Metal artefact reduction for accurate tumour delineation in radiotherapy

Background and purpose: Two techniques for metal artefact reduction for computed tomography were studied in order to identify their impact on tumour delineation in radiotherapy. Materials and methods: Using specially designed phantoms containing metal implants (dental, spine and hip) as well as patient images, we investigated the impact of two methods for metal artefact reduction on (A) the size and severity of metal artefacts and the accuracy of Hounsfield Unit (HU) representation, (B) the visual impact of metal artefacts on image quality and (C) delineation accuracy. A metal artefact reduction algorithm (MAR) and two types of dual energy virtual monochromatic (DECT VM) reconstructions were used separately and in combination to identify the optimal technique for each implant site. Results: The artefact area and severity was reduced (by 48–76% and 58–79%, MAR and DECT VM respectively) and accurate Hounsfield-value representation was increased by 22–82%. For each energy, the observers preferred MAR over non-MAR reconstructions (p < 0.01 for dental and hip cases, p < 0.05 for the spine case). In addition, DECT VM was preferred for spine implants (p < 0.01). In all cases, techniques that improved target delineation significantly (p < 0.05) were identified. Conclusions: DECT VM and MAR techniques improve delineation accuracy and the optimal of reconstruction technique depends on the type of metal implant

Leuconostoc performance in soy-based fermentations – Survival, acidification, sugar metabolism, and flavor comparisons

Leuconostoc spp. is often regarded as the flavor producer, responsible for the production of acetoin and diacetyl in dairy cheese. In this study, we investigate seven plant-derived Leuconostoc strains, covering four species, in their potential as a lyophilized starter culture for flavor production in fermented soy-based cheese alternatives. We show that the process of lyophilization of Leuconostoc can be feasible using a soy-based lyoprotectant, with survivability up to 63% during long term storage. Furthermore, the storage in this media improves the subse-quent growth in a soy-based substrate in a strain specific manner. The utilization of individual raffinose family oligosaccharides was strain dependent, with Leuconostoc pseudomesenteroides NFICC99 being the best consumer. Furthermore, we show that all investigated strains were able to produce a range of volatile flavor compounds found in dairy cheese products, as well as remove certain dairy off-flavors from the soy-based substrate like hexanal and 2-pentylfuran. Also here, NFICC99 was strain producing most cheese-related volatile flavor com-pounds, followed by Leuconostoc mesenteroides NFICC319. These findings provide initial insights into the development of Leuconostoc as a potential starter culture for plant-based dairy alternatives, as well as a promising approach for generation of stable, lyophilized cultures

The identification and functional annotation of RNA structures conserved in vertebrates

Structured elements of RNA molecules are essential in, e.g., RNA stabilization, localization, and protein interaction, and their conservation across species suggests a common functional role. We computationally screened vertebrate genomes for conserved RNA structures (CRSs), leveraging structure-based, rather than sequence-based, alignments. After careful correction for sequence identity and GC content, we predict ∼516,000 human genomic regions containing CRSs. We find that a substantial fraction of human–mouse CRS regions (1) colocalize consistently with binding sites of the same RNA binding proteins (RBPs) or (2) are transcribed in corresponding tissues. Additionally, a CaptureSeq experiment revealed expression of many of our CRS regions in human fetal brain, including 662 novel ones. For selected human and mouse candidate pairs, qRT-PCR and in vitro RNA structure probing supported both shared expression and shared structure despite low abundance and low sequence identity. About 30,000 CRS regions are located near coding or long noncoding RNA genes or within enhancers. Structured (CRS overlapping) enhancer RNAs and extended 3′ ends have significantly increased expression levels over their nonstructured counterparts. Our findings of transcribed uncharacterized regulatory regions that contain CRSs support their RNA-mediated functionality.</jats:p

\u27Jump start\u27 childcare-based intervention to promote physical activity in pre-schoolers: six-month findings from a cluster randomised trial

