Reducing the within-patient variability of breathing for radiotherapy delivery in conscious, unsedated cancer patients using a mechanical ventilator

OBJECTIVE: Variability in the breathing pattern of patients with cancer during radiotherapy requires mitigation, including enlargement of the planned treatment field, treatment gating and breathing guidance interventions. Here, we provide the first demonstration of how easy it is to mechanically ventilate patients with breast cancer while fully conscious and without sedation, and we quantify the resulting reduction in the variability of breathing. METHODS: 15 patients were trained for mechanical ventilation. Breathing was measured and the left breast anteroposterior displacement was measured using an Osiris surface-image mapping system (Qados Ltd, Sandhurst, UK). RESULTS: Mechanical ventilation significantly reduced the within-breath variability of breathing frequency by 85% (p < 0.0001) and that of inflation volume by 29% (p < 0.006) when compared with their spontaneous breathing pattern. During mechanical ventilation, the mean amplitude of the left breast marker displacement was 5 ± 1 mm, the mean variability in its peak inflation position was 0.5 ± 0.1 mm and that in its trough inflation position was 0.4 ± 0.0 mm. Their mean drifts were not significantly different from 0 mm min(−1) (peak drift was −0.1 ± 0.2 mm min(−1) and trough drift was −0.3 ± 0.2 mm min(−1)). Patients had a normal resting mean systolic blood pressure (131 ± 5 mmHg) and mean heart rate [75 ± 2 beats per minute (bpm)] before mechanical ventilation. During mechanical ventilation, the mean blood pressure did not change significantly, mean heart rate fell by 2 bpm (p < 0.05) with pre-oxygenation and rose by only 4 bpm (p < 0.05) during pre-oxygenation with hypocapnia. No patients reported discomfort and all 15 patients were always willing to return to the laboratory on multiple occasions to continue the study. CONCLUSION: This simple technique for regularizing breathing may have important applications in radiotherapy. ADVANCES IN KNOWLEDGE: Variations in the breathing pattern introduce major problems in imaging and radiotherapy planning and delivery and are currently addressed to only a limited extent by asking patients to breathe to auditory or visual guidelines. We provide the first demonstration that a completely different technique, of using a mechanical ventilator to take over the patients' breathing for them, is easy for patients who are conscious and unsedated and reduces the within-patient variability of breathing. This technique has potential advantages in radiotherapy over currently used breathing guidance interventions because it does not require any active participation from or feedback to the patient and is therefore worthy of further clinical evaluation

Space Station Engineering Design Issues

Space Station Freedom topics addressed include: general design issues; issues related to utilization and operations; issues related to systems requirements and design; and management issues relevant to design

"Freezing" the Tumor in a Known Position During Radiation Therapy In Regard to Boda-Heggemann et al

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Perovskite-perovskite tandem photovoltaics with optimized bandgaps

We demonstrate four and two-terminal perovskite-perovskite tandem solar cells with ideally matched bandgaps. We develop an infrared absorbing 1.2eV bandgap perovskite, $FA_{0.75}Cs_{0.25}Sn_{0.5}Pb_{0.5}I_3$, that can deliver 14.8 % efficiency. By combining this material with a wider bandgap $FA_{0.83}Cs_{0.17}Pb(I_{0.5}Br_{0.5})_3$ material, we reach monolithic two terminal tandem efficiencies of 17.0 % with over 1.65 volts open-circuit voltage. We also make mechanically stacked four terminal tandem cells and obtain 20.3 % efficiency. Crucially, we find that our infrared absorbing perovskite cells exhibit excellent thermal and atmospheric stability, unprecedented for Sn based perovskites. This device architecture and materials set will enable 'all perovskite' thin film solar cells to reach the highest efficiencies in the long term at the lowest costs

Cross-Reactivity and Expansion of Dengue-Specific T cells During Acute Primary and Secondary Infections in Humans

Serotype-cross-reactive memory T cells responding to secondary dengue virus (DENV) infection are thought to contribute to disease. However, epitope-specific T cell responses have not been thoroughly compared between subjects with primary versus secondary DENV infection. We studied CD8+ T cells specific for the HLA-A*1101-restricted NS3133 epitope in a cohort of A11+ DENV-infected patients throughout acute illness and convalescence. We compared the expansion, serotype-cross-reactivity, and activation of these cells in PBMC from patients experiencing primary or secondary infection and mild or severe disease by flow cytometry. Our results show expansion and activation of DENV-specific CD8+ T cells during acute infection, which are predominantly serotype-cross-reactive regardless of DENV infection history. These data confirm marked T cell activation and serotype-cross-reactivity during the febrile phase of dengue; however, A11-NS3133-specific responses did not correlate with prior antigenic exposure or current disease severity

