The Effects of Astaxanthin on Cognitive Function and Neurodegeneration in Humans: A Critical Review.

Oxidative stress is a key contributing factor in neurodegeneration, cognitive ageing, cognitive decline, and diminished cognitive longevity. Issues stemming from oxidative stress both in relation to cognition and other areas, such as inflammation, skin health, eye health, and general recovery, have been shown to benefit greatly from antioxidant use. Astaxanthin is a potent antioxidant, which has been outlined to be beneficial for cognitive function both in vitro and in vivo. Given the aforementioned promising effects, research into astaxanthin with a focus on cognitive function has recently been extended to human tissue and human populations. The present critical review explores the effects of astaxanthin on cognitive function and neurodegeneration within human populations and samples with the aim of deciphering the merit and credibility of the research findings and subsequently their potential as a basis for therapeutic use. Implications, limitations, and areas for future research development are also discussed. Key findings include the positive impacts of astaxanthin in relation to improving cognitive function, facilitating neuroprotection, and slowing neurodegeneration within given contexts.

Characterization of Coinfections in Patients with COVID-19.

Background: Little is known about coinfections in patients with COVID-19, with antibiotics often initiated empirically. Objectives: To determine the rates and characteristics of early and late coinfections in COVID-19 patients and to characterize the use of anti-infective agents, especially antibiotics. Methods: This retrospective chart review involved patients with COVID-19 who were admitted to Lions Gate Hospital (Vancouver, British Columbia) between January 1 and June 30, 2020. Data were extracted from electronic medical records, and descriptive statistics were used to analyze the data. Results: Of the 48 patients admitted during the study period, 10 (21%) were determined to have coinfections: 3 (6%) had early coinfections and 7 (15%) had late coinfections. Early empiric use of antibiotics was observed in 32 (67%) patients; for 29 (91%) of these 32 patients, the therapy was deemed inappropriate. Patients with coinfections had longer hospital stays and more complications. Conclusions: Despite low rates of early coinfection, empiric antibiotics were started for a majority of the patients. Most late coinfections occurred in patients in the intensive care unit who required mechanical ventilation. Patients with coinfections had poorer outcomes than those without coinfections.

Contexte: On sait peu de choses sur les co-infections chez les patients atteints de COVID-19, les médicaments antibiotiques étant souvent initiés de manière empirique. Objectifs: Déterminer les taux et les caractéristiques des co-infections précoces et tardives chez les patients atteints de COVID-19 et caractériser l'utilisation d'anti-infectieux, en particulier les antibiotiques. Méthodes: Cet examen rétrospectif des dossiers portait sur des patients atteints de COVID-19 qui ont été admis à l'hôpital Lions Gate, à Vancouver (Colombie-Britannique), entre le 1er janvier et le 30 juin 2020. Les données ont été extraites des dossiers médicaux électroniques et des statistiques descriptives ont été utilisées pour analyser les données. Résultats: Sur les 48 patients admis au cours de la période d'étude, 10 patients (21 %) présentaient des co-infections: 3 patients (6 %) avaient des co-infections précoces et 7 (15 %), des co-infections tardives. Une utilisation empirique précoce d'antibiotiques a été observée chez 32 patients (67 %); pour 29 de ces 32 patients (91 %), le traitement a été jugé inapproprié. Les séjours à l'hôpital des patients co-infectés étaient plus longs et ils présentaient davantage de complications. Conclusions: Malgré de faibles taux de co-infection précoce, des antibiotiques empiriques ont été instaurés pour la majorité des patients. La plupart des co-infections tardives sont survenues chez des patients de l'unité de soins intensifs nécessitant une ventilation mécanique. Les résultats des patients avec co-infections étaient moins bons que ceux sans co-infections.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients.

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome. Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC_PC_19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix.

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

BackgroundWhilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. MethodsHere, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. ResultsOur analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61 - 0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. ConclusionsAlthough clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome.

Automation and Expansion of EMMA Assembly for Fast-Tracking Mammalian System Engineering.

