Simulation and Synthesis in Medical Imaging

This editorial introduces the Special Issue on Simulation and Synthesis in Medical Imaging. In this editorial, we define so-far ambiguous terms of simulation and synthesis in medical imaging. We also briefly discuss the synergistic importance of mechanistic (hypothesis-driven) and phenomenological (data-driven) models of medical image generation. Finally, we introduce the twelve papers published in this issue covering both mechanistic (5) and phenomenological (7) medical image generation. This rich selection of papers covers applications in cardiology, retinopathy, histopathology, neurosciences, and oncology. It also covers all mainstream diagnostic medical imaging modalities. We conclude the editorial with a personal view on the field and highlight some existing challenges and future research opportunities

Wide variation in susceptibility of transmitted/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency

© 2016 The Author(s).The gag gene is highly polymorphic across HIV-1 subtypes and contributes to susceptibility to protease inhibitors (PI), a critical class of antiretrovirals that will be used in up to 2 million individuals as second-line therapy in sub Saharan Africa by 2020. Given subtype C represents around half of all HIV-1 infections globally, we examined PI susceptibility in subtype C viruses from treatment-naïve individuals. PI susceptibility was measured in a single round infection assay of full-length, replication competent MJ4/gag chimeric viruses, encoding the gag gene and 142 nucleotides of pro derived from viruses in 20 patients in the Zambia-Emory HIV Research Project acute infection cohort. Ten-fold variation in susceptibility to PIs atazanavir and lopinavir was observed across 20 viruses, with EC50 s ranging 0.71-6.95 nM for atazanvir and 0.64-8.54 nM for lopinavir. Ten amino acid residues in Gag correlated with lopinavir EC50 (p < 0.01), of which 380 K and 389I showed modest impacts on in vitro drug susceptibility. Finally a significant relationship between drug susceptibility and replication capacity was observed for atazanavir and lopinavir but not darunavir. Our findings demonstrate large variation in susceptibility of PI-naïve subtype C viruses that appears to correlate with replication efficiency and could impact clinical outcomes

Eye Closure Interacts with Music to Influence Vividness and Content of Directed Imagery

Goal-directed, intentional mental imagery generation supports a range of daily self-regulatory activities, such as planning, decision-making, and recreational escapism. Many clinical interventions for mood and anxiety disorders also use imagery and their effectiveness can be affected by an individual's ability to manipulate vividness and content of mental imagery. Prior literature points towards music as a promising candidate to influence imagination in such settings, but basic questions remain regarding how music affects mental imagery and how it interacts with basic, well-established parameters, such as facilitatory effects of eye closure. One hundred participants listened to music and a silent control whilst performing a guided mental imagery task. Specifically, participants saw a short video of a figure journeying towards a landmark and imagined a continuation of the journey with either closed or open eyes. After each trial, participants reported vividness and content of their imagined journeys. Bayesian Mixed Effects Models obtained strong evidence of greater vividness, duration, as well as distance travelled in music conditions compared to silent conditions. Additionally, interactive effects of music and eye closure were found for both vividness and the emotional valence of imagined content, where music effects were disproportionately amplified by eye closure. Findings further support music's potential to manipulate the perceptual, spatial-temporal, as well as emotional sentiment of deliberately generated mental imagery

Knowledge and attitudes towards dementia in adolescent students

Background: Improving people’s knowledge, perceptions and attitudes of dementia is important in the formation of dementia-friendly communities. However, at present, there is very little evidence from adolescents, who are already the junior members of such communities and will be carers in their own rights in the future. Our aim was to evaluate adolescents’ knowledge and attitudes of dementia. Methods: Four-hundred and fifty adolescents, aged 15–18 years, from schools in Sussex (UK) were invited to complete a series of questions that assessed their dementia knowledge and attitudes. Results: A total of 359 adolescent students completed the questionnaire. Out of 15 questions on dementia knowledge, participants were on average able to answer less than half correctly (M = 6.65, standard deviation = 2.34). Responses to the attitudes questionnaire showed that adolescent students had both positive and negative attitudes toward dementia. Discussion: There is scope for adolescents attending school to improve their dementia knowledge and attitudes. More effort is needed to embed initial dementia understanding in the school curriculum which will improve awareness about dementia at an earlier age and will enhance dementia-friendly communities

The Effectiveness of a Home Care Program for Supporting Caregivers of Persons with Dementia in Developing Countries: A Randomised Controlled Trial from Goa, India

