Space-time clustering analyses of childhood acute lymphoblastic leukaemia by immunophenotype

Space-time clustering analyses of acute lymphoblastic leukaemia in children, by immunophenotype, were carried out using a population-based registry. Significant evidence was found of space-time clustering for cases of the precursor B-cell sub-type, in the childhood peak, based on time and location at birth

Quality research in healthcare: are researchers getting enough statistical support?

BACKGROUND: Reviews of peer-reviewed health studies have highlighted problems with their methodological quality. As published health studies form the basis of many clinical decisions including evaluation and provisions of health services, this has scientific and ethical implications. The lack of involvement of methodologists (defined as statisticians or quantitative epidemiologists) has been suggested as one key reason for this problem and this has been linked to the lack of access to methodologists. This issue was highlighted several years ago and it was suggested that more investments were needed from health care organisations and Universities to alleviate this problem. METHODS: To assess the current level of methodological support available for health researchers in England, we surveyed the 25 National Health Services Trusts in England, that are the major recipients of the Department of Health's research and development (R&D) support funding. RESULTS AND DISCUSSION: The survey shows that the earmarking of resources to provide appropriate methodological support to health researchers in these organisations is not widespread. Neither the level of R&D support funding received nor the volume of research undertaken by these organisations showed any association with the amount they spent in providing a central resource for methodological support for their researchers. CONCLUSION: The promotion and delivery of high quality health research requires that organisations hosting health research and their academic partners put in place funding and systems to provide appropriate methodological support to ensure valid research findings. If resources are limited, health researchers may have to rely on short courses and/or a limited number of advisory sessions which may not always produce satisfactory results

A Corticothalamic Circuit Trades off Speed for Safety during Decision-Making under Motivational Conflict

Decisions to act while pursuing goals in the presence of danger must be made quickly but safely. Premature decisions risk injury or death, whereas postponing decisions risk goal loss. Here we show how mice resolve these competing demands. Using microstructural behavioral analyses, we identified the spatiotemporal dynamics of approach–avoidance decisions under motivational conflict in male mice. Then we used cognitive modeling to show that these dynamics reflect the speeded decision-making mechanisms used by humans and nonhuman primates, with mice trading off decision speed for safety of choice when danger loomed. Using calcium imaging in paraventricular thalamus and optogenetic inhibition of the prelimbic cortex to paraventricular thalamus pathway, we show that this speed-safety trade off occurs because increases in paraventricular thalamus activity increase decision caution, thereby increasing approach–avoid decision times in the presence of danger. Our findings demonstrate that a discrete brain circuit involving the paraventricular thalamus and its prefrontal input adjusts decision caution during motivational conflict, trading off decision speed for decision safety when danger is close. We identify the corticothalamic pathway as central to cognitive control during decision-making under conflict

Classification and incidence of cancers in adolescents and young adults in England 1979–1997

Cancer patients aged 15–24 years have distinct special needs. High quality cancer statistics are required for service planning. Data presented by primary site are inappropriate for this age group. We have developed a morphology-based classification and applied it to national cancer registration data for England 1979–1997. The study included 25 000 cancers and 134 million person–years at risk. Rates for each diagnostic group by age, sex and time period (1979–83, 1984–87, 1988–92, 1993–1997) were calculated. Overall rates in 15–19 and 20–24-year-olds were 144 and 226 per million person–years respectively. Lymphomas showed the highest rates in both age groups. Rates for leukaemias and bone tumours were lower in 20–24 year olds. Higher rates for carcinomas, central nervous system tumours, germ-cell tumours, soft tissue sarcomas and melanoma were seen in the older group. Poisson regression showed incidence increased over the study period by an average of 1.5% per annum (P<0.0001). Significant increases were seen in non-Hodgkins lymphoma (2.3%), astrocytoma (2.3%), germ-cell tumours (2.3%), melanoma (5.1%) and carcinoma of the thyroid (3.5%) and ovary (3.0%). Cancers common in the elderly are uncommon in adolescents and young adults. The incidence of certain cancers in the latter is increasing. Future studies should be directed towards aetiology

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio

Under-five mortality: spatial-temporal clusters in Ifakara HDSS in South-eastern Tanzania.

