Genotypic variation in the promoter region of the CRH-248 gene interacts with early rearing experiences to disrupt the development of the HPA axis in infant rhesus macaques (Macaca mulatta).

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype-a gene-by-environment interaction that leaves a lasting developmental signature.

LLIN Evaluation in Uganda Project (LLINEUP): modelling the impact of COVID-19-related disruptions on delivery of long-lasting insecticidal nets on malaria indicators in Uganda.

BACKGROUND: Disruptions in malaria control due to COVID-19 mitigation measures were predicted to increase malaria morbidity and mortality in Africa substantially. In Uganda, long-lasting insecticidal nets (LLINs) are distributed nationwide every 3-4 years, but the 2020-2021 campaign was altered because of COVID-19 restrictions so that the timing of delivery of new nets was different from the original plans made by the National Malaria Control Programme. METHODS: A transmission dynamics modelling exercise was conducted to explore how the altered delivery of LLINs in 2020-2021 impacted malaria burden in Uganda. Data were available on the planned LLIN distribution schedule for 2020-2021, and the actual delivery. The transmission model was used to simulate 100 health sub-districts, and parameterized to match understanding of local mosquito bionomics, net use estimates, and seasonal patterns based on data collected in 2017-2019 during a cluster-randomized trial (LLINEUP). Two scenarios were compared; simulated LLIN distributions matching the actual delivery schedule, and a comparable scenario simulating LLIN distributions as originally planned. Model parameters were otherwise matched between simulations. RESULTS: Approximately 70% of the study population received LLINs later than scheduled in 2020-2021, although some areas received LLINs earlier than planned. The model indicates that malaria incidence in 2020 was substantially higher in areas that received LLINs late. In some areas, early distribution of LLINs appeared less effective than the original distribution schedule, possibly due to attrition of LLINs prior to transmission peaks, and waning LLIN efficacy after distribution. On average, the model simulations predicted broadly similar overall mean malaria incidence in 2021 and 2022. After accounting for differences in cluster population size and LLIN distribution dates, no substantial increase in malaria burden was detected. CONCLUSIONS: The model results suggest that the disruptions in the 2020-2021 LLIN distribution campaign in Uganda did not substantially increase malaria burden in the study areas.

Behavioral inhibition in a translational nonhuman primate model: A pilot study of Kagan's behavioral inhibition paradigm modified for use in infant rhesus macaques (Macaca mulatta).

Behavioral inhibition (BI), a temperamental trait first described by Jerome Kagan, is characterized by wariness to unfamiliar persons and novel situations. BI is a moderately stable trait, with biological and genetic underpinnings. Kagan's methodology for assessing BI is widely used in humans. Although this paradigm could be readily translated for use in nonhuman primates, thereby increasing generalizability from nonhuman primates to humans and fortifying evidence that BI is evolutionarily conserved, researchers have not done so. To address this, this study utilized a modified version of Kagan's paradigm to assess behaviors and biological markers of BI in nonhuman primates. Over the first 5 weeks of life, nursery-reared rhesus monkeys (Macaca mulatta; N = 12) were rated using the standardized Infant Behavior Assessment Scale for nonhuman primates on measures related to BI (consolability, irritability, struggle, and predominant state). Three months later, behavioral assessments were made in relation to a novel playroom, an unfamiliar peer, and a variety of attention-grabbing, unfamiliar stimuli, followed by the introduction of a human stranger. Behaviors from Kagan's studies of BI in toddlers (freezing, exploration, and latency to approach) and physiological measures related to BI (heart rate) were assessed. Random effects models showed that subjects rated high in temperamental BI spent less time exploring the environment and socializing with peers and more time freezing (an indication of anxiety in rhesus monkeys). These findings suggest that Kagan's paradigm is readily adapted for use in nonhuman primates and support the utility of rhesus monkeys as translational models for assessing the causes and consequences of human BI. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Recurrent Pouch Volvulus Following Ileoanal J-Pouch Anastomosis: A Case Report.