OBJECTIVES: To develop and evaluate the effectiveness of a home based intervention in reducing caregiver burden, promoting caregiver mental health and reducing behavioural problems in elderly persons with dementia. METHODOLOGY AND PRINCIPAL FINDINGS: This was a randomised controlled trial in which the person with dementia-caregiver dyad was randomly allocated either to receive the intervention immediately or to a waiting list group which received the intervention after 6 months. It was carried out in communities based in two talukas (administrative blocks) in Goa, India. Mild to moderate cases with dementia (diagnosed using the DSM IV criteria and graded using the Clinical Dementia Rating scale) and their caregivers were included in the trial. Community based intervention provided by a team consisting of Home Care Advisors who were supervised by a counselor and a psychiatrist, focusing on supporting the caregiver through information on dementia, guidance on behaviour management, a single psychiatric assessment and psychotropic medication if needed. We measured caregiver mental health (General Health Questionnaire), caregiver burden (Zarit Burden Score), distress due to behavioural disturbances (NPI-D), behavioural problems in the subject (NPI-S) and activities of daily living in the elder with dementia (EASI). Outcome evaluations were masked to the allocation status. We analysed each outcome with a mixed effects model. 81 families enrolled in the trial; 41 were randomly allocated to the intervention. 59 completed the trial and 18 died during the trial. The intervention led to a significant reduction of GHQ (-1.12, 95% CI -2.07 to -0.17) and NPI-D scores (-1.96, 95%CI -3.51 to -0.41) and non-significant reductions in the ZBS, EASI and NPI-S scores. We also observed a non-significant reduction in the total number of deaths in people with dementia in the intervention arm (OR 0.34, 95% CI 0.01 to 1.03). CONCLUSION: Home based support for caregivers of persons with dementia, which emphasizes the use of locally available, low-cost human resources, is feasible, acceptable and leads to significant improvements in caregiver mental health and burden of caring. ClinicalTrials.gov NCT00479271

"The contribution of chronic diseases to the prevalence of dependence among older people in Latin America, China and India: a 10/66 Dementia Research Group population-based survey"

<p>Abstract</p> <p>Background</p> <p>The number of older people is set to increase dramatically worldwide. Demographic changes are likely to result in the rise of age-related chronic diseases which largely contribute to years lived with a disability and future dependence. However dependence is much less studied although intrinsically linked to disability. We investigated the prevalence and correlates of dependence among older people from middle income countries.</p> <p>Methods</p> <p>A one-phase cross-sectional survey was carried out at 11 sites in seven countries (urban sites in Cuba, Venezuela, and Dominican Republic, urban and rural sites in Peru, Mexico, China and India). All those aged 65 years and over living in geographically defined catchment areas were eligible. In all, 15,022 interviews were completed with an informant interview for each participant. The full 10/66 Dementia Research Group survey protocol was applied, including ascertainment of depression, dementia, physical impairments and self-reported diagnoses. Dependence was interviewer-rated based on a key informant's responses to a set of open-ended questions on the participant's needs for care. We estimated the prevalence of dependence and the independent contribution of underlying health conditions. Site-specific prevalence ratios were meta-analysed, and population attributable prevalence fractions (PAPF) calculated.</p> <p>Results</p> <p>The prevalence of dependence increased with age at all sites, with a tendency for the prevalence to be lower in men than in women. Age-standardised prevalence was lower in all sites than in the USA. Other than in rural China, dementia made the largest independent contribution to dependence, with a median PAPF of 34% (range 23%-59%). Other substantial contributors were limb impairment (9%, 1%-46%), stroke (8%, 2%-17%), and depression (8%, 1%-27%).</p> <p>Conclusion</p> <p>The demographic and health transitions will lead to large and rapid increases in the numbers of dependent older people particularly in middle income countries (MIC). The prevention and control of chronic neurological and neuropsychiatric diseases and the development of long-term care policies and plans should be urgent priorities.</p

Expansion of oxygen minimum zones may reduce available habitat for tropical pelagic fishes

