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Background To reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP). Methods and findings From July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) Conclusions In this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros. Trial Registration ClinicalTrials.gov NCT05406479., Author(s): Bouke Catherine de Jong 1,*, Said Nourdine 2, Auke Thomas Bergeman 3, Zahara Salim 2, Silahi Halifa Grillone 2, Sofie Marijke Braet 1, Mohamed Wirdane Abdou 2, Rian Snijders [...]

BackgroundTo reduce leprosy risk in contacts of patients with leprosy by around 50%, the World Health Organization (WHO) recommends leprosy post-exposure prophylaxis (PEP) using single-dose rifampicin (SDR). Results from a cluster randomized trial in the Comoros and Madagascar suggest that PEP with a double dose of rifampicin led to a similar reduction in incident leprosy, prompting the need for stronger PEP. The objective of this Phase 2 trial was to assess safety of a bedaquiline-enhanced PEP regimen (intervention arm, bedaquiline 800 mg with rifampicin 600 mg, BE-PEP), relative to the WHO recommended PEP with rifampicin 600 mg alone (control arm, SDR-PEP).Methods and findingsFrom July 2022 to January 2023, consenting participants were screened for eligibility, including a heart rate-corrected QT interval (QTc) 50 ms or exceeded 450 ms after PEP administration. Per protocol, all children were analyzed together, with no significant difference in mean QTc increase for BE-PEP compared to SDR-PEP, although non-inferiority of BE-PEP in children was not demonstrated in unadjusted analysis, as the upper limit of the 95% CI of 10.4 ms exceeded the predefined margin of 10 ms. Adjusting for baseline QTc, the regression coefficient and 95% CI (3.3; -1.4, 8.0) met the 10 ms non-inferiority margin. No significant differences in ALT or AST levels were noted between the intervention and control arms, although a limitation of the study was false elevation of ALT/AST during adult recruitment due to a technical error. In both study arms, one serious adverse event was reported, both considered unlikely related to the study drugs. Dizziness, nausea, headache, and diarrhea among adults, and headaches in children, were nonsignificantly more frequently observed in the BE-PEP group.ConclusionsIn this study, we observed that safety of single-dose bedaquiline 800 mg in combination with rifampicin is comparable to rifampicin alone, although non-inferiority of QTc changes was demonstrated in children only after adjusting for the baseline QTc measurements. A Phase 3 cluster randomized efficacy trial is currently ongoing in the Comoros.Trial registrationClinicalTrials.gov NCT05406479.

This article discusses the important role that optical lithography has played in realizing Moore's Law. With the introduction of Artificial Intelligence, Machine Learning, and the Internet of Things, the demand for computing power and data storage capacity has never been as large as today. Optical lithography has been able to keep up with the resolution demand by increasing the Numerical Aperture of the projection Lens, decreasing the wavelength and innovative resist schemes. After the introduction of Immersion lithography and Double patterning, EUV was introduced by the industry. Although the transition from 193 nm lithography to EUV lithography was very difficult, EUV follows the same scaling laws as Optical Lithography. The conclusion is that the scaling laws of Optical Lithography continue to support Moore's Law, through the development of high NA EUV Lithography.

Abstract Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance indicating that human-mediated transport may serve as a pathway of the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate.

