Search

ABSTRACT Microbial activities in sub-alpine forest soil influence global cycling of the potent greenhouse gas methane. Understanding the dynamics of methane-oxidizing bacterial communities, particularly the roles of potentially active versus total microbial populations, is necessary for reducing uncertainty in global methane budget estimates. However, our understanding of the factors influencing methane cycling in forest soils is limited by our lack of knowledge about the biology of the microbes involved and how these communities are shaped by their environment. Here, we compared the composition and potential activity of microbial communities using 16S rRNA gene amplicon sequencing of total genomic DNA (gDNA) and potentially active complementary DNA (cDNA) from shallow soil in Red Butte Canyon (Salt Lake City, Utah, USA). We compared riparian and upland soils at two time points in the growing season and found distinct differences in both the community composition of the gDNA and cDNA libraries and the potential drivers of these community structures. Aerobic methane-oxidizing bacteria (methanotrophs) were detected in all samples, with cDNA libraries containing a higher average relative abundance and diversity of methanotrophs compared to gDNA libraries. Methane flux at the sample sites did not significantly correlate to the relative abundance (gDNA) or potential activity (cDNA) of methanotrophs. In the cDNA libraries, there were significant positive correlations between the abundance of Methylococcaceae family methanotrophs and several non-methanotrophic methylotrophs previously found to be associated with methane-oxidizing bacterial communities. These findings suggest a complex relationship between methane-cycling bacterial communities and methane flux and highlight the need for further in situ studies to understand the environmental and ecological influences of these microbial consortia.IMPORTANCEMethane-oxidizing bacteria are found in diverse soil and sediment environments and play an important role in mitigating flux of this potent greenhouse gas into the atmosphere. However, it is unclear how these bacteria and their associated communities are structured in the environment and how their activity ultimately influences methane flux. In this work, we examine the composition and structure of methane-oxidizing bacterial communities in sub-alpine forest soil and find soil- and time-specific differences between the stable and potentially active populations. We also find that the potentially active populations of certain methanotrophs and non-methanotrophs are positively correlated. This work provides a step toward refining our understanding of microbially mediated biogeochemical cycles.

A unique cell envelope contributes to the antibiotic resistance of the pathogen Acinetobacter baumannii. Here, Geisinger et al. identify A. baumannii mutants with altered antibiotic susceptibility, infer the function of uncharacterized proteins involved in envelope synthesis, and predict antibiotic synergies.

Targeting systemically-administered drugs and genes to specific regions of the central nervous system (CNS) remains a challenge. With applications extending into numerous disorders and cancers, there is an obvious need for approaches that facilitate the delivery of therapeutics across the impervious blood-brain barrier (BBB). Focused ultrasound (FUS) is an emerging treatment method that leverages acoustic energy to oscillate simultaneously administered contrast agent microbubbles. This FUS-mediated technique temporarily disrupts the BBB, allowing ordinarily impenetrable agents to diffuse and/or convect into the CNS. Under magnetic resonance image guidance, FUS and microbubbles enable regional targeting—limiting the large, and potentially toxic, dosage that is often characteristic of systemically-administered therapies. Subsequent to delivery across the BBB, therapeutics face yet another challenge: penetrating the electrostatically-charged, mesh-like brain parenchyma. Non-bioadhesive, encapsulated nanoparticles can help overcome this additional barrier to promote widespread treatment in selected target areas. Furthermore, nanoparticles offer significant advantages over conventional systemically-administered therapeutics. Surface modifications of nanoparticles can be engineered to enhance targeted cellular uptake, and nanoparticle formulations can be tailored to control many pharmacokinetic properties such as rate of drug liberation, distribution, and excretion. For instance, nanoparticles loaded with gene plasmids foster relatively stable transfection, thus obviating the need for multiple, successive treatments. As the formulations and applications of these nanoparticles can vary greatly, this review article provides an overview of FUS coupled with polymeric or lipid-based nanoparticles currently utilized for drug delivery, diagnosis, and assessment of function in the CNS.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20098-z

The article discusses the 2023 Annual Meeting of the Inland Bird Banding Association, which took place in Nashville, Tennessee. The meeting included various presentations and workshops on topics such as bird banding, bird research, and zoonotic disease surveillance. One presentation focused on the surveillance of West Nile virus in migratory warblers in Central Illinois, while another discussed the role of bird banding in zoonotic disease surveillance. The article also mentioned the development of a standardized fat-classing scheme for landbird migration and compared the results of bird identification between human observers and the Merlin Sound technology. [Extracted from the article]

