in vertical programme delivery can support overarching systems strengthening efforts that are designed to promote the attainment of health equity. METHODS: We use a qualitative case study approach to explore how policy and programme reform of the NTD programme in Liberia supports systems change to enable the development of integrated people-centred services. RESULTS: A cumulation of factors, catalysed by the shock to the health system presented by the Ebola epidemic, created a window of opportunity for policy change. However, programmatic change aimed at achieving person-centred practice was more challenging. Deep reliance on donor funding for health service delivery in Liberia limits the availability of flexible funding, and the ongoing funding prioritization towards specific disease conditions limits flexibility in health systems design that can shape more person-centred care. CONCLUSION: Sheikh et al.'s four key aspects of people centred health systems, that is, (1) putting peoples voices and needs first; (2) people centredness in service delivery; (3) relationships matter: health systems as social institutions; and (4) values drive people centred health systems, enable the illumination of varying push and pull factors that can facilitate or hinder the alignment of DMDI interventions with the development of people-centred health systems to support disease programme integration and the attainment of health equity.

The testis-specific E3 ubiquitin ligase RNF133 is required for fecundity in mice.

BACKGROUND: Ubiquitination is a post-translational modification required for a number of physiological functions regulating protein homeostasis, such as protein degradation. The endoplasmic reticulum (ER) quality control system recognizes and degrades proteins no longer needed in the ER through the ubiquitin-proteasome pathway. E2 and E3 enzymes containing a transmembrane domain have been shown to function in ER quality control. The ER transmembrane protein UBE2J1 is a E2 ubiquitin-conjugating enzyme reported to be essential for spermiogenesis at the elongating spermatid stage. Spermatids from Ube2j1 KO male mice are believed to have defects in the dislocation step of ER quality control. However, associated E3 ubiquitin-protein ligases that function during spermatogenesis remain unknown. RESULTS: We identified four evolutionarily conserved testis-specific E3 ubiquitin-protein ligases [RING finger protein 133 (Rnf133); RING finger protein 148 (Rnf148); RING finger protein 151 (Rnf151); and Zinc finger SWIM-type containing 2 (Zswim2)]. Using the CRISPR/Cas9 system, we generated and analyzed the fertility of mutant mice with null alleles for each of these E3-encoding genes, as well as double and triple knockout (KO) mice. Male fertility, male reproductive organ, and sperm-associated parameters were analyzed in detail. Fecundity remained largely unaffected in Rnf148, Rnf151, and Zswim2 KO males; however, Rnf133 KO males displayed severe subfertility. Additionally, Rnf133 KO sperm exhibited abnormal morphology and reduced motility. Ultrastructural analysis demonstrated that cytoplasmic droplets were retained in Rnf133 KO spermatozoa. Although Rnf133 and Rnf148 encode paralogous genes that are chromosomally linked and encode putative ER transmembrane E3 ubiquitin-protein ligases based on their protein structures, there was limited functional redundancy of these proteins. In addition, we identified UBE2J1 as an E2 ubiquitin-conjugating protein that interacts with RNF133. CONCLUSIONS: Our studies reveal that RNF133 is a testis-expressed E3 ubiquitin-protein ligase that plays a critical role for sperm function during spermiogenesis. Based on the presence of a transmembrane domain in RNF133 and its interaction with the ER containing E2 protein UBE2J1, we hypothesize that these ubiquitin-regulatory proteins function together in ER quality control during spermatogenesis.

Probing the Role of CYP2 Enzymes in the Atropselective Metabolism of Polychlorinated Biphenyls Using Liver Microsomes from Transgenic Mouse Models.