Climate model predictions1, 2 and observations3, 4 reveal regional declines in oceanic dissolved oxygen, which are probably influenced by global warming5. Studies indicate ongoing dissolved oxygen depletion and vertical expansion of the oxygen minimum zone (OMZ) in the tropical northeast Atlantic Ocean6, 7. OMZ shoaling may restrict the usable habitat of billfishes and tunas to a narrow surface layer8, 9. We report a decrease in the upper ocean layer exceeding 3.5 ml l−1 dissolved oxygen at a rate of ≤1 m yr−1 in the tropical northeast Atlantic (0–25° N, 12–30° W), amounting to an annual habitat loss of ~5.95×1013 m3, or 15% for the period 1960–2010. Habitat compression and associated potential habitat loss was validated using electronic tagging data from 47 blue marlin. This phenomenon increases vulnerability to surface fishing gear for billfishes and tunas8, 9, and may be associated with a 10–50% worldwide decline of pelagic predator diversity10. Further expansion of the Atlantic OMZ along with overfishing may threaten the sustainability of these valuable pelagic fisheries and marine ecosystems

Post-mortem brain analyses of the Lothian Birth Cohort 1936:Extending lifetime cognitive and brain phenotyping to the level of the synapse

INTRODUCTION: Non-pathological, age-related cognitive decline varies markedly between individuals andplaces significant financial and emotional strain on people, their families and society as a whole.Understanding the differential age-related decline in brain function is critical not only for the development oftherapeutics to prolong cognitive health into old age, but also to gain insight into pathological ageing suchas Alzheimer’s disease. The Lothian Birth Cohort of 1936 (LBC1936) comprises a rare group of people forwhom there are childhood cognitive test scores and longitudinal cognitive data during older age, detailedstructural brain MRI, genome-wide genotyping, and a multitude of other biological, psycho-social, andepidemiological data. Synaptic integrity is a strong indicator of cognitive health in the human brain;however, until recently, it was prohibitively difficult to perform detailed analyses of synaptic and axonalstructure in human tissue sections. We have adapted a novel method of tissue preparation at autopsy toallow the study of human synapses from the LBC1936 cohort in unprecedented morphological andmolecular detail, using the high-resolution imaging techniques of array tomography and electronmicroscopy. This allows us to analyze the brain at sub-micron resolution to assess density, proteincomposition and health of synapses. Here we present data from the first donated LBC1936 brain andcompare our findings to Alzheimer’s diseased tissue to highlight the differences between healthy andpathological brain ageing. RESULTS: Our data indicates that compared to an Alzheimer’s disease patient, the cognitively normalLBC1936 participant had a remarkable degree of preservation of synaptic structures. However,morphological and molecular markers of degeneration in areas of the brain associated with cognition(prefrontal cortex, anterior cingulate cortex, and superior temporal gyrus) were observed. CONCLUSIONS: Our novel post-mortem protocol facilitates high-resolution neuropathological analysis of the well-characterized LBC1936 cohort, extending phenotyping beyond cognition and in vivo imaging to nowinclude neuropathological changes, at the level of single synapses. This approach offers an unprecedentedopportunity to study synaptic and axonal integrity during ageing and how it contributes to differences in agerelatedcognitive change. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40478-015-0232-0) contains supplementary material, which is available to authorized users

Reliability of 1-repetition maximum estimation for upper and lower body muscular strength measurement in untrained middle aged type 2 diabetic patients

Purpose: The 1-repetition maximum (1-RM) test is the gold standard test for evaluating maximal dynamic strength of groups of muscles. However, safety of actual 1-RM testing is questionable in clinical situations such as type 2 diabetes (T2D), where an estimated 1-RM test is preferred. It is unclear if acceptable test retest reliability exists for the estimated 1-RM test in middle aged T2D patients. This study examined the reliability of the estimated 1-RM strength test in untrained middle aged T2D subjects.Methods: Twenty five untrained diabetic males (n=19) and females (n=6) aged 40.7+0.4 years participated in the study. Participants undertook the first estimated 1-RM test for five exercises namely supine bench press, leg press, lateral pull, leg extension and seated biceps curls. A familiarisation session was provided three to five days before the first test. 1-RM was estimated for all participants by Brzycki 1-RM prediction equation. Another identical 1-RM estimation procedure occurred one week after first test. Intraclass correlation coefficients (ICC), paired t-test, standard error of measurement (SEM), Bland-Altman plots, and estimation of 95% CI were used to assess reliability.Results: Test-retest reliability was excellent (ICC2,1=0.98-0.99) for all measurements with the highest for leg extension (ICC2,1=0.99). The SEM was lowest for lateral pull and leg extension exercises. Paired t-tests showed non-significant differences between the means of 2 sessions across three of five exercises.Conclusions: The study findings suggest that estimation of 1-RM is reliable for upper and lower body muscular strength measurement in untrained middle aged T2D patients.https://doi.org/10.5812/asjsm.345493pubpub