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Abstract Background The RTS,S malaria vaccine has been prequalified for use in endemic settings prioritizing areas with moderate to high disease transmission. The impact of a vaccine at the population level may differ from observations during clinical trial due to programmatic, and individual-related factors, among others. The objective of this study was to assess the impact of the RTS,S malaria vaccine on uncomplicated malaria among children aged 12–59 months in the Phase IV study districts, Upper East Region, Ghana. Methods A retrospective study was conducted using routine malaria surveillance data for the period 2020–2022. The burden of uncomplicated malaria was compared between the implementing (Kasena Nankana East and West districts) and comparator areas (Builsa North and South districts). The impact of RTS,S malaria vaccine was assessed by estimating the percentage reduction in uncomplicated malaria and incidence averted in the implementing area, accounting for the effect of confounders. Results Over 50,000 episodes of uncomplicated malaria among children aged 12–59 months were included in the study. Uncomplicated malaria was reduced by 33% (95%CI 29–36) over the entire study period, but the malaria incidence averted declined from 324/1,000 (95% CI 298–339; p

Abstract Background In May 2019, Ghana piloted the introduction of RTS,S malaria vaccine into routine immunization in 42 districts of seven of the 16 regions. The RTS,S malaria vaccine implementation programme (MVIP) post-introduction evaluation (PIE) conducted in Ghana, assessed the immunization system as well as healthcare worker and caregiver experiences during the phase-one rollout but was less expressive on quantitative grading of the respective thematic areas of the vaccine introduction plan. Given the utility of summary statistics in programme evaluation and communication, this follow-up study aimed to provide an overall rating of the country's performance regarding the MVIP . Methods A retrospective study was conducted from 10th January to 5th February 2024. It involved review of records to assess key thematic areas of the national MVIP plan, using a study tool adapted from the WHO New Vaccine Introduction (NVI) checklist. A composite score ranging from zero to 100 per cent was generated to assess the country's overall performance regarding introduction of the malaria vaccine, rated on a Likert scale as comprehensive, good, fair, and poor. Results The overall performance in the MVIP was rated 78.9% (30/38) corresponding to a grading of “good” on the Likert scale. Performance indicators under thematic areas including policy, national coordination mechanisms, waste management, health worker training, and pharmacovigilance were completely achieved. However, some weaknesses were exhibited in areas such as financial consideration, cold chain, logistics, and vaccine management, and monitoring and evaluation. Conclusion Ghana’s MVIP demonstrated remarkable strengths worth leveraging to improve the national immunization programme. The weaknesses observed in some of the thematic areas present opportunities to engage key immunization partners and stakeholders towards aligning efforts to ensure a more robust expansion phase. The lessons from the MVIP may be relevant to areas introducing malaria vaccine irrespective of the product type—RTS,S or R21.

Introduction: The uptake trend of a new vaccine is unpredictable and may reflect the quality of introduction process and community acceptance. The objective of this study was to conduct a trend analysis of RTS,S malaria vaccine uptake in the seven pilot regions of Ghana from 2019 to 2022. The findings are envisaged to strengthen malaria vaccine introductions in the future. Methods: A retrospective analysis was conducted on routine childhood immunisation data for 2019–2022. Coverages for the first (RTS,S1), second (RTS,S2), third (RTS,S3) and fourth (RTS,S4) doses of malaria vaccine; third dose of diphtheria, tetanus, pertussis-containing vaccine (DTP3/Penta3); first dose measles-rubella (MR1) and second dose measles-rubella (MR2) vaccines were calculated. Dropout rates and uptake gaps were estimated to assess variations in the uptake of consecutive RTS,S schedules; and the differences in the uptake of RTS,S and the comparator vaccines, respectively. Results: Nationally, the coverages of the first three doses of the RTS,S malaria vaccine rose sharply from 2019 (RTS,S1 = 54.9 %; RTS,S2 = 54.6 %; RTS,S3 = 38.6 %) through 2020 (RTS,S1 = 70.7 %; RTS,S2 = 67.4 %; RTS,S3 = 66.3 %) to peaks in 2021 (RTS,S1 = 76.0 %; RTS,S2 = 73.1 %; RTS,S3 = 74.2 %), and declined marginally in 2022 (RTS,S1 = 74.0 %; RTS,S2 = 69.9 %; RTS,S3 = 71.3 %). For the fourth dose, the low uptake in 2020 (7.5 %) was followed by a steep rise in 2021 (46.9 %) that continued, but at a reduced rate to 50.6% in 2022. The dropout rates and uptake gaps were initially high but declined consistently over the study period. Generally, the trends in vaccination coverages, and dropout rates and uptake gaps at the national level were reflected in the respective regions. Conclusion: The coverage of RTS,S malaria vaccine improved consistently over the study period despite the low uptake in the early phase of the pilot. While the decreasing dropout rates and uptake gaps may indicate improved community acceptance, strengthening immunisation service delivery is crucial in sustaining the observed trajectory.