Chiral polychlorinated biphenyls (PCB) are environmentally relevant developmental neurotoxicants. Because their hydroxylated metabolites (OH-PCBs) are also neurotoxic, it is necessary to determine how PCB metabolism affects the developing brain, for example, in mouse models. Because the cytochrome P450 isoforms involved in the metabolism of chiral PCBs remain unexplored, we investigated the metabolism of PCB 91 (2,2',3,4',6-pentachlorobiphenyl), PCB 95 (2,2',3,5',6-pentachlorobiphenyl), PCB 132 (2,2',3,3',4,6'-hexachlorobiphenyl), and PCB 136 (2,2',3,3',6,6'-hexachlorobiphenyl) using liver microsomes from male and female Cyp2a(4/5)bgs-null, Cyp2f2-null, and wild-type mice. Microsomes, pooled by sex, were incubated with 50 µM PCB for 30 min, and the levels and enantiomeric fractions of the OH-PCBs were determined gas chromatographically. All four PCB congeners appear to be atropselectively metabolized by CYP2A(4/5)BGS and CYP2F2 enzymes in a congener- and sex-dependent manner. The OH-PCB metabolite profiles of PCB 91 and PCB 132, PCB congeners with one para-chlorine substituent, differed between null and wild-type mice. No differences in the metabolite profiles were observed for PCB 95 and PCB 136, PCB congeners without a para-chlorine group. These findings suggest that Cyp2a(4/5)bgs-null and Cyp2f2-null mice can be used to study how a loss of a specific metabolic function (e.g., deletion of Cyp2a(4/5)bgs or Cyp2f2) affects the toxicity of chiral PCB congeners.

Financing care for Severe Stigmatizing Skin Diseases (SSSDs) in Liberia: challenges and opportunities.

INTRODUCTION: Neglected tropical diseases (NTDs) are an important global health challenge, however, little is known about how to effectively finance NTD related services. Integrated management in particular, is put forward as an efficient and effective treatment modality. This is a background study to a broader health economic evaluation, seeking to document the costs of integrated case management of NTDs versus standard care in Liberia. In the current study, we document barriers and facilitators to NTD care from a health financing perspective. METHODS: We carried out key informant interviews with 86 health professionals and 16 national health system policymakers. 46 participants were active in counties implementing integrated case management and 40 participants were active in counties implementing standard care. We also interviewed 16 patients and community members. All interviews were transcribed and analysed using the thematic framework approach. FINDINGS: We found that decentralization for NTD financing is not yet achieved - financing and reporting for NTDs is still centralized and largely donor-driven as a vertical programme; government involvement in NTD financing is still minimal, focused mainly on staffing, but non-governmental organisations (NGOs) or international agencies are supporting supply and procurement of medications. Donor support and involvement in NTDs are largely coordinated around the integrated case management. Quantification for goods and budget estimations are specific challenges, given the high donor dependence, particularly for NTD related costs and the government's limited financial role at present. These challenges contribute to stockouts of medications and supplies at clinic level, while delays in payments of salaries from the government compromise staff attendance and retention. For patients, the main challenges are high transportation costs, with inflated charges due to fear and stigma amongst motorbike taxi riders, and out-of-pocket payments for medication during stockouts and food/toiletries (for in-patients). CONCLUSION: Our findings contribute to the limited work on financing of SSSD services in West African settings and provide insight on challenges and opportunities for financing and large costs in accessing care by households, which is also being exacerbated by stigma.

Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets.

BACKGROUND: The development of a safe, effective, reversible, non-hormonal contraceptive method for men has been an ongoing effort for the past few decades. However, despite significant progress on elucidating the function of key proteins involved in reproduction, understanding male reproductive physiology is limited by incomplete information on the genes expressed in reproductive tissues, and no contraceptive targets have so far reached clinical trials. To advance product development, further identification of novel reproductive tract-specific genes leading to potentially druggable protein targets is imperative. RESULTS: In this study, we expand on previous single tissue, single species studies by integrating analysis of publicly available human and mouse RNA-seq datasets whose initial published purpose was not focused on identifying male reproductive tract-specific targets. We also incorporate analysis of additional newly acquired human and mouse testis and epididymis samples to increase the number of targets identified. We detected a combined total of 1178 genes for which no previous evidence of male reproductive tract-specific expression was annotated, many of which are potentially druggable targets. Through RT-PCR, we confirmed the reproductive tract-specific expression of 51 novel orthologous human and mouse genes without a reported mouse model. Of these, we ablated four epididymis-specific genes (Spint3, Spint4, Spint5, and Ces5a) and two testis-specific genes (Pp2d1 and Saxo1) in individual or double knockout mice generated through the CRISPR/Cas9 system. Our results validate a functional requirement for Spint4/5 and Ces5a in male mouse fertility, while demonstrating that Spint3, Pp2d1, and Saxo1 are each individually dispensable for male mouse fertility. CONCLUSIONS: Our work provides a plethora of novel testis- and epididymis-specific genes and elucidates the functional requirement of several of these genes, which is essential towards understanding the etiology of male infertility and the development of male contraceptives.

Admixture between Ancient Lineages, Selection, and the Formation of Sympatric Stickleback Species-Pairs.