For individuals suffering from severe refractory ulcerative colitis (UC) who are unresponsive to medical treatment, a total proctocolectomy and ileal pouch-anal anastomosis (IPAA) surgery is the gold-standard treatment. However, its complications include anastomotic leaks, pelvic or perianal abscesses, and rare complications such as pouch volvulus. To our knowledge, there is a scarcity of case reports on patients with, specifically, a recurrent pouch volvulus. We present a case of a 57-year-old female with refractory UC who had undergone this treatment with no initial complications; 15 years later, she presented with intermittent bouts of obstruction. An exploratory laparotomy was performed; however, no adhesions or necrosis were found. Following investigations, pouch volvulus was confirmed. She subsequently underwent four endoscopic decompressions in the same year and ultimately received an enteropexy of the pouch. The volvulus reoccurred and, ultimately, the decision was made to perform a loop ileostomy. The patient, to date, is alive and doing well with her permanent ileostomy.

A primary microcephaly-associated sas-6 mutation perturbs centrosome duplication, dendrite morphogenesis, and ciliogenesis in Caenorhabditis elegans.

The human SASS6(I62T) missense mutation has been linked with the incidence of primary microcephaly in a Pakistani family, although the mechanisms by which this mutation causes disease remain unclear. The SASS6(I62T) mutation corresponds to SAS-6(L69T) in Caenorhabditis elegans. Given that SAS-6 is highly conserved, we modeled this mutation in C. elegans and examined the sas-6(L69T) effect on centrosome duplication, ciliogenesis, and dendrite morphogenesis. Our studies revealed that all the above processes are perturbed by the sas-6(L69T) mutation. Specifically, C. elegans carrying the sas-6(L69T) mutation exhibit an increased failure of centrosome duplication in a sensitized genetic background. Further, worms carrying this mutation also display shortened phasmid cilia, an abnormal phasmid cilia morphology, shorter phasmid dendrites, and chemotaxis defects. Our data show that the centrosome duplication defects caused by this mutation are only uncovered in a sensitized genetic background, indicating that these defects are mild. However, the ciliogenesis and dendritic defects caused by this mutation are evident in an otherwise wild-type background, indicating that they are stronger defects. Thus, our studies shed light on the novel mechanisms by which the sas-6(L69T) mutation could contribute to the incidence of primary microcephaly in humans.

Variation in the serotonin transporter genotype is associated with maternal restraint and rejection of infants: A nonhuman primate (Macaca mulatta) model.

Studies show that maternal behaviors are mediated by the bivariate serotonin transporter (5-HTT) genotype, although the findings are mixed, with some studies showing that mothers with the s allele exhibit increased maternal sensitivity, while other studies show that mothers with the s allele show decreased maternal sensitivity. Nonhuman primate studies offer increased control over extraneous variables and may contribute to a better understanding of the effects of the 5-HTT genotype on maternal sensitivity. This study assesses the influence of 5-HTT genotype variation on maternal sensitivity in parenting in 125 rhesus macaque mothers (Macaca mulatta) during the first three-months of their infants' lives, an age well before typical infants undergo weaning. Mothers were genotyped for the 5-HTT genotype and maternal behaviors were collected, including neglectfulness, sensitivity, and premature rejections during undisturbed social interactions. Results showed that mothers homozygous for the s allele rejected their infants the most and restrained their infants the least, an indication that mothers with the s allele are more likely to neglect their infants' psychological and physical needs. These findings suggest that, at an age when an infant's needs are based on warmth, security, and protection, mothers with an s allele exhibit less sensitive maternal behaviors. High rates of rejections and low rates of restraints are behaviors that typically characterize premature weaning and are inappropriate for their infant's young age. This study is an important step in understanding the etiology of variability in maternal warmth and care, and further suggests that maternal 5-HTT genotype should be examined in studies assessing genetic influences on variation in maternal sensitivity, and ultimately, mother-infant attachment quality.

Assessing the variability in experimental hut trials evaluating insecticide-treated nets against malaria vectors.

Experimental hut trials (EHTs) are used to evaluate indoor vector control interventions against malaria vectors in a controlled setting. The level of variability present in the assay will influence whether a given study is well powered to answer the research question being considered. We utilised disaggregated data from 15 previous EHTs to gain insight into the behaviour typically observed. Using simulations from generalised linear mixed models to obtain power estimates for EHTs, we show how factors such as the number of mosquitoes entering the huts each night and the magnitude of included random effects can influence study power. A wide variation in behaviour is observed in both the mean number of mosquitoes collected per hut per night (ranging from 1.6 to 32.5) and overdispersion in mosquito mortality. This variability in mortality is substantially greater than would be expected by chance and should be included in all statistical analyses to prevent false precision of results. We utilise both superiority and non-inferiority trials to illustrate our methodology, using mosquito mortality as the outcome of interest. The framework allows the measurement error of the assay to be reliably assessed and enables the identification of outlier results which could warrant further investigation. EHTs are increasingly playing an important role in the evaluation and regulation of indoor vector control interventions so it is important to ensure that these studies are adequately powered.