Introduction: Savannah Region witnessed a decline in measles-rubella (MR) vaccination coverage prior to the measles outbreak in 2022. This study aimed to assess contributory factors of the low routine MR vaccination coverage and proffer recommendations to improve vaccination uptake. Methods: A cross-sectional study was conducted in two districts (Bole and Central Gonja) of Savannah Region from December 2022 to June 2023. Caregivers of children 18–59 months were randomly selected and interviewed using a structured questionnaire. Bivariate and multivariate logistic regression were performed to assess predictors of MR vaccination status. Results: Children of caregivers with inadequate knowledge of MR vaccination (AOR = 0.58, 95 %CI: 0.47–0.72), travelled more than five km to access health services (AOR = 0.48, 95 %CI: 0.39–0.59), described health workers attitude as poor (AOR = 0.44, 95 %CI: 0.26–0.74), and those who sought treatment for adverse events following immunization (AEFI) from the pharmacy (AOR = 0.65, 95 %CI: 0.51–0.84) were less likely to complete MR vaccination. On the contrary, children of female sex (AOR = 1.27, 95 %CI: 1.05–1.53), aged 24–59 month (AOR = 2.56, 95 %CI: 1.05–1.53), caregivers with primary or secondary education (AOR = 1.43, 95 %CI: 1.11–1.84; and AOR = 2.23, 95 %CI: 1.64–3.03 respectively), and those who did not experience rescheduling of vaccination sessions (AOR = 1.61, 95 % CI: 1.25–2.01) were more likely to complete routine MR vaccination schedule. Conclusion: Inadequate caregiver knowledge, poor geographical access to health services, poor healthcare worker attitude, and non-institutional management of AEFI significantly contributed to the low MR vaccination uptake in the Savannah Region. Adopting tailored approaches to addressing these factors could improve vaccination coverage.

Background: Multidrug resistant bacterial and fungal pathogens are resistant to a number of significant front-line drugs, hence, identification of new inhibitory agents to combat them is crucial. In this study, we aim to evaluate the activity of Pandemic Box compounds from Malaria Medicines Venture (MMV) against A. baumannii and P. aeruginosa bacterial, C. auris, C. albicans and A. niger fungal clinical isolates. Methods: Isolates were initially screened with 201 antibacterial and 46 antifungal compounds (10 μM) using a microbroth dilution in triplicates to determine MIC. A persister assay was performed for bacterial pathogens. Results: Out of 201 antibacterial compounds, twenty-nine and seven compounds inhibited the growth of A. baumannii and P. aeruginosa at 10 μM, respectively. MMV1580854, MMV1579788, eravacycline and epetraborole inhibited both the bacterial test isolates. In a persister assay, MMV1634390 showed complete bactericidal effect against A. baumannii. With antifungal activity compounds, C. auris responded to15 compounds, Six compounds inhibited C. albicans and one was effective against A. niger at 10 μM. The ratio of Minimum Fungicidal Concentration (MFC): Minimum Inhibitory Concentration (MIC) of MMV1782110 was 2 against C. auris. Eberconazole, amorolfine and luliconazole are fungicidal targeting C. albicans at a MFC: MIC ratio of 2. Conclusion: Five compounds from MMV Pandemic Box were found to be inhibiting colistin and ceftazidime resistant A. baumannii clinical isolate, also against colistin and β-lactam resistant P. aeruginosa clinical isolate. MMV1634390 showed complete bactericidal effect against A. baumannii in a persister assay. MMV1782110, Eberconazole, amorolfine and luliconazole exhibited potent anti-fungal activity. Further investigations are warranted to identify the targets and mechanism.

Introduction Current traveller health surveillance is ‘top-down’. Mobile-based surveillance could capture infection symptoms in real time. We aimed to evaluate the spectrum of illness in travellers using a mobile app-based system.Methods This study (ClinicalTrials.gov NCT04672577) used an application called Infection Tracking in Travellers (ITIT) that records travel-related illness symptoms with associated geolocation and weather data. The free ITIT app is available in 14 languages. Participants were recruited globally from April 2022 to July 2023. Participants >18 years of age travelled internationally and provided electronic consent. Incentives included the provision of travel health information imported from the WHO website. Symptoms were recorded with daily pop-up questionnaires and symptom severity was assessed using a Likert scale. Two post-travel questionnaires were administered. Logistic mixed models examined factors relating to symptom presence, and a random forest model examined symptom impact.Results 609 participants were recruited until July 2023. Participants had an average age of 37 years (18–79), and an average travel duration of 26 days (2–281). Most participants were travelling for leisure/tourism (401; 66%), followed by ‘visiting friends and relatives’ (99; 16%) and business travel (80; 13%). All continents were visited by at least one traveller. Of 470 registered trips, symptoms were reported on 163 trips (35%). Gastrointestinal symptoms were reported on 87 trips (19%) and respiratory symptoms on 81 trips (17%). The most important factors in predicting the presence of symptoms were duration of travel, travelling in winter and high humidity. Diarrhoea, headache and nausea were symptoms with most impact on daily activities. Post-travel questionnaires showed that 12% of surveyed participants experienced symptoms with several episodes of self-treatment. Two diagnoses were recorded: Lyme disease and amoebic dysentery.Conclusion The digital tool ITIT successfully captures the spectrum of travel-related illness. This detailed epidemiology is crucial for outbreak detection and for the formulation of travel medicine guidelines.Trial registration number NCT04672577.

