Estimating the population health impact of a multi-cancer early detection genomic blood test to complement existing screening in the US and UK

Background: Multi-cancer early detection (MCED) next-generation-sequencing blood tests represent a potential paradigm shift in screening. Methods: We estimated the impact of screening in the US and UK. We used country-specific parameters for uptake, and test-specific sensitivity and false-positive rates for current screening: breast, colorectal, cervical and lung (US only) cancers. For the MCED test, we used cancer-specific sensitivities by stage. Outcomes included the true-positive:false-positive (TP:FP) ratio; and the cost of diagnostic investigations among screen positives, per cancer detected (Diagcost). Outcomes were estimated for recommended screening only, and then when giving the MCED test to anyone without cancer detected by current screening plus similarly aged adults ineligible for recommended screening. Results: In the US, current screening detects an estimated 189,498 breast, cervical, colorectal and lung cancers. An MCED test with 25–100% uptake detects an additional 105,526–422,105 cancers (multiple types). The estimated TP:FP (Diagcost) was 1.43 ($89,042) with current screening but only 1:1.8 ($7060) using an MCED test. For the UK the corresponding estimates were 1:18 (£10,452) for current screening, and 1:1.6 (£2175) using an MCED test. Conclusions: Adding an MCED blood test to recommended screening can potentially be an efficient strategy. Ongoing randomised studies are required for full efficacy and cost-effectiveness evaluations

Eye movements reveal a dissociation between memory encoding and retrieval in adults with autism

People with Autism Spectrum Disorder (ASD) exhibit subtle deficits in recollection, which have been proposed to arise from encoding impairments, though a direct link has yet to be demonstrated. In the current study, we used eye-tracking to obtain trial-specific measures of encoding (eye movement patterns) during incidental (natural viewing) and intentional (strategic) encoding conditions in adults with ASD and typical controls. Using this approach, we tested the degree to which differences in encoding might contribute to recollection impairments, or whether group differences in memory primarily emerge at retrieval. Following encoding of scenes, participants were asked to distinguish between old and similar lure scenes and provide 'remember'/'familiar' responses. Intentional encoding increased eye movements and subsequent recollection in both groups to a similar degree, but the ASD group were impaired overall at the memory task and used recollection less frequently. In controls, eye movements at encoding predicted subsequent correct responses and subsequent recollection on a trial-by-trial basis, as expected. In contrast, despite a similar pattern of eye movements during encoding in the two groups, eye movements did not predict trial-by-trial subsequent memory in ASD. Furthermore, recollection was associated with lower similarity between encoding- and retrieval-related eye movements in the ASD group compared to the control group. The eye-tracking results therefore provide novel evidence for a dissociation between encoding and recollection-based retrieval in ASD.This research was supported by a James S. McDonnell Scholar Award to J.S.S., and an Economic and Social Research Council Award to R.A.C. We would like to thank all the participants who gave their time for this experiment, as well as the Autism Research Centre, Cambridge for helping with participant recruitment and providing access to the eye-tracking equipment used for this study

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Investigating the experience of Moodle adoption through expert voices

Virtual learning environments (VLEs) such as Moodle are now widely used in universities and other organisations. One crucial factor in the successful employment of such platforms is the ability and commitment of teaching staff to adopt the system. Despite the importance of this role, there has been little work to examine the experience of using VLEs in practice. This paper presents initial, qualitative research aimed at understanding how Moodle is being used and the different experiences and perspectives of the staff involved. To generate themes and areas of interest for future investigation this paper uses interview data from two “expert witnesses” who have a deep understanding of how the platform is used. Emergent themes include: divergence between confident and basic users; the spread of usage within an academic community; lack of progression to innovative teaching methods