Abstract Background Reducing the risk of recurrent Plasmodium vivax malaria is critical for malaria control and elimination. Primaquine (PQ) is the only widely available drug against P. vivax dormant liver stages, but is recommended as a 14-day regimen, which can undermine adherence to a complete course of treatment. Methods This is a mixed-methods study to assess socio-cultural factors influencing adherence to a 14-day PQ regimen in a 3-arm, treatment effectiveness trial in Papua, Indonesia. The qualitative strand, consisting of interviews and participant observation was triangulated with a quantitative strand in which trial participants were surveyed using a questionnaire. Results Trial participants differentiated between two types of malaria: tersiana and tropika, equivalent to P. vivax and Plasmodium falciparum infection, respectively. The perceived severity of both types was similar with 44.0% (267/607) perceiving tersiana vs. 45.1% (274/607) perceiving tropika as more severe. There was no perceived differentiation whether malaria episodes were due to a new infection or relapse; and 71.3% (433/607) acknowledged the possibility of recurrence. Participants were familiar with malaria symptoms and delaying health facility visit by 1–2 days was perceived to increase the likelihood of a positive test. Prior to health facility visits, symptoms were treated with leftover drugs kept at home (40.4%; 245/607) or bought over the counter (17.0%; 103/607). Malaria was considered to be cured with ‘blue drugs’ (referring to dihydroartemisinin-piperaquine). Conversely, ‘brown drugs,’ referring to PQ, were not considered malaria medication and instead were perceived as supplements. Adherence to malaria treatment was 71.2% (131/184), in the supervised arm, 56.9% (91/160) in the unsupervised arm and 62.4% (164/263) in the control arm; p = 0.019. Adherence was 47.5% (47/99) among highland Papuans, 51.7% (76/147) among lowland Papuans, and 72.9% (263/361) among non-Papuans; p

Measurement(s) metagenomics analysis • Cytochrome C Oxidase Subunit 1 Technology Type(s) amplicon sequencing • Dideoxy Chain Termination DNA Sequencing Factor Type(s) tree species • geographic location • mean annual temperature • mean annual precipitation Sample Characteristic - Organism Fungi • Insecta Sample Characteristic - Environment dormant tree twigs Machine-accessible metadata file describing the reported data: https://doi.org/10.6084/m9.figshare.16764229

The rare and threatened Heliosciadium repens grows in moist grasslands and has a distinct life cycle. Plants reproduce both clonally, although ramets tend to be short‐lived, and sexually, with seeds that can form a persistent soil seed bank. The germination requirements of H. repens were investigated, yielding important information for its habitat management and conservation.We examined the soil seed bank in three populations and carried out germination experiments and embryo growth measurements with fresh seeds in laboratory, greenhouse and outdoor conditions. We also investigated the effects of storage and burial of seeds.H. repens formed a long‐term persistent (>6 years) soil seed bank with very pronounced primary dormancy, but no secondary dormancy or dormancy cycles. Seeds can germinate throughout the growing season when temperatures are sufficiently high. Embryo growth and seed germination are triggered by light and, to a lesser extent, daily temperature fluctuations.Seeds of H. repens seem to have developed a unique germination syndrome with several strategies to remain dormant in the soil until optimal conditions are present for seedling establishment and survival. Both sexual reproduction and seed bank formation are crucial for the long‐term survival of the populations. [ABSTRACT FROM AUTHOR]

Abstract The 1,5‐benzothiazepane structure is an important heterocyclic moiety present in a variety of commercial drugs and pharmaceuticals. This privileged scaffold exhibits a diversity of biological activities, including antimicrobial, antibacterial, anti‐epileptic, anti‐HIV, antidepressant, antithrombotic and anticancer properties. Its important pharmacological potential renders research into the development of new and efficient synthetic methods of high relevance. In the first part of this review, an overview of different synthetic approaches toward 1,5‐benzothiazepane and its derivatives is provided, ranging from established protocols to recent (enantioselective) methods that promote sustainability. In the second part, several structural characteristics influencing biological activity are briefly explored, providing a few insights into the structure‐activity relationships of these compounds.