Abstract Reduction of post-weaning diarrhoea caused by ETEC is a principal objective in pig farming in terms of welfare benefits. This study determined the effects of genetic susceptibility and dietary strategies targeting inflammation and fimbriae adherence on F4-ETEC shedding and diarrhoea in weaned piglets in an experimental challenge model. A DNA marker test targeting single nucleotide polymorphism 2 (SNP2) identified piglets as heterozygous (SNP2+, susceptible) or homozygous (SNP2-, resistant) to developing F4ac-ETEC diarrhoea. A total of 50 piglets, 25 SNP2+ and 25 SNP2-, were weaned at 30 days of age and equally distributed to different treatments (n = 10): Positive control (PC): piglets fed with a negative control diet and provided with colistin via drinking water; Negative control (NC): piglets fed with a negative control diet; Tall oil fatty acids (TOFA): piglets fed with a negative control diet + 1.0 g TOFA/kg feed; Yeast hydrolysate (YH): piglets fed with a negative control diet + 1.5 g YH/kg feed derived from Saccharomyces cerevisiae; and Combination (COM): piglets fed with a negative control diet + 1.0 g TOFA and 1.5 g YH/kg feed. On day 10 post-weaning, all piglets were infected with F4-ETEC by oral administration. Piglets fed with PC, TOFA, YH or COM had a lower faecal shedding of F4-ETEC than NC piglets (P

Abstract Background Non-tuberculous mycobacteria (NTM) are a group of bacteria that cause rare lung infections and are increasingly recognized as causative agents of opportunistic and device-associated infections in humans. In Gabon, there is a lack of data on NTM species identification and drug susceptibility. The aim of this study was to identify the frequency of NTM species and their genotypic susceptibility pattern to commonly used antibiotics for NTM infections in Gabon. Methods A cross-sectional study was conducted at the CERMEL TB laboratory from January 2020 to December 2022, NTM subspecies identification and drug susceptibility testing to macrolides and aminoglycosides were performed using the genotype NTM-DR kit. Results The study found that out of 524 culture-positive specimens, 146 (28%) were NTM, with the predominant group being Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABC). All MAC isolates were fully susceptible to macrolides and aminoglycosides, while five MABC isolates carried mutations indicative of reduced susceptibility to macrolide and aminoglycoside drugs. Conclusions These findings suggest that clinicians may use macrolides and aminoglycosides to manage NTM infections caused by MAC, but further investigation is required to determine MABC drug susceptibility.

Background: The recent emergence of pan-drug-resistant (PDR) K. pneumoniae strains hinders the success rate of treatment procedures for patients. High mortality, extended duration of hospitalization with high costs is associated with such infections. Discovery and identification of new drugs are inevitable to combat PDR clinical pathogens. We aim to identify and evaluate new compounds in vitro against a PDR clinical K. pneumoniae isolate using compounds of Pathogen Box and Pandemic Response Box from Medicines for Malaria Venture (MMV). Methods: The PDR strain was initially screened with the 601 compounds from both Boxes at 10 ​μM concentration. Formation of dormant cells against the drug activity was assessed using persister assay. MIC was determined for the drugs inhibiting PDR K. pneumoniae during initial screening. Results: Five compounds were identified to inhibit the test strain. MMV1580854 (94.60 ​%), MMV1579788 (94.65 ​%), MMV1578574 (eravacycline; 93.13 ​%), MMV1578566 (epetraborole; 95.29 ​%) and MMV1578564 (96.32 ​%) were able to exhibit a higher percentage of growth inhibition. Persisters were found to be growing in a range from 104 to 107 ​CFU/ml. Minimum inhibitory concentrations (MIC) of all compounds were ≥ 2 ​μM except for MMV1579788, which had a MIC of ≥ 5 ​μM. Conclusion: Five novel compounds were identified against the highly evolved pan-drug-resistant K. pneumoniae. Among the five, epetraborole andMMV1578564 were identified as highly potent based on the persister frequency and MICs. The pan-drug resistant clinical isolate used in this study was found to be acting differently from the reference or wild type strains against the test compounds in a previous study.

Abstract Host genotype is important for enterotoxigenic E. coli (ETEC) susceptibility. We conducted two trials to evaluate the effect of CHCF1 genotype on incidence of ETEC diarrhea. In trial 1 (n = 15 pigs), pigs were inoculated with 108 CFU or 1010 CFU doses of an ETEC F4ac strain. In trial 2 (n = 33 pigs), pigs were inoculated with ETEC F4ab or F4ac. Across trials, all inoculated pigs that developed ETEC diarrhea were CHCF1 heterozygous susceptible (6/6). No inoculated CHCF1 homozygous resistant pigs developed ETEC diarrhea (0/26). Susceptibility towards ETEC F4ac/ab infection might correspond with CHCF1 genotype.

IntroductionThe association between the porcine pre-weaning gut microbiota composition and diversity, and subsequent post-weaning diarrhea (PWD) susceptibility is currently being studied. In this longitudinal study, we examined the association between pre-weaning fecal microbiome composition and diversity, and PWD development in a Danish sow herd.MethodsForty-five pigs were followed from birth until 7 days after weaning (post-natal day (PND) 33). At PND 33, the pigs were categorized as PWD cases or healthy controls based on fecal consistency. We compared their fecal microbiomes at PND 8, late lactation (PND 27) and 7 days post weaning (PND 33) using 16S rRNA V3 region high-throughput sequencing. At PND 27 and 33, we also weighed the pigs, assessed fecal shedding of hemolytic Escherichia coli by culture and characterized hemolytic isolates by ETEC virulence factors with PCR and by whole genome sequencing.ResultsA total of 25 out of 45 pigs developed PWD and one Enterotoxigenic E. coli strain with F18:LT:EAST1 virotype was isolated from most pigs. At PND 33, we found differences in beta diversity between PWD and healthy pigs (R2 = 0.027, p = 0.009) and that body weight was associated with both alpha and beta diversity. Pre-weaning fecal microbiome diversity did not differ between PWD and healthy pigs and we found no significant, differentially abundant bacteria between them.ConclusionIn the production herd under study, pre-weaning fecal microbiome diversity and composition were not useful indicators of PWD susceptibility.

