UAV and satellite remote sensing for inland water quality assessments: a literature review.

High spatial and temporal resolution data is crucial to comprehend the dynamics of water quality fully, support informed decision-making, and allow efficient management and protection of water resources. Traditional in situ water quality measurement techniques are both time-consuming and labor-intensive, resulting in databases with limited spatial and temporal frequency. To address these challenges, satellite-driven water quality assessment has emerged as an efficient and effective solution, offering comprehensive data on larger-scale water bodies. Numerous studies have utilized multispectral and hyperspectral remote sensing data from various sensors to assess water quality, yielding promising results. However, the recent popularity of unmanned aerial vehicle (UAV) remote sensing can be attributed to its high spatial and temporal resolution, flexibility, ability to capture data at different times of day, and relatively low cost compared to traditional platforms. This study presents a comprehensive review of the current state of the art in monitoring water quality in small inland water bodies using satellite and UAV remote sensing data. It encompasses an overview of atmospheric correction algorithms and the assessment of different water quality parameters. Furthermore, the review addresses the challenges associated with monitoring water quality in these bodies of water and emphasizes the potential of UAVs to overcome these challenges by providing accurate and reliable data.

Effect of hydrogen sulfide on glycolysis-based energy production in mouse erythrocytes.

Hydrogen sulfide (H2 S) is a gasotransmitter that regulates both physiological and pathophysiological processes in mammalian cells. Recent studies have demonstrated that H2 S promotes aerobic energy production in the mitochondria in response to hypoxia, but its effect on anaerobic energy production has yet to be established. Glycolysis is the anaerobic process by which ATP is produced through the metabolism of glucose. Mammalian red blood cells (RBCs) extrude mitochondria and nucleus during erythropoiesis. These cells would serve as a unique model to observe the effect of H2 S on glycolysis-mediated energy production. The purpose of this study was to determine the effect of H2 S on glycolysis-mediated energy production in mitochondria-free mouse RBCs. Western blot analysis showed that the only H2 S-generating enzyme expressed in mouse RBCs is 3-mercaptopyruvate sulfurtransferase (MST). Supplement of the substrate for MST stimulated, but the inhibition of the same suppressed, the endogenous production of H2 S. Both exogenously administered H2 S salt and MST-derived endogenous H2 S stimulated glycolysis-mediated ATP production. The effect of NaHS on ATP levels was not affected by oxygenation status. On the contrary, hypoxia increased intracellular H2 S levels and MST activity in mouse RBCs. The mitochondria-targeted H2 S donor, AP39, did not affect ATP levels of mouse RBCs. NaHS at low concentrations (3-100 µM) increased ATP levels and decreased cell viability after 3 days of incubation in vitro. Higher NaHS concentrations (300-1000 µM) lowered ATP levels, but prolonged cell viability. H2 S may offer a cytoprotective effect in mammalian RBCs to maintain oxygen-independent energy production.

Examining tensions in the past and present uses of concepts.

Examining tensions between the past and present uses of scientific concepts can help clarify their contributions as tools in experimental practices. This point can be illustrated by considering the concepts of mental imagery and hallucinations: despite debates over their respective referential reliabilities remaining unresolved within their interdependent histories, both are used as independently stable concepts in neuroimaging experiments. Building on an account of how these concepts function as tools structured for pursuit of diverging goals in experiments, this paper explores this tension by re-examining the continued reliance of each concept on inverse characterisations inherited from the nominally-discarded 'mediator-view' of sensory-like mental phenomena (SLMP). In doing so, I seek to demonstrate how examining unresolved tensions can help highlight that entrenched associations can remain both integral to, and obscured by, the uses of concepts as goal-directed tools within experimental practices.

Intracortical motor networks are affected in both the contralateral and ipsilateral hemisphere during single limb cold water immersion.