There are different methods that may be used to estimate the future demand for radiotherapy services in a population ranging from expert opinion through to complex modelling techniques. This manuscript describes the use of evidence-based treatment guidelines to determine indications for radiotherapy. It also uses epidemiological data to estimate the proportion of the population who have attributes that suggest a benefit from radiotherapy in order to calculate the overall proportion of a population of new cases of cancer who appropriately could be recommended to undergo radiotherapy. Evidence-based methods are transparent and adaptable to different populations but require extensive information about the indications for radiotherapy and the proportion of cancer cases with those indications in the population. In 2003 this method produced an estimate that 52.4% of patients with a registered cancer-type had an indication for radiotherapy. The model was updated in 2012 because of changes in cancer incidence, stage distributions and indications for radiotherapy. The new estimate of the optimal radiotherapy utilisation rate was 48.3%. The decrease was due to changes in the relative frequency of cancer types and some changes in indications for radiotherapy. Actual rates of radiotherapy utilisation in most populations still fall well below this benchmark. [ABSTRACT FROM AUTHOR]

Background and Purpose: Stereotactic ablative body radiotherapy (SABR) is increasingly used for early-stage lung cancer, however the impact of dose to the heart and cardiac substructures remains largely unknown. The study investigated doses received by cardiac substructures in SABR patients and impact on survival., Materials and Methods: SSBROC is an Australian multi-centre phase II prospective study of SABR for stage I non-small cell lung cancer. Patients were treated between 2013 and 2019 across 9 centres. In this secondary analysis of the dataset, a previously published and locally developed open-source hybrid deep learning cardiac substructure automatic segmentation tool was deployed on the planning CTs of 117 trial patients. Physical doses to 18 cardiac structures and EQD2 converted doses (α/β = 3) were calculated. Endpoints evaluated include pericardial effusion and overall survival. Associations between cardiac doses and survival were analysed with the Kaplan-Meier method and Cox proportional hazards models., Results: Cardiac structures that received the highest physical mean doses were superior vena cava (22.5 Gy) and sinoatrial node (18.3 Gy). The highest physical maximum dose was received by the heart (51.7 Gy) and right atrium (45.3 Gy). Three patients developed grade 2, and one grade 3 pericardial effusion. The cohort receiving higher than median mean heart dose (MHD) had poorer survival compared to those who received below median MHD (p = 0.00004). On multivariable Cox analysis, male gender and maximum dose to ascending aorta were significant for worse survival., Conclusions: Patients treated with lung SABR may receive high doses to cardiac substructures. Dichotomising the patients according to median mean heart dose showed a clear difference in survival. On multivariable analyses gender and dose to ascending aorta were significant for survival, however cardiac substructure dosimetry and outcomes should be further explored in larger studies., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Radiotherapy (RT) is an integral component in the treatment of breast cancer. The aims of this study were to estimate the cost per 5-year Local Control (LC) and Overall Survival (OS) benefits of the first course of RT, based on breast cancer stage, and the potential cost savings with adoption of the FAST-Forward protocol., Methods and Materials: All RT activities for breast cancer RT July 2017-June 2020 and their associated costs were consolidated together. The average cost of treatment course was calculated (average cost per fraction X average no. of fractions). Cost per outcome was estimated based on published gains in 5-year LC and OS with optimal use of radiotherapy., Results: 481 patients with breast cancer were analysed. The average cost per fraction was $285 AUD (£148 GBP) for all stages. The average costs for 5-year LC and OS gain were $31,483 AUD (£16 392 GBP) and $235,435 AUD (£122 566 GBP) respectively for all stages. The estimated costs for 5-year LC outcomes were $29,675 AUD (£15 450 GBP), $34,675 AUD (£18 053 GBP) and $32,478 AUD (£16 910 GBP) for Stage I-III respectively. The estimated costs for 5-year OS were $455,909 AUD (£237 378 GBP), $532,727 AUD (£ 277 375 GBP) and $60,717 AUD (£31 614 GBP) for Stage I-III respectively. 266 patients had characteristics that made them eligible for the FAST-Forward protocol. A cost saving of $2592-3864 AUD (£1350-2012 GBP) per patient was estimated had these patients been treated with the protocol., Conclusions: The cost of RT for LC outcome is similar across stages. The greatest value for OS outcome was seen in patients with Stage III breast cancer, due to the greater survival benefit with RT in these patients compared with Stage I-II breast cancer. Significant cost savings can be made by implementing the FAST-Forward protocol., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: The objective of this study was to develop a two-year overall survival model for inoperable stage I-III non-small cell lung cancer (NSCLC) patients using routine radiation oncology data over a federated (distributed) learning network and evaluate the potential of decision support for curative versus palliative radiotherapy., Methods: A federated infrastructure of data extraction, de-identification, standardisation, image analysis, and modelling was installed for seven clinics to