BACKGROUND: Participation in adequate levels of physical activity during the early years is important for health and development. We report the 6-month effects of an 18-month multicomponent intervention on physical activity in early childhood education and care (ECEC) settings in low-income communities. METHODS: A cluster randomised controlled trial was conducted in 43 ECEC settings in disadvantaged areas of New South Wales, Australia. Three-year-old children were recruited and assessed in the first half of 2015 with follow-up 6 months later. The intervention was guided by Social Cognitive Theory and included five components. The primary outcome was minutes per hour in total physical activity during ECEC hours measured using Actigraph accelerometers. Intention-to-treat analysis of the primary outcome was conducted using a generalized linear mixed model. RESULTS: A total of 658 children were assessed at baseline. Of these, 558 (85%) had valid accelerometer data (mean age 3.38y, 52% boys) and 508 (77%) had valid accelerometry data at 6-month follow-up. Implementation of the intervention components ranged from 38 to 72%. There were no significant intervention effects on mins/hr. spent in physical activity (adjusted difference = - 0.17 mins/hr., 95% CI (- 1.30 to 0.97), p = 0.78). A priori sub-group analyses showed a greater effect among overweight/obese children in the control group compared with the intervention group for mins/hr. of physical activity (2.35mins/hr., [0.28 to 4.43], p = 0.036). CONCLUSIONS: After six-months the Jump Start intervention had no effect on physical activity levels during ECEC. This was largely due to low levels of implementation. Increasing fidelity may result in higher levels of physical activity when outcomes are assessed at 18-months

Social acceptance of death and its implication for end‐of‐life care

Aims To understand how the social patterns about death influence end‐of‐life care from the perspective of healthcare professionals. Design A qualitative study according to the theory of Glaser and Strauss. Methods A purposeful sample of 47 participants with different roles (nurses, physicians and clinical psychologists) were involved in four focus groups and 17 interviews in 2017–2019. Responses were audio‐recorded, transcribed verbatim and analysed using computer‐assisted qualitative data. Results A core category ‘the theory of social patterns about death’ emerged, which is explained by three categories: the culture of concealment and stubbornness towards death, the effort and internal work to make death a part of existence, and the influence of the social patterns of coping with death on end‐of life care and healthcare professionals. Our results suggest that social coping with death is affected by a network of concealment and obstinacy towards death. Conclusion Recognizing death as part of life and thinking about death itself are social coping strategies. Although healthcare professionals occupy a privileged place in this process, the culture of concealment of death influences end‐of‐life care. Impact The social process that leads to the loneliness of the dying in our days has been theorized. However, social acceptance of death also influences healthcare professionals’ attitudes towards death. Thus, healthcare professionals’ own attitudes may affect the end‐of‐life care given to dying individuals and their families. The social patterns of death may contribute to the healthcare professionals’ negative attitudes towards death. The concept of dignified death has been linked to the notion of humanization of healthcare. Death should be approached from a more naturalistic perspective by healthcare professionals, healthcare and academic institutions

