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The future of spatial epidemiology in the AI era: enhancing machine learning approaches with explicit spatial structure.
Spatial epidemiology, defined as the study of spatial patterns in disease burdens or health outcomes, aims to estimate disease risk or incidence by identifying geographical risk factors and populations at risk (Morrison et al., 2024). Research in spatial epidemiology relies on both conventional approaches and Machine- Learning (ML) algorithms to explore geographic patterns of diseases and identify influential factors (Pfeiffer & Stevens, 2015). Traditional spatial techniques, including spatial autocorrelation using global Moran's I, Geary's C (Amgalan et al., 2022), and Ripley's K Function (Kan et al., 2022), Local Indicators of Spatial Association (LISA) (Sansuk et al., 2023), hotspot analysis by Getis-Ord Gi* (Lun et al., 2022), spatial lag models (Rey & Franklin, 2022), and Geographically Weighted Regression (GWR) (Kiani et al., 2024) are designed to explicitly incorporate the spatial structure of data into spatial modelling, often referred to as spatially aware models (Reich et al., 2021). Beyond these models, several other spatially aware approaches that have been widely applied in epidemiological studies include but are not limited to Bayesian spatial models that account for spatial uncertainty in disease mapping, such as Bayesian Hierarchical models, Conditional Autoregressive (CAR), and Besage, York, and Mollie' (BYM) models (Louzada et al., 2021). Bayesian methods are statistically rigorous techniques that assume neighboring regions share similar values. Kulldorff's Spatial Scan Statistic is another traditional spatial technique that uses a moving circular window to extract significant disease clusters (Tango, 2021). Moreover, geostatistical models such as Kriging and Inverse Distance Weighting (IDW) allow for continuous spatial interpolation of health data (Nayak et al., 2021). [...].
The Ebola Data Platform: A prospective, standardised, clinical dataset collected during the 2013-2016 West African Ebola outbreak.
The Ebola Data Platform (EDP) was developed to strengthen knowledge and capacity across health, research, and humanitarian communities to reduce the impact of Ebola through responsible data use. This collaborative initiative was established by West African governments, NGOs, academic organisations, and intra-governmental health organisations directly involved in the 2013-2016 West African Ebola outbreak. The platform was established to provide a centralised, standardised dataset of individual patient data collected during the outbreak for the purpose of research to improve Ebola treatment and control, and includes over 13,600 patient records of individuals infected and treated from 22 different Ebola treatment centres across Guinea, Sierra Leone, Liberia, and Nigeria. Patient data are available from treatment centre triage and admission, inpatient clinical observations, and outcomes, with outpatient follow-up available for some datasets. Data include signs and symptoms, pre-existing comorbidities, vital signs, laboratory testing, treatments, complications, dates of admission and discharge, mortality, viral strains, and other data. This publication describes characteristics of the EDP dataset, its architecture, methods for data access and tools for utilising the dataset.
Evaluating prediction of short-term tolerability of five type 2 diabetes drug classes using routine clinical features: UK population-based study
Aims: A precision medicine approach in type 2 diabetes (T2D) needs to consider potential treatment risks alongside established benefits for glycaemic and cardiometabolic outcomes. Considering five major T2D drug classes, we aimed to describe variation in short-term discontinuation (a proxy of overall tolerability) by drug and patient routine clinical features and determine whether combining features in a model to predict drug class-specific tolerability has clinical utility. Materials and Methods: UK routine clinical data (Clinical Practice Research Datalink, 2014–2020) of people with T2D initiating glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP4i), sodium-glucose co-transporter-2 inhibitors (SGLT2i), thiazolidinediones (TZD) and sulfonylureas (SU) in primary care were studied. We first described the proportions of short-term (3-month) discontinuation by drug class across subgroups stratified by routine clinical features. We then assessed the performance of combining features to predict discontinuation by drug class using a flexible machine learning algorithm (a Bayesian Additive Regression Tree). Results: Amongst 182 194 treatment initiations, discontinuation varied modestly by clinical features. Higher discontinuation on SGLT2i and GLP-1RA was seen for older patients and those with longer diabetes duration. For most other features, discontinuation differences were similar by drug class, with higher discontinuation for patients who had previously discontinued metformin, females and people of South-Asian and Black ethnicities. Lower discontinuation was seen for patients currently taking statins and blood pressure medication. The model combining all sociodemographic and clinical features had a low ability to predict discontinuation (AUC = 0.61). Conclusions: A model-based approach to predict drug-specific discontinuation for individual patients with T2D has low clinical utility. Instead of likely tolerability, prescribing decisions in T2D should focus on drug-specific side-effect risks and differences in the glycaemic and cardiometabolic benefits of available medication classes.
