Four-dimensional Cone Beam CT Reconstruction and Enhancement using a Temporal Non-Local Means Method

Four-dimensional Cone Beam Computed Tomography (4D-CBCT) has been developed to provide respiratory phase resolved volumetric imaging in image guided radiation therapy (IGRT). Inadequate number of projections in each phase bin results in low quality 4D-CBCT images with obvious streaking artifacts. In this work, we propose two novel 4D-CBCT algorithms: an iterative reconstruction algorithm and an enhancement algorithm, utilizing a temporal nonlocal means (TNLM) method. We define a TNLM energy term for a given set of 4D-CBCT images. Minimization of this term favors those 4D-CBCT images such that any anatomical features at one spatial point at one phase can be found in a nearby spatial point at neighboring phases. 4D-CBCT reconstruction is achieved by minimizing a total energy containing a data fidelity term and the TNLM energy term. As for the image enhancement, 4D-CBCT images generated by the FDK algorithm are enhanced by minimizing the TNLM function while keeping the enhanced images close to the FDK results. A forward-backward splitting algorithm and a Gauss-Jacobi iteration method are employed to solve the problems. The algorithms are implemented on GPU to achieve a high computational efficiency. The reconstruction algorithm and the enhancement algorithm generate visually similar 4D-CBCT images, both better than the FDK results. Quantitative evaluations indicate that, compared with the FDK results, our reconstruction method improves contrast-to-noise-ratio (CNR) by a factor of 2.56~3.13 and our enhancement method increases the CNR by 2.75~3.33 times. The enhancement method also removes over 80% of the streak artifacts from the FDK results. The total computation time is ~460 sec for the reconstruction algorithm and ~610 sec for the enhancement algorithm on an NVIDIA Tesla C1060 GPU card.Comment: 20 pages, 3 figures, 2 table

The First Implementation of Respiratory Triggered 4DCBCT on a Linear Accelerator

Four Dimensional Cone Beam Computed Tomography (4DCBCT) is an image guidance strategy used for patient positioning in radiotherapy. In conventional implementations of 4DCBCT, a constant gantry speed and a constant projection pulse rate are used. Unfortunately, this leads to higher imaging doses than are necessary because a large number of redundant projections are acquired. In theoretical studies, we have previously demonstrated that by suppressing redundant projections the imaging dose can be reduced by 40-50% for a majority of patients with little reduction in image quality. The aim of this study was to experimentally realise the projection suppression technique, which we have called Respiratory Triggered 4DCBCT (RT-4DCBCT). A real-time control system was developed that takes the respiratory signal as input and computes whether to acquire, or suppress, the next projection trigger during 4DCBCT acquisition. The CIRS dynamic thorax phantom was programmed with a 2cm peak-to-peak motion and periods ranging from 2 to 8 seconds. Image quality was assessed by computing the edge response width of a 3cm imaging insert placed in the phantom as well as the signal to noise ratio of the phantoms tissue and the contrast to noise ratio between the phantoms lung and tissue. The standard deviation in the Superior-Inferior direction of the 3cm imaging insert was used to assess intra-phase bin displacement variations with a higher standard deviation implying more motion blur. The 4DCBCT imaging dose was reduced by 8.6%, 41%, 54%, 70% and 77% for patients with 2, 3, 4, 6 and 8 second breathing periods respectively when compared to conventional 4DCBCT. The standard deviation of the intra-phase bin displacement variation of the 3cm imaging insert was reduced by between 13% and 43% indicating a more consistent position for the projections within respiratory phases. For the 4 second breathing period, the edge response width was reduced by 39% (0.8mm) with only a 6-7% decrease in the signal to noise and contrast to noise ratios. RT-4DCBCT has been experimentally realised and reduced to practice on a linear accelerator with a measurable imaging dose reductions over conventional 4DCBCT and little degradation in image quality

Creative leisure activities, mental health and well-being during 5 months of the COVID-19 pandemic: a fixed effects analysis of data from 3725 US adults

Introduction: We investigated whether changes in engagement in home-based creative activities were associated with changes in depressive symptoms, anxiety symptoms and life satisfaction during the COVID-19 pandemic, aiming to replicate findings from the UK in a USA sample. Methods: 3725 adults were included from the COVID-19 Social Study in the USA, a panel study collecting data weekly during the COVID-19 pandemic. We measured engagement in eight types of creative leisure activities on the previous weekday between April and September 2020. Data were analysed using fixed effects regression models. Results: Increased time spent gardening was associated with reductions in depressive and anxiety symptoms and enhanced life satisfaction. Spending more time doing woodwork/DIY and arts/crafts were also associated with enhanced life satisfaction. However, more time watching television, films or other similar media (not for information on COVID-19) was associated with increased depressive symptoms. Other creative activities were not associated with mental health or well-being. Conclusion: Some findings differ from evidence obtained in the UK, demonstrating the importance of replicating research across countries. Our findings should also be considered when formulating guidelines for future stay-at-home directives, enabling individuals to stay well despite the closure of public resources