Despite difficulties to document transmission pathways (assumed to be airborne), increased risk of leprosy infection has been shown for individuals living in close contact with patients. However, variations in the concept of ‘close contacts’ are used in different settings and studies. We conduct this review to identify criteria of space (location, geographical variables, distance, indoor vs outdoor), time (including frequency and duration), physical exposure (skin to skin, sexual), and relationship (familial, occupational, social) involved in the definition of ‘close contacts’ in leprosy studies. We expect this review to provide an overview of the (lack of) conceptualization of this term and its variations across settings. Primary studies and reviews are eligible for inclusion in this review. The main source of records will be the PubMed interface. Secondary searches will be conducted in Google Scholar, as well as through the reference lists of selected publications. The search strategy is based on the combination of the condition of interest (leprosy) and the concept under study (‘contact’). The findings of this review will be presented using thematic narrative synthesis, tables, and figures. The protocol is written in line with the Prisma Extension for Scoping reviews (PRISMA-ScR).

Despite difficulties to document transmission pathways (assumed to be airborne), increased risk of leprosy infection has been shown for individuals living in close contact with patients. However, variations in the concept of ‘close contacts’ are used in different settings and studies. We conduct this review to identify criteria of space (location, geographical variables, distance, indoor vs outdoor), time (including frequency and duration), physical exposure (skin to skin, sexual), and relationship (familial, occupational, social) involved in the definition of ‘close contacts’ in leprosy studies. We expect this review to provide an overview of the (lack of) conceptualization of this term and its variations across settings. Primary studies and reviews are eligible for inclusion in this review. The main source of records will be the PubMed interface. Secondary searches will be conducted in Google Scholar, as well as through the reference lists of selected publications. The search strategy is based on the combination of the condition of interest (leprosy) and the concept under study (‘contact’). The findings of this review will be presented using thematic narrative synthesis, tables, and figures. The protocol is written in line with the Prisma Extension for Scoping reviews (PRISMA-ScR).

Abstract Background The importance of community involvement in the response against disease outbreaks has been well established. However, we lack insights into local communities’ experiences in coping with the current COVID-19 pandemic. This study explored both the impact of, and response to, COVID-19 within the Orthodox Jewish communities of Antwerp (Belgium) during the first lockdown period (March 2020 – May 2020). Methods We conducted an explorative qualitative study using a participatory approach. First, we performed a community mapping to identify relevant stakeholders. Through the active involvement of a community advisory board and based on qualitative interviews with key-informants and community members, we elicited lived experiences, attitudes, and perceptions towards COVID-19. Interviews were conducted both face-to-face and using online web conferencing technology. Data were analyzed inductively according to the principles of thematic analysis. Results Government-issued outbreak control measures presented context-specific challenges to the Orthodox Jewish communities in Antwerp. They related mainly to the remote organization of religious life, and practicing physical distancing in socially and culturally strongly connected communities. Existing community resources were rapidly mobilized to adapt to the outbreak and to self-organize response initiatives within communities. The active involvement of community and religious leaders in risk communication proved to be of great importance to facilitate the coverage and uptake of pandemic control measures while protecting essential community values and traditions. Creating bottom-up and community-adapted communication strategies, including addressing language barriers and involving Rabbis in the dissemination of prevention messages, fostered a feeling of trust in government’s response measures. However, unmet information and prevention needs were also identified, such as the need for inclusive communication by public authorities and the need to mitigate the negative effects of stigmatization. Conclusion The experiences of Orthodox Jewish communities in Antwerp demonstrate a valuable example of a feasible community-centered approach to health emergencies. Increasing the engagement of communities in local decision-making and governance structures remains a key strategy to respond to unmet information and prevention needs.

