Quantifying inter-fraction cardiac substructure displacement during radiotherapy via magnetic resonance imaging guidance

Emerging evidence suggests cardiac substructures are highly radiosensitive during radiation therapy for cancer treatment. However, variability in substructure position after tumor localization has not been well characterized. This study quantifies inter-fraction displacement and planning organ at risk volumes (PRVs) of substructures by leveraging the excellent soft tissue contrast of magnetic resonance imaging (MRI). Eighteen retrospectively evaluated patients underwent radiotherapy for intrathoracic tumors with a 0.35 T MRI-guided linear accelerator. Imaging was acquired at a 17–25 s breath-hold (resolution 1.5 × 1.5 × 3 mm3). Three to four daily MRIs per patient (n = 71) were rigidly registered to the planning MRI-simulation based on tumor matching. Deep learning or atlas-based segmentation propagated 13 substructures (e.g., chambers, coronary arteries, great vessels) to daily MRIs and were verified by two radiation oncologists. Daily centroid displacements from MRI-simulation were quantified and PRVs were calculated. Across substructures, inter-fraction displacements for 14% in the left–right, 18% in the anterior-posterior, and 21% of fractions in the superior-inferior were \u3e 5 mm. Due to lack of breath-hold compliance, ~4% of all structures shifted \u3e 10 mm in any axis. For the chambers, median displacements were 1.8, 1.9, and 2.2 mm in the left–right, anterior-posterior, and superior-inferior axis, respectively. Great vessels demonstrated larger displacements (\u3e 3 mm) in the superior-inferior axis (43% of shifts) and were only 25% (left–right) and 29% (anterior-posterior) elsewhere. PRVs from 3 to 5 mm were determined as anisotropic substructure-specific margins. This exploratory work derived substructure-specific safety margins to ensure highly effective cardiac sparing. Findings require validation in a larger cohort for robust margin derivation and for applications in prospective clinical trials

Barriers to healthcare access and experiences of stigma: Findings from a coproduced Long Covid case-finding study

Background and Aim Long Covid is often stigmatised, particularly in people who are disadvantaged within society. This may prevent them from seeking help and could lead to widening health inequalities. This coproduced study with a Community Advisory Board (CAB) of people with Long Covid aimed to understand healthcare and wider barriers and stigma experienced by people with probable Long Covid. Methods An active case finding approach was employed to find adults with probable, but not yet clinically diagnosed, Long Covid in two localities in London (Camden and Merton) and Derbyshire, England. Interviews explored the barriers to care and the stigma faced by participants and were analysed thematically. This study forms part of the STIMULATE-ICP Collaboration. Findings Twenty-three interviews were completed. Participants reported limited awareness of what Long Covid is and the available pathways to management. There was considerable self-doubt among participants, sometimes reinforced by interactions with healthcare professionals (HCPs). Participants questioned their deservedness in seeking healthcare support for their symptoms. Hesitancy to engage with healthcare services was motivated by fear of needing more investigation and concerns regarding judgement about the ability to carry out caregiving responsibilities. It was also motivated by the complexity of the clinical presentation and fear of all symptoms being attributed to poor mental health. Participants also reported trying to avoid overburdening the health system. These difficulties were compounded by experiences of stigma and discrimination. The emerging themes reaffirmed a framework of epistemic injustice in relation to Long Covid, where creating, interpreting and conveying knowledge has varied credibility based on the teller's identity characteristics and/or the level of their interpretive resources. Conclusion We have codeveloped recommendations based on the findings. These include early signposting to services, dedicating protected time to listening to people with Long Covid, providing a holistic approach in care pathways, and working to mitigate stigma. Regardless of the diagnosis, people experiencing new symptoms must be encouraged to seek timely medical help. Clear public health messaging is needed among communities already disadvantaged by epistemic injustice to raise awareness of Long Covid, and to share stories that encourage seeking care and to illustrate the adverse effects of stigma

