Research Protocol: A cluster randomised controlled trial to evaluate the Family SKILLS programme for reception year students from families in which English is an additional language

This paper describes a cluster randomized controlled trial of Family SKILLS, an intervention targeted at reception year children and their parents for whom English is an additional language. The trial will commence in the autumn of 2016 and run for one year. 155 primary schools in England will take part in the study. NatCen Social Research has been appointed to conduct the trial by the Education Endowment Foundation, the Bell Foundation and Unbound Philanthropy who are co-funding this research. The Family SKILLS intervention will be delivered by a number of delivery partner organisations coordinated by a consortium comprising Learning Unlimited, the Campaign for Learning and University College London, Institute for Education

Safety and reactogenicity of a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis

The leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open-label observational study to establish a controlled human infection model (CHIM) of sand fly-transmitted cutaneous leishmaniasis (CL) caused by Leishmania major. Between 24 January and 12 August 2022, we exposed 14 participants to L. major-infected Phlebotomus duboscqi. The primary objective was to demonstrate effectiveness of lesion development (take rate) and safety (absence of CL lesion at 12 months). Secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. Lesion development was terminated by therapeutic biopsy (between days 14 and 42 after bite) in ten participants with clinically compatible lesions, one of which was not confirmed by parasite detection. We estimated an overall take rate for CL development of 64% (9/14). Two of ten participants had one and one of ten participants had two lesion recurrences 4-8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but as expected, scarring due to a combination of CL and the biopsy procedure was evident. All participants were lesion free at >12-month follow-up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This CHIM offers opportunities for vaccine candidate selection based on human efficacy data and for a greater understanding of immune-mediated pathology. ClinicalTrials.gov identifier: NCT04512742

Systematic functional analysis of Leishmania protein kinases identifies regulators of differentiation or survival

Differentiation between distinct stages is fundamental for the life cycle of intracellular protozoan parasites and for transmission between hosts, requiring stringent spatial and temporal regulation. Here, we apply kinome-wide gene deletion and gene tagging in Leishmania mexicana promastigotes to define protein kinases with life cycle transition roles. Whilst 162 are dispensable, 44 protein kinase genes are refractory to deletion in promastigotes and are likely core genes required for parasite replication. Phenotyping of pooled gene deletion mutants using bar-seq and projection pursuit clustering reveal functional phenotypic groups of protein kinases involved in differentiation from metacyclic promastigote to amastigote, growth and survival in macrophages and mice, colonisation of the sand fly and motility. This unbiased interrogation of protein kinase function in Leishmania allows targeted investigation of organelle-associated signalling pathways required for successful intracellular parasitism

Parasites of sticklebacks [Actinopterygii: Gasterosteidae] from South-Eastern Baltic Sea [Poland]

A total of 142 individuals of Gasterosteus aculeatus L. and 22 individuals of Pungitius pungitius (L.) from several areas of the coastal waters of the Gdańsk Bay both brackish- and freshwater were examined for parasites. The survey was carried out within 1988-1991. Six parasite species, namely: Gyrodactylus arcuatus, Apatemon gracilis, Sphaerostomum bramae, Phyllodistomum folium, Neoechinorhynchus rutili, and Argulus foliaceus were recovered from sticklebacks caught in freshwater habitats; while the other 4 parasites: Apatemon annuligerum, Bothriocephalus sp., Schistocephalus solidus, Proteocephalus percae occurred only in fish from brackish-water areas. Additional 5 parasites: Trichodina domerguei, Diplostomum pungitii, Diplostomum spathaceum, Rhaphidascaris acus, and Thersitina gasterostei were recorded in fishes from both habitats

Trapped field of YBCO bulk superconductors prepared by infiltration growth process

Single grain Y₁Ba₂Cu₃O_{7-x} (YBCO) bulk superconductors were prepared from different starting precursors. In the first case, Y₂Ba₁Cu₁O₅ (Y211) powder as the solid phase and the liquid phase of mixture of YBa₂Cu₃O_{7-x}+BaCuO₂+CuO powders were used. In the second case, the solid phase was prepared from the mixture of Y₂O₃+BaCuO₂ instead of the conventionally used Y211, and as the liquid phase a mixture of Y₂O₃+BaCuO₂+CuO powders was used. The trapped field measurements at 77 K were performed and microstructure of samples was studied by polarized light microscopy. The positive influence of Y₂O₃+BaCuO₂ starting precursor on the oxygenation, Y211 particle refinement and measured trapped field is shown

Magnetosome size distribution in magnetotactic bacteria

Praca analizuje rozkład statystyczny magnetosomów w bakterii magnetotaktycznej. Zawiera również teoretyczne uzasadnienie dotyczące procesu biomineralizacji, który prowadzi do produkcji jednodomenowych nanocząstek wewnątrz bakterii.The paper analyzes a statistic distribution of magnetosomes in magnetotactic bacteria. It also contains theoretical reasoning on the nature of a biomineralization process which aims to produce single-domain nanoparticles inside bacteria

Prenatal dexamethasone treatment for classic 21-hydroxylase deficiency in Europe

Objective: To assess the current medical practice in Europe regarding prenatal dexamethasone (Pdex) treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. Design and methods: A questionnaire was designed and distributed, including 17 questions collecting quantitative and qualitative data. Thirty-six medical centres from 14 European countries responded and 30 out of 36 centres were reference centres of the European Reference Network on Rare Endocrine Conditions, EndoERN. Results: Pdex treatment is currently provided by 36% of the surveyed centres. The treatment is initiated by different specialties, that is paediatricians, endocrinologists, gynaecologists or geneticists. Regarding the starting point of Pdex, 23% stated to initiate therapy at 4–5 weeks postconception (wpc), 31% at 6 wpc and 46 % as early as pregnancy is confirmed and before 7 wpc at the latest. A dose of 20 µg/kg/day is used. Dose distribution among the centres varies from once to thrice daily. Prenatal diagnostics for treated cases are conducted in 72% of the responding centres. Cases treated per country and year vary between 0.5 and 8.25. Registries for long-term follow-up are only available at 46% of the centres that are using Pdex treatment. National registries are only available in Sweden and France. Conclusions: This study reveals a high international variability and discrepancy in the use of Pdex treatment across Europe. It highlights the importance of a European cooperation initiative for a joint international prospective trial to establish evidence-based guidelines on prenatal diagnostics, treatment and follow-up of pregnancies at risk for CAH