Stipules are generally regarded as the outgrowths of the leaf base in angiosperms. Other interpretations see stipules as independent organs comparable to leaves. Stipules have been recognized as an important trait for plant taxonomy and identification, and there has been great progress in the understanding of their morphology, development, origin, function, and gene regulation over time. Therefore, this review will briefly summarize past research and aims to clarify the occurrence, location, and morphology of stipules in the families recognized by APG IV and reconstruct their ancestral states. Additionally, the developmental morphology of different types of stipule is presented through scanning electron microcopy observations and a survey of the existing literature. The difference between stipules and ligules is discussed in relation to the occurrence of postgenitally or congenitally fused 'continuous' stipules. A distinction is made between 'true' stipules and 'pseudostipules'. The origin of stipules at the base of the leaf is explained from different perspectives. About one-third of the families are reported to have stipules, mostly concentrated in the Rosid clade with the highest level of diversity. On the basis of the ancestral state reconstructions, stipules may be absent in the ancestors of angiosperms, but are present in the ancestor of Rosids, with a pair appearing on both sides of the petiole base. The transition between paired and annular stipules is discussed, the latter arising postgenitally or congenitally. Several hypotheses are discussed to explain the abundance of stipules in the Rosid clade and their limited presence in the Asterid clade. [ABSTRACT FROM AUTHOR]

Objective To obtain the perspectives of some small- and medium-sized organizations on the World Health Organization (WHO) prequalification programme for medicines and to ascertain organizations' unmet needs. Methods We conducted an exploratory, qualitative study in 2018 among 17 representatives of 15 small- and medium-sized Belgian and non-Belgian organizations who purchase medicines for humanitarian, development or public programmes in low- and middle-income countries. We used semi-structured interviews to obtain respondents' views and experiences of using WHO prequalification guidance when procuring medicines. We identified emerging themes and formulated recommendations about the activities of the WHO Prequalification Team. Findings Most respondents suggested expanding prequalification to essential antibiotics, particularly paediatric formulations; and insulin, antihypertensives and cancer treatments. Respondents were concerned about irregular availability of WHO-prequalified medicines in the marketplace and sometimes high prices of prequalified products. Small organizations, in particular, had difficulties negotiating low-volume purchases. Organizations working in primary health care and hospitals seldom referred to the prequalified lists. Conclusion We recommend that the WHO-prequalified products be expanded to include essential antibiotics and medicines for noncommunicable diseases. The WHO Prequalification Team could require prequalified manufacturers to make publicly available the details of their authorized distributors and facilitate a process of harmonization of quality assurance policies across all donors. Prequalification of distributors and procurement agencies could help create more transparent and stringent mechanisms. We urge WHO Member States and funders to sustain support for the WHO Prequalification Team, which remains important for the fulfilment of universal health coverage. [phrase omitted] [phrase omitted] Objectif Connaitre le point de vue de quelques petites et moyennes organisations vis-a-vis du Programme de prequalification des medicaments dirige par Organisation mondiale de la Sante (OMS), et determiner quels sont les besoins non satisfaits de ces organisations. Methodes Nous avons mene une etude qualitative exploratoire en 2018 aupres de 17 representants de 15 petites et moyennes organisations belges et non belges qui se procurent des medicaments pour des programmes humanitaires, publics ou de developpement dans des pays a faible et moyen revenu. Nous avons conduit des entretiens semi-structures afin de recueillir les avis et experiences des repondants concernant les conseils de prequalification fournis par l'OMS au moment d'acheter des medicaments. Nous avons identifie de nouveaux themes et formule des recommandations autour des activites de l'equipe de prequalification de l'OMS. Resultats La plupart des repondants ont suggere d'elargir la prequalification aux antibiotiques essentiels, en particulier les formulations pediatriques, ainsi qu'a l'insuline, aux antihypertenseurs et aux traitements contre le cancer. Plusieurs repondants ont exprime leur inquietude quant a la disponibilite irreguliere des medicaments prequalifies par l'OMS sur le marche, mais aussi aux prix parfois eleves des produits prequalifies. De leur cote, les petites organisations eprouvent des difficultes a negocier l'achat de faibles volumes. Enfin, les organisations qui travaillent dans le secteur des hopitaux et soins de sante primaires se referent rarement aux listes de prequalification. Conclusion Nous recommandons de completer la liste des produits prequalifies etablie par l'OMS afin d'inclure des medicaments et antibiotiques essentiels pour les maladies non transmissibles. Par ailleurs, l'equipe de prequalification de l'OMS pourrait exiger des fabricants prequalifies de publier les coordonnees de leurs distributeurs agrees et de favoriser l'harmonisation des politiques d'assurance de la qualite chez tous leurs donateurs. La prequalification des distributeurs et des organismes d'achat pourrait contribuer a creer des mecanismes plus rigoureux et transparents. Nous encourageons les bailleurs de fonds et Etats Membres de l'OMS a soutenir durablement l'equipe de prequalification de l'OMS, qui demeure un outil important dans l'instauration d'une couverture maladie universelle. [phrase omitted] Objetivo Obtener las perspectivas de algunas organizaciones pequenas y medianas sobre el programa de precalificacion de medicamentos de la Organizacion Mundial de la Salud (OMS) y determinar las necesidades que las organizaciones no han cubierto. Metodos En 2018 se realizo un estudio cualitativo y exploratorio entre 17 representantes de 15 organizaciones pequenas y medianas belgas y no belgas que compran medicamentos para programas humanitarios, de desarrollo o publicos en paises de ingresos bajos y medios. Se utilizaron entrevistas semiestructuradas para conocer las opiniones y las experiencias de los encuestados sobre el uso de la orientacion de precalificacion de la OMS en la compra de los medicamentos. Se identificaron temas emergentes y se formularon recomendaciones sobre las actividades del Equipo de precalificacion de la OMS. Resultados La mayoria de los encuestados sugirieron que se ampliara la precalificacion a los antibioticos esenciales, en particular a los medicamentos pediatricos, y a la insulina, los antihipertensivos y los tratamientos contra el cancer. Los encuestados se mostraron preocupados por la disponibilidad irregular de los medicamentos precalificados por la OMS en el mercado y, a veces, por los precios altos de los productos precalificados. En particular, las organizaciones pequenas tenian dificultades para negociar las adquisiciones de bajo volumen. Las organizaciones que trabajaban en la atencion primaria de la salud y en los hospitales se remitian a las listas de medicamentos precalificados pocas veces. Conclusion Se recomienda que los productos precalificados por la OMS se amplien para incluir los antibioticos y los medicamentos esenciales de las enfermedades no transmisibles. El Equipo de precalificacion de la OMS podria exigir a los fabricantes precalificados que publiquen los datos de sus distribuidores autorizados y faciliten un proceso de armonizacion de las politicas relacionadas con la garantia de calidad para todos los donantes. La precalificacion de los distribuidores y de las agencias de adquisiciones podria ayudar a crear mecanismos mas transparentes y rigurosos. Se insta a los Estados miembros de la OMS y a los financiadores a que mantengan su apoyo al Equipo de precalificacion de la OMS, que sigue siendo importante para el cumplimiento de la cobertura sanitaria universal., Introduction A key element of achieving universal health coverage in target 3.8 of the sustainable development goals is 'access to safe, effective, quality and affordable essential medicines and vaccines for [...]

