Reducing 4DCBCT imaging time and dose: the first implementation of variable gantry speed 4DCBCT on a linear accelerator.

Four dimensional cone beam computed tomography (4DCBCT) uses a constant gantry speed and imaging frequency that are independent of the patient's breathing rate. Using a technique called respiratory motion guided 4DCBCT (RMG-4DCBCT), we have previously demonstrated that by varying the gantry speed and imaging frequency, in response to changes in the patient's real-time respiratory signal, the imaging dose can be reduced by 50-70%. RMG-4DCBCT optimally computes a patient specific gantry trajectory to eliminate streaking artefacts and projection clustering that is inherent in 4DCBCT imaging. The gantry trajectory is continuously updated as projection data is acquired and the patient's breathing changes. The aim of this study was to realise RMG-4DCBCT for the first time on a linear accelerator. To change the gantry speed in real-time a potentiometer under microcontroller control was used to adjust the current supplied to an Elekta Synergy's gantry motor. A real-time feedback loop was developed on the microcontroller to modulate the gantry speed and projection acquisition in response to the real-time respiratory signal so that either 40, RMG-4DCBCT40, or 60, RMG-4DCBCT60, uniformly spaced projections were acquired in 10 phase bins. Images of the CIRS dynamic Thorax phantom were acquired with sinusoidal breathing periods ranging from 2 s to 8 s together with two breathing traces from lung cancer patients. Image quality was assessed using the contrast to noise ratio (CNR) and edge response width (ERW). For the average patient, with a 3.8 s breathing period, the imaging time and image dose were reduced by 37% and 70% respectively. Across all respiratory rates, RMG-4DCBCT40 had a CNR in the range of 6.5 to 7.5, and RMG-4DCBCT60 had a CNR between 8.7 and 9.7, indicating that RMG-4DCBCT allows consistent and controllable CNR. In comparison, the CNR for conventional 4DCBCT drops from 20.4 to 6.2 as the breathing rate increases from 2 s to 8 s. With RMG-4DCBCT, the ERW in the direction of motion of the imaging insert decreases from 2.1 mm to 1.1 mm as the breathing rate increases from 2 s to 8 s while for conventional 4DCBCT the ERW increases from 1.9 mm to 2.5 mm. Image quality can be controlled during 4DCBCT acquisition by varying the gantry speed and the projection acquisition in response to the patient's real-time respiratory signal. However, although the image sharpness, i.e. ERW, is improved with RMG-4DCBCT, the ERW depends on the patient's breathing rate and breathing regularity

Long-term efficacy and safety of eculizumab in Japanese patients with generalized myasthenia gravis : a subgroup analysis of the REGAIN open-label extension study

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52-week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with open-label eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (-2.4 [1.34] and - 3.3 [0.651); Quantitative Myasthenia Gravis (-2.9 [1.98] and - 4.3 [0.79]); Myasthenia Gravis Composite (-4.5 [2.63] and - 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (-8.6 [5.68) and - 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population

Anode modification of polyfluorene-based polymer light-emitting devices

A glycerol-modified poly(3,4-ethylene dioxythiophene) (PEDOT): poly(styrene sulfonate) (PSS) layer was used as an anode buffer layer in polymer light-emitting devices using poly(9,9-dioctylfluorene) (F8) as the emitter. Devices with a configuration of indium tin oxide/PEDOT:PSS (with or without glycerol)/F8/CsF/Al were fabricated. It was found that the glycerol-modified device showed a much larger current density than the unmodified device. At an operating voltage of 6 V, the glycerol-modified device showed a luminance of 1300Cd/m 2 and a current efficiency of 1.7 Cd/A compared to the corresponding values of 500Cd/m 2 and 1.3 Cd/A in the unmodified device. Analysis by ultraviolet spectroscopy suggests that the two devices have the same energy level structure and the performance improvement should not be due to change in the PEDOT/polymer interface. It was further found that incorporating a suitable amount of glycerol into the PEDOT:PSS layer can increase its conductivity by six times. This leads to a better balance in the hole and electron currents and thus improved device efficiency. © 2002 American Institute of Physics.published_or_final_versio

Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort

INTRODUCTION: There is a lack of population level data on risk factors and impact of severe COVID-19 in pregnancy. The aims of this study were to determine the characteristics, and maternal and perinatal outcomes associated with severe COVID-19 in pregnancy compared with those with mild and moderate COVID-19 and to explore the impact of timing of birth. MATERIAL AND METHODS: This was a secondary analysis of a national, prospective cohort study. All pregnant women admitted to hospital in the UK with symptomatic SARS-CoV-2 from March 1, 2020 to October 31, 2021 were included. The severity of maternal infection (need for high flow or invasive ventilation, intensive care admission or died), pregnancy and perinatal outcomes, and the impact of timing of birth were analyzed using multivariable logistic regression. RESULTS: Of 4436 pregnant women, 13.9% (n = 616) had severe infection. Women with severe infection were more likely to be aged ≥30 years (adjusted odds ratio [aOR] aged 30-39 1.48, 95% confidence interval [CI] 1.20-1.83), be overweight or obese (aOR 1.73, 95% CI 1.34-2.25 and aOR 2.52 95% CI 1.97-3.23, respectively), be of mixed ethnicity (aOR 1.93, 95% CI 1.17-3.21) or have gestational diabetes (aOR 1.43, 95% CI 1.09-1.87) compared with those with mild or moderate infection. Women with severe infection were more likely to have a pre-labor cesarean birth (aOR 8.84, 95% CI 6.61-11.83), a very or extreme preterm birth (28-31+ weeks' gestation, aOR 18.97, 95% CI 7.78-14.85; <28 weeks' gestation, aOR 12.35, 95% CI 6.34-24.05) and their babies were more likely to be stillborn (aOR 2.51, 95% CI 1.35-4.66) or admitted to a neonatal unit (aOR 11.61, 95% CI 9.28-14.52). Of 112 women with severe infection who were discharged and gave birth at a later admission, the majority gave birth ≥36 weeks (85.7%), noting that three women in this group (2.7%) had a stillbirth. CONCLUSIONS: Severe COVID-19 in pregnancy increases the risk of adverse outcomes. Information to promote uptake of vaccination should specifically target those at greatest risk of severe outcomes. Decisions about timing of birth should be informed by multidisciplinary team discussion; however, our data suggest that women with severe infection who do not require early delivery have mostly good outcomes but that those with severe infection at term may warrant rapid delivery

Severity of maternal infection and perinatal outcomes during periods of SARS-CoV-2 wildtype, alpha, and delta variant dominance in the UK: prospective cohort study

OBJECTIVE: To compare the severity of maternal infection and perinatal outcomes during periods in which wildtype, alpha variant, and delta variant of SARS-CoV-2 were dominant in the UK. DESIGN: Prospective cohort study. SETTING: 194 obstetric units across the UK, during the following periods: between 1 March and 30 November 2020 (wildtype dominance), between 1 December 2020 and 15 May 2021 (alpha variant dominance), and between 16 May and 31 October 2021 (delta variant dominance). PARTICIPANTS: 4436 pregnant women admitted to hospital with covid-19 related symptoms. MAIN OUTCOME MEASURES: Moderate to severe maternal SARS-CoV-2 infection (indicated by any of the following: oxygen saturation <95% on admission, need for oxygen treatment, evidence of pneumonia on imaging, admission to intensive care, or maternal death), and pregnancy and perinatal outcomes (including mode and gestation of birth, stillbirth, live birth, admission to neonatal intensive care, and neonatal death). RESULTS: 1387, 1613, and 1436 pregnant women were admitted to hospital with covid-19 related symptoms during the wildtype, alpha, and delta dominance periods, respectively; of these women, 340, 585, and 614 had moderate to severe infection, respectively. The proportion of pregnant women admitted with moderate to severe infection increased during the subsequent alpha and delta dominance periods, compared with the wildtype dominance period (wildtype 24.5% v alpha 36.2% (adjusted odds ratio 1.98, 95% confidence interval 1.66% to 2.37%); wildtype 24.5% v delta 42.8% (2.66, 2.21 to 3.20)). Compared with the wildtype dominance period, women admitted during the alpha dominance period were significantly more likely to have pneumonia, require respiratory support, and be admitted to intensive care; these three risks were even greater during the delta dominance period (wildtype v delta: pneumonia, adjusted odds ratio 2.52, 95% confidence interval 2.06 to 3.09; respiratory support, 1.90, 1.52 to 2.37; and intensive care, 2.71, 2.06 to 3.56). Of 1761 women whose vaccination status was known, 38 (2.2%) had one dose and 16 (1%) had two doses before their diagnosis (of whom 14 (88%) had mild infection). The proportion of women receiving drug treatment for SARS-CoV-2 management was low, but did increase between the wildtype dominance period and the alpha and delta dominance periods (10.4% wildtype v 14.9% alpha (2.74, 2.08 to 3.60); 10.4% wildtype v 13.6% delta (2.54, 1.90 to 3.38)). CONCLUSIONS: While limited by the absence of variant sequencing data, these findings suggest that during the periods when the alpha and delta variants of SARS-CoV-2 were dominant, covid-19 was associated with more severe maternal infection and worse pregnancy outcomes than during the wildtype dominance period. Most women admitted with SARS-CoV-2 related symptoms were unvaccinated. Urgent action to prioritise vaccine uptake in pregnancy is essential. STUDY REGISTRATION: ISRCTN40092247