Ecological speciation has become a popular model for the development and maintenance of reproductive isolation in closely related sympatric pairs of species or ecotypes. An implicit assumption has been that such pairs originate (possibly with gene flow) from a recent, genetically homogeneous ancestor. However, recent genomic data have revealed that currently sympatric taxa are often a result of secondary contact between ancestrally allopatric lineages. This has sparked an interest in the importance of initial hybridization upon secondary contact, with genomic reanalysis of classic examples of ecological speciation often implicating admixture in speciation. We describe a novel occurrence of unusually well-developed reproductive isolation in a model system for ecological speciation: the three-spined stickleback (Gasterosteus aculeatus), breeding sympatrically in multiple lagoons on the Scottish island of North Uist. Using morphological data, targeted genotyping, and genome-wide single-nucleotide polymorphism data, we show that lagoon resident and anadromous ecotypes are strongly reproductively isolated with an estimated hybridization rate of only ∼1%. We use palaeoecological and genetic data to test three hypotheses to explain the existence of these species-pairs. Our results suggest that recent, purely ecological speciation from a genetically homogeneous ancestor is probably not solely responsible for the evolution of species-pairs. Instead, we reveal a complex colonization history with multiple ancestral lineages contributing to the genetic composition of species-pairs, alongside strong disruptive selection. Our results imply a role for admixture upon secondary contact and are consistent with the recent suggestion that the genomic underpinning of ecological speciation often has an older, allopatric origin.

How should community health workers in fragile contexts be supported: qualitative evidence from Sierra Leone, Liberia and Democratic Republic of Congo.

BACKGROUND: Community health workers (CHWs) are critical players in fragile settings, where staff shortages are particularly acute, health indicators are poor and progress towards Universal Health Coverage is slow. Like other health workers, CHWs need support to contribute effectively to health programmes and promote health equity. Yet the evidence base of what kind of support works best is weak. We present evidence from three fragile settings-Sierra Leone, Liberia and Democratic Republic of Congo on managing CHWs, and synthesise recommendations for best approaches to support this critical cadre. METHODS: We used a qualitative study design to explore how CHWs are managed, the challenges they face and potential solutions. We conducted interviews with decision makers and managers (n = 37), life history interviews with CHWs (n = 15) and reviewed policy documents. RESULTS: Fragility disrupts education of community members so that they may not have the literacy levels required for the CHW role. This has implications for the selection, role, training and performance of CHWs. Policy preferences about selection need discussion at the community level, so that they reflect community realities. CHWs' scope of work is varied and may change over time, requiring ongoing training. The modular, local and mix of practical and classroom training approach worked well, helping to address gender and literacy challenges and developing a supportive cohort of CHWs. A package of supervision, community support, regular provision of supplies, performance rewards and regular remuneration is vital to retention and performance of CHWs. But there are challenges with supervision, scarcity of supplies, inadequate community recognition and unfulfilled promises about allowances. Clear communication about incentives with facility staff and communities is required as is their timely delivery. CONCLUSIONS: This is the first study that has explored the management of CHWs in fragile settings. CHWs' interface role between communities and health systems is critical because of their embedded positionality and the trusting relationships they (often) have. Their challenges are aligned to those generally faced by CHWs but chronic fragility exacerbates them and requires innovative problem solving to ensure that countries and communities are not left behind in reforming the way that CHWs are supported.

Dedicated MRI in the emergency department to expedite diagnostic management of hip fracture.

PURPOSE: To determine the effect on time to diagnosis of making MRI imaging for hip fractures available directly in the emergency department (ED). METHODS: We conducted a retrospective observational study of patients with MRI imaging of the hip for suspected occult fracture, comparing time to diagnosis and time to disposition of populations imaged in the year preceding and the year following installation of an MRI scanner in the ED. RESULTS: Time to diagnosis of hip fractures was 709 min before installation of a dedicated ED MRI scanner and 280 min after, a 60% reduction. Including the MRI in the diagnostic workup did not increase ED throughput time, and we were able to save 48% of the patients who had an ED-based MRI from an admission to the hospital. CONCLUSION: Implementation of an MRI scanner for dedicated emergency department use enables faster hip fracture diagnosis and surgical consultation, or definitive disposition without increasing ED throughput time.

Optimising the performance of frontline implementers engaged in the NTD programme in Nigeria: lessons for strengthening community health systems for universal health coverage.