With applications from functional genomics to the production of therapeutic biologics, libraries of mammalian expression vectors have become a cornerstone of modern biological investigation and engineering. Multiple modular vector platforms facilitate the rapid design and assembly of vectors. However, such systems approach a technical bottleneck when a library of bespoke vectors is required. Utilizing the flexibility and robustness of the Extensible Mammalian Modular Assembly (EMMA) toolkit, we present an automated workflow for the library-scale design, assembly, and verification of mammalian expression vectors. Vector design is simplified using our EMMA computer-aided design tool (EMMA-CAD), while the precision and speed of acoustic droplet ejection technology are applied in vector assembly. Our pipeline facilitates significant reductions in both reagent usage and researcher hands-on time compared with manual assembly, as shown by system Q-metrics. To demonstrate automated EMMA performance, we compiled a library of 48 distinct plasmid vectors encoding either CRISPR interference or activation modalities. Characterization of the workflow parameters shows that high assembly efficiency is maintained across vectors of various sizes and design complexities. Our system also performs strongly compared with manual assembly efficiency benchmarks. Alongside our automated pipeline, we present a straightforward strategy for integrating gRNA and Cas modules into the EMMA platform, enabling the design and manufacture of valuable genome editing resources.

EMMA-CAD: Design Automation for Synthetic Mammalian Constructs.

Computational design tools are the cornerstone of synthetic biology and have underpinned its rapid development over the past two decades. As the field has matured, the scale of biological investigation has expanded dramatically, and researchers often must rely on computational tools to operate in the high-throughput investigational space. This is especially apparent in the modular design of DNA expression circuits, where complexity is accumulated rapidly. Alongside our automated pipeline for the high-throughput construction of Extensible Modular Mammalian Assembly (EMMA) expression vectors, we recognized the need for an integrated software solution for EMMA vector design. Here we present EMMA-CAD (https://emma.cailab.org), a powerful web-based computer-aided design tool for the rapid design of bespoke mammalian expression vectors. EMMA-CAD features a variety of functionalities, including a user-friendly design interface, automated connector selection underpinned by rigorous computer optimization algorithms, customization of part libraries, and personalized design spaces. Capable of translating vector assembly designs into human- and machine-readable protocols for vector construction, EMMA-CAD integrates seamlessly into our automated EMMA pipeline, hence completing an end-to-end design to production workflow.

Formulating and Deploying Strength Amplification Controllers for Lower-Body Walking Exoskeletons.

Augmenting the physical strength of a human operator during unpredictable human-directed (volitional) movements is a relevant capability for several proposed exoskeleton applications, including mobility augmentation, manual material handling, and tool operation. Unlike controllers and augmentation systems designed for repetitive tasks (e.g., walking), we approach physical strength augmentation by a task-agnostic method of force amplification-using force/torque sensors at the human-machine interface to estimate the human task force, and then amplifying it with the exoskeleton. We deploy an amplification controller that is integrated into a complete whole-body control framework for controlling exoskeletons that includes human-led foot transitions, inequality constraints, and a computationally efficient prioritization. A powered lower-body exoskeleton is used to demonstrate behavior of the control framework in a lab environment. This exoskeleton can assist the operator in lifting an unknown backpack payload while remaining fully backdrivable.

Postsynthetic Modification of ZIF-8 Membranes via Membrane Surface Ligand Exchange for Light Hydrocarbon Gas Separation Enhancement.

The ability to tailor the pore structure of metal-organic framework (MOF) membranes enables synthesis of new or modified MOF membranes with enhanced separation characteristics. This work employs a modified version of solvent-assisted ligand exchange, termed membrane surface ligand exchange (MSLE), to modify the pore structure of zeolitic imidazolate framework-8 (ZIF-8) membranes. This paper is the first to perform a time-based, ex situ characterization and gas permeation study of ZIF-8 MSLE with 5,6-DBIM (DBIM, dimethylbenzimidazole) to effectively narrow the ZIF-8 pores, enhance light hydrocarbon gas-phase separations, and give insight into the exchange mechanism with respect to time and temperature. The results show that relatively fast exchange kinetics occur mainly at the outer surface of the ZIF-8 membrane during the initial 30 min of exchange and enables significant (40-70%) increases in propylene/propane selectivity with minimal (10-20%) propylene permeance losses for the modified ZIF-8 membranes. We postulate as the reaction time proceeds, the ligand-exchange rate slows as the DBIM linker diffuses into the ZIF-8 membrane beyond the external surface, exchanges with the original linker, disrupts the original framework's crystallinity, and then increases long-range order/crystallinity as the reaction proceeds. The H2/C2 separation factor increases with increased 5,6-DBIM content in the ZIF-8 framework which is facilitated by increased MSLE time and reaction temperature.