Seasonal dynamics of Anopheles stephensi and its implications for mosquito detection and emergent malaria control in the Horn of Africa.

Invasion of the malaria vector Anopheles stephensi across the Horn of Africa threatens control efforts across the continent, particularly in urban settings where the vector is able to proliferate. Malaria transmission is primarily determined by the abundance of dominant vectors, which often varies seasonally with rainfall. However, it remains unclear how An. stephensi abundance changes throughout the year, despite this being a crucial input to surveillance and control activities. We collate longitudinal catch data from across its endemic range to better understand the vector's seasonal dynamics and explore the implications of this seasonality for malaria surveillance and control across the Horn of Africa. Our analyses reveal pronounced variation in seasonal dynamics, the timing and nature of which are poorly predicted by rainfall patterns. Instead, they are associated with temperature and patterns of land use; frequently differing between rural and urban settings. Our results show that timing entomological surveys to coincide with rainy periods is unlikely to improve the likelihood of detecting An. stephensi. Integrating these results into a malaria transmission model, we show that timing indoor residual spraying campaigns to coincide with peak rainfall offers little improvement in reducing disease burden compared to starting in a random month. Our results suggest that unlike other malaria vectors in Africa, rainfall may be a poor guide to predicting the timing of peaks in An. stephensi-driven malaria transmission. This highlights the urgent need for longitudinal entomological monitoring of the vector in its new environments given recent invasion and potential spread across the continent.

Quantifying the direct and indirect protection provided by insecticide treated bed nets against malaria.

Long lasting insecticidal nets (LLINs) provide both direct and indirect protection against malaria. As pyrethroid resistance evolves in mosquito vectors, it will be useful to understand how the specific benefits LLINs afford individuals and communities may be affected. Here we use modelling to show that there is no minimum LLIN usage needed for users and non-users to benefit from community protection. Modelling results also indicate that pyrethroid resistance in local mosquitoes will likely diminish the direct and indirect benefits from insecticides, leaving the barrier effects intact, but LLINs are still expected to provide enhanced benefit over untreated nets even at high levels of pyrethroid resistance.

The realized efficacy of indoor residual spraying campaigns falls quickly below the recommended WHO threshold when coverage, pace of spraying and residual efficacy on different wall types are considered.

Indoor residual spraying (IRS) has been and remains an important malaria control intervention in southern Mozambique, South Africa and Eswatini. A better understanding of the effectiveness of IRS campaigns is critical to guide future elimination efforts. We analyze the three IRS campaigns conducted during a malaria elimination demonstration project in southern Mozambique, the "Magude project", and propose a new method to calculate the efficacy of IRS campaigns adjusting for IRS coverage, pace of house spraying and IRS residual efficacy on different wall types. Anopheles funestus sensu lato (s.l.) and An. gambiae s.l. were susceptible to pirimiphos-methyl and DDT. Anopheles funestus s.l. was resistant to pyrethroids, with 24h post-exposure mortality being lower for An. funestus sensu stricto (s.s.) than for An. parensis (collected indoors). The percentage of structures sprayed was above 90% and percentage of people covered above 86% in all three IRS campaigns. The percentage of households sprayed was above 83% in 2015 and 2016, but not assessed in 2017. Mosquito mortality 24h post-exposure stayed above 80% for 196 days after the 2016 IRS campaign and 222 days after the 2017 campaign and was 1.5 months longer on mud walls than on cement walls. This was extended by up to two months when 120h post-exposure mortality was considered. The district-level realized IRS efficacy was 113 days after the 2016 campaign. While the coverage of IRS campaigns in Magude were high, IRS protection did not remain optimal for the entire high malaria transmissions season. The use of a longer-lasting IRS product could have further supported the interruption of malaria transmission in the district. To better estimate the protection afforded by IRS campaigns, National Malaria Control Programs and partners are encouraged to adjust the calculation of IRS efficacy for IRS coverage, pace of house spraying during the campaign and IRS efficacy on different wall types combined with wall type distribution in the sprayed area.