BACKGROUND: The control and elimination of Neglected Tropical Diseases (NTDs) is dependent on mass administration of medicines (MAM) in communities and schools by community drug distributers (CDDs) who are supported and supervised by health facility staff (FLHF) and teachers. Understanding how to motivate, retain and optimise their performance is essential to ensure communities accept medicines. This study aimed to capture and translate knowledge, problems and solutions, identified by implementers, to enhance NTD programme delivery at the community level in Nigeria. METHODS: Qualitative data was collected through participatory stakeholder workshops organised around two themes: (i) identification of problems and (ii) finding solutions. Eighteen problem-focused workshops and 20 solution-focussed workshops were held with FLHF, CDDs and teachers in 12 purposively selected local government areas (LGA) across two states in Nigeria, Ogun and Kaduna States. RESULT: The problems and solutions identified by frontline implementers were organised into three broad themes: technical support, social support and incentives. Areas identified for technical support included training, supervision, human resource management and workload, equipment and resources and timing of MAM implementation. Social support needs were for more equitable drug distributor selection processes, effective community sensitisation mechanisms and being associated with the health system. Incentives identified were both non-financial and financial including receiving positive community feedback and recognition and monetary remuneration. The results led to the development of the 'NTD frontline implementer's framework' which was adapted from the Community Health Worker (CHW) Generic Logic Model by Naimoli et al. (Hum Resour Health 12:56, 2014). CONCLUSION: Maximising performance of frontline implementers is key to successful attainment of NTD goals and other health interventions. As NTDs are viewed as a 'litmus test' for universal health coverage, the lessons shared here could cut across programmes aiming to achieve equitable coverage. It is critical to strengthen the collaboration between health systems and communities so that together they can jointly provide the necessary support for frontline implementers to deliver health for all. This research presents additional evidence that involving frontline implementers in the planning and implementation of health interventions through regular feedback before, during and after implementation has the potential to strengthen health outcomes.

The changing global landscape of health and disease: addressing challenges and opportunities for sustaining progress towards control and elimination of neglected tropical diseases (NTDs).

The drive to control neglected tropical diseases (NTDs) has had many successes but to reach defined targets new approaches are required. Over the last decade, NTD control programmes have benefitted from increased resources, and from effective partnerships and long-term pharmaceutical donations. Although the NTD agenda is broader than those diseases of parasitic aetiology there has been a massive up-scaling of the delivery of medicines to some billion people annually. Recipients are often the poorest, with the aspiration that NTD programmes are key to universal health coverage as reflected within the 2030 United Nations sustainable development goals (SDGs). To reach elimination targets, the community will need to adapt global events and changing policy environments to ensure programmes are responsive and can sustain progress towards NTD targets. Innovative thinking embedded within regional and national health systems is needed. Policy makers, managers and frontline health workers are the mediators between challenge and change at global and local levels. This paper attempts to address the challenges to end the chronic pandemic of NTDs and achieve the SDG targets. It concludes with a conceptual framework that illustrates the interactions between these key challenges and opportunities and emphasizes the health system as a critical mediator.

Promoting sustainable research partnerships: a mixed-method evaluation of a United Kingdom-Africa capacity strengthening award scheme.

BACKGROUND: Research partnerships between high-income countries (HICs) and low- or middle-income countries (LMICs) are a leading model in research capacity strengthening activities. Although numerous frameworks and guiding principles for effective research partnerships exist, few include the perspective of the LMIC partner. This paper draws out lessons for establishing and maintaining successful research collaborations, based on partnership dynamics, from the perspectives of both HIC and LMIC stakeholders through the evaluation of a research capacity strengthening partnership award scheme. METHODS: A mixed-method retrospective evaluation approach was used. Initially, a cross-sectional survey was administered to all award holders, which focused on partnership outputs and continuation. Fifty individuals were purposively selected to participate in interviews or focus group discussions from 12 different institutions in HICs and LMICs; the sample included the research investigators, research assistants, laboratory scientists and post-doctoral students. The evaluation collected data on critical elements of research partnership dynamics such as research outputs, nature of the partnership, future plans and research capacity. Quantitative data were analysed descriptively and qualitative data were analysed using an iterative framework approach. RESULTS: The majority of United Kingdom and African award holders stated they would like to pursue future collaborations together. Key aspects within partnerships that appeared to influence this were; the perceived benefits of the partnership at the individual and institutional level such as publication of papers or collaborative grants; ability to influence 'research culture' and instigate critical thinking among mid-career researchers; previous working relationships, for example supervisor-student relationships; and equity within partnerships linked to partnership formation and experience of United Kingdom partners within LMICs. Factors which may hinder development of long term partnerships were also identified such as financial control or differing expectations of partners. CONCLUSIONS: This paper provides evidence of what encourages international research partnerships for capacity strengthening to continue past award tenure, from the perspective of researchers in high and LMICs. Although every partnership is unique and individual experiences subjective, this paper provides extension and support of key principles and mechanisms that can contribute to successful research partnerships between researchers.