Technical Note: Validation and implementation of a wireless transponder tracking system for gated stereotactic ablative radiotherapy of the liver.

PURPOSE: Tracking soft-tissue targets has recently been cleared as a new application of Calypso, an electromagnetic wireless transponder tracking system, allowing for gated treatment of the liver based on the motion of the target volume itself. The purpose of this study is to describe the details of validating the Calypso system for wireless transponder tracking of the liver and to present the clinical workflow for using it to deliver gated stereotactic ablative radiotherapy (SABR). METHODS: A commercial 3D diode array motion system was used to evaluate the dynamic tracking accuracy of Calypso when tracking continuous large amplitude motion. It was then used to perform end-to-end tests to evaluate the dosimetric accuracy of gated beam delivery for liver SABR. In addition, gating limits were investigated to determine how large the gating window can be while still maintaining dosimetric accuracy. The gating latency of the Calypso system was also measured using a customized motion phantom. RESULTS: The average absolute difference between the measured and expected positional offset was 0.3 mm. The 2%/2 mm gamma pass rates for the gated treatment delivery were greater than 97%. When increasing the gating limits beyond the known extent of planned motion, the gamma pass rates decreased as expected. The 2%/2 mm gamma pass rate for a 1, 2, and 3 mm increase in gating limits was measured to be 97.8%, 82.9%, and 61.4%, respectively. The average gating latency was measured to be 63.8 ms for beam-hold and 195.8 ms for beam-on. Four liver patients with 17 total fractions have been successfully treated at our institution. CONCLUSIONS: Wireless transponder tracking was validated as a dosimetrically accurate way to provide gated SABR of the liver. The dynamic tracking accuracy of the Calypso system met manufacturer's specification, even for continuous large amplitude motion that can be encountered when tracking liver tumors close to the diaphragm. The measured beam-hold gating latency was appropriate for targets that will traverse the gating limit each respiratory cycle causing the beam to be interrupted constantly throughout treatment delivery.

Implementation of an in-house visual feedback system for motion management during radiation therapy.

In this Technical Note, we describe an in-house video goggles feedback system assembled using several commercially available products. This goggle video feed-back system is currently being used at University of Louisville and Mayo Clinic for both CT simulation and linac treatment delivery. The setup details, including specific recommendations, are provided, along with an alternative option for using the video goggles system.

Commissioning of a motion system to investigate dosimetric consequences due to variability of respiratory waveforms.

A commercially available six-dimensional (6D) motion system was assessed for accuracy and clinical use in our department. Positional accuracy and respiratory waveform reproducibility were evaluated for the motion system. The system was then used to investigate the dosimetric consequences of respiratory waveform variation when an internal target volume (ITV) approach is used for motion management. The maximum deviations are 0.3 mm and 0.22° for translation and rotation accuracy, respectively, for the tested clinical ranges. The origin reproducibility is less than±0.1 mm. The average differences are less than 0.1 mm with a maximum standard deviation of 0.8 mm between waveforms of actual patients and replication of those waveforms by HexaMotion for three breath-hold and one free-breathing waveform. A modified gamma analysis shows greater than 98% agreement with a 0.5 mm and 100 ms threshold. The motion system was used to investigate respiratory waveform variation and showed that, as the amplitude of the treatment waveform increases above that of the simulation waveform, the periphery of the target volume receives less dose than expected. However, by using gating limits to terminate the beam outside of the simulation amplitude, the results are as expected dosimetrically. Specifically, the average dose difference in the periphery between treating with the simulation waveform and the larger amplitude waveform could be up to 12% less without gating limits, but only differed 2% or less with the gating limits in place. The general functionality of the system performs within the manufacturer's specifications and can accurately replicate patient specific waveforms. When an ITV approach is used for motion management, we found the use of gating limits that coincide with the amplitude of the patient waveform at simulation helpful to prevent the potential underdosing of the target due to changes in patient respiration.