The mosquito vectors that sustained malaria transmission during the Magude project despite the combined deployment of indoor residual spraying, insecticide-treated nets and mass-drug administration.

The "Magude project" aimed but failed to interrupt local malaria transmission in Magude district, southern Mozambique, by using a comprehensive package of interventions, including indoor residual spraying (IRS), pyrethroid-only long-lasting insecticide treated nets (LLINs) and mass-drug administration (MDA). Here we present detailed information on the vector species that sustained malaria transmission, their association with malaria incidence and behaviors, and their amenability to the implemented control interventions. Mosquitoes were collected monthly between May 2015 and October 2017 in six sentinel sites in Magude district, using CDC light traps both indoors and outdoors. Anopheles arabiensis was the main vector during the project, while An. funestus s.s., An. merus, An. parensis and An. squamosus likely played a secondary role. The latter two species have never previously been found positive for Plasmodium falciparum in southern Mozambique. The intervention package successfully reduced vector sporozoite rates in all species throughout the project. IRS was effective in controlling An. funestus s.s. and An. parensis, which virtually disappeared after its first implementation, but less effective at controlling An. arabiensis. Despite suboptimal use, LLINs likely provided significant protection against An. arabiensis and An. merus that sought their host largely indoors when people where in bed. Adding IRS on top of LLINs and MDA likely added value to the control of malaria vectors during the Magude project. Future malaria elimination attempts in the area could benefit from i) increasing the use of LLINs, ii) using longer-lasting IRS products to counteract the increase in vector densities observed towards the end of the high transmission season, and iii) a higher coverage with MDA to reduce the likelihood of human infection. However, additional interventions targeting vectors that survive IRS and LLINs by biting outdoors or indoors before people go to bed, will be likely needed to achieve local malaria elimination.

Opening the Conversation: study protocol for a Phase III trial to evaluate a couple-based intervention to reduce reproductive and sexual distress among young adult breast and gynecologic cancer survivor couples.

BACKGROUND: Reproductive and sexual health (RSH) concerns are common and distressing for young adults diagnosed with breast and gynecologic cancer and their partners. This study evaluates the efficacy of a virtual couple-based intervention called Opening the Conversation (OC). The OC intervention is grounded in theory and evidence-based practice and was adapted to improve coping and communication specifically in relation to RSH concerns after cancer. METHODS: This Phase III trial is conducted in a fully remote setting and enrolls young adult couples (current age 18-44 years) with a history of breast or gynecologic cancer (stage 1-4, diagnosed under age 40) within the past 6 months to 5 years. Eligible dyads are recruited from across the USA. The target sample size is 100 couples. Dyads are randomly assigned to receive either the 5-session OC intervention or a 4-session active control intervention (Side by Side). The primary outcomes are change in reproductive distress and sexual distress. Secondary outcomes include communication about reproductive concerns, communication about sexual concerns, depressive symptoms, sexual function, relationship quality, relationship intimacy, sexual satisfaction, self-efficacy to communicate about sex and intimacy, and quality of life. An exploratory aim examines whether dyadic coping and communication quality mediate intervention effects on survivors' and partners' reproductive distress or sexual distress. Self-report outcome measures are assessed for both groups at baseline (T1), 2 weeks post-treatment (T2), and 3 months post-treatment (T3). DISCUSSION: Despite the importance of RSH for quality of life for young adult cancer survivors and their partners, evidence-based interventions that help couples navigate RSH concerns are lacking. This randomized controlled trial will determine the efficacy of a novel couple-based intervention to reduce distress related to RSH concerns for younger couples after breast or gynecologic cancer, in comparison to an active control intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04806724. Registered on Mar 19, 2021.

Inferring the epidemiological benefit of indoor vector control interventions against malaria from mosquito data.