Progress in D-brane model building

The state of the art in D-brane model building is briefly reviewed, focusing on recent achievements in the construction of D=4 N = 1 type II string vacua with semi-realistic gauge sectors. Such progress relies on a better understanding of the spectrum of BPS D-branes, the effective field theory obtained from them and the explicit construction of vacua. We first consider D-branes in standard Calabi-Yau compactifications, and then the more involved case of compactifications with fluxes. We discuss how the non-trivial interplay between D-branes and fluxes modifies the previous model-building rules, as well as provides new possibilities to connect string theory to particle physics.Comment: Using w-art.cls, 27 pages, 6 figures. Based on a talk given at the RTN `Constituents, Fundamental Forces and Symmetries of the Universe' Workshop and Midterm meeting in Napoli, October 2006. v2: typos corrected and references adde

Social Class

Discussion of class structure in fifth-century Athens, historical constitution of theater audiences, and the changes in the comic representation of class antagonism from Aristophanes to Menander

Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors

Background: Limits on the frequency of whole blood donation exist primarily to safeguard donor health. However, there is substantial variation across blood services in the maximum frequency of donations allowed. We compared standard practice in the UK with shorter inter-donation intervals used in other countries. Methods: In this parallel group, pragmatic, randomised trial, we recruited whole blood donors aged 18 years or older from 25 centres across England, UK. By use of a computer-based algorithm, men were randomly assigned (1:1:1) to 12-week (standard) versus 10-week versus 8-week inter-donation intervals, and women were randomly assigned (1:1:1) to 16-week (standard) versus 14-week versus 12-week intervals. Participants were not masked to their allocated intervention group. The primary outcome was the number of donations over 2 years. Secondary outcomes related to safety were quality of life, symptoms potentially related to donation, physical activity, cognitive function, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin. This trial is registered with ISRCTN, number ISRCTN24760606, and is ongoing but no longer recruiting participants. Findings: 45 263 whole blood donors (22 466 men, 22 797 women) were recruited between June 11, 2012, and June 15, 2014. Data were analysed for 45 042 (99·5%) participants. Men were randomly assigned to the 12-week (n=7452) versus 10-week (n=7449) versus 8-week (n=7456) groups; and women to the 16-week (n=7550) versus 14-week (n=7567) versus 12-week (n=7568) groups. In men, compared with the 12-week group, the mean amount of blood collected per donor over 2 years increased by 1·69 units (95% CI 1·59–1·80; approximately 795 mL) in the 8-week group and by 0·79 units (0·69–0·88; approximately 370 mL) in the 10-week group (p&lt;0·0001 for both). In women, compared with the 16-week group, it increased by 0·84 units (95% CI 0·76–0·91; approximately 395 mL) in the 12-week group and by 0·46 units (0·39–0·53; approximately 215 mL) in the 14-week group (p&lt;0·0001 for both). No significant differences were observed in quality of life, physical activity, or cognitive function across randomised groups. However, more frequent donation resulted in more donation-related symptoms (eg, tiredness, breathlessness, feeling faint, dizziness, and restless legs, especially among men [for all listed symptoms]), lower mean haemoglobin and ferritin concentrations, and more deferrals for low haemoglobin (p&lt;0·0001 for each) than those observed in the standard frequency groups. Interpretation: Over 2 years, more frequent donation than is standard practice in the UK collected substantially more blood without having a major effect on donors' quality of life, physical activity, or cognitive function, but resulted in more donation-related symptoms, deferrals, and iron deficiency. Funding: NHS Blood and Transplant, National Institute for Health Research, UK Medical Research Council, and British Heart Foundation

The use of Complementary and Alternative Medicine in pregnancy: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC)

Objectives - To report the frequency of Complementary and Alternative Medicine (CAM) use by a population of pregnant women in the UK. Design - Four postal self-completion questionnaires completed at 8, 12, 18 and 32 weeks’ gestation provided the source of CAMs used. Questions asked for written descriptions about the use of any treatments, pills, medicines, ointments, homeopathic medicines, herbal medicines, supplements, drinks and herbal teas. Setting - An observational, population-based, cohort study of parents and children of 14,541 pregnant women residing within the former county of Avon in south-west England. Data was available for 14,115 women. Results - Over a quarter (26.7%; n = 3774) of women had used a CAM at least once in pregnancy, the use rising from 6% in the 1st trimester to 12.4% in the 2nd to 26.3% in the 3rd. Herbal teas were the most commonly reported CAM at any time in pregnancy (17.7%; n = 2499) followed by homeopathic medicine (14.4%; n = 2038) and then herbal medicine (5.8%; n = 813). The most commonly used herbal product was chamomile used by 14.6% of women, the most commonly used homeopathic product was Arnica used by 3.1% of women. Other CAMs (osteopathy, aromatherapy, acupuncture/acupressure, Chinese herbal medicine, chiropractic, cranial sacral therapy, hypnosis, non-specific massage and reflexology) accounted for less than 1% of users. Conclusions - CAM use in pregnancy, where a wide range of CAMs has been assessed, has not been widely reported. Studies that have been conducted report varying results to this study (26.7%) by between 13.3% and 87% of pregnant women. Survey results will be affected by a number of factors namely the inclusion/exclusion of vitamins and minerals, the timing of data collection, the country of source, the number of women surveyed, and the different selection criteria of either recruiting women to the study or of categorising and identifying a CAM treatment or product