Time-dependent ARMA modeling of genomic sequences

<p>Abstract</p> <p>Background</p> <p>Over the past decade, many investigators have used sophisticated time series tools for the analysis of genomic sequences. Specifically, the correlation of the nucleotide chain has been studied by examining the properties of the power spectrum. The main limitation of the power spectrum is that it is restricted to stationary time series. However, it has been observed over the past decade that genomic sequences exhibit non-stationary statistical behavior. Standard statistical tests have been used to verify that the genomic sequences are indeed not stationary. More recent analysis of genomic data has relied on time-varying power spectral methods to capture the statistical characteristics of genomic sequences. Techniques such as the evolutionary spectrum and evolutionary periodogram have been successful in extracting the time-varying correlation structure. The main difficulty in using time-varying spectral methods is that they are extremely unstable. Large deviations in the correlation structure results from very minor perturbations in the genomic data and experimental procedure. A fundamental new approach is needed in order to provide a stable platform for the non-stationary statistical analysis of genomic sequences.</p> <p>Results</p> <p>In this paper, we propose to model non-stationary genomic sequences by a time-dependent autoregressive moving average (TD-ARMA) process. The model is based on a classical ARMA process whose coefficients are allowed to vary with time. A series expansion of the time-varying coefficients is used to form a generalized Yule-Walker-type system of equations. A recursive least-squares algorithm is subsequently used to estimate the time-dependent coefficients of the model. The non-stationary parameters estimated are used as a basis for statistical inference and biophysical interpretation of genomic data. In particular, we rely on the TD-ARMA model of genomic sequences to investigate the statistical properties and differentiate between coding and non-coding regions in the nucleotide chain. Specifically, we define a quantitative measure of randomness to assess how far a process deviates from white noise. Our simulation results on various gene sequences show that both the coding and non-coding regions are non-random. However, coding sequences are "whiter" than non-coding sequences as attested by a higher index of randomness.</p> <p>Conclusion</p> <p>We demonstrate that the proposed TD-ARMA model can be used to provide a stable time series tool for the analysis of non-stationary genomic sequences. The estimated time-varying coefficients are used to define an index of randomness, in order to assess the statistical correlations in coding and non-coding DNA sequences. It turns out that the statistical differences between coding and non-coding sequences are more subtle than previously thought using stationary analysis tools: Both coding and non-coding sequences exhibit statistical correlations, with the coding regions being "whiter" than the non-coding regions. These results corroborate the evolutionary periodogram analysis of genomic sequences and revoke the stationary analysis' conclusion that coding DNA behaves like random sequences.</p

Goal directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload:A trial protocol for a randomised, blinded trial (GODIF trial)

Funding Information: SW has received a grant from Merchant Jakob Ehrenreich and wife Grete Ehrenreich's Foundation to production of trial drug for the GODIF trial. AP has received research funding from the Novo Nordisk Foundation, Health Insurance Denmark (Sygeforsikringen Danmark), Fresenius Kabi, Denmark, and Pfizer, Denmark. MO has received research funding from Fresenius Medical Care, Baxter and Biomerieux. MHB has received research funding for the GODIF trial from Novo Nordisk Foundation, Jakob Madsen's and wife Olga Madsen's Foundation, Svend Andersen's Foundation, and Health Insurance Denmark (Sygeforsikringen Danmark). No authors received any financial gain. All other authors declared no conflicts of interest. Publisher Copyright: © 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.Background: Fluid overload is a risk factor for mortality in intensive care unit (ICU) patients. Administration of loop diuretics is the predominant treatment of fluid overload, but evidence for its benefit is very uncertain when assessed in a systematic review of randomised clinical trials. The GODIF trial will assess the benefits and harms of goal directed fluid removal with furosemide versus placebo in ICU patients with fluid overload. Methods: An investigator-initiated, international, randomised, stratified, blinded, parallel-group trial allocating 1000 adult ICU patients with fluid overload to infusion of furosemide versus placebo. The goal is to achieve a neutral fluid balance. The primary outcome is days alive and out of hospital 90 days after randomisation. Secondary outcomes are all-cause mortality at day 90 and 1-year after randomisation; days alive at day 90 without life support; number of participants with one or more serious adverse events or reactions; health-related quality of life and cognitive function at 1-year follow-up. A sample size of 1000 participants is required to detect an improvement of 8% in days alive and out of hospital 90 days after randomisation with a power of 90% and a risk of type 1 error of 5%. The conclusion of the trial will be based on the point estimate and 95% confidence interval; dichotomisation will not be used. ClinicalTrials.gov identifier: NCT04180397. Perspective: The GODIF trial will provide important evidence of possible benefits and harms of fluid removal with furosemide in adult ICU patients with fluid overload.Peer reviewe