NEW FINDINGS: What is the central question of this study? How does single limb cold water immersion affect corticomotor function and intracortical circuitry in the motor cortex of each cerebral hemisphere? What is the main finding and its importance? Immersion of a single limb in very cold water caused an increase in corticomotor excitability and intracortical facilitation, and a decrease in intracortical inhibition, in the motor cortex of both hemispheres. These findings provide evidence that intense sensory stimuli induce widespread changes in motor circuitry in the contralateral, as well as the ipsilateral, hemisphere. ABSTRACT: Although responses to noxious stimuli have been extensively studied for the contralateral hemisphere, little is known about how the ipsilateral hemisphere may be affected. Therefore, this study examined how exposing a single limb to noxious cold stimuli affects motor output arising from both the contralateral and ipsilateral hemisphere. A total of 17 healthy adults participated in three experiments. Single- and paired-pulse TMS protocols were used to identify how immersing a single upper limb in cold water (4.0 ± 0.5 °C) affects inhibitory and facilitatory circuits in the primary motor cortex (M1) of the contralateral (experiment 1) and ipsilateral (experiment 2) hemisphere. The third experiment used a reaction time task to assess the functional consequences of acute adaptations in the ipsilateral M1. The target muscle in all experiments was the extensor carpi radialis brevis (ECRB). Immersion of a single limb in cold water increased self-perception of pain and temperature, and increased EMG amplitude of the immersed limb. During immersion, motor evoked potentials and intracortical facilitation increased, whereas short interval intracortical inhibition decreased, for both the ipsilateral M1 and contralateral M1. Activity in the ipsilateral hemisphere to the limb immersed in cold water also slowed reaction time for the non-immersed limb. Our findings suggest that altered motor responses from single limb cold water immersion are not restricted to a single hemisphere. Instead, widespread activation of somatosensory systems influences inhibitory and facilitatory circuits in the primary motor cortex of each hemisphere.

Anesthetic Errors During Procedures in the United States.

OBJECTIVES: The purpose of this study was to identify the incidence of anesthetic errors per discharges in the United States within these errors, the incidence of death. A secondary aim was to identify any association between the mortality and patient comorbidities. METHODS: A retrospective analysis of the hospitals in the United States using the Nationwide Inpatient Sample (NIS) database during 2007-2014 was performed. The study population consisted of patients who were recorded as inpatient discharges who experienced complications as a result of incorrect anesthetic administration resulting from either an overdose or inappropriate medication administration in the United States. RESULTS: Between 2007 and 2014, a total of 17,116 anesthetic errors were reported. There was a substantial decrease in the total number of these errors over time, from 2483 in 2007 to 1391 in 2014 (44% decrease). There were 131 reported deaths in this cohort (0.77% mortality rate), with 61 mortalities in teaching hospitals (0.86% mortality rate) and 57 in nonteaching hospitals (0.73% mortality rate). During the study period, deaths decreased from 21 in 2007 (0.85% mortality rate) to 11 in 2014 (0.79% mortality rate), corresponding with a 7.1% decrease in the mortality rate. Comorbidities associated with a significant increase in mortality from anesthetic substances included fluid and electrolyte disorders (odds ratio 8.82, 95% confidence interval 5.24-14.83, P < 0.001) and coagulopathies (odds ratio 5.26, 95% confidence interval 2.53-10.93, P < 0.001). CONCLUSIONS: Our study showed that although the incidence of anesthetic errors is small, they do still exist in our hospitals. Certain comorbidities appear to predispose patients to increased risk. The subsets of patients who appear to be at the greatest risk include those with preexisting electrolyte and fluid disorders and coagulopathies.

Separated response function ratios in exclusive, forward π(±) electroproduction.

The study of exclusive π(±) electroproduction on the nucleon, including separation of the various structure functions, is of interest for a number of reasons. The ratio RL=σL(π-)/σL(π+) is sensitive to isoscalar contamination to the dominant isovector pion exchange amplitude, which is the basis for the determination of the charged pion form factor from electroproduction data. A change in the value of RT=σT(π-)/σT(π+) from unity at small -t, to 1/4 at large -t, would suggest a transition from coupling to a (virtual) pion to coupling to individual quarks. Furthermore, the mentioned ratios may show an earlier approach to perturbative QCD than the individual cross sections. We have performed the first complete separation of the four unpolarized electromagnetic structure functions above the dominant resonances in forward, exclusive π(±) electroproduction on the deuteron at central Q(2) values of 0.6, 1.0, 1.6 GeV(2) at W=1.95 GeV, and Q(2)=2.45 GeV(2) at W=2.22 GeV. Here, we present the L and T cross sections, with emphasis on RL and RT, and compare them with theoretical calculations. Results for the separated ratio RL indicate dominance of the pion-pole diagram at low -t, while results for RT are consistent with a transition between pion knockout and quark knockout mechanisms.

Assessment of vascular and endothelial dysfunction in nutritional studies.