Temporal correlations between RBD-ACE2 blocking and binding antibodies to SARS-CoV-2 variants in CoronaVac-vaccinated individuals and their persistence in COVID-19 patients.
Antibodies play a crucial role in protection against SARS-CoV-2. Understanding the correlation between binding and functional antibodies is essential to determine whether binding antibody levels can reliably predict neutralizing activity. We assessed antibody responses in 111 individuals vaccinated with the inactivated vaccine CoronaVac and 111 COVID-19 patients in Thailand. Plasma levels of ACE2-blocking antibodies targeting the receptor-binding domain (RBD) of SARS-Co-V2 variants were measured before vaccination and at 14 and 28 days after the second dose using a multiplex surrogate virus neutralization test. Anti-spike and anti-nucleocapsid antibodies were quantified by electrochemiluminescence immunoassay, and anti-RBD IgG by ELISA. After vaccination, blocking, anti-spike, and IgG antibody levels increased but declined rapidly within a month, whereas antibody levels in COVID-19 patients increased and persisted. Blocking and anti-spike antibody correlated at day 14 post-vaccination but not at day 28. In COVID-19 patients, correlations were moderate at day 14, and stronger at day 28. Correlations were weaker for Omicron subvariants than for the ancestral strain and non-Omicron variants. The weak correlation between blocking and anti-RBD IgG suggests binding antibodies might not predict neutralizing activity. These findings highlight the temporal nature of CoronaVac-induced immunity and the need for booster doses and variant-adapted vaccine.
Combined effects of hydrological conditions and socioeconomic factors on the seasonal dynamics of severe fever with thrombocytopenia syndrome in China, 2011–2022: a modelling study
Background: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral hemorrhagic fever with expanding geographical range. The determinants of the seasonal dynamics of SFTS remain poorly understood. Methods: Monthly SFTS cases from 604 counties in five provinces with high-notification rate in China (2011–2022) were analyzed using hierarchical Bayesian spatiotemporal and distributed lag nonlinear models. Cumulative and month-specific effects of meteorological factors were assessed, with socioeconomic factors as modifiers. Findings: The cumulative effect peaked at 21.97 °C (RR = 1.24, 95% CI: 1.10–1.40) and the month-specific effect peaked at 25.67 °C (RR = 1.38, 95% CI: 1.26–1.51) without time lag. Increased precipitation significantly amplified the risk of SFTS with a notable lag effect observed. Both drought and wet conditions heightened the risk of SFTS occurrence substantially, with cumulative RR peaking at 3.13 (95% CI: 1.58–6.23) for Standardized Precipitation Evapotranspiration Index (SPEI-1) of −2.5, indicating drought conditions, and peaking at 1.51 (95% CI: 1.00–2.27) for SPEI-1 of 2.16, indicating wet conditions. The highest month-specific RR was observed at an SPEI-1 of −2.5 with a 2-month lag and at 1.81 with a 1-month lag, respectively. The risk of SFTS was higher in low-urbanization areas during drought, while was higher in high-urbanization areas with wet conditions. Interpretation: Climatic factors significantly influence SFTS dynamics, with socioeconomic conditions modifying these effects. Integrating climate factors into surveillance and early warning systems is essential for targeted prevention and control. Funding: National Natural Science Foundation of China (No. 82330103 and No. 42201497), Youth Innovation Promotion Association (No. 2023000117), and the Wellcome Trust [220211].