Characterizing Sensitive Cardiac Substructure Excursion Due to Respiration

PURPOSE: Whole-heart dose metrics are not as strongly linked to late cardiac morbidities as radiation doses to individual cardiac substructures. Our aim was to characterize the excursion and dosimetric variation throughout respiration of sensitive cardiac substructures for future robust safety margin design. METHODS AND MATERIALS: Eleven patients with cancer treatments in the thorax underwent 4-phase noncontrast 4-dimensional computed tomography (4DCT) with T2-weighted magnetic resonance imaging in end-exhale. The end-exhale phase of the 4DCT was rigidly registered with the magnetic resonance imaging and refined with an assisted alignment surrounding the heart from which 13 substructures (chambers, great vessels, coronary arteries, etc) were contoured by a radiation oncologist on the 4DCT. Contours were deformed to the other respiratory phases via an intensity-based deformable registration for radiation oncologist verification. Measurements of centroid and volume were evaluated between phases. Mean and maximum dose to substructures were evaluated across respiratory phases for the breast (n = 8) and thoracic cancer (n = 3) cohorts. RESULTS: Paired t tests revealed reasonable maintenance of geometric and anatomic properties (P \u3c .05 for 4/39 volume comparisons). Maximum displacements \u3e5 mm were found for 24.8%, 8.5%, and 64.5% of the cases in the left-right, anterior-posterior, and superior-inferior axes, respectively. Vector displacements were largest for the inferior vena cava and the right coronary artery, with displacements up to 17.9 mm. In breast, the left anterior descending artery D(mean) varied 3.03 ± 1.75 Gy (range, 0.53-5.18 Gy) throughout respiration whereas lung showed patient-specific results. Across all patients, whole heart metrics were insensitive to breathing phase (mean and maximum dose variations \u3c0.5 Gy). CONCLUSIONS: This study characterized the intrafraction displacement of the cardiac substructures through the respiratory cycle and highlighted their increased dosimetric sensitivity to local dose changes not captured by whole heart metrics. Results suggest value of cardiac substructure margin generation to enable more robust cardiac sparing and to reduce the effect of respiration on overall treatment plan quality

Prospective associations between bullying victimisation, internalised stigma, and mental health in South African adolescents living with HIV

Background: Adolescents living with HIV may be at elevated risk of psychological problems, which are correlated with negative health outcomes. In cross-sectional research with HIV-affected adolescents, bullying victimisation and internalised HIV stigma have been associated with poorer psychological health. We extended these findings and tested longitudinal associations between bullying victimisation, internalised stigma, and mental health among adolescents living with HIV. We also tested whether relationships between bullying victimisation and psychological symptoms were mediated by internalised stigma. Method: Adolescents living with HIV (n = 1060, 10–19 years, 55% female), who had ever initiated HIV treatment in 53 public health facilities in the Eastern Cape, South Africa, were interviewed and followed up 18 months later (n = 995, 94% retention). Participants completed well-validated measures of depression, anxiety, posttraumatic stress, bullying victimisation, and internalised stigma. Results: After adjusting for baseline mental health and sociodemographic characteristics, baseline internalised stigma prospectively predicted poorer outcomes on all psychological measures

Barriers and facilitators to seeking and accessing mental health support in primary care and the community among female migrants in Europe: a “feminisms” systematic review

BackgroundRecent years have seen record levels of migration to Europe. Female migrants are at heightened risk of developing mental health disorders, yet they face barriers to accessing mental health services in their host countries. This systematic review aims to summarise the barriers and facilitators to accessing mental health support for female migrants in Europe.MethodsThe review follows PRISMA guidelines, and the protocol was pre-published on PROSPERO. Six electronic databases were searched: CINAHL, Global Health Database, Medline, PsycARTICLES, PsycINFO and Web of Science. Thematic analysis was undertaken on the identified studies. A feminist quality appraisal tool was applied.ResultsEight qualitative, six quantitative and five mixed methods studies were identified. Barriers included a lack of information, stigma, religious and cultural practices and beliefs, and a lack of consideration of gender-specific needs within the health system. Gender-sensitive services, supportive general practitioners and religious leaders facilitated access.ConclusionsThe design of mental health research, services, policies, and commissioning of support for migrants must consider female migrant needs. Mental health support services must be culturally aware and gender sensitive

From ‘sugar daddies’ to ‘sugar babies’: exploring a pathway among age-disparate sexual relationships, condom use and adolescent pregnancy in South Africa

Background: Adolescent pregnancy has been linked to adverse outcomes. Most studies proposing risk pathways for adolescent pregnancy in South Africa are qualitative, hypothesising links among age-disparate relationships, reduced condom use and higher pregnancy rates. No known South African studies have quantitatively explored pathways to adolescent pregnancy. Objectives: This study aimed to: (i) identify the factors associated with adolescent pregnancy and (ii) explore a pathway of risk by assessing whether condom use mediated the relationship between age-disparate sexual relationships and adolescent pregnancy. Methods: A cross-sectional survey of 447 sexually active girls aged 10–19 years was undertaken in six health districts of South Africa. Multivariate logistic regressions controlled for confounders. Mediation tests used bootstrapping. Results: Consistent condom use (ß = –2.148, odds ratio (OR) = 8.566, P = 0.001) and school enrolment (ß = –1.600, OR = 0.202, P = 0.001) were associated with lower pregnancy rates. Age-disparate sex (ß = 1.093, OR = 2.982, P = 0.001) and long-term school absences (ß = 1.402, OR = 4.061, P = 0.001) were associated with higher pregnancy rates. The indirect effect of age-disparate sex on adolescent pregnancy through condom use was significant, irrespective of age, age at sexual initiation, poverty and residential environment (B = 0.4466, s.d. = 0.1303, confidence interval: 0.2323–0.7428). Conclusion: This survey supports hypotheses that inability to negotiate condom use in age-disparate sexual relationships may drive adolescent pregnancy. Interventions addressing these relationships, facilitating condom use and increasing access to sexual health services among adolescents might avert unwanted pregnancies