Percent depth-dose distribution discrepancies from very small volume ion chambers.

As very small ion chambers become commercially available, medical physicists may be inclined to use them during the linear accelerator commissioning process to better characterize the beam in steep dose gradient areas. For this work, a total of eight different ion chambers (volumes from 0.007 cc to 0.6 cc) and four different scanning systems were used to scan PDDs at both +300V and -300V biases. We observed a reproducible, significant difference (overresponse with depth) in PDDs acquired when using very small ion chambers, with specific bias/water tank combinations - up to 5% at a depth of 25 cm in water. This difference was not observed when the PDDs were sampled using the ion chamber in static positions in conjunction with an external electrometer. This suggests noise/signal interference produced by the controller box and cable system assemblies, which can become relatively significant for the very small current signals collected by very small ion chambers, especially at depth as the signal level is even further reduced. Based on the results observed here, the use of very small active volume chambers under specific scanning conditions may lead to collection of erroneous data, introducing systematic errors into the treatment planning system. In case the use of such a chamber is required, we recommend determining whether such erroneous effect exists by comparing the scans with those obtained with a larger chamber.

Site-specific tolerance tables and indexing device to improve patient setup reproducibility.

While the implementation of tools such as image-guidance and immobilization devices have helped to prevent geometric misses in radiation therapy, many treatments remain prone to error if these items are not available, not utilized for every fraction, or are misused. The purpose of this project is to design a set of site-specific treatment tolerance tables to be applied to the treatment couch for use in a record and verify (R&V) system that will insure accurate patient setup with minimal workflow interruption. This project also called for the construction of a simple indexing device to help insure reproducible patient setup for patients that could not be indexed with existing equipment. The tolerance tables were created by retrospective analysis on a total of 66 patients and 1,308 treatments, separating them into five categories based on disease site: lung, head and neck (H&N), breast, pelvis, and abdomen. Couch parameter tolerance tables were designed to encompass 95% of treatments, and were generated by calculating the standard deviation of couch vertical, longitudinal, and lateral values using the first day of treatment as a baseline. We also investigated an alternative method for generating the couch tolerances by updating the baseline values when patient position was verified with image guidance. This was done in order to adapt the tolerances to any gradual changes in patient setup that would not correspond with a mistreatment. The tolerance tables and customizable indexing device were then implemented for a trial period in order to determine the feasibility of the system. During this trial period we collected data from 1,054 fractions from 65 patients. We then analyzed the number of treatments that would have been out of tolerance, as well as whether or not the tolerances or setup techniques should be adjusted. When the couch baseline values were updated with every imaging fraction, the average rate of tolerance violations was 10% for the lung, H&N, abdomen, and pelvis treatments. Using the indexing device, tolerances for patients with pelvic disease decreased (e.g., from 5.3 cm to 4.3 cm longitudinally). Unfortunately, the results from breast patients were highly variable due to the complexity of the setup technique, making the couch an inadequate surrogate for measuring setup accuracy. In summary, we have developed a method to turn the treatment couch parameters within the R&V system into a useful alert tool, which can be implemented at other institutions, in order to identify potential errors in patient setup.

Quantification of planning target volume margin when using a robotic radiosurgery system to treat lung tumors with spine tracking.