Safety and efficacy of single-dose primaquine to interrupt Plasmodium falciparum malaria transmission in children compared with adults: a systematic review and individual patient data meta-analysis.
BACKGROUND: Adding a single dose of primaquine to artemisinin-based combination therapy (ACT) for the treatment of falciparum malaria can reduce the transmission of Plasmodium falciparum and could limit the spread of artemisinin partial resistance, including in Africa, where the disease burden is greatest. We aimed to compare the safety and efficacy of single-dose primaquine plus ACT between young children (aged <5 years) and older children (aged 5 years to <15 years) and adults (aged ≥15 years), and between low and moderate-to-high transmission areas. METHODS: For this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, OpenGrey.eu, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform, from database inception to April 3, 2024, with no language restrictions. We included prospective studies on efficacy against falciparum malaria that enrolled at least one child younger than 15 years and involved a study group given a single dose of primaquine (≤0·75 mg/kg) plus ACT. Studies involving mass drug administration, healthy volunteers, or patients with severe malaria or mixed (with non-falciparum) infections were excluded. For inclusion in the efficacy analysis, data on transmission potential (as determined by gametocytaemia, infectivity, or both) at enrolment and follow-up (day 3, day 7, or day 14) were required; the safety analysis required data on haemoglobin concentrations or haematocrit values at enrolment and at one or more follow-up visits by day 7, any data on adverse events, or both. After independent screening of the search results by two reviewers, the investigators of eligible studies were invited to contribute individual patient data. We quantified day 7 gametocyte carriage, probability of infecting a mosquito, decreases (>25%) in haemoglobin concentration associated with anaemia, and adverse events until day 28 using regression analyses, with random study-site intercepts to account for clustered data. These analyses were registered with PROSPERO, CRD42021279363 (safety) and CRD42021279369 (efficacy). FINDINGS: Of 5697 records identified by the search, 30 studies were eligible for analysis. Of these, individual patient data were shared for 23 studies, including 6056 patients from 16 countries: 1171 (19·3%) young children (aged <5 years), 2827 (46·7%) older children (aged 5 years to <15 years), and 2058 (34·0%) adults (aged ≥15 years). Adding a single low dose of primaquine (0·2-0·25 mg/kg) to ACTs reduced day 7 gametocyte positivity (adjusted odds ratio [aOR] 0·34, 95% CI 0·22-0·52; p<0·001) and infectivity to mosquitoes over time (aOR per day 0·02, 0·01-0·07, p<0·001). No difference was found in the effect of single low-dose primaquine both on gametocyte positivity in young children compared with older children (1·08, 0·52-2·23; p=0·84) and adults (0·50, 0·20-1·25; p=0·14) and between low-transmission and moderate-to-high transmission settings (1·07, 0·46-2·52; p=0·86), and on infectivity to mosquitoes in young children compared with older children (1·36, 0·07-27·71; p=0·84) and adults (0·31, 0·01-8·84; p=0·50) and between low-transmission and moderate-to-high transmission settings (0·18, 0·01-2·95; p=0·23). Gametocyte clearance was also similar for different ACTs (dihydroartemisinin-piperaquine vs artemether-lumefantrine) when combined with a primaquine target dose of 0·25 mg/kg (1·56, 0·65-3·79; p=0·32 at day 7). However, patients given a primaquine dose of less than 0·2 mg/kg with dihydroartemisinin-piperaquine were more likely to have gametocytaemia than those treated with artemether-lumefantrine (5·68, 1·38-23·48; p=0·016 at day 7). There was no increase in anaemia-associated declines in haemoglobin concentration (>25%) at a primaquine dose of 0·25 mg/kg, regardless of age group, transmission setting, and glucose-6-phosphate dehydrogenase status. The risks of adverse events of grade 2 or higher and of serious adverse events were similar between primaquine and no-primaquine groups, including in young children. INTERPRETATION: Regardless of malaria transmission intensity and age group, a single dose of 0·25 mg/kg primaquine is safe and efficacious for reducing P falciparum transmission. These findings underscore the need for primaquine formulations suitable for young children, and also provide supportive evidence to expand the use of single low-dose primaquine in regions with a moderate-to-high transmission rate that are threatened by artemisinin partial resistance. FUNDING: The EU and the Bill & Melinda Gates Foundation.