Vascular and endothelial dysfunction (VED) is emerging as a potential set of early markers of cardiovascular disease risk and tests for its measurement have been widely used in clinical research. The aim of this viewpoint is to describe and discuss the current usage of these measures in well-designed nutritional trials, using the potential relationship between fruit juice intake and VED as example. A search was conducted using the NHS evidence portal including studies published in English between January 1980 and October 2013. Only 10 suitable studies were selected, which investigated the effect of fruit juice intake on VED, among which 4 interventions used flow-mediated dilatation, 2 arterial stiffness, 2 a combination of arterial stiffness and flow-mediated dilatation, 2 carotid intimal media thickness and 1 iontophoresis with laser Doppler. Despite minimal effects reported on classical CVD markers, such as lipids, 8 out of the 10 identified studies reported an effect on endothelial function following juice consumption, indicating that VED tests can be effectively used in human dietary interventions to identify relationships between bioactive compounds from fruit and CVD risk. However, paucity of available data, scarcity of compound bioavailability and metabolism information, strong heterogeneity among experimental methodologies and a number of limitations to study designs, still limit the interpretation of the results obtained through these measures. Future, well-designed studies with greater attention to consider use of VED measures are needed to strengthen the utility of VED tests in nutrition research such as those investigating the impact of polyphenol-rich juices and CVD risk.

Plasticity-led and mutation-led evolutions are different modes of the same developmental gene regulatory network.

The standard theory of evolution proposes that mutations cause heritable variations, which are naturally selected, leading to evolution. However, this mutation-led evolution (MLE) is being questioned by an alternative theory called plasticity-led evolution (PLE). PLE suggests that an environmental change induces adaptive phenotypes, which are later genetically accommodated. According to PLE, developmental systems should be able to respond to environmental changes adaptively. However, developmental systems are known to be robust against environmental and mutational perturbations. Thus, we expect a transition from a robust state to a plastic one. To test this hypothesis, we constructed a gene regulatory network (GRN) model that integrates developmental processes, hierarchical regulation, and environmental cues. We then simulated its evolution over different magnitudes of environmental changes. Our findings indicate that this GRN model exhibits PLE under large environmental changes and MLE under small environmental changes. Furthermore, we observed that the GRN model is susceptible to environmental or genetic fluctuations under large environmental changes but is robust under small environmental changes. This indicates a breakdown of robustness due to large environmental changes. Before the breakdown of robustness, the distribution of phenotypes is biased and aligned to the environmental changes, which would facilitate rapid adaptation should a large environmental change occur. These observations suggest that the evolutionary transition from mutation-led to plasticity-led evolution is due to a developmental transition from robust to susceptible regimes over increasing magnitudes of environmental change. Thus, the GRN model can reconcile these conflicting theories of evolution.

Computationally reproducing results from meta-analyses in ecology and evolutionary biology using shared code and data.

Many journals in ecology and evolutionary biology encourage or require authors to make their data and code available alongside articles. In this study we investigated how often this data and code could be used together, when both were available, to computationally reproduce results published in articles. We surveyed the data and code sharing practices of 177 meta-analyses published in ecology and evolutionary biology journals published between 2015-17: 60% of articles shared data only, 1% shared code only, and 15% shared both data and code. In each of the articles which had shared both (n = 26), we selected a target result and attempted to reproduce it. Using the shared data and code files, we successfully reproduced the targeted results in 27-73% of the 26 articles, depending on the stringency of the criteria applied for a successful reproduction. The results from this sample of meta-analyses in the 2015-17 literature can provide a benchmark for future meta-research studies gauging the computational reproducibility of published research in ecology and evolutionary biology.

Is communication guidance mistaken? Qualitative study of parent-oncologist communication in childhood cancer.

BACKGROUND: Guidance encourages oncologists to engage patients and relatives in discussing the emotions that accompany cancer diagnosis and treatment. We investigated the perspectives of parents of children with leukaemia on the role of paediatric oncologists in such discussion. METHODS: Qualitative study comprising 33 audio-recorded parent-oncologist consultations and semi-structured interviews with 67 parents during the year following diagnosis. RESULTS: Consultations soon after the diagnosis were largely devoid of overt discussion of parental emotion. Interviewed parents did not describe a need for such discussion. They spoke of being comforted by oncologists' clinical focus, by the biomedical information they provided and by their calmness and constancy. When we explicitly asked parents 1 year later about the oncologists' role in emotional support, they overwhelmingly told us that they did not want to discuss their feelings with oncologists. They wanted to preserve the oncologists' focus on their child's clinical care, deprecated anything that diverted from this and spoke of the value of boundaries in the parent-oncologist relationship. CONCLUSION: Parents were usually comforted by oncologists, but this was not achieved in the way suggested by communication guidance. Communication guidance would benefit from an enhanced understanding of how emotional support is experienced by those who rely on it.