A Synthesis of Global Urbanization Projections

This chapter reviews recent literature on global projections of future urbanization, covering the population, economic and physical extent perspectives. We report on several recent findings based on studies and reports on global patterns of urbanization. Specifically, we review new literature that makes projections about the spatial pattern, rate, and magnitude of urbanization change in the next 30–50 years. While projections should be viewed and utilized with caution, the chapter synthesis reports on several major findings that will have significant socioeconomic and environmental impacts including the following: By 2030, world urban population is expected to increase from the current 3.4 billion to almost 5 billion; Urban areas dominate the global economy – urban economies currently generate more than 90 % of global Gross Value Added; From 2000 to 2030, the percent increase in global urban land cover will be over 200 % whereas the global urban population will only grow by a little over 70 %. Our synthesis of recent projections suggest that between 50%–60% of the total urban land in existence in 2030 will be built in the first three decades of the 21st century. Challenges and limitations of urban dynamic projections are discussed, as well as possible innovative applications and potential pathways towards sustainable urban futures

A Repeated Measures Experiment of Green Exercise to Improve Self-Esteem in UK School Children

Exercising in natural, green environments creates greater improvements in adult's self-esteem than exercise undertaken in urban or indoor settings. No comparable data are available for children. The aim of this study was to determine whether so called 'green exercise' affected changes in self-esteem; enjoyment and perceived exertion in children differently to urban exercise. We assessed cardiorespiratory fitness (20 m shuttle-run) and self-reported physical activity (PAQ-A) in 11 and 12 year olds (n = 75). Each pupil completed two 1.5 mile timed runs, one in an urban and another in a rural environment. Trials were completed one week apart during scheduled physical education lessons allocated using a repeated measures design. Self-esteem was measured before and after each trial, ratings of perceived exertion (RPE) and enjoyment were assessed after completing each trial. We found a significant main effect (F (1,74), = 12.2, p<0.001), for the increase in self-esteem following exercise but there was no condition by exercise interaction (F (1,74), = 0.13, p = 0.72). There were no significant differences in perceived exertion or enjoyment between conditions. There was a negative correlation (r = -0.26, p = 0.04) between habitual physical activity and RPE during the control condition, which was not evident in the green exercise condition (r = -0.07, p = 0.55). Contrary to previous studies in adults, green exercise did not produce significantly greater increases in self-esteem than the urban exercise condition. Green exercise was enjoyed more equally by children with differing levels of habitual physical activity and has the potential to engage less active children in exercise. © 2013 Reed et al

Reduced Hippocampal Functional Connectivity During Episodic Memory Retrieval in Autism

Increasing recent research has sought to understand the recollection impairments experienced by individuals with autism spectrum disorder (ASD). Here, we tested whether these memory deficits reflect a reduction in the probability of retrieval success or in the precision of memory representations. We also used functional magnetic resonance imaging (fMRI) to study the neural mechanisms underlying memory encoding and retrieval in ASD, focusing particularly on the functional connectivity of core episodic memory networks. Adults with ASD and typical control participants completed a memory task that involved studying visual displays and subsequently using a continuous dial to recreate their appearance. The ASD group exhibited reduced retrieval success, but there was no evidence of a difference in retrieval precision. fMRI data revealed similar patterns of brain activity and functional connectivity during memory encoding in the 2 groups, though encoding-related lateral frontal activity predicted subsequent retrieval success only in the control group. During memory retrieval, the ASD group exhibited attenuated lateral frontal activity and substantially reduced hippocampal connectivity, particularly between hippocampus and regions of the fronto-parietal control network. These findings demonstrate notable differences in brain function during episodic memory retrieval in ASD and highlight the importance of functional connectivity to understanding recollection-related retrieval deficits in this population.This work was supported by a James S. McDonnell Foundation Scholar Award to J.S.S. and was carried out within the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and the Wellcome Trust. R.A.C. was funded by the Economic and Social Research Council and P.M.B. by the Wellcome Trust

Age- and Sex-Specific Mortality Patterns in an Emerging Wildlife Epidemic: The Phocine Distemper in European Harbour Seals