PURPOSE: The use of fiducial markers or direct tumor visualization allows for tumor tracking and ultimately smaller planning target volume (PTV) margins in the treatment of lung tumors, yet many patients are either not amenable to fiducial marker placement or their tumors are unable to be visualized on orthogonal-axis x-ray images. Spine tracking is an alternative method for tumor localization but is limited by the assumption that the location of the lung tumor relative to the spine is constant. The purpose of this study was to quantify the additional PTV margin needed when spine tracking is used to ensure the internal target volume (ITV) receives the prescription dose during treatment. METHODS AND MATERIALS: Daily cone beam computed tomography images, registered based on tumor position, from 63 patients with lung cancer treated with stereotactic body radiation therapy were collected and analyzed. Rigid registrations were reperformed so that the position of the spine on the cone beam computed tomography image was aligned to its position on the planning computed tomography. Shifts from the treatment position to the new position were recorded, and per-patient mean shifts and standard deviations were calculated, as well as group systematic and random standard deviations. These data were used with van Herk's margin recipe to determine the additional margin required to adequately treat the patient population if spine tracking were used instead of direct daily tumor imaging. A retrospective dosimetric analysis was also performed on 6 patients with lung cancer previously treated by CyberKnife using spine tracking to determine the potential decrease in target coverage attributable to insufficient margin on the ITV. This analysis was performed by shifting the PTV volume relative to the CyberKnife treatment geometry to simulate a setup error caused by tracking the spine as opposed to the tumor. RESULTS: The additional margins calculated by van Herk's margin recipe to adequately cover the ITV with the 95% isodose surface for 90% of the entire patient population in the vertical, longitudinal, and lateral directions were 6.4, 6.0, and 4.5 mm, respectively. The retrospective analysis showed a decrease in PTV coverage from 95.6% to 93.1% and an increase in new conformity index by 2.7% when the average shift data were used to simulate setup error. When the maximum shift data were used to simulate the worst possible outcome, PTV coverage decreased to 73.4% and the new conformity index increased by 26.8%. CONCLUSIONS: Standard margins of 5 mm on the ITV for patients with lung cancer being treated with stereotactic body radiation therapy are insufficient and may result in geographic misses of the tumor when spine tracking is used to locate the position of the tumor in the lung. Therefore, we recommend the addition of 5-mm margins in all directions for a total of 10 mm to take into account the change in position of the tumor relative to the spine from the time of simulation to treatment.

The efficacy of mitomycin-C in the treatment of laryngotracheal stenosis.

OBJECTIVE: The purpose of this study is to evaluate whether the addition of topical mitomycin-C (MMC) application to the wound site after endoscopic treatment of laryngotracheal stenosis (LTS) resulted in measurable improvement in clinical outcomes. STUDY DESIGN AND SETTING: A retrospective chart review of patients with LTS treated by the senior author over a 6-year period was performed. The treatment groups were stratified into two main categories: 1) endoscopic treatment alone and 2) endoscopic treatment + topical MMC. The "symptom-free" interval was determined (in months) for each subject using a two-tailed t test for statistical analysis of the control/study groups. RESULTS: Sixty-seven procedures were performed in 36 patients with LTS with a mean of 1.86 surgical treatments per patient. The mean duration of the symptom-free interval after endoscopic treatment for LTS was 4.9 months in the endoscopic-only treatment group and 23.2 months in the endoscopic group receiving topical MMC. The symptom-free interval observed in the MMC group was significantly longer than the control subjects (P = 1 x 10). CONCLUSIONS: The results of this study suggest that MMC is an effective adjuvant in the treatment of LTS. The results of this study provide strong supporting evidence that topical MMC is an effective adjuvant in the treatment of LTS.

A novel method to correct for pitch and yaw patient setup errors in helical tomotherapy.

An accurate means of determining and correcting for daily patient setup errors is important to the cancer outcome in radiotherapy. While many tools have been developed to detect setup errors, difficulty may arise in accurately adjusting the patient to account for the rotational error components. A novel, automated method to correct for rotational patient setup errors in helical tomotherapy is proposed for a treatment couch that is restricted to motion along translational axes. In tomotherapy, only a narrow superior/inferior section of the target receives a dose at any instant, thus rotations in the sagittal and coronal planes may be approximately corrected for by very slow continuous couch motion in a direction perpendicular to the scanning direction. Results from proof-of-principle tests indicate that the method improves the accuracy of treatment delivery, especially for long and narrow targets. Rotational corrections about an axis perpendicular to the transverse plane continue to be implemented easily in tomotherapy by adjustment of the initial gantry angle.