Predicting and reasoning about replicability using structured groups.

This paper explores judgements about the replicability of social and behavioural sciences research and what drives those judgements. Using a mixed methods approach, it draws on qualitative and quantitative data elicited from groups using a structured approach called the IDEA protocol ('investigate', 'discuss', 'estimate' and 'aggregate'). Five groups of five people with relevant domain expertise evaluated 25 research claims that were subject to at least one replication study. Participants assessed the probability that each of the 25 research claims would replicate (i.e. that a replication study would find a statistically significant result in the same direction as the original study) and described the reasoning behind those judgements. We quantitatively analysed possible correlates of predictive accuracy, including self-rated expertise and updating of judgements after feedback and discussion. We qualitatively analysed the reasoning data to explore the cues, heuristics and patterns of reasoning used by participants. Participants achieved 84% classification accuracy in predicting replicability. Those who engaged in a greater breadth of reasoning provided more accurate replicability judgements. Some reasons were more commonly invoked by more accurate participants, such as 'effect size' and 'reputation' (e.g. of the field of research). There was also some evidence of a relationship between statistical literacy and accuracy.

Predicting reliability through structured expert elicitation with the repliCATS (Collaborative Assessments for Trustworthy Science) process.

As replications of individual studies are resource intensive, techniques for predicting the replicability are required. We introduce the repliCATS (Collaborative Assessments for Trustworthy Science) process, a new method for eliciting expert predictions about the replicability of research. This process is a structured expert elicitation approach based on a modified Delphi technique applied to the evaluation of research claims in social and behavioural sciences. The utility of processes to predict replicability is their capacity to test scientific claims without the costs of full replication. Experimental data supports the validity of this process, with a validation study producing a classification accuracy of 84% and an Area Under the Curve of 0.94, meeting or exceeding the accuracy of other techniques used to predict replicability. The repliCATS process provides other benefits. It is highly scalable, able to be deployed for both rapid assessment of small numbers of claims, and assessment of high volumes of claims over an extended period through an online elicitation platform, having been used to assess 3000 research claims over an 18 month period. It is available to be implemented in a range of ways and we describe one such implementation. An important advantage of the repliCATS process is that it collects qualitative data that has the potential to provide insight in understanding the limits of generalizability of scientific claims. The primary limitation of the repliCATS process is its reliance on human-derived predictions with consequent costs in terms of participant fatigue although careful design can minimise these costs. The repliCATS process has potential applications in alternative peer review and in the allocation of effort for replication studies.

Anatomic Snuffbox (Distal Radial Artery) and Radial Artery Access for Treatment of Intracranial Aneurysms with FDA-Approved Flow Diverters.

BACKGROUND AND PURPOSE: Transradial access for neurointerventional procedures has been proved a safer and more comfortable alternative to femoral artery access. We present our experience with transradial (distal radial/anatomic snuffbox and radial artery) access for treatment of intracranial aneurysms using all 3 FDA-approved flow diverters. MATERIALS AND METHODS: This was a high-volume, dual-center, retrospective analysis of each institution's data base between June 2018 and June 2020 and a collection of all patients treated with flow diversion via transradial access. Patient demographic information and procedural and radiographic data were obtained. RESULTS: Seventy-four patients were identified (64 female patients) with a mean age of 57.5 years with a total of 86 aneurysms. Most aneurysms were located in the anterior circulation (93%) and within the intracranial ICA (67.4%). The mean aneurysm size was 5.5 mm. Flow diverters placed included the Pipeline Embolization Device (Flex) (PED, n = 65), the Surpass Streamline Flow Diverter (n = 8), and the Flow-Redirection Endoluminal Device (FRED, n = 1). Transradial access was successful in all cases, but femoral crossover was required in 3 cases (4.1%) due to tortuous anatomy and inadequate support of the catheters in 2 cases and an inability to navigate to the target vessel in a patient with an aberrant right subclavian artery. All 71 other interventions were successfully performed via the transradial approach (95.9%). No access site complications were encountered. Asymptomatic radial artery occlusion was encountered in 1 case (3.7%). CONCLUSIONS: Flow diverters can be successfully placed via the transradial approach with high technical success, low access site complications, and a low femoral crossover rate.

