A randomized trial of 13-Cis retinoic acid in children with advanced neuroblastoma after high-dose therapy

One hundred and seventy-five children with Stage 3 or 4 neuroblastoma who had obtained a good response to conventional therapy were randomly allocated to 13-Cis retinoic acid at a dose of 0.75 mg/kg/day or placebo for up to 4 years. Toxicity was mild but no advantage in event-free survival was shown for the children receiving retinoic acid. © 2000 Cancer Research Campaig

Clinical realism: a new literary genre and a potential tool for encouraging empathy in medical students

Background: Empathy has been re-discovered as a desirable quality in doctors. A number of approaches using the medical humanities have been advocated to teach empathy to medical students. This paper describes a new approach using the medium of creative writing and a new narrative genre: clinical realism. Methods: Third year students were offered a four week long Student Selected Component (SSC) in Narrative Medicine and Creative Writing. The creative writing element included researching and creating a character with a life-changing physical disorder without making the disorder the focus of the writing. The age, gender, social circumstances and physical disorder of a character were randomly allocated to each student. The students wrote repeated assignments in the first person, writing as their character and including details of living with the disorder in all of their narratives. This article is based on the work produced by the 2013 cohort of students taking the course, and on their reflections on the process of creating their characters. Their output was analysed thematically using a constructivist approach to meaning making. Results: This preliminary analysis suggests that the students created convincing and detailed narratives which included rich information about living with a chronic disorder. Although the writing assignments were generic, they introduced a number of themes relating to illness, including stigma, personal identity and narrative wreckage. Some students reported that they found it difficult to relate to “their” character initially, but their empathy for the character increased as the SSC progressed. Conclusion: Clinical realism combined with repeated writing exercises about the same character is a potential tool for helping to develop empathy in medical students and merits further investigation

Improved outcome in children with advanced stage B-cell non-Hodgkin's lymphoma (B-NHL): results of the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol

From July 1990 to March 1996, 112 children with stage III or IV B-cell non-Hodgkin's lymphoma (B-NHL) with up to 70% FAB L3-type blasts (n= 42) in the bone marrow without central nervous system (CNS) disease were treated on the United Kingdom Children Cancer Study Group (UKCCSG) 9002 protocol (identical to the French LMB 84). The median age was 8.3 years. There were 81 boys and 31 girls. According to the extent of the primary disease, patients were sub-staged into three groups: IIIA with unresectable abdominal tumour (n= 39); IIIB with abdominal multiorgan involvement (n= 57) and IIIX with extra-abdominal primary lymphoma often presenting as pleural effusion (n= 16). Univariate and multivariate analyses were carried out to evaluate the prognostic significance of lactate dehydrogenase (LDH) level at diagnosis, the sub-stage and the time to achieve complete remission (CR). With a median follow up of 48 months (range 12–92), the overall and event free survival (EFS) is 87% (95% confidence interval (CI) 79.2–92.1%) and 83.7% (95% CI 76.3–89.2%) respectively. Six patients (5.4%) never achieved CR, of whom one is alive following high-dose therapy. Eight patients (7.1%) relapsed after achieving CR, three are alive after second-line therapy. There were three early toxic deaths (2.7%), mainly from infection, and one late death from a second cancer. There was no significant difference in EFS according to LDH level at diagnosis, the sub-stage or the time to CR. This study confirms the overall good prognosis and low rate of toxic deaths in patients with advanced B-NHL treated with this intensive regimen. No significant difference in EFS according to the sub-stage, the time to achieve CR or LDH level at diagnosis making it difficult to identify a group that should not receive intensive therapy. © 2000 Cancer Research Campaig

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

institutional framework of in action against land degradation

While econometric and spatial data are increasingly helpful to quantify and locate the extent and costs of land degradation, there is still little understanding of the contextual factors that determine or influence the land users' practices that aggravate or counteract land degradation. In this chapter, we take an institutional economic approach to analyse the persistence of degrading practices, the low adoption of sustainable land management (SLM), or the eventual organisational reaction to land degradation. The chapter reviews four examples of land degradation in different contexts to reveal the multiple driving forces and contextual factors. We then propose a conceptual framework to better understand the incentive structure and factors determining the land users' decision making. A layered analysis of the social phenomena is applied, following Williamson (2000). The chapter shows how actions at different layers can help improve land management. The chapter concludes with practical recommendations for the institutional economic analysis of land degradation

Habitat Fragmentation can Modulate Drought Effects on the Plant-soil-microbial System in Mediterranean Holm Oak (Quercus ilex) Forests

© 2015, Springer Science+Business Media New York. Ecological transformations derived from habitat fragmentation have led to increased threats to above-ground biodiversity. However, the impacts of forest fragmentation on soils and their microbial communities are not well understood. We examined the effects of contrasting fragment sizes on the structure and functioning of soil microbial communities from holm oak forest patches in two bioclimatically different regions of Spain. We used a microcosm approach to simulate the annual summer drought cycle and first autumn rainfall (rewetting), evaluating the functional response of a plant-soil-microbial system. Forest fragment size had a significant effect on physicochemical characteristics and microbial functioning of soils, although the diversity and structure of microbial communities were not affected. The response of our plant-soil-microbial systems to drought was strongly modulated by the bioclimatic conditions and the fragment size from where the soils were obtained. Decreasing fragment size modulated the effects of drought by improving local environmental conditions with higher water and nutrient availability. However, this modulation was stronger for plant-soil-microbial systems built with soils from the northern region (colder and wetter) than for those built with soils from the southern region (warmer and drier) suggesting that the responsiveness of the soil-plant-microbial system to habitat fragmentation was strongly dependent on both the physicochemical characteristics of soils and the historical adaptation of soil microbial communities to specific bioclimatic conditions. This interaction challenges our understanding of future global change scenarios in Mediterranean ecosystems involving drier conditions and increased frequency of forest fragmentation