A randomized controlled comparison between combined spinal-epidural and single-shot spinal techniques in morbidly obese parturients undergoing cesarean delivery: time for initiation of anesthesia.

BACKGROUND: There is no current consensus on the optimal technique for subarachnoid anesthesia in morbidly obese parturients even though some providers prefer the combined spinal-epidural (CSE) over single-shot spinal (SSS) technique. In this randomized controlled study, we compared the time required for initiation of subarachnoid anesthesia between SSS and CSE techniques in morbidly obese parturients undergoing elective cesarean delivery. METHODS: Morbidly obese parturients presenting for elective cesarean delivery were randomized to receive subarachnoid anesthesia performed either with a SSS or a CSE technique. The spinal procedure in the sitting position was attempted by an experienced resident for up to 10 minutes, and if unsuccessful, the attending obstetric anesthesiologist assumed control of the procedure. The primary outcome was the time it took from the insertion of the introducer needle (SSS group) or insertion of the epidural needle (CSE group) to the end of intrathecal injection of drugs (procedure time). RESULTS: Forty-four patients were enrolled and completed the study. Three were excluded due to protocol violations. Of the remaining, 21 patients were in the SSS group and 20 in the CSE group. Demographic variables and mean (SD) body mass index (48.7 ± 7.6 kg/m for SSS; 49.9 ± 8.6 kg/m for CSE) were not different between groups. The median [interquartile range] for procedure time was 210 [116-692] seconds and 180 [75-450] seconds for SSS and CSE groups, respectively (P = 0.36), while the 95% confidence interval (CI) of the difference was -80 to +180 seconds. The first operator completed the procedure in <10 minutes in 71% of subjects in the SSS group and 95% of those in the CSE group (P = 0.09) and the 95% CI of the difference was -2% to +45%. There were more attempts to successful completion of the procedure in the SSS group (P = 0.007) with its 95% CI of the difference being +1 to +6. CONCLUSION: Our results suggest that the CSE technique is noninferior to the SS technique in morbidly obese parturients for time of initiation of subarachnoid anesthesia and may be accomplished with fewer attempts than the SSS technique with experienced residents.

Illness experiences and mental health challenges associated with female genital schistosomiasis in Cameroon: a gender analysis.