Fast automated cell phenotype image classification

BACKGROUND: The genomic revolution has led to rapid growth in sequencing of genes and proteins, and attention is now turning to the function of the encoded proteins. In this respect, microscope imaging of a protein's sub-cellular localisation is proving invaluable, and recent advances in automated fluorescent microscopy allow protein localisations to be imaged in high throughput. Hence there is a need for large scale automated computational techniques to efficiently quantify, distinguish and classify sub-cellular images. While image statistics have proved highly successful in distinguishing localisation, commonly used measures suffer from being relatively slow to compute, and often require cells to be individually selected from experimental images, thus limiting both throughput and the range of potential applications. Here we introduce threshold adjacency statistics, the essence which is to threshold the image and to count the number of above threshold pixels with a given number of above threshold pixels adjacent. These novel measures are shown to distinguish and classify images of distinct sub-cellular localization with high speed and accuracy without image cropping. RESULTS: Threshold adjacency statistics are applied to classification of protein sub-cellular localization images. They are tested on two image sets (available for download), one for which fluorescently tagged proteins are endogenously expressed in 10 sub-cellular locations, and another for which proteins are transfected into 11 locations. For each image set, a support vector machine was trained and tested. Classification accuracies of 94.4% and 86.6% are obtained on the endogenous and transfected sets, respectively. Threshold adjacency statistics are found to provide comparable or higher accuracy than other commonly used statistics while being an order of magnitude faster to calculate. Further, threshold adjacency statistics in combination with Haralick measures give accuracies of 98.2% and 93.2% on the endogenous and transfected sets, respectively. CONCLUSION: Threshold adjacency statistics have the potential to greatly extend the scale and range of applications of image statistics in computational image analysis. They remove the need for cropping of individual cells from images, and are an order of magnitude faster to calculate than other commonly used statistics while providing comparable or better classification accuracy, both essential requirements for application to large-scale approaches

Qualitative Real-Time Schlieren and Shadowgraph Imaging of Human Exhaled Airflows: An Aid to Aerosol Infection Control

Using a newly constructed airflow imaging system, airflow patterns were visualized that were associated with common, everyday respiratory activities (e.g. breathing, talking, laughing, whistling). The effectiveness of various interventions (e.g. putting hands and tissues across the mouth and nose) to reduce the potential transmission of airborne infection, whilst coughing and sneezing, were also investigated. From the digital video footage recorded, it was seen that both coughing and sneezing are relatively poorly contained by commonly used configurations of single-handed shielding maneuvers. Only some but not all of the forward momentum of the cough and sneeze puffs are curtailed with various hand techniques, and the remaining momentum is disseminated in a large puff in the immediate vicinity of the cougher, which may still act as a nearby source of infection. The use of a tissue (in this case, 4-ply, opened and ready in the hand) proved to be surprisingly effective, though the effectiveness of this depends on the tissue remaining intact and not ripping apart. Interestingly, the use of a novel ‘coughcatcher’ device appears to be relatively effective in containing coughs and sneezes. One aspect that became evident during the experimental procedures was that the effectiveness of all of these barrier interventions is very much dependent on the speed with which the user can put them into position to cover the mouth and nose effectively

Enantiopure titanocene complexes: direct evidence for paraptosis in cancer cells

Tolerated by normal tissues, anti-cancer therapies based on titanium compounds are limited by low efficacy/selectivity and lack of understanding of their mode(s) of action. In vitro antitumour activity and mode of cell death incurred by enantiopure TiCl2{n-C5H4CHEt(2 MeOPh)}2 (abbreviated CpR 2TiCl2) has been investigated. The in vitro anti-tumour activity of CpR 2TiCl2 is selective for cancer cells; in clonogenic assays, (S,S)-CpR 2TiCl2 was twice as effective at inhibiting colony formation than other stereoisomers after 24 h exposure. HPLC, MS and NMR techniques determined hydrolysis of CpR 2TiCl2; data strongly correlate with soluble [CpR 2Ti(OH (OH2)]+ being the biological trigger. Treatment of cells with CpR 2TiCl2 provoked extensive cytoplasmic vacuolization, endoplasmic reticulum (ER) swelling and activation of MAPKinase signal transduction, consistent with ligand-induced paraptosis, type III cell death, which is morphologically distinct from, and independent of apoptosis. Indeed, distinct from cisplatin, CpR 2TiCl2 failed to perturb cell cycle dynamics, induce γH2AX foci or evoke apoptosis in MDA-MB-468 and HCT-116 cells

Airflow Dynamics of Human Jets: Sneezing and Breathing - Potential Sources of Infectious Aerosols

10.1371/journal.pone.0059970PLoS ONE84