Analyses of the dynamics of diseases in wild populations typically assume all individuals to be identical. However, profound effects on the long-term impact on the host population can be expected if the disease has age and sex dependent dynamics. The Phocine Distemper Virus (PDV) caused two mass mortalities in European harbour seals in 1988 and in 2002. We show the mortality patterns were highly age specific on both occasions, where young of the year and adult (>4 yrs) animals suffered extremely high mortality, and sub-adult seals (1–3 yrs) of both sexes experienced low mortality. Consequently, genetic differences cannot have played a main role explaining why some seals survived and some did not in the study region, since parents had higher mortality levels than their progeny. Furthermore, there was a conspicuous absence of animals older than 14 years among the victims in 2002, which strongly indicates that the survivors from the previous disease outbreak in 1988 had acquired and maintained immunity to PDV. These specific mortality patterns imply that contact rates and susceptibility to the disease are strongly age and sex dependent variables, underlining the need for structured epidemic models for wildlife diseases. Detailed data can thus provide crucial information about a number of vital parameters such as functional herd immunity. One of many future challenges in understanding the epidemiology of the PDV and other wildlife diseases is to reveal how immune system responses differ among animals in different stages during their life cycle. The influence of such underlying mechanisms may also explain the limited evidence for abrupt disease thresholds in wild populations

Physician Practice Patterns and Variation in the Delivery of Preventive Services

BACKGROUND: Strategies to improve preventive services delivery (PSD) have yielded modest effects. A multidimensional approach that examines distinctive configurations of physician attributes, practice processes, and contextual factors may be informative in understanding delivery of this important form of care. OBJECTIVE: We identified naturally occurring configurations of physician practice characteristics (PPCs) and assessed their association with PSD, including variation within configurations. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred thirty-eight family physicians in 84 community practices and 4,046 outpatient visits. MEASUREMENTS: Physician knowledge, attitudes, use of tools and staff, and practice patterns were assessed by ethnographic and survey methods. PSD was assessed using direct observation of the visit and medical record review. Cluster analysis identified unique configurations of PPCs. A priori hypotheses of the configurations likely to perform the best on PSD were tested using a multilevel random effects model. RESULTS: Six distinct PPC configurations were identified. Although PSD significantly differed across configurations, mean differences between configurations with the lowest and highest PSD were small (i.e., 3.4, 7.7, and 10.8 points for health behavior counseling, screening, and immunizations, respectively, on a 100-point scale). Hypotheses were not confirmed. Considerable variation of PSD rates within configurations was observed. CONCLUSIONS: Similar rates of PSD can be attained through diverse physician practice configurations. Significant within-configuration variation may reflect dynamic interactions between PPCs as well as between these characteristics and the contexts in which physicians function. Striving for a single ideal configuration may be less valuable for improving PSD than understanding and leveraging existing characteristics within primary care practices

Tomato protoplast DNA transformation: physical linkage and recombination of exogenous DNA sequences

Tomato protoplasts have been transformed with plasmid DNA's, containing a chimeric kanamycin resistance gene and putative tomato origins of replication. A calcium phosphate-DNA mediated transformation procedure was employed in combination with either polyethylene glycol or polyvinyl alcohol. There were no indications that the tomato DNA inserts conferred autonomous replication on the plasmids. Instead, Southern blot hybridization analysis of seven kanamycin resistant calli revealed the presence of at least one kanamycin resistance locus per transformant integrated in the tomato nuclear DNA. Generally one to three truncated plasmid copies were found integrated into the tomato nuclear DNA, often physically linked to each other. For one transformant we have been able to use the bacterial ampicillin resistance marker of the vector plasmid pUC9 to 'rescue' a recombinant plasmid from the tomato genome. Analysis of the foreign sequences included in the rescued plasmid showed that integration had occurred in a non-repetitive DNA region. Calf-thymus DNA, used as a carrier in transformation procedure, was found to be covalently linked to plasmid DNA sequences in the genomic DNA of one transformant. A model is presented describing the fate of exogenously added DNA during the transformation of a plant cell. The results are discussed in reference to the possibility of isolating DNA sequences responsible for autonomous replication in tomato.