obtain clinical and imaging features and survival information for patients treated in 2011-2019. A logistic regression model was trained for the 2011-2016 curative patient cohort and validated for the 2017-2019 cohort. Features were selected with univariate and model-based analysis and optimised using bootstrapping. System performance was assessed by the receiver operating characteristic (ROC) and corresponding area under curve (AUC), C-index, calibration metrics and Kaplan-Meier survival curves, with risk groups defined by model probability quartiles. Decision support was evaluated using a case-control analysis using propensity matching between treatment groups., Results: 1655 patient datasets were included. The overall model AUC was 0.68. Fifty-eight percent of patients treated with palliative radiotherapy had a low-to-moderate risk prediction according to the model, with survival times not significantly different (p = 0.87 and 0.061) from patients treated with curative radiotherapy classified as high-risk by the model. When survival was simulated by risk group and model-indicated treatment, there was an estimated 11% increase in survival rate at two years (p < 0.01)., Conclusion: Federated learning over multiple institution data can be used to develop and validate decision support systems for lung cancer while quantifying the potential impact of their use in practice. This paves the way for personalised medicine, where decisions can be based more closely on individual patient details from routine care., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: Delineation variations and organ motion produce difficult-to-quantify uncertainties in planned radiation doses to targets and organs at risk. Similar to manual contouring, most automatic segmentation tools generate single delineations per structure; however, this does not indicate the range of clinically acceptable delineations. This study develops a method to generate a range of automatic cardiac structure segmentations, incorporating motion and delineation uncertainty, and evaluates the dosimetric impact in lung cancer., Materials and Methods: Eighteen cardiac structures were delineated using a locally developed auto-segmentation tool. It was applied to lung cancer planning CTs for 27 curative (planned dose ≥50 Gy) cases, and delineation variations were estimated by using ten mapping-atlases to provide separate substructure segmentations. Motion-related cardiac segmentation variations were estimated by auto-contouring structures on ten respiratory phases for 9/27 cases that had 4D-planning CTs. Dose volume histograms (DVHs) incorporating these variations were generated for comparison., Results: Variations in mean doses (Dmean), defined as the range in values across ten feasible auto-segmentations, were calculated for each cardiac substructure. Over the study cohort the median variations for delineation uncertainty and motion were 2.20-11.09 Gy and 0.72-4.06 Gy, respectively. As relative values, variations in Dmean were between 18.7%-65.3% and 7.8%-32.5% for delineation uncertainty and motion, respectively. Doses vary depending on the individual planned dose distribution, not simply on segmentation differences, with larger dose variations to cardiac structures lying within areas of steep dose gradient., Conclusion: Radiotherapy dose uncertainties from delineation variations and respiratory-related heart motion were quantified using a cardiac substructure automatic segmentation tool. This predicts the 'dose range' where doses to structures are most likely to fall, rather than single DVH curves. This enables consideration of these uncertainties in cardiotoxicity research and for future plan optimisation. The tool was designed for cardiac structures, but similar methods are potentially applicable to other OARs., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: Accurate and consistent delineation of cardiac substructures is challenging. The aim of this work was to validate a novel segmentation tool for automatic delineation of cardiac structures and subsequent dose evaluation, with potential application in clinical settings and large-scale radiation-related cardiotoxicity studies., Materials and Methods: A recently developed hybrid method for automatic segmentation of 18 cardiac structures, combining deep learning, multi-atlas mapping and geometric segmentation of small challenging substructures, was independently validated on 30 lung cancer cases. These included anatomical and imaging variations, such as tumour abutting heart, lung collapse and metal artefacts. Automatic segmentations were compared with manual contours of the 18 structures using quantitative metrics, including Dice similarity coefficient (DSC), mean distance to agreement (MDA) and dose comparisons., Results: A comparison of manual and automatic contours across all cases showed a median DSC of 0.75-0.93 and a median MDA of 2.09-3.34 mm for whole heart and chambers. The median MDA for great vessels, coronary arteries, cardiac valves, sinoatrial and atrioventricular conduction nodes was 3.01-8.54 mm. For the 27 cases treated with curative intent (planned target volume dose ≥50 Gy), the median dose difference was -1.12 to 0.57 Gy (absolute difference of 1.13-3.25%) for the mean dose to heart and chambers; and -2.25 to 4.45 Gy (absolute difference of 0.94-6.79%) for the mean dose to substructures., Conclusion: The novel hybrid automatic segmentation tool reported high accuracy and consistency over a validation set with challenging anatomical and imaging variations. This has promising applications in substructure dose calculations of large-scale datasets and for future studies on long-term cardiac toxicity., (Copyright © 2023. Published by Elsevier Ltd.)