The safe and reliable operation of autonomous agricultural vehicles requires an advanced environment perception system. An important component of perception systems is vision-based algorithms for detecting objects and other structures in the fields. This paper presents an ensemble method for combining outputs of three scene understanding tasks: semantic segmentation, object detection and anomaly detection in the agricultural context. The proposed framework uses an object detector to detect seven agriculture-specific classes. The anomaly detector detects all other objects that do not belong to these classes. In addition, the segmentation map of the field is utilized to provide additional information if the objects are located inside or outside the field area. The detections of different algorithms are combined at inference time, and the proposed ensemble method is independent of underlying algorithms. The results show that combining object detection with anomaly detection can increase the number of detected objects in agricultural scene images.

Abstract Background Control of schistosomiasis remains a priority in endemic areas. Local epidemiological data are necessary for a tailored control programme, including data on population behaviour in relation to the disease. The objective of this study was to assess schistosomiasis-related knowledge, attitudes and practices in the general population of Lambaréné, a small city in Gabon, in order to optimise the design and implementation of a local control programme that is tailored to need. Methods The study was cross-sectional in nature. Eligible adults and children living in the study area who volunteered (with informed consent) to participate in the study were interviewed using standardised questionnaires, one of which was a simplified version of the primary questionnaire for participants aged 6–13 years. Data on the participants’ knowledge, attitudes and practices that enhance the risk for contracting schistosomiasis were collected. Results A total of 602 participants were included. The mean (± standard deviation) age was 21.2 (± 15.0) years, the female:male gender ratio was 1.6 and 289 (48%) participants completed the simplified version the questionnaire. Of the 602 participants, 554 (92%) reported past or current contact with freshwater, 218 (36%) reported a history of a diagnosis of schistosomiasis and 193 (32%) reported past intake of praziquantel medication. The overall levels of knowledge and adequate attitudes toward schistosomiasis among young adults and adults were 68 and 73%, respectively. The proportion of participants pursuing risk-enhancing practices (REP) was 60% among the whole study population. Location was significantly associated with differences in knowledge and REP levels. A history of confirmed schistosomiasis and larger family size were significantly associated with an increase in good knowledge and REP levels. However, the indication of freshwater-associated activities was only associated with a significant increase in the REP level. Conclusions The results of this survey reveal a high level of population exposure to schistosomiasis, which is in line with known prevalence of schistosomiasis in Lambaréné and its surroundings. The local population has a reasonable level of knowledge of and adequate attitudes toward schistosomiasis but the level of REP is high, particularly in areas where piped water is absent. In terms of interventions, improving hygiene should have the highest priority, but in a context where provision of safe water is difficult to achieve, the effectiveness of praziquantel treatment and the education of at-risk populations on the need for protective behaviours should be a prominent feature of any local control programme. Graphical abstract

Transnational cooperation is a common strategy for addressing research and development (R&D) issues resulting from similar challenges that cut across administrative borders. Value chains for food and drinks are complex, and transdisciplinary work is recognised as a method for solving complex issues. The Northern Cereals project ran from 2015 to 2018, and its goal was to increase cereal production and the value of grain products in four regions in the Northern Periphery programme area. The project included both R&D, but the main emphasis was on development, and was carried out by transdisciplinary cooperation between R&D partners and small and medium-sized enterprises (SMEs). By reviewing the project’s methods, outcomes and composition, we discuss if a framework of transnational and transdisciplinary cooperation can help to develop the value chain from local barley to beer. We found that transnational cooperation was achieved successfully, that stakeholder involvement was crucial, but that academic disciplines such as marketing and innovation could have been included. In addition, we recognised that much work remains to further increase cereal production and the use of local grain in the Northern Periphery region, but believe that this project has laid a good foundation for further progress.