The cause of malaria transmission has been known for over a century but it is still unclear whether entomological measures are sufficiently reliable to inform policy decisions in human health. Decision-making on the effectiveness of new insecticide-treated nets (ITNs) and the indoor residual spraying of insecticide (IRS) have been based on epidemiological data, typically collected in cluster-randomised control trials. The number of these trials that can be conducted is limited. Here we use a systematic review to highlight that efficacy estimates of the same intervention may vary substantially between trials. Analyses indicate that mosquito data collected in experimental hut trials can be used to parameterize mechanistic models for Plasmodium falciparum malaria and reliably predict the epidemiological efficacy of quick-acting, neuro-acting ITNs and IRS. Results suggest that for certain types of ITNs and IRS using this framework instead of clinical endpoints could support policy and expedite the widespread use of novel technologies.

The retromer complex regulates C. elegans development and mammalian ciliogenesis.

The mammalian retromer consists of subunits VPS26 (either VPS26A or VPS26B), VPS29 and VPS35, and a loosely associated sorting nexin (SNX) heterodimer or a variety of other SNX proteins. Despite involvement in yeast and mammalian cell trafficking, the role of retromer in development is poorly understood, and its impact on primary ciliogenesis remains unknown. Using CRISPR/Cas9 editing, we demonstrate that vps-26-knockout worms have reduced brood sizes, impaired vulval development and decreased body length, all of which have been linked to ciliogenesis defects. Although preliminary studies did not identify worm ciliary defects, and impaired development limited additional ciliogenesis studies, we turned to mammalian cells to investigate the role of retromer in ciliogenesis. VPS35 localized to the primary cilium of mammalian cells, and depletion of VPS26, VPS35, VPS29, SNX1, SNX2, SNX5 or SNX27 led to decreased ciliogenesis. Retromer also coimmunoprecipitated with the centriolar protein, CP110 (also known as CCP110), and was required for its removal from the mother centriole. Herein, we characterize new roles for retromer in C. elegans development and in the regulation of ciliogenesis in mammalian cells, suggesting a novel role for retromer in CP110 removal from the mother centriole.

Feasibility of Mindful After Cancer: Pilot Study of a Virtual Mindfulness-Based Intervention for Sexual Health in Cancer Survivorship.

BACKGROUND: Mindfulness-based interventions (MBIs) are increasingly recognized as an effective strategy for supporting female cancer survivors experiencing sexual health concerns. AIM: To examine the feasibility of a sexual health MBI, Mindful After Cancer, which was adapted to meet the needs of breast and gynecologic cancer survivors in a community setting and for delivery via videoconference. METHODS: A mixed-methods approach was used to evaluate the acceptability, feasibility, and appropriateness of the 8-week virtual MBI. Weekly sessions were 1.5-2 hours in duration and included guided meditations and group discussion about sexuality after cancer and mindfulness in daily life. Home practice activities related to both mindfulness practice and sexual health. Participants completed online surveys at baseline and 1-month post-intervention. A purposive sample of 10 participants were invited to complete a follow-up interview 2-3 months post-intervention. OUTCOMES: Primary outcomes included both qualitative and quantitative assessments of acceptability, appropriateness, and feasibility of the Mindful After Cancer intervention for sexual health in cancer survivorship. RESULTS: Twenty-two women completed the intervention (Mean age 53.2 years, SD = 9.4, Range= 39-73), with time since diagnosis ranging from 1 to 27 years (Mean 6.0 years, SD = 5.9). Participants completed 6.8 sessions on average (Range = 2 - 8) and 77% reported that the time commitment was manageable. Both qualitative and quantitative findings support the feasibility, acceptability, and appropriateness of the intervention. CLINICAL IMPLICATIONS: Many cancer survivors experience sexual dysfunction and related distress after diagnosis and well after treatment ends, yet there are few interventions available. Improved access to effective interventions can improve the delivery of survivorship care and patient outcomes. STRENGTHS & LIMITATIONS: The sample size is small for this pilot study, and a control group was not included. The intervention was offered over two time periods, one prior to COVID-19 pandemic and one during the pandemic, resulting in both limitations associated with potential differences between the experiences of participants and the opportunity to learn more about the feasibility of the intervention during times of crisis. CONCLUSION: Results suggest that virtual delivery of the MBI is feasible, acceptable, and appropriate for breast and gynecologic cancer survivors. Gorman JR, Drizin JH, Smith E, et al. Feasibility of Mindful After Cancer: Pilot Study of a Virtual Mindfulness-Based Intervention for Sexual Health in Cancer Survivorship. J Sex Med 2022;19:1131-1146.