The Primuloid clade or Primulaceae sensus lato is well supported and contains several pollination syndromes, including wind pollination and insect pollination with pollen, nectar, or oil as a reward. Previous studies have recognized two types of nectaries (floral and extrafloral) with different distributions (e.g. ovary, stigma, style, pedicel). This study aimed to reassess the diversity of nectary types, and their distribution and evolution within the clade. Flowers were selected to represent the four subfamilies Maesoideae, Theophrastoideae, Primuloideae, and Myrsinoideae. The flowers were investigated for nectary tissue with electron microscopy, light microscopy, and sugar tests. Nectar is mainly exuded by gynoecial nectarostomata (in Maeseoideae, Theophrastoideae, Primuloideae, and a few basal Myrsinoideae, such as Stimpsonia and Coris) distributed at the base, middle, and top part of the ovary. Myrsinoideae is the exception with an absence of a nectary linked to buzz-pollination, or presenting nectariferous or oil-producing trichomes on the perianth and stamens. The evolution of nectaries is variable in the Primuloid clade, with Primuloideae apparently the starting point of an evolutionary reversal in terms of nectary evolution within this clade, and a high diversity of nectaries within the Myrsinoideae representing various trends that are currently under-investigated. The evolution of floral nectaries in Primulaceae presents an exciting shift from nectar-producing flowers towards a loss of nectaries, and an evolutionary reversal with a shift to the co-option of either oil-producing trichomes or nectar-producing trichomes. [ABSTRACT FROM AUTHOR]