Background and Purpose: There is a paucity of studies examining variation in the use of palliative radiation therapy (RT) fractionation for brain metastases. The aim of this study is to assess variation in palliative RT fractionation given for brain metastases in New South Wales (NSW), Australia, and identify factors associated with variation., Materials and Methods: This is a population-based cohort of patients who received whole brain RT (WBRT) for brain metastases (2009-2014), as captured in the NSW Central Cancer Registry. A logistic regression model was used to identify factors associated with fractionation type., Results: Of the 2,698 patients that received WBRT, 1,389 courses (51%) were < 6 fractions, 1,050 courses (39%) were 6-10 fractions, and 259 courses (10%) were > 10 fractions. Older patients were more likely to be treated with shorter courses (P < 0.0001). Patients with primary lung cancers were more likely to receive shorter courses compared with other primary cancers (P < 0.0001). Patients without surgical excision were more likely to receive < 6 fractions compared to those who underwent surgical excision. Shorter courses were more likely to be delivered to patients with the most disadvantaged socioeconomic status (SES) compared with patients with the least disadvantaged SES (P < 0.0001). There were significant fluctuations in the proportion of courses using lower number of fractions over time from 2009 to 2014, but no apparent trend (P = 0.02). There was wide variation in the proportion of shorter courses across residence local health districts, ranging from 24% to 69% for < 6 fractions, 21% to 72% for 6-10 fractions, and 4% to 20% for > 10 fractions (P < 0.0001)., Conclusion: This study has identified significant unwarranted variations in fractionation for WBRT in NSW. Accelerating the uptake of shorter fractionation regimens, if warranted through evidence, should be prioritised to enhance evidence-based care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Adoption of single-fraction radiation therapy (SFRT) has not been universal in the palliative treatment of bone metastases, despite evidence supporting its safety and efficacy. The aim of this study was to assess SFRT use for bone metastases in New South Wales (NSW), Australia, and the rate of 30-day mortality (30DM)., Materials and Methods: This is a population-based cohort of patients who received palliative radiation therapy (RT) for bone metastases (2009-2014), as captured in the NSW Central Cancer Registry. A logistic regression model was used to identify factors associated with fractionation type. The proportion of patients dying within 30-days from treatment start date was calculated., Results: Of the 14,602 courses of palliative RT delivered for bone metastases, 30% were SFRT. SFRT was more likely to be delivered to older patients: ≥80 years (34%) versus < 60 years (28%). Patients with lower socioeconomic status (SES) (35%) were more likely to receive SFRT compared with higher SES (25%). SFRT delivered to patients from outer regional area of residence (34%) were higher compared to those from the major city (29%). The proportion of SFRT delivered to patients with comorbidities ≥2 (34%) was higher than patients with no comorbidity (29%). SFRT was associated with higher 30DM of 21% compared with 11% for multi-fraction RT (MFRT)., Conclusion: SFRT is underused for the treatment of bone metastases in NSW. This is an impetus to develop tools making SFRT obligatory in this setting unless there is good justification not to., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Background: To describe the population benefit of radiotherapy in a high-income setting if evidence-based guidelines were routinely followed., Methods: Australian decision tree models were utilized. Radiotherapy alone (RT) benefit was defined as the absolute proportional benefit of radiotherapy compared with no treatment for radical indications, and of radiotherapy over surgery alone for adjuvant indications. Chemoradiotherapy (CRT) benefit was the absolute incremental benefit of concurrent chemoradiotherapy over RT. Five-year local control (LC) and overall survival (OS) benefits were measured. Citation databases were systematically queried for benefit data. Meta-analysis and sensitivity analysis were performed., Findings: 48% of all cancer patients have indications for radiotherapy, 34% curative and 14% palliative. RT provides 5-year LC benefit in 10.4% of all cancer patients (95% Confidence Interval 9.3, 11.8) and 5-year OS benefit in 2.4% (2.1, 2.7). CRT provides 5-year LC benefit in an additional 0.6% of all cancer patients (0.5, 0.6), and 5-year OS benefit for an additional 0.3% (0.2, 0.4). RT benefit was greatest for head and neck (LC 32%, OS 16%), and cervix (LC 33%, OS 18%). CRT LC benefit was greatest for rectum (6%) and OS for cervix (3%) and brain (3%). Sensitivity analysis confirmed a robust model., Interpretation: Radiotherapy provides significant 5-year LC and OS benefits as part of evidence-based cancer care. CRT provides modest additional benefits., (Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.)