Durability of three types of dual active ingredient long-lasting insecticidal net compared to a pyrethroid-only LLIN in Tanzania: methodology for a prospective cohort study nested in a cluster randomized controlled trial.

BACKGROUND: Progress achieved by long-lasting insecticidal nets (LLINs) against malaria is threatened by widespread selection of pyrethroid resistance among vector populations. LLINs with non-pyrethroid insecticides are urgently needed. This study aims to assess the insecticide and textile durability of three classes of dual-active ingredient (A.I.) LLINs using techniques derived from established WHO LLIN testing methods to set new standards of evaluation. METHODS: A WHO Phase 3 active ingredients and textile durability study will be carried out within a cluster randomized controlled trial in 40 clusters in Misungwi district, Tanzania. The following treatments will be evaluated: (1) Interceptor®G2 combining chlorfenapyr and the pyrethroid alpha-cypermethrin, (2) Royal Guard® treated with pyriproxyfen and alpha-cypermethrin, (3) Olyset™ Plus which incorporates a synergist piperonyl butoxide and the pyrethroid permethrin, and (4) a reference standard alpha-cypermethrin only LLIN (Interceptor®). 750 nets will be followed in 5 clusters per intervention arm at 6, 12, 24 and 36 months post distribution for survivorship and hole index assessment. A second cohort of 1950 nets per net type will be identified in 10 clusters, of which 30 LLINs will be withdrawn for bio-efficacy and chemical analysis every 6 months up to 36 months and another 30 collected for experimental hut trials every year. Bio-efficacy will be assessed using cone bioassays and tunnel tests against susceptible and resistant laboratory strains of Anopheles gambiae sensu stricto. Efficacy of field-collected nets will be compared in six experimental huts. The main outcomes will be Anopheles mortality up to 72 h post exposure, blood feeding and egg maturation using ovary dissection to assess impact on fecundity. CONCLUSIONS: Study findings will help develop bio-efficacy and physical durability criteria for partner A.I., in relation to the cRCT epidemiological and entomological outcomes, and refine preferred product characteristics of each class of LLIN. If suitable, the bioassay and hut outcomes will be fitted to transmission models to estimate correlation with cRCT outcomes. TRIAL REGISTRATION NUMBER: NCT03554616.

An evidence synthesis approach for combining different data sources illustrated using entomological efficacy of insecticides for indoor residual spraying.

BACKGROUND: Prospective malaria public health interventions are initially tested for entomological impact using standardised experimental hut trials. In some cases, data are collated as aggregated counts of potential outcomes from mosquito feeding attempts given the presence of an insecticidal intervention. Comprehensive data i.e. full breakdowns of probable outcomes of mosquito feeding attempts, are more rarely available. Bayesian evidence synthesis is a framework that explicitly combines data sources to enable the joint estimation of parameters and their uncertainties. The aggregated and comprehensive data can be combined using an evidence synthesis approach to enhance our inference about the potential impact of vector control products across different settings over time. METHODS: Aggregated and comprehensive data from a meta-analysis of the impact of Pirimiphos-methyl, an indoor residual spray (IRS) product active ingredient, used on wall surfaces to kill mosquitoes and reduce malaria transmission, were analysed using a series of statistical models to understand the benefits and limitations of each. RESULTS: Many more data are available in aggregated format (N = 23 datasets, 4 studies) relative to comprehensive format (N = 2 datasets, 1 study). The evidence synthesis model had the smallest uncertainty at predicting the probability of mosquitoes dying or surviving and blood-feeding. Generating odds ratios from the correlated Bernoulli random sample indicates that when mortality and blood-feeding are positively correlated, as exhibited in our data, the number of successfully fed mosquitoes will be under-estimated. Analysis of either dataset alone is problematic because aggregated data require an assumption of independence and there are few and variable data in the comprehensive format. CONCLUSIONS: We developed an approach to combine sources from trials to maximise the inference that can be made from such data and that is applicable to other systems. Bayesian evidence synthesis enables inference from multiple datasets simultaneously to give a more informative result and highlight conflicts between sources. Advantages and limitations of these models are discussed.

Adapting a Theory-Informed Intervention to Help Young Adult Couples Cope With Reproductive and Sexual Concerns After Cancer.