Abstract Background In onchocerciasis-endemic areas, particularly in those with a sub-optimal onchocerciasis control programme, a high prevalence of epilepsy is observed. Both onchocerciasis and epilepsy are stigmatizing conditions. The first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium (12–14 October 2017) and during this meeting, an OAE alliance was established. In this paper, we review what is known about epilepsy-associated stigma in onchocerciasis-endemic regions, and present the recommendations of the OAE alliance working group on stigma. Main body For this scoping review, literature searches were performed on the electronic databases PubMed, Scopus and Science Direct using the search terms “epilepsy AND onchocerciasis AND stigma”. Hand searches were also undertaken using Google Scholar, and in total seven papers were identified that addressed epilepsy-related stigma in an onchocercisasis-endemic area. Due to the limited number of published research papers on epilepsy-associated stigma in onchocerciasis-endemic areas, other relevant literature that describes important aspects related to stigma is discussed. The thematic presentation of this scoping review follows key insights on the barriers to alleviating the social consequences of stigma in highly affected onchocerciasis-endemic areas, which were established by experts during the working group on stigma and discrimination at the first international workshop on OAE. These themes are: knowledge gaps, perceived disease aetiology, access to education, marriage restrictions, psycho-social well-being, burden on the care-giver and treatment seeking behaviour. Based on the literature and expert discussions during the OAE working group on stigma, this paper describes important issues regarding epilepsy-related stigma in onchocerciasis-endemic regions and recommends interventions that are needed to reduce stigma and discrimination for the improvement of the psycho-social well-being of persons with epilepsy. Conclusions Educating healthcare workers and communities about OAE, strengthening onchocerciasis elimination programs, decreasing the anti-epileptic treatment gap, improving the care of epilepsy-related injuries, and prioritising epilepsy research is the way forward to decreasing the stigma associated with epilepsy in onchocerciasis-endemic regions.

BackgroundA high prevalence of epilepsy has been observed in several onchocerciasis-endemic villages in the Sanaga River basin, Cameroon. Recent studies suggest that ivermectin, a drug that is distributed annually with the aim of eliminating onchocerciasis, may have a protective effect against acquiring onchocerciasis-associated epilepsy (OAE). This study, therefore, provides an in-depth understanding of both the complex therapeutic landscape for epilepsy as well as the experiences related to the 'community-directed treatment with ivermectin' (CDTI) campaign in order to identify a more trenchant path forward in the fight against epilepsy.Methodology/principal findingsBased on a mixed methods study combining a qualitative strand with a quantitative survey, we found that epilepsy was perceived to have had an epidemic emergence in the past and was still considered an important health issue in the study area. Socio-economic status, availability and accessibility of drugs and practitioners, as well as perceived aetiology shaped therapeutic itineraries for epilepsy, which included frequenting (in)formal biomedical health care providers, indigenous and/or faith healing practitioners. Ivermectin uptake for onchocerciasis was generally well known and well regarded. The CDTI faced structural and logistical bottlenecks undermining equal access and optimal adherence to the drug.Conclusions/significanceLocally accessible, uninterrupted, sustainable and comprehensive health-service delivery is essential to help alleviate the epilepsy burden on afflicted households. Addressing structural challenges of CDTI and communicating the potential link with epilepsy to local populations at risk could optimize the uptake of this potentially significant tool in OAE prevention.