Systematic review of the addition of vincristine plus steroid pulses in maintenance treatment for childhood acute lymphoblastic leukaemia - an individual patient data meta-analysis involving 5,659 children.

Vincristine plus steroid pulses have long been a part of maintenance treatment in many protocols for childhood acute lymphoblastic leukaemia (ALL). A collaborative individual patient data meta-analysis of all randomised trials of the addition of vincristine plus prednisone/prednisolone (VP) pulses in childhood ALL was updated and extended to include trials comparing vincristine plus dexamethasone (VD) pulses to maintenance without pulses. VP pulses improved event-free survival (EFS) (70.1% vs. 62.0% at 5 years; odds ratio (OR) = 0.71; 95% confidence interval (CI) = 0.61-0.84; P = 0.00004); VD pulses did not have a significant effect (80.9% vs. 79.9% 5 year EFS; OR = 0.94; 95% CI = 0.80-1.11; P = 0.5). Heterogeneity between groups (VP or VD) was significant (P = 0.02). Neither treatment clearly affected overall survival. The difference between the VP and VD results is probably due to the greater early intensity of the backbone of the VD trial protocols and improved outcome seen in the VD trials, which were more recent. Pulses may still be useful in cases where less intensive early therapy is used and the balance between these treatments in terms of both effectiveness and toxicity needs to be considered.

Geographical and temporal distribution of cancer survival in teenagers and young adults in England.

BACKGROUND: Between 1979 and 2001, an analysis of cancer survival in young people in England, aged 13 to 24 years, showed overall improvements. However, for some diagnostic groups, little or no increases were observed. The aim of this study was to analyse the regional distribution of cancer survival in teenagers and young adults in England in order to identify patterns and potential for improvements at a regional scale. METHODS: We examined geographical and temporal patterns in relative survival in cancer patients aged 13-24 years in England during the time period 1979-2001. Cancer cases were grouped according to an internationally recognised morphology-based diagnostic scheme. RESULTS: For most diagnostic groups, there was little variation in survival between regions, except for testicular germ cell tumours (P=0.006) and colorectal carcinoma (P=0.002). For certain diagnostic groups, the temporal pattern in survival differed between regions. However, in regions that showed poor survival during the early part of the study period, greatest improvements were observed in groups such as acute lymphoid leukaemia, acute myeloid leukaemia, testicular tumours and melanoma. CONCLUSION: In conclusion, there was a reduction in the differences in survival between regions during the study period.

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981-2002.

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0-14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981-2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27-2.99) for osteosarcoma, 1.90 (1.58-2.21) for Ewing sarcoma and 0.21 (0.11-0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6-5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981-2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91-0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98-1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered.

Survival from cancer in teenagers and young adults in England, 1979-2003.

Cancer is the leading cause of disease-related death in teenagers and young adults aged 13-24 years (TYAs) in England. We have analysed national 5-year relative survival among more than 30,000 incident cancer cases in TYAs. For cancer overall, 5-year survival improved from 63% in 1979-84 to 74% during 1996-2001 (P<0.001). However, there were no sustained improvements in survival over time among high-grade brain tumours and bone and soft tissue sarcomas. Survival patterns varied by age group (13-16, 17-20, 21-24 years), sex and diagnosis. Survival from leukaemia and brain tumours was better in the youngest age group but in the oldest from germ-cell tumours (GCTs). For lymphomas, bone and soft tissue sarcomas, melanoma and carcinomas, survival was not significantly associated with age. Females had a better survival than males except for GCTs. Most groups showed no association between survival and socioeconomic deprivation, but for leukaemias, head and neck carcinoma and colorectal carcinoma, survival was significantly poorer with increasing deprivation. These results will aid the development of national specialised service provision for this age group and identify areas of clinical need that present the greatest challenges.

Childhood leukaemia: long-term excess mortality and the proportion 'cured'.