History of scrub typhus in Indonesia.
Scrub typhus is a common but underrecognized cause of fever in the Asia-Pacific region. This review is the first to examine the history of scrub typhus in the context of notable historical events in Indonesia. Scrub typhus was first observed in 1902 and has since been documented through colonial and modern times. However, the available evidence is sparse. This lack of data is influenced by wider factors, including geopolitical climate and socio-economic factors. During the colonial era and World War II, research focused on economic and military interests. There were research gaps during the unstable period following independence in 1945. More research commenced only in the 1970s, mainly under the auspices of the Ministry of Health. Since 2000, there have been sporadic attempts to study scrub typhus on several major islands (Java, Sumatra, Sulawesi, Borneo, Bali). We found 51 relevant articles documenting the presence of the pathogen and its vectors, with only a single case confirmed with standard laboratory testing. This lack of data, combined with low awareness and diagnostic capacity, makes it difficult for policymakers to appreciate the impact of scrub typhus. Indonesia needs sustainable and continuous surveillance systems, infrastructure and research funding to ensure diseases of public health importance are not neglected.
Understanding the primary healthcare context in rural South and Southeast Asia: a village profiling study.
BACKGROUND: Understanding contextual factors is critical to the success of health service planning and implementation. However, few contextual data are available at the village level in rural South and Southeast Asia. This study addressed the gap by profiling representative villages across seven sites in Thailand (n=3), Cambodia, Laos, Myanmar and Bangladesh. METHODS: Key informant surveys supplemented by other information sources were used to collect data from 687 villages on four key indicators (literacy rate, and percentages of attended deliveries, fully immunised children and latrine coverage), as well as access to various services. Data were analysed descriptively. RESULTS: Sites varied considerably. Five were highly diverse ethno-culturally and linguistically, and all relied on primary health centres and village health/malaria workers as the main providers of primary healthcare. These were generally bypassed by severely ill patients for urban first-level referral hospitals and private sector facilities. While >75% of villages were near primary schools, educational attainment was generally low. Over 70% of villages at each site had mobile phone coverage and availability of electricity was high (≥65% at all sites bar Myanmar). CONCLUSION: These results illustrate the similarities and differences of villages in this region that must be considered in public health research and policymaking.
Comparing HemoCue® and Quantitative Buffy Coat® and Coulter Counter-measured haemoglobin concentrations in African children with acute uncomplicated malaria: a Bland-Altman analysis.
BACKGROUND: Anaemia is a deleterious consequence of malaria, and its accurate diagnosis is crucial for effective management. However, laboratory methods for measuring haemoglobin (Hb) concentration, like the Coulter Counter and the Quantitative Buffy Coat® (QBC®), are costly and not widely accessible in resource-limited settings. The point-of-care HemoCue® test is a cheaper alternative and suitable in rural areas. The study aimed to determine the level of agreement between Coulter Counter/QBC® vs. HemoCue®-measured Hb concentrations by Bland-Altman analysis. METHODS: As part of a randomized, placebo-controlled trial of single low-dose primaquine in Ugandan and Congolese children with acute uncomplicated Plasmodium falciparum malaria, Hb concentrations were measured on days 0, 3, 7, and 28 using Coulter Counter (Uganda, n = 1880 paired values), QBC® (DR Congo, n = 1984 paired values) and HemoCue® Hb-301™. The predefined clinically acceptable limits were set at ± 0.5 g/dL. RESULTS: The Bland-Altman analysis showed that the HemoCue® minus Coulter Counter mean Hb difference was - 0.15 g/dL with lower and upper limits of agreement of - 3.68 g/dL and 3.39 g/dL, respectively. Corresponding HemoCue® minus QBC® values were - 0.23 g/dL, - 1.66 g/dL and 1.22 g/dL. Linear regression of Hb concentration differences vs. mean Hb concentrations showed negative correlations: r = - 0.43 and r = - 0.34 for HemoCue® vs. Coulter Counter and HemoCue® vs. QBC®, respectively. CONCLUSIONS: Compared to Coulter and QBC®, mean HemoCue® measured Hb concentrations were lower and, compared to the Coulter or QBC® methods, had an overall tendency to measure lower Hb concentrations with increasing Hb concentrations. Upper and lower limits of agreement were wider than the predefined clinically acceptable limits of ± 0.5 g/dL. HemoCue® should be used with caution in settings where decisions about blood transfusions are made.