Abstract Background Sub-Saharan Africa carries most of the global burden of schistosomiasis. To optimize disease control and reduce morbidity, precise data are needed for control measures adapted to the local epidemiological situation. The objective of this study is to provide baseline information on schistosomiasis dynamics, including praziquantel (PZQ) treatment outcome in children and young adults living in the vicinity of Lambaréné, Gabon. Methods Eligible volunteers were included into a prospective longitudinal study. Urine filtration technique was used to detect eggs in urine for schistosomiasis diagnosis. Subjects were treated with 60 mg of PZQ once per month for three consecutive months, and the outcome was assessed by cure rate (CR) and egg reduction rate (ERR). Results A total of 328 volunteers were enrolled in the study with a mean (± SD) age of 12.2 ± 4.7 years-old. The female-to-male ratio was 0.99. Out of 258 participants in total, 45% had schistosomiasis during the survey and 43% presented with heavy infections. The incidences of haematuria and schistosomiasis were 0.11 and 0.17 person-years, respectively. After the first and third dose of PZQ, overall ERR of 93% and 95% were found, respectively; while the CR were 78% and 88%, respectively. Both ERR (100 vs 88%) and CR (90 vs 68%) were higher among females than males after the first dose. The CR increased for both groups after the third dose to 95% and 80%, respectively. After the first PZQ dose, ERR was higher for heavy compared to light infections (94 vs 89%), while the CR was higher for light than for heavy infections (87 vs 59%). After the third PZQ dose, ERR increased only for light infections to 99%, while CR increased to 98% and 75% for light and for heavy infections, respectively. The reinfection rate assessed at a mean of 44.6 weeks post-treatment was 25%. Conclusions The prevalence of schistosomiasis is moderate in communities living in the vicinity of Lambaréné, where a subpopulation with a high risk of reinfection bears most of the burden of the disease. To improve schistosomiasis control in this scenario, we suggest education of these high-risk groups to seek themselves a one-year PZQ treatment. Trial registration clinicaltrials.gov Identifier NCT 02769103. Registered 11 May 2016, retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT02769013

ESA provides Sentinel-1 synthetic aperture radar satellite data freely for research and industry. The Sentinel-1 data have shown the potential for remotely monitoring conditions in individual agricultural fields on a weekly basis. Researchers have access to the same Sentinel-1 dataset, so independent validation should be possible. Well documented studies performed with Sentinel-1 will allow other researchers the ability to reproduce the experiments and either validate or repudiate the presented findings. Based on the current state-of-the-art study, a web service was provided for the agricultural domain, which can be downloaded freely from Github. The running web service provides the ability to monitor local conditions by using the recorded Sentinel-1 information, combined with a priori knowledge from broad acre fields. Correlating the Sentinel-1 data to actual conditions related to a specific application is still a task that individual researchers must perform to utilize the service. In this paper, we present our methodology for converting the Sentinel-1 data to a form that is more accessible to researchers in the agricultural domain. Therefore, the goal of the current study was to make the Sentinel-1 data available efficiently, so that the experts in this field can focus on correlating and comparing it to reference data and measurements collected in the field. The function of the web service is illustrated with concrete application examples in the agricultural domain.

We report an experimental study on the gain of the Raman signal of aqueous mixtures and liquid water when confined in aerogel-lined capillaries of various lengths of up to 20 cm and various internal diameters between 530 and 1000 µm. The lining was made of hydrophobised silica aerogel, and the carrier capillary body consisted of fused silica or borosilicate glass. Compared to the Raman signal detected from bulk liquid water with the same Raman probe, a Raman signal 27 times as large was detected when the liquid water was confined in a 20 cm-long capillary with an internal diameter of 700 µm. In comparison with silver-lined capillaries of the same length and same internal diameter, the aerogel-lined capillaries featured a superior Raman signal gain and a longer gain stability when exposed to mixtures of water, sugar, ethanol and acetic acid.

Vertebrate macrophages are a highly heterogeneous cell population, but while Drosophila blood is dominated by a macrophage-like lineage (plasmatocytes), until very recently these cells were considered to represent a homogeneous population. Here, we present our identification of enhancer elements labelling plasmatocyte subpopulations, which vary in abundance across development. These subpopulations exhibit functional differences compared to the overall population, including more potent injury responses and differential localisation and dynamics in pupae and adults. Our enhancer analysis identified candidate genes regulating plasmatocyte behaviour: pan-plasmatocyte expression of one such gene (Calnexin14D) improves wound responses, causing the overall population to resemble more closely the subpopulation marked by the Calnexin14D-associated enhancer. Finally, we show that exposure to increased levels of apoptotic cell death modulates subpopulation cell numbers. Taken together this demonstrates macrophage heterogeneity in Drosophila, identifies mechanisms involved in subpopulation specification and function and facilitates the use of Drosophila to study macrophage heterogeneity in vivo.

Objectives Sierra Leone has one of the highest maternal mortality ratios in the world. Timely and well-coordinated referrals are necessary to reduce delays in providing adequate care for women with obstetric complications. This study describes factors affecting timely and adequate referral of women with obstetric complications in rural areas of Sierra Leone as viewed by health workers in rural health facilities.Design Qualitative research with semi-structured interviews using open-ended questions. Data were analysed by systematic text condensation.Setting Interviews were held in nine peripheral health units in rural Sierra Leone.Participants 19 health workers including nurses, midwives and clinical health officers participated in nine interviews.Results From the interviews, four major themes describing possible factors of delay in referral of women in need of emergency obstetric care emerged: (1) communication between healthcare workers; (2) underlying influences on decision-making; (3) women’s compliance to referral and (4) logistic constraints.Several factors in rural Sierra Leone are perceived to complicate timely and adequate referral of women in need of emergency obstetric care. Notable among these factors are fear among women for being referred and fear among healthcare workers for having maternal deaths or severe obstetric complications occurring at their own facilities. Furthermore, decision-making of healthcare workers whether to refer a woman or not is negatively influenced by a hierarchical culture with high power distance between healthcare workers.Conclusion Factors identified that complicate timely and adequate referral of women in need of emergency obstetric care must be considered in efforts to reduce maternal mortality. Possible interventions that may reduce delay in referral include increased communication by mobile phones between health workers for advice and feedback regarding referrals, involvement of influential stakeholders to increase women’s compliance to referral, and consistent use of standardised management protocols.

