Research priorities for children's cancer: a James Lind Alliance Priority Setting Partnership in the UK.

OBJECTIVES: To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities. PARTICIPANTS: Children and survivors of childhood cancer, diagnosed before age 16, their families, friends and professionals who work with this population. RESULTS: Four hundred and eighty-eight people submitted 1299 potential questions. These were refined into 108 unique questions; 4 were already answered and 3 were under active study, therefore, removed. Three hundred and twenty-seven respondents completed the shortlisting survey. Seventy-one children submitted questions in the children's surveys, eight children attended a workshop to prioritise these questions. The Top 5 questions from children were taken to the final workshop where 23 questions in total were discussed by 25 participants (young adults, carers and professionals). The top priority was 'can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?' CONCLUSIONS: We have identified research priorities for children's cancer from the perspectives of children, survivors, their families and the professionals who care for them. Questions reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact of cancer. These should inform funding of future research as they are the questions that matter most to the people who could benefit from research.

Aposematic signaling and seasonal variation in dorsal pelage in a venomous mammal.

In mammals, colouration patterns are often related to concealment, intraspecific communication, including aposematic signals, and physiological adaptations. Slow lorises (Nycticebus spp.) are arboreal primates native to Southeast Asia that display stark colour contrast, are highly territorial, regularly enter torpor, and are notably one of only seven mammal taxa that possess venom. All slow loris species display a contrasting stripe that runs cranial-caudally along the median sagittal plane of the dorsum. We examine whether these dorsal markings facilitate background matching, seasonal adaptations, and intraspecific signaling. We analyzed 195 images of the dorsal region of 60 Javan slow loris individuals (Nycticebus javanicus) from Java, Indonesia. We extracted greyscale RGB values from dorsal pelage using ImageJ software and calculated contrast ratios between dorsal stripe and adjacent pelage in eight regions. We assessed through generalized linear mixed models if the contrast ratio varied with sex, age, and seasonality. We also examined whether higher contrast was related to more aggressive behavior or increased terrestrial movement. We found that the dorsal stripe of N. javanicus changed seasonally, being longer and more contrasting in the wet season, during which time lorises significantly increased their ground use. Stripes were most contrasting in younger individuals of dispersal age that were also the most aggressive during capture. The dorsal stripe became less contrasting as a loris aged. A longer stripe when ground use is more frequent can be related to disruptive colouration. A darker anterior region by younger lorises with less fighting experience may allow them to appear larger and fiercer. We provide evidence that the dorsum of a cryptic species can have multimodal signals related to concealment, intraspecific communication, and physiological adaptations.

The Prevalence and Distribution of Neurodegenerative Compound-Producing Soil Streptomyces spp.

Recent work from our labs demonstrated that a metabolite(s) from the soil bacterium Streptomyces venezuelae caused dopaminergic neurodegeneration in Caenorhabditis elegans and human neuroblastoma cells. To evaluate the capacity for metabolite production by naturally occurring streptomycetes in Alabama soils, Streptomyces were isolated from soils under different land uses (agriculture, undeveloped, and urban). More isolates were obtained from agricultural than undeveloped soils; there was no significant difference in the number of isolates from urban soils. The genomic diversity of the isolates was extremely high, with only 112 of the 1509 isolates considered clones. A subset was examined for dopaminergic neurodegeneration in the previously established C. elegans model; 28.3% of the tested Streptomyces spp. caused dopaminergic neurons to degenerate. Notably, the Streptomyces spp. isolates from agricultural soils showed more individual neuron damage than isolates from undeveloped or urban soils. These results suggest a common environmental toxicant(s) within the Streptomyces genus that causes dopaminergic neurodegeneration. It could also provide a possible explanation for diseases such as Parkinson's disease (PD), which is widely accepted to have both genetic and environmental factors.