Sustainable antimicrobial resistance surveillance: time for a global funding mechanism.
Antimicrobial resistance (AMR) is predicted to outstrip malaria, HIV, and tuberculosis combined as the leading infectious cause of death by 2050. Strengthening the knowledge and evidence base for AMR with surveillance and research is one of the five main objectives of the WHO Global Action Plan on AMR. While recent efforts to strengthen diagnosis and surveillance have been encouraging, these are unlikely to be sustainable without continued funding support in most low-resource settings. We estimated the continued costs of a standard national AMR surveillance system in low-income and middle-income countries (LMICs). For 46 LMICs, the costs would account for more than 2% of their total domestic general government health expenditure (GGHE-D), and for 28 of these countries, the costs are more than 5% of their total GGHE-D. This high cost is not sustainable without a long-term global financing mechanism.
Antiviral efficacy of fluoxetine in early symptomatic COVID-19: an open-label, randomised, controlled, adaptive platform trial (PLATCOV).
BACKGROUND: The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro, and observational and clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended in therapeutic guidelines and their antiviral activity in vivo has not been characterised. METHODS: PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. We recruited low-risk adult outpatients aged 18-50 with early symptomatic COVID-19 (symptoms <4 days) between 5 April 2022 and 8 May 2023. Patients were assigned using block randomisation to one of eleven treatment arms including oral fluoxetine (40 mg/day for 7 days), or no study drug. Uniform randomisation ratios were applied across the active treatment groups while the no study drug group comprised ≥20% of patients at all times. The primary endpoint was the rate of oropharyngeal viral clearance assessed until day 7. Measurements were taken daily between days 0 and 7 and analysed in a modified intention-to-treat population (>2 days follow-up).The viral clearance rate was estimated under a Bayesian hierarchical linear model fitted to the log10 viral densities measured in standardised duplicate oropharyngeal swab eluates taken daily over one week (18 measurements per patient). Secondary endpoints were all-cause hospital admission at 28 days, and time to resolution of fever and symptoms. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907). FINDINGS: 271 patients were concurrently randomised to either fluoxetine (n = 120) or no study drug (n = 151). All patients had received at least one COVID-19 vaccine dose and 67% were female (182/271). In the primary analysis, viral clearance rates following fluoxetine were compatible with a small or no increase relative to the no study drug arm (15% increase; 95% credible interval (CrI): -2 to 34%). There were no deaths or hospitalisations in either arm. There were no significant differences in times to symptom resolution or fever clearance between the fluoxetine and the no study drug arms (although only a quarter of patients were febrile at baseline). Fluoxetine was well tolerated, there were no serious adverse events and only one grade 3 adverse event in the intervention arm. INTERPRETATION: Overall, the evidence from this study is compatible with fluoxetine having a weak in vivo antiviral activity against SARS-CoV-2, although the primary endpoint is also compatible with no effect. This level of antiviral efficacy is substantially less than with other currently available antiviral drugs. FUNDING: Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator.
Advancing artemisinin resistance monitoring using a high sensitivity ddPCR assay for Pfkelch13 mutation detection in Asia.