BACKGROUND\ud \ud Childhood mortality remains an important subject, particularly in sub-Saharan Africa where levels are still unacceptably high. To achieve the set Millennium Development Goals 4, calls for comprehensive application of the proven cost-effective interventions. Understanding spatial clustering of childhood mortality can provide a guide in targeting the interventions in a more strategic approach to the population where mortality is highest and the interventions are most likely to make an impact.\ud \ud METHODS\ud \ud Annual child mortality rates were calculated for each village, using person-years observed as the denominator. Kulldorff's spatial scan statistic was used for the identification and testing of childhood mortality clusters. All under-five deaths that occurred within a 10-year period from 1997 to 2006 were included in the analysis. Villages were used as units of clusters; all 25 health and demographic surveillance sites (HDSS) villages in the Ifakara health and demographic surveillance area were included.\ud \ud RESULTS\ud \ud Of the 10 years of analysis, statistically significant spatial clustering was identified in only 2 years (1998 and 2001). In 1998, the statistically significant cluster (p < 0.01) was composed of nine villages. A total of 106 childhood deaths were observed against an expected 77.3. The other statistically significant cluster (p < 0.05) identified in 2001 was composed of only one village. In this cluster, 36 childhood deaths were observed compared to 20.3 expected. Purely temporal analysis indicated that the year 2003 was a significant cluster (p < 0.05). Total deaths were 393 and expected were 335.8. Spatial-temporal analysis showed that nine villages were identified as statistically significant clusters (p < 0.05) for the period covering January 1997-December 1998. Total observed deaths in this cluster were 205 while 150.7 were expected.\ud \ud CONCLUSION\ud \ud There is evidence of spatial clustering in childhood mortality within the Ifakara HDSS. Further investigations are needed to explore the source of clustering and identify strategies of reaching the cluster population with the existing effective interventions. However, that should happen alongside delivery of interventions to the broader population

Understanding animal fears: a comparison of the cognitive vulnerability and harm-looming models

Background: The Cognitive Vulnerability Model holds that both clinical and sub-clinical manifestations of animal fears are a result of how an animal is perceived, and can be used to explain both individual differences in fear acquisition and the uneven distribution of fears in the population. This study looked at the association between fear of a number of animals and perceptions of the animals as uncontrollable, unpredictable, dangerous and disgusting. Also assessed were the perceived loomingness, prior familiarity, and negative evaluation of the animals as well as possible conditioning experiences. Methods: 162 first-year University students rated their fear and perceptions of four high-fear and four low-fear animals. Results: Perceptions of the animals as dangerous, disgusting and uncontrollable were significantly associated with fear of both high- and low-fear animals while perceptions of unpredictability were significantly associated with fear of high-fear animals. Conditioning experiences were unrelated to fear of any animals. In multiple regression analyses, loomingness did not account for a significant amount of the variance in fear beyond that accounted for by the cognitive vulnerability variables. However, the vulnerability variables accounted for between 20% and 51% of the variance in all animals fears beyond that accounted for by perceptions of the animals as looming. Perceptions of dangerousness, uncontrollability and unpredictability were highly predictive of the uneven distribution of animal fears. Conclusion: This study provides support for the Cognitive Vulnerability Model of the etiology of specific fears and phobias and brings into question the utility of the harm-looming model in explaining animal fearJason M Armfiel

Spatial quantitation of drugs in tissues using liquid extraction surface analysis mass spectrometry imaging

Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported

An infectious aetiology for childhood brain tumours? Evidence from space–time clustering and seasonality analyses

To investigate whether infections or other environmental exposures may be involved in the aetiology of childhood central nervous system tumours, we have analysed for space–time clustering and seasonality using population-based data from the North West of England for the period 1954 to 1998. Knox tests for space–time interactions between cases were applied with fixed thresholds of close in space, <5 km, and close in time, <1 year apart. Addresses at birth and diagnosis were used. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. Tests for heterogeneity and Edwards' test for sinusoidal variation were applied to examine changes of incidence with month of birth or diagnosis. There was strong evidence of space–time clustering, particularly involving cases of astrocytoma and ependymoma. Analyses of seasonal variation showed excesses of cases born in the late Autumn or Winter. Results are consistent with a role for infections in a proportion of cases from these diagnostic groups. Further studies are needed to identify putative infectious agents