Who Engaged in Home-Based Arts Activities During the COVID-19 Pandemic? A Cross-Sectional Analysis of Data From 4,731 Adults in the United States

Arts engagement is a health-related behavior that may be influenced by social inequalities. While the COVID-19 pandemic provided new opportunities for some people to engage in the arts, it might have created barriers for others. We aimed to examine whether there was social patterning in home-based arts engagement during the pandemic in the United States, and whether predictors of engagement differed according to the type of arts activity. We included 4,731 adults who participated in the United States COVID-19 Social Study between April and July 2020. Three types of home-based arts engagement were considered: reading for pleasure, arts or crafts activities, and digital arts activities. Using logistic regression models, we tested cross-sectional associations between a broad range of demographic, socioeconomic, psychosocial, and health-related factors as well as adverse events and worries during lockdown and each type of arts engagement. The factors most strongly associated with all three types of arts engagement were social support, social network size, age, race/ethnicity, keyworker status, and experiencing physical or psychological abuse during the pandemic. However, most socioeconomic and health-related factors were not associated with arts engagement, including household income and mental and physical health problems. Overall, our findings indicate that the social gradient in arts engagement was reduced in the first 4 months of the COVID-19 pandemic in the United States. Given the health benefits of arts engagement, the potential diversification of arts audiences during the pandemic is promising for both population-level health and wellbeing and the future of the arts and cultural sector

High rates of carbon and dinitrogen fixation suggest a critical role of benthic pioneer communities in the energy and nutrient dynamics of coral reefs

Following coral mortality in tropical reefs, pioneer communities dominated by filamentous and crustose algae efficiently colonize substrates previously occupied by coral tissue. This phenomenon is particularly common after mass coral mortality following prolonged bleaching events associated with marine heatwaves. Pioneer communities play an important role for the biological succession and reorganization of reefs after disturbance. However, their significance for critical ecosystem functions previously mediated by corals, such as the efficient cycling of carbon (C) and nitrogen (N) within the reef, remains uncertain. We used 96 carbonate tiles to simulate the occurrence of bare substrates after disturbance in a coral reef of the central Red Sea. We measured rates of C and dinitrogen (N-2) fixation of pioneer communities on these tiles monthly over an entire year. Coupled with elemental and stable isotope analyses, these measurements provide insights into macronutrient acquisition, export and the influence of seasonality. Pioneer communities exhibited high rates of C and N(2)fixation within 4-8 weeks after the introduction of experimental bare substrates. Ranging from 13 to 25 mu mol C cm(-2) day(-1)and 8 to 54 nmol N cm(-2) day(-1), respectively, C and N(2)fixation rates were comparable to reported values for established Red Sea coral reefs. This similarity indicates that pioneer communities may quickly compensate for the loss of benthic productivity by corals. Notably, between 40% and 85% of fixed organic C was exported into the environment, constituting a vital source of energy for the coral reef food web. Our findings suggest that benthic pioneer communities may play a crucial, yet overlooked role in the C and N dynamics of oligotrophic coral reefs by contributing to the input of new C and N after coral mortality. While not substituting other critical ecosystem functions provided by corals (e.g. structural habitat complexity and coastal protection), pioneer communities likely contribute to maintaining coral reef nutrient cycling through the accumulation of biomass and import of macronutrients following coral loss. A freePlain Language Summarycan be found within the Supporting Information of this article.Peer reviewe

Closing a gap in tropical forest biomass estimation : taking crown mass variation into account in pantropical allometries