The spread of Pfkelch13 mutations in Southeast Asia threatens the effectiveness of artemisinin-based combination therapies (ACTs) for malaria. Previous studies revealed a high prevalence of key mutations, including C580Y, P574L, and R561H, emphasizing the need for the surveillance to combat drug resistance. This study, we developed a droplet digital PCR (ddPCR) assay for the rapid screening of common mutations including P441L, Y493H, P527H, G538V, R539T, I543T, R561H, P574L, C580Y, and A675V. The assay was designed to detect minor populations of mutant strain within multiple infection, offering high sensitivity and specificity using artificial mixtures of mutant and wild-type alleles. Field samples collected in Thailand during 2015-2020 and in 2023 (N = 130) were also analyzed to validate the assay in a real-world setting. The ddPCR assay demonstrated exceptional performance, with 100% sensitivity and 90% specificity. The R539T, R561H, and C580Y mutations were detected in clinical samples collected from several study sites in Thailand. Notably, the R561H mutation was detected in 100% of the P. falciparum isolates from Mae Hong Son, Thailand in 2023, underscoring the assay's utility in identifying critical mutations associated with drug resistance. Moreover, ddPCR can detect multiple parasite populations in clinical samples and can be used to analyze the ratios of wild-type and mutant alleles. These results validate the assay's ability to serve as a powerful tool for the early detection of minor allele frequencies, facilitating the timely implementation of interventions to curb the spread of ACT resistance. The ddPCR assays developed in this study provide a sensitive and specific method for detecting Pfkelch13 mutations, allowing the identification of minor parasite populations with artemisinin resistance. These assays enhance our ability to monitor and respond to malaria drug resistance, offering a crucial tool for early detection and contributing to global malaria elimination efforts.
Leptospirosis, melioidosis, and rickettsioses in the vicious circle of neglect.
The global priorities in the field of infectious diseases are constantly changing. While emerging viral infections have regularly dominated public health attention, which has only intensified after the COVID-19 pandemic, numerous bacterial diseases have previously caused, and continue to cause, significant morbidity and mortality-deserving equal attention. Three potentially life-threatening endemic bacterial diseases (leptospirosis, melioidosis, and rickettsioses) are a huge public health concern especially in low- and middle-income countries. Despite their continued threat, these diseases do not receive proportionate attention from global health organizations and are not even included on the WHO list of neglected tropical diseases (NTDs). This, in turn, has led to a vicious circle of neglect with continued, yet conceivably preventable, hospitalizations and deaths each year especially in the vulnerable population. This is a call from a group of multi-institutional experts on the urgent need to directly address the circle of neglect and raise support in terms of funding, research, surveillance, diagnostics, and therapeutics to alleviate the burden of these 3 diseases.
Experiences, perceptions and ethical considerations of the malaria infection study in Thailand.
BACKGROUND: Thailand has made significant progress in malaria control efforts in the past decade, with a decline in the number of reported cases. However, due to cross-border movements over the past 5 years, reported malaria cases in Thailand have risen. The Malaria Infection Study in Thailand (MIST) involves deliberate infection of healthy volunteers with Plasmodium vivax malaria parasites, and the assessment of the efficacy of potential vaccine and drug candidates in order to understand acquired protection against malaria parasites. METHODS: This paper drew from ethics and social science qualitative study called MIST-ETHICS embedded within the MIST studies. MIST-ETHICS aimed to describe and understand the experiences, perceptions and ethical considerations of the MIST studies. Data were obtained from semi-structured interviews and a focus group discussion. A total of 46 participants participated in MIST-ETHICS . RESULTS: Three major themes emerged: experiences and perceptions of MIST, reasons for joining MIST, and ethical considerations. We found that although compensation was a motivation for participation, this was secondary to it being beneficial to self (health checks; link to health networks; building merit) and others (medical research contribution; altruism). Participants expressed varied opinions regarding the requirement of a university degree as one of the inclusion criteria for MIST. CONCLUSIONS: Our study revealed widespread concerns about long-term health effects and safety. Ethical considerations, including obtaining valid informed consent and ensuring participant inclusivitiy, were deem essential. Despite some debate regarding eligibility criteria, most participants agreed that the informed consent process was robust, accompanied by a strong sense of responsibility to contribute to the greater good. We emphasize the importance of continuously gathering participants' feedback for quality control, such as improving information materials to clarify the purpose of initial phases, their contributing to later phases, and the rationale behind each selection criterion. TRIAL REGISTRATION: This manuscript is part of the clinical trials registered under ClinicalTrials.gov IDs NCT04083508 (MIST1) registered on 5 Sep 2019 and NCT05071079 (MIST2) registered on 28 July 2021. However, the manuscript pertains to a qualitative study that does not require trial registration.