Sepsis has been recognised as a global health priority by the United Nations World Health Assembly, which adopted a resolution in 2017 to improve sepsis prevention, diagnosis, and management globally. This study investigated how sepsis is prioritised in Gabon. From May to November 2021, we conducted a qualitative study in healthcare stakeholders at the local, regional, and national levels. Stakeholders included the Ministry of Health (MOH), ethics/regulatory bodies, research institutions, academic institutions, referral hospitals, international funders, and the media. Twenty-three multisectoral stakeholders were interviewed. Respondents indicated that sepsis is not yet prioritised in Gabon due to the lack of evidence of its burden. They also suggest that the researchers should focus on linkages between sepsis and the countries’ existing health sector priorities to accelerate sepsis prioritisation in health policy. Stakeholder awareness and engagement might be accelerated by involving the media in the generation of communication strategies around sepsis awareness and prioritisation. There is a need for local, regional and national evidence to be generated by researchers and taken up by policymakers, focusing on linkages between sepsis and a country’s existing health sector priorities. The MOH should set sepsis reporting structures and develop appropriate sepsis guidelines for identification, management, and prevention.

The objective of this pilot malacological survey was to identify the snail intermediate hosts for Schistosoma haematobium in endemic rural and semi-urban areas of Gabon. Snails were collected, morphologically identified, and tested for infection by cercarial shedding. Released cercariae were morphologically identified using low-power light microscopy. A total of six species of snails were collected throughout the study area, with Bulinus truncatus, B. forskalii, and Potadoma spp. being the most predominant species collected. Only the Bulinus species were tested for infection by cercarial shedding, of which only B. truncatus shed cercariae. Some B. truncatus shed mammalian schistosome cercariae, while others shed Gymnocephalus cercariae. Our results indicate that B. truncatus appears to be a potential intermediate host of schistosomiasis in Gabon, where cases of S. haematobium, S. guineensis, and S. intercalatum infection are reported. However, it will be important to further understand the species diversity and transmission dynamics of schistosomes.

Anemia is a common condition in sow herds. We aimed to study the effects of severe iron deficiency during gestation on sow and piglet health outcomes with an experimental model for blood-removal-induced iron deficiency anemia. In total, 18 multiparous sows (8 in trial I and 10 in trial II) were allocated to either a blood removal group or a control group. Hematologic parameters were monitored at regular intervals and the tissue iron concentrations were measured for the sows and newborn piglets after farrowing. In trial I, the mean liver iron content was reduced to 46.7 µg/g in the blood removal sows compared to 252.6 µg/g in the controls (p < 0.001). In trial II, sows in the blood removal group had lower iron content in the liver (147.8 µg/g), kidney (46.3 µg/g) and spleen (326.5 µg/g) compared to the control sows (323.2 µg/g, 81.3 µg/g and 728.9 µg/g, respectively; p = 0.009, 0.016, 0.01, respectively). In trial I, piglets from sows in the blood removal group had significantly decreased hematocrit (Hct), red blood cells (RBC) and a tendency for reduced hemoglobin (Hb) compared to the control piglets. We established a blood removal model that resulted in mild- to severe degrees of sow anemia and reduced tissue iron stores at farrowing.

An amendment to this paper has been published and can be accessed via the original article.

Both routine and research tuberculosis (TB) laboratory capacity urgently need to be expanded in large parts of Sub-Saharan Africa. In 2009, the Centre de Recherches Médicales de Lambaréné (CERMEL) took a strategic decision to expand its activities by building TB laboratory capacity to address research questions and to improve routine diagnostic and treatment capacity. Over the past 7 years, a standard laboratory has been developed that is contributing significantly to TB diagnosis, treatment, and control in Gabon; training has also been provided for TB research staff in Central Africa. CERMEL has a cordial relationship with the Gabon National TB Control Programme (PNLT), which has culminated in a successful Global Fund joint application. This endeavour is considered a model for similar developments needed in areas of high TB prevalence and where TB control remains poor to date.

Sierra Leone has a high tuberculosis (TB) burden with a prevalence of 441 cases per 100 000 population. As a result of the Global Fund, some facilities in the country have access to improved diagnostics, including Xpert MTB/RIF testing, of particular use in diagnosing those at risk of drug resistance, in the form of rifampicin-resistant (RR) TB. This quality improvement project describes how a small, rural district general hospital in Masanga village improved the diagnosis of TB and RR-TB by creating a formal link with the regional hospital in Makeni city. In an effort to improve diagnosis, all patients with a suspicion of TB and one of the following would have a sample sent for Xpert MTB/RIF testing: previous TB treatment (of any course length), HIV positive or known contact of a RR-TB case. The samples were transported by the logistics team, who already drove weekly from Masanga to Makeni for supplies, and the results were texted to the clinician in charge of the medical ward. Over the course of the first 4 months of this intervention, 34 samples had Xpert MTB/RIF testing performed compared with two samples in the previous 12 months since the machine had been installed. This yielded nine additional diagnoses of TB (in patients with negative or unavailable smear results) and five diagnoses of RR-TB with subsequent appropriate isolation and transfer to the central tertiary centre. This study shows that it is feasible to centralise Xpert MTB/RIF testing in low-resource settings using creative methods for sample transfer and results dissemination, leading to both improved diagnostics and infection control.