Survival from childhood leukaemia has increased, but the proportion of children cured is unknown. The proportion 'cured' is defined as the proportion of survivors for whom, as a group, there is no longer excess mortality compared to the general population. Average time to cure is defined as the time since diagnosis at which the excess mortality rate has declined to or below a predetermined small value. Data on children diagnosed with leukaemia during 1971-2000 in Great Britain were used to estimate trends in survival, the proportion cured and the average time to cure. Five-year survival for all types of leukaemia combined rose from 33 to 79% by 2000. The percentage cured rose from 25 to 68% by 1995; it is predicted to increase to 73% for those diagnosed more recently. Average time to cure increased from 12 years (95% confidence interval (CI): 11-14) to 19 years (95% CI: 14-26) for lymphoid leukaemia (average annual increase of 0.3 years; P<0.001), but remained at about 5 years for acute nonlymphoblastic leukaemia. The proportion of children cured of leukaemia has risen dramatically, but the period of excess mortality associated with lymphoid leukaemia has also increased, possibly because of late relapse, secondary malignancy and toxicity from treatment.

Rates of inclusion of teenagers and young adults in England into National Cancer Research Network clinical trials: report from the National Cancer Research Institute (NCRI) Teenage and Young Adult Clinical Studies Development Group.

Poor inclusion rates into clinical trials for teenagers and young adults (TYA; aged 13-24 years) have been assumed but not systematically investigated in England. We analysed accrual rates (AR) from 1 April 2005 up to 31 March 2007 to National Cancer Research Network (NCRN) Phase III trials for the commonest tumour types occurring in TYA and children: leukaemia, lymphoma, brain and central nervous system, bone sarcomas and male germ cell tumours. AR for 2005-2007 were 43.2% for patients aged 10-14 years, 25.2% for patients aged 15-19 years, and 13.1% for patients aged 20-24 years in the tumour types analysed. Compared with accrual from 1 April 2005 to 31 March 2006, AR between 1 April 2006 and 31 March 2007 increased for those aged 10-14 and 15-19 years, but fell for those aged 20-24 years. AR varied considerably among cancer types. Despite four trials being available, patients over 16 years with central nervous system tumours were not recruited. Rates of participation in clinical trials in England from 2005 to 2007 were much lower for TYA older than 15 years compared with children and younger teenagers. The variations in open trials, trial age eligibility criteria and extent of trial activation in treatment centres in part explain this observation. Other possible influences, such as difficulties associated with the consent of TYA require further evaluation. Closer dialogue between those involved in planning and running trials for children and for adults is necessary to improve trial availability and recruitment. Further research is required to identify trends in trial availability and accrual for those tumours constituting the remaining 26% of TYA cancers.

Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia: a randomised trial.

BACKGROUND: 6-mercaptopurine has been a standard component of long-term continuing treatment for childhood lymphoblastic leukaemia, whereas 6-thioguanine has been mainly used for intensification courses. Since preliminary data have shown that 6-thioguanine is more effective than 6-mercaptopurine, we compared the efficacy and toxicity of the two drugs for childhood lymphoblastic leukaemia. METHODS: Consecutive children with lymphoblastic leukaemia diagnosed in the UK and Ireland between April, 1997, and June, 2002, were randomly assigned either 6-thioguanine (750 patients) or 6-mercaptopurine (748 patients) during interim maintenance and continuing therapy. All patients received 6-thioguanine during intensification courses. We analysed event-free and overall survival on an intention-to-treat basis. We obtained toxicity data using an adverse-event reporting system, with follow-up questionnaires to seek detailed information for specific toxicities. This trial is registered with the International Standard Randomised Controlled Number 26727615 with the name ALL97. FINDINGS: After a median follow up of 6 years, there was no difference in event-free or overall survival between the two treatment groups. Although 6-thioguanine conferred a significantly lower risk of isolated CNS relapse than did 6-mercaptopurine (odds ratio [OR] 0.53, 95% CI 0.30-0.92, p=0.02), the benefit was offset by an increased risk of death in remission (2.22, 1.20-4.14, p=0.01), mainly due to infections during continuing therapy. Additionally, 95 patients developed veno-occlusive disease of the liver. Of these, 82 were randomly assigned 6-thioguanine, representing 11% of all 6-thioguanine recipients. On long-term follow-up, about 5% of 6-thioguanine recipients have evidence of non-cirrhotic portal hypertension due to periportal liver fibrosis or nodular regenerative hyperplasia. INTERPRETATION: Compared with 6-mercaptopurine, 6-thioguanine causes excess toxicity without an overall benefit. 6-mercaptopurine should remain the thiopurine of choice for continuing therapy of childhood lymphoblastic leukaemia.