OBJECTIVE: Most young adults diagnosed with breast or gynecologic cancers experience adverse reproductive or sexual health (RSH) outcomes due to cancer and its treatment. However, evidence-based interventions that specifically address the RSH concerns of young adult and/or LGBTQ+ survivor couples are lacking. Our goal is to develop a feasible and acceptable couple-based intervention to reduce reproductive and sexual distress experience by young adult breast and gynecologic cancer survivor couples with diverse backgrounds. METHODS: We systematically adapted an empirically supported, theoretically grounded couple-based intervention to address the RSH concerns of young couples coping with breast or gynecologic cancer through integration of stakeholder perspectives. We interviewed 11 couples (22 individuals) with a history of breast or gynecologic cancer to review and pretest intervention materials. Three of these couples were invited to review and comment on intervention modifications. Content experts in RSH and dyadic coping, clinicians, and community advisors (one heterosexual couple and one LGBTQ+ couple, both with cancer history) participated throughout the adaptation process. RESULTS: Findings confirmed the need for an online, couple-based intervention to support young couples experiencing RSH concerns after breast or gynecologic cancer. Qualitative themes suggested intervention preferences for: (1) A highly flexible intervention that can be tailored to couples' specific RSH concerns; (2) Active steps to help members of a dyad "get on the same page" in their relationship and family building plans; (3) A specific focus on raising partners' awareness about how cancer can affect body image and physical intimacy; and (4) Accessible, evidence-based information about RSH for both partners. These results, along with feedback from stakeholders, informed adaptation and finalization of the intervention content and format. The resulting virtual intervention, Opening the Conversation, includes five weekly sessions offering training to couples in communication and dyadic coping skills for addressing RSH concerns. CONCLUSION: The systematic adaptation process yielded a theory-informed intervention for young adult couples facing breast and gynecological cancers, which will be evaluated in a randomized controlled trial. The long-term goal is to implement and disseminate Opening the Conversation broadly to reach young adult couples with diverse backgrounds who are experiencing RSH concerns in cancer survivorship.

Design and methods for a quasi-experimental pilot study to evaluate the impact of dual active ingredient insecticide-treated nets on malaria burden in five regions in sub-Saharan Africa.

BACKGROUND: Vector control tools have contributed significantly to a reduction in malaria burden since 2000, primarily through insecticidal-treated bed nets (ITNs) and indoor residual spraying. In the face of increasing insecticide resistance in key malaria vector species, global progress in malaria control has stalled. Innovative tools, such as dual active ingredient (dual-AI) ITNs that are effective at killing insecticide-resistant mosquitoes have recently been introduced. However, large-scale uptake has been slow for several reasons, including higher costs and limited evidence on their incremental effectiveness and cost-effectiveness. The present report describes the design of several observational studies aimed to determine the effectiveness and cost-effectiveness of dual-AI ITNs, compared to standard pyrethroid-only ITNs, at reducing malaria transmission across a variety of transmission settings. METHODS: Observational pilot studies are ongoing in Burkina Faso, Mozambique, Nigeria, and Rwanda, leveraging dual-AI ITN rollouts nested within the 2019 and 2020 mass distribution campaigns in each country. Enhanced surveillance occurring in select study districts include annual cross-sectional surveys during peak transmission seasons, monthly entomological surveillance, passive case detection using routine health facility surveillance systems, and studies on human behaviour and ITN use patterns. Data will compare changes in malaria transmission and disease burden in districts receiving dual-AI ITNs to similar districts receiving standard pyrethroid-only ITNs over three years. The costs of net distribution will be calculated using the provider perspective including financial and economic costs, and a cost-effectiveness analysis will assess incremental cost-effectiveness ratios for Interceptor® G2, Royal Guard®, and piperonyl butoxide ITNs in comparison to standard pyrethroid-only ITNs, based on incidence rate ratios calculated from routine data. CONCLUSIONS: Evidence of the effectiveness and cost-effectiveness of the dual-AI ITNs from these pilot studies will complement evidence from two contemporary cluster randomized control trials, one in Benin and one in Tanzania, to provide key information to malaria control programmes, policymakers, and donors to help guide decision-making and planning for local malaria control and elimination strategies. Understanding the breadth of contexts where these dual-AI ITNs are most effective and collecting robust information on factors influencing comparative effectiveness could improve uptake and availability and help maximize their impact.