BACKGROUND:Malaria burden remains high in the sub-Saharan region where helminths are prevalent and where children are often infected with both types of parasites. Although the effect of helminths on malaria infection is evident, the impact of these co-infections is not clearly elucidated yet and the scarce findings are conflicting. In this study, we investigated the effect of schistosomiasis, considering soil-transmitted helminths (STH), on prevalence and incidence of Plasmodium falciparum infection. METHODOLOGY:This longitudinal survey was conducted in school-age children living in two rural communities in the vicinity of Lambaréné, Gabon. Thick blood smear light microscopy, urine filtration and the Kato-Katz technique were performed to detect malaria parasites, S. haematobium eggs and, STH eggs, respectively. P. falciparum carriage was assessed at inclusion, and incidence of malaria and time to the first malaria event were recorded in correlation with Schistosoma carriage status. Stratified multivariate analysis using generalized linear model was used to assess the risk of plasmodium infection considering interaction with STH, and survival analysis to assess time to malaria. MAIN FINDINGS:The overall prevalence on subject enrolment was 30%, 23% and 9% for S. haematobium, P. falciparum infections and co-infection with both parasites, respectively. Our results showed that schistosomiasis in children tends to increase the risk of plasmodium infection but a combined effect with Trichuris trichiura or hookworm infection clearly increase the risk (aOR = 3.9 [95%CI: 1.7-9.2]). The incidence of malaria over time was 0.51[95%CI: 0.45-0.57] per person-year and was higher in the Schistosoma-infected group compared to the non-infected group (0.61 vs 0.43, p = 0.02), with a significant delay of time-to first-malaria event only in children aged from 6 to 10-years-old infected with Schistosoma haematobium. CONCLUSIONS:Our results suggest that STH enhance the risk for P. falciparum infection in schistosomiasis-positive children, and when infected, that schistosomiasis enhances susceptibility to developing malaria in young children but not in older children.

The Notch receptor is an evolutionarily highly conserved transmembrane protein essential to a wide spectrum of cellular systems, and its deregulation has been linked to a vast number of developmental disorders and malignancies. Regulated Notch function is critical for the generation of T-cells, in which abnormal Notch signaling results in leukemia. Notch activation through trans-activation of the receptor by one of its ligands expressed on adjacent cells has been well defined. In this canonical ligand-dependent pathway, Notch receptor undergoes conformational changes upon ligand engagement, stimulated by a pulling-force on the extracellular fragment of Notch that results from endocytosis of the receptor-bound ligand into the ligand-expressing cell. These conformational changes in the receptor allow for two consecutive proteolytic cleavage events to occur, which release the intracellular region of the receptor into the cytoplasm. It can then travel to the nucleus, where it induces gene transcription. However, there is accumulating evidence that other pathways may induce Notch signaling. A ligand-independent mechanism of Notch activation has been described in which receptor processing is initiated via cell-internal signals. These signals result in the internalization of Notch into endosomal compartments, where chemical changes existing in this microenvironment result in the conformational modifications required for receptor processing. This review will present mechanisms underlying both canonical ligand-dependent and non-canonical ligand-independent Notch activation pathways and discuss the latter in the context of Notch signaling in T-cells.

Runs of homozygosity (ROH) and genome wide association study (GWAS) were used to identify genomic regions of entropion in Austrian Fleckvieh cattle. Entropion is an eye disorder where the eye lids turn inward, causing inflammations, cornea damage or even blindness if left untreated. A total of 196 bulls genotyped by BovineSNP50 BeadChip were analysed, nine of which had the disorder confirmed by a veterinarian, ten were unconfirmed and 177 were healthy control animals. Runs of homozygosity analysis highlighted regions on seven chromosomes where the proportion of animals in ROH significantly (p

Rapid robotic system development has created a demand for multi-disciplinary methods and tools to explore and compare design alternatives. In this paper, we present a collaborative modeling technique that combines discrete-event models of controller software with continuous-time models of physical robot components. The proposed co-modeling method utilizes the Vienna development method (VDM) and MATLAB for discrete-event modeling and 20-sim for continuous-time modeling. The model-based development of a mobile robot mink feeding system is used to illustrate the collaborative modeling method. Simulations are used to evaluate the robot model output response in relation to operational demands. An example of a load-carrying challenge in relation to the feeding robot is presented, and a design space is defined with candidate solutions in both the mechanical and software domains. Simulation results are analyzed using design space exploration (DSE), which evaluates candidate solutions in relation to preselected optimization criteria. The result of the analysis provides developers with an overview of the impacts of each candidate solution in the chosen design space. Based on this overview of solution impacts, the developers can select viable candidates for deployment and testing with the actual robot.