Accurately monitoring tropical forest carbon stocks is a challenge that remains outstanding. Allometric models that consider tree diameter, height and wood density as predictors are currently used in most tropical forest carbon studies. In particular, a pantropical biomass model has been widely used for approximately a decade, and its most recent version will certainly constitute a reference model in the coming years. However, this reference model shows a systematic bias towards the largest trees. Because large trees are key drivers of forest carbon stocks and dynamics, understanding the origin and the consequences of this bias is of utmost concern. In this study, we compiled a unique tree mass data set of 673 trees destructively sampled in five tropical countries (101 trees > 100 cm in diameter) and an original data set of 130 forest plots (1 ha) from central Africa to quantify the prediction error of biomass allometric models at the individual and plot levels when explicitly taking crown mass variations into account or not doing so. We first showed that the proportion of crown to total tree aboveground biomass is highly variable among trees, ranging from 3 to 88 %. This proportion was constant on average for trees = 45 Mg. This increase coincided with a progressive deviation between the pantropical biomass model estimations and actual tree mass. Taking a crown mass proxy into account in a newly developed model consistently removed the bias observed for large trees (> 1 Mg) and reduced the range of plot- level error (in %) from [-23; 16] to [0; 10]. The disproportionally higher allocation of large trees to crown mass may thus explain the bias observed recently in the reference pantropical model. This bias leads to far- from- negligible, but often overlooked, systematic errors at the plot level and may be easily corrected by taking a crown mass proxy for the largest trees in a stand into account, thus suggesting that the accuracy of forest carbon estimates can be significantly improved at a minimal cost

Pharmacokinetic boosting of olaparib:A randomised, cross-over study (PROACTIVE-study)

Background: Pharmacokinetic (PK) boosting is the intentional use of a drug-drug interaction to enhance systemic drug exposure. PK boosting of olaparib, a CYP3A-substrate, has the potential to reduce PK variability and financial burden. The aim of this study was to investigate equivalence of a boosted, reduced dose of olaparib compared to the non-boosted standard dose. Methods: This cross-over, multicentre trial compared olaparib 300 mg twice daily (BID) with olaparib 100 mg BID boosted with the strong CYP3A-inhibitor cobicistat 150 mg BID. Patients were randomised to the standard therapy followed by the boosted therapy, or vice versa. After seven days of each therapy, dense PK sampling was performed for noncompartmental PK analysis. Equivalence was defined as a 90% Confidence Interval (CI) of the geometric mean ratio (GMR) of the boosted versus standard therapy area under the plasma concentration-time curve (AUC0–12 h) within no-effect boundaries. These boundaries were set at 0.57–1.25, based on previous pharmacokinetic studies with olaparib capsules and tablets. Results: Of 15 included patients, 12 were eligible for PK analysis. The GMR of the AUC0–12 h was 1.45 (90% CI 1.27–1.65). No grade ≥3 adverse events were reported during the study. Conclusions: Boosting a 100 mg BID olaparib dose with cobicistat increases olaparib exposure 1.45-fold, compared to the standard dose of 300 mg BID. Equivalence of the boosted olaparib was thus not established. Boosting remains a promising strategy to reduce the olaparib dose as cobicistat increases olaparib exposure Adequate tolerability of the boosted therapy with higher exposure should be established.</p

Heart failure after treatment for breast cancer

Background: We aimed to develop dose–response relationships for heart failure (HF) following radiation and anthracyclines in breast cancer treatment, and to assess HF associations with trastuzumab and endocrine therapies. Methods and results: A case–control study was performed within a cohort of breast cancer survivors treated during 1980–2009. Cases (n = 102) had HF as first cardiovascular diagnosis and were matched 1:3 on age and date of diagnosis. Individual cardiac radiation doses were estimated, and anthracycline doses and use of trastuzumab and endocrine therapy were abstracted from oncology notes. For HF cases who received radiotherapy, the estimated median mean heart dose (MHD) was 6.8 Gy [interquartile range (IQR) 0.9–13.7]. MHD was not associated with HF risk overall [excess rate ratio (ERR) = 1%/Gy, 95% confidence interval (CI) −2 to 10]. In patients treated with anthracyclines, exposure of ≥20% of the heart to ≥20 Gy was associated with a rate ratio of 5.7 (95% CI 1.7–21.7) compared to <10% exposed to ≥20 Gy. For cases who received radiotherapy, median cumulative anthracycline dose was 247 mg/m2 (IQR 240–319). A dose-dependent increase was observed after anthracycline without trastuzumab (ERR = 1.5% per mg/m2, 95% CI 0.5–4.1). After anthracycline and trastuzumab, the rate ratio was 34.9 (95% CI 11.1–110.1) compared to no chemotherapy. Conclusions: In absence of anthracyclines, breast cancer radiotherapy was not associated with increased HF risk. Strongly elevated HF risks were observed after treatment with anthracyclines and also after treatment with trastuzumab. The benefits of these systemic treatments usually exceed the risks of HF, but our results emphasize the need to support ongoing efforts to evaluate preventative strategies