Bringing the real world into the classroom through team-based live brief projects
Team-based project work in higher education provides opportunities to enhance collaborative learning, to strengthen students' academic skills in a work-related context, and to instil valuable transferable skills that relate to the modern workplace. This chapter explores existing literature on live briefs, their relevance to graduate employability, and how the involvement of external stakeholders can bring real-world experience into the classroom as part of a social constructivist approach to learning. Alongside an analysis of the different approaches documented in the literature, Live Brief examples are presented from a final-year undergraduate Computing and Software Engineering learning context within a higher education Institution based in England. The pedagogical underpinnings, benefits, ethical considerations, and challenges of live briefs are discussed along with other factors such as the value of student-staff-stakeholder partnerships, the importance of collaboration between academia and industry, potential applications of Generative Artificial Intelligence (GenAI), and the power of Social and Emotional Learning (SEL) through engagement with social issues.
Population genomics and transcriptomics of Plasmodium falciparum in Cambodia and Vietnam uncover key components of the artemisinin resistance genetic background.
The emergence of Plasmodium falciparum parasites resistant to artemisinins compromises the efficacy of Artemisinin Combination Therapies (ACTs), the global first-line malaria treatment. Artemisinin resistance is a complex genetic trait in which nonsynonymous SNPs in PfK13 cooperate with other genetic variations. Here, we present population genomic/transcriptomic analyses of P. falciparum collected from patients with uncomplicated malaria in Cambodia and Vietnam between 2018 and 2020. Besides the PfK13 SNPs, several polymorphisms, including nonsynonymous SNPs (N1131I and N821K) in PfRad5 and an intronic SNP in PfWD11 (WD40 repeat-containing protein on chromosome 11), appear to be associated with artemisinin resistance, possibly as new markers. There is also a defined set of genes whose steady-state levels of mRNA and/or splice variants or antisense transcripts correlate with artemisinin resistance at the base level. In vivo transcriptional responses to artemisinins indicate the resistant parasite's capacity to decelerate its intraerythrocytic developmental cycle (IDC), which can contribute to the resistant phenotype. During this response, PfRAD5 and PfWD11 upregulate their respective alternatively/aberrantly spliced isoforms, suggesting their contribution to the protective response to artemisinins. PfRAD5 and PfWD11 appear under selective pressure in the Greater Mekong Sub-region over the last decade, suggesting their role in the genetic background of the artemisinin resistance.
Community responses to a novel house design: A qualitative study of "Star Homes" in Mtwara, southeastern Tanzania.
INTRODUCTION: To evaluate the impact of a novel design "Star Home" on the incidence of malaria, respiratory tract infections and diarrheal diseases among children, randomly selected households in Mtwara, Tanzania were offered a free, new Star Home. Drawing on longitudinal qualitative research that accompanied the Star Homes study, this article describes the experiences of residents and the wider community of living with these buildings. METHODS: A total of four rounds of face-to-face interviews were undertaken with residents of Star Homes (n = 37), control (wattle/daub) homes (n = 21), neighboring households n = 6), community members (n = 17) and community leaders (n = 6). The use of Star Homes was also observed over these four time periods between 2021 and 2023. Interviews were conducted in Swahili, transcribed, and translated into English for thematic analysis. RESULTS: Star Homes residents appreciated several aspects of the Star Homes, including overall comfort, access to water and electricity, and clean toilets. There were concerns about some design elements, such as poorly closing doors, stoves perceived as inefficient, and the façade, which was susceptible to rainwater ingress. The houses were not always used as intended by their developers, for example, residents were sleeping downstairs instead of upstairs because of cold floors or difficulties using the stairs. Star Homes residents described how the structures triggered praise but also envy from other community members. CONCLUSIONS: The findings highlight the need for close attention to the use of novel design houses and careful sensitization around the potential benefits of dwellings to ensure that the intended health impacts of interventions are achieved.
Neurological manifestations of COVID-19 in adults and children.
Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age.