Craniofacial development is orchestrated by transcription factor-driven regulatory networks, epigenetic modifications, and signaling pathways. Signaling molecules and their receptors rely on endo-lysosomal trafficking to prevent accumulation on the plasma membrane. ESCRT (Endosomal Sorting Complexes Required for Transport) machinery is recruited to endosomal membranes enabling degradation of such endosomal cargoes. Studies in vitro and in invertebrate models established the requirements of the ESCRT machinery in membrane remodeling, endosomal trafficking, and lysosomal degradation of activated membrane receptors. However, investigations during vertebrate development have been scarce. By ENU-induced mutagenesis, we isolated a mouse line, Vps25ENU/ENU, carrying a hypomorphic allele of the ESCRT-II component Vps25, with craniofacial anomalies resembling features of human congenital syndromes. Here, we assessed the spatiotemporal dynamics of Vps25 and additional ESCRT-encoding genes during murine development. We show that these genes are ubiquitously expressed although enriched in discrete domains of the craniofacial complex, heart, and limbs. ESCRT-encoding genes, including Vps25, are expressed in both cranial neural crest-derived mesenchyme and epithelium. Unlike constitutive ESCRT mutants, Vps25ENU/ENU embryos display late lethality. They exhibit hypoplastic lower jaw, stunted snout, dysmorphic ear pinnae, and secondary palate clefting. Thus, we provide the first evidence for critical roles of ESCRT-II in craniofacial morphogenesis and report perturbation of NOTCH signaling in craniofacial domains of Vps25ENU/ENU embryos. Given the known roles of NOTCH signaling in the developing cranium, and notably the lower jaw, we propose that the NOTCH pathway partly mediates the craniofacial defects of Vps25ENU/ENU mouse embryos.

The ~2,000-km-long Central Range of New Guinea is a hotspot of modern carbon sequestration due to the chemical weathering of igneous rocks with steep topography in the warm wet tropics. These high mountains formed in a collision between the Australian plate and ophiolite-bearing volcanic arc terranes, but poor resolution of the uplift and exhumation history has precluded assessments of the impact on global climate change. Here, we develop a palinspastic reconstruction of the Central Range orogen with existing surface geological constraints and seismic data to generate time-temperature paths and estimate volumes of eroded material. New (U-Th)/He thermochronology data reveal rapid uplift and regional denudation between 10 and 6 Mya. Erosion fluxes from the palinspastic reconstruction, calibrated for time with the thermochronological data, were used as input to a coupled global climate and weathering model. This model estimates 0.6 to 1.2 °C of cooling associated with the Late Miocene rise of New Guinea due to increased silicate weathering alone, and this CO2 sink continues to the present. Our data and modeling experiments support the hypothesis that tropical arc-continent collision and the rise of New Guinea contributed to Neogene cooling due to increased silicate weathering.

There are multiple factors that contribute to the warpage problems where molten part is distorted during solidification in rotational molding. A novel warpage simulation model is developed accounting for the effect of various process parameters like crystallinity change, temperature-dependent polymer properties, and cooling rate. The polymer material properties were readily not available; they were constructed from literature data with adaptation to the process condition and their significance on simulation results is discussed in detail. A systematic detailed simulation analysis of warpage in box part was done and results were compared with experimental values published in literature. The warpage magnitude under seven different cooling methods are presented. It was found that externally water cooled parts exhibited maximum warpage which is also corroborated by literature data while the parts cooled by water on either sides of the part show reduction in warpage. The warpage simulation results show an agreement with deviation ranging from 1.2% to 69% with experimental values. Highlights * A novel thermal expansion coefficient approach was adopted for the first time to develop warpage simulation of rotationally moulded parts. * Inclusion of temperature-dependent thermo-mechanical properties of polymer in the simulation model. * The cooling rate is directly proportional to the warpage in the parts. * Validating warpage simulation results for seven different cooling methods with experimental measurements. * Maximum warpage is seen where the highest temperature difference exists between part and mould. KEYWORDS process parameters, rotational molding, shrinkage, simulation, warpage, 1 | INTRODUCTION Control and prediction of warpage problem in rotational molding (1) of polymer parts is long overdue. All thermoplastic processing methods inevitably include heating the polymer to the [...]

Optimal nutrition is important after preterm birth to facilitate normal brain development. Human milk is rich in sialic acid and preterm infants may benefit from supplementing formula with sialyllactose to support neurodevelopment. Using pigs as models, we hypothesized that sialyllactose supplementation improves brain development after preterm birth. Pigs (of either sex) were delivered by cesarean section at 90% gestation and fed a milk diet supplemented with either an oligosaccharide-enriched whey with sialyllactose (n = 20) or lactose (n = 20) for 19 days. Cognitive performance was tested in a spatial T-maze. Brains were collected for ex vivo magnetic resonance imaging (MRI), gene expression, and sialic acid measurements. For reference, term piglets (n = 14) were artificially reared under identical conditions and compared with vaginally born piglets naturally reared by the sow (n = 12). A higher proportion of sialyllactose supplemented preterm pigs reached the T-maze learning criteria relative to control preterm pigs (p < 0.05), and approximated the cognition level of term reference pigs (p < 0.01). Furthermore, supplemented pigs had upregulated genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in hippocampus. Sialyllactose supplementation did not lead to higher levels of sialic acid in the hippocampus or change MRI endpoints. Contrary, these parameters were strongly influenced by postconceptional age and postnatal rearing conditions. In conclusion, oligosaccharide-enriched whey with sialyllactose improved spatial cognition, with effects on hippocampal genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in preterm pigs. Dietary sialic acid enrichment may improve brain development in infants.

IntroductionThere are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100.MethodsParticipant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed.ResultsThe mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI).DiscussionAmong the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.