BACKGROUND: This paper highlights the role of cultural and structural gaps that shape illness experiences of women with manifestations of female genital schistosomiasis (FGS) and their impacts upon mental well-being. METHODS: Using ethnography, case study narrative accounts of women manifesting symptoms of FGS, as well as interviews with health workers within FGS-endemic rural fishing communities in Cameroon, we present experiences of women affected by FGS, alongside information on FGS health service provision. RESULTS: Our results show how gendered power dynamics in decision making, gendered experiences around menstrual health and structural gaps in service provision, combine and lead to poor mental well-being. Subfertility brings a heavy psychosocial toll from external blame and rejection, exacerbated by internalised stigma and the challenge of not being able to fulfil cultural and gendered social norms. CONCLUSIONS: Gender analysis is key to developing context-embedded understanding and addressing FGS-related challenges. With context-specific experiences demonstrating FGS comorbidity with mental ill health, there is a need to prioritise mental health integration at policy level through a person-centred approach. Furthermore, to address stigma and discrimination, campaigns to raise awareness in Cameroon, and beyond, are needed. CONTEXTE: Cet article met en évidence le rôle des lacunes culturelles et structurelles qui façonnent les expériences des femmes atteintes de schistosomiase génitale féminine (SGF) et leur impact sur le bien-être mental. LA MÉTHODE: À l'aide de l'ethnographie, de récits d'études de cas de femmes présentant des symptômes de schistosomiase génitale féminine, et d'entretiens avec des agents de santé au sein de communautés de pêcheurs ruraux endémiques de la schistosomiase génitale féminine au Cameroun, nous présentons les expériences des femmes touchées par le SGF, ainsi que des informations sur les services de santé liés au SGF. RÉSULTATS: Nos résultats montrent comment la dynamique du pouvoir dans la prise de décision, les expériences de la santé menstruelle et les lacunes structurelles dans la fourniture de services, interagissent et conduisent à un manque de bien-être psychologique. La sous-fécondité entraîne un lourd fardeau psychosocial du fait du blâme et de rejet externes auxquelles sont assujetties les personnes souffrant de la maladie, ce qui est exacerbé par la stigmatisation intériorisée et le défi que représente leur incapacité à respecter les normes sociales culturelles et sexospécifiques. CONCLUSION: L'analyse de genre est essentielle pour développer une compréhension intégrée au contexte et pour relever les défis liés aux SGF. les défis liés à l'ESF. Avec des expériences spécifiques au contexte démontrant la comorbidité de la FGS avec la mauvaise santé mentale, il est nécessaire de donner la priorité à l'intégration de la santé mentale au niveau politique par le biais d'une approche centrée sur la personne. l'intégration de la santé mentale au niveau politique par une approche centrée sur la personne. En outre, pour lutter contre la stigmatisation et la stigmatisation et la discrimination, des campagnes de sensibilisation sont nécessaires au Cameroun et au-delà. ANTECEDENTES: En este documento se pone de relieve el papel de las brechas culturales y estructurales que dan forma a las experiencias de enfermedad de las mujeres con manifestaciones de Esquistosomiasis Genital Femenina (EGF), y sus impactos en el bienestar mental. MÉTODO: Utilizando la etnografía, estudios de caso mediante relatos narrativos de mujeres que manifiestan síntomas de EGF y entrevistas con trabajadores sanitarios de comunidades pesqueras rurales endémicas en Camerún, presentamos las experiencias de las mujeres afectadas por la EGF, junto con información sobre la prestación de servicios sanitarios para la EGF. RESULTADOS: Nuestros resultados muestran cómo la dinámica de poder de género en la toma de decisiones, las experiencias de género en torno a la salud menstrual y las deficiencias estructurales en la prestación de servicios se combinan y conducen a un bienestar mental deficiente. La subfertilidad conlleva un alto coste psicosocial debido a la culpa y el rechazo externos, exacerbados por el estigma interiorizado y el reto de no poder cumplir las normas culturales y de género. CONCLUSIÓN: El análisis de género es clave para desarrollar una comprensión integrada en el contexto y abordarlos retos relacionados con la EGF. Dado que las experiencias específicas de cada contexto demuestran la comorbilidad de las EGF con la enfermedad mental, es necesario priorizar la integración de la salud mental en las políticas a través de un enfoque centrado en la persona. Además, para hacer frente al estigma y la discriminación, son necesarias campañas de sensibilización en Camerún y en otros lugares.

Multimethod evaluation of health services integration for neglected tropical diseases requiring case management in Liberia.

INTRODUCTION: The WHO neglected tropical disease (NTD) roadmap stresses the importance of integrating NTDs requiring case management (CM) within the health system. The NTDs programme of Liberia is among the first to implement an integrated approach and evaluate its impact. METHODS: A retrospective study of three of five CM-NTD-endemic counties that implemented the integrated approach was compared with cluster-matched counties with non-integrated CM-NTD. We compared trends in CM-NTD integrated versus non-integrated county clusters. We conducted a pre-post comparison of WHO high-level outcomes using data collected during intervention years compared with baseline in control counties. Changes in health outcomes, effect sizes for different diseases and rate ratios with statistically significant differences were determined. Complementary qualitative research explored CM-NTD stakeholders' perceptions, analysed through the framework approach, which is a transparent, multistage approach for qualitative thematic interdisciplinary data analysis. RESULTS: The detection rates for all diseases combined improved significantly in the intervention compared with the control clusters. Besides leprosy, detection rates improved with large effects, over fourfold increase with statistically significant effects for individual diseases (p<0.000; 95% CI 3.5 to 5.4). Access to CM-NTD services increased in integrated counties by 71 facilities, compared with three facilities in non-integrated counties. Qualitative findings highlight training and supervision as inputs underpinning increases in case detection, but challenges with refresher training, medicine supply and incentives negatively impact quality, equity and access. CONCLUSIONS: Integrating CM-NTDs improves case detection, accessibility and availability of CM-NTD services, promoting universal health coverage. Early case detection and the quality of care need further strengthening.