Quantum states made to measure

Recent progress in manipulating quantum states of light and matter brings quantum-enhanced measurements closer to prospective applications. The current challenge is to make quantum metrologic strategies robust against imperfections.Comment: 4 pages, 3 figures, Commentary for Nature Photonic

Severity of maternal SARS-CoV-2 infection and perinatal outcomes of women admitted to hospital during the omicron variant dominant period using UK Obstetric Surveillance System data: prospective, national cohort study.

OBJECTIVES: To describe the severity of maternal infection when the omicron SARS-CoV-2 variant (B.1.1.529) was dominant (15 December 2021 to 14 March 2022) and describe outcomes by symptoms and vaccination status. DESIGN: Prospective, national cohort study using the UK Obstetric Surveillance System. SETTING: 94 hospitals in the UK with a consultant led maternity unit. PARTICIPANTS: Pregnant women admitted to hospital for any cause with a positive SARS-CoV-2 test. MAIN OUTCOME MEASURES: Symptomatic or asymptomatic infection, vaccination status by doses before admission, and severity of maternal infection (moderate or severe infection according to modified World Health Organization's criteria). RESULTS: Of 3699 women who were admitted to hospital, 986 (26.7%, 95% confidence interval 25.3% to 28.1%) had symptoms; of these, 144 (14.6%, 12.5% to 17.0%) had a moderate to severe infection, 99 (10.4%, 8.6% to 12.5%) of 953 received respiratory support, and 30 (3.0%, 2.1% to 4.3%) were admitted to an intensive care unit. Covid-19 specific drug treatment was given to 13 (43.3%) of the 30 women in intensive care. Four women with symptoms died (0.4%, 0.1% to 1.1%). Vaccination status was known for 845 (85.6%) women with symptoms; 489 (58.9%) were unvaccinated and only 55 (6.5%) had three doses. Moderate to severe infection was reported for 93 (19.0%) of 489 unvaccinated women with symptoms, decreasing to three (5.5%) of 55 after three doses. Among the 30 women with symptoms who were admitted to intensive care, 23 (76.7%) were unvaccinated and none had received three doses. CONCLUSION: Most women with severe covid-19 disease were unvaccinated and vaccine coverage among pregnant women admitted to hospital with SARS-CoV-2 was low. Ongoing action to prioritise and advocate for vaccine uptake in pregnancy is essential. A better understanding of the persistent low use of drug treatments is an urgent priority. TRIAL REGISTRATION: ISRCTN 40092247

Morphological adaptations linked to flight efficiency and aerial lifestyle determine natal dispersal distance in birds

Natal dispersal—the movement from birthplace to breeding location—is often considered the most significant dispersal event in an animal's lifetime. Natal dispersal distances may be shaped by a variety of intrinsic and extrinsic factors, and remain poorly quantified in most groups, highlighting the need for indices that capture variation in dispersal among species. In birds, it is hypothesized that dispersal distance can be predicted by flight efficiency, which can be estimated using wing morphology. However, the use of morphological indices to predict dispersal remains contentious and the mechanistic links between flight efficiency and natal dispersal are unclear. Here, we use phylogenetic comparative models to test whether hand-wing index (HWI, a morphological proxy for wing aspect ratio) predicts natal dispersal distance across a global sample of 114 bird species. In addition, we assess whether HWI is correlated with flight usage in foraging and daily routines. We find that HWI is a strong predictor of both natal dispersal distance and a more aerial lifestyle. Our results support the use of HWI as a valid proxy for relative natal dispersal distance, and also suggest that evolutionary adaptation to aerial lifestyles is a major factor connecting flight efficiency with patterns of natal dispersal

Guaranteed violation of a Bell inequality without aligned reference frames or calibrated devices

Bell tests---the experimental demonstration of a Bell inequality violation---are central to understanding the foundations of quantum mechanics, underpin quantum technologies, and are a powerful diagnostic tool for technological developments in these areas. To date, Bell tests have relied on careful calibration of the measurement devices and alignment of a shared reference frame between the two parties---both technically demanding tasks in general. Surprisingly, we show that neither of these operations are necessary, violating Bell inequalities with near certainty with (i) unaligned, but calibrated, measurement devices, and (ii) uncalibrated and unaligned devices. We demonstrate generic quantum nonlocality with randomly chosen local measurements on a singlet state of two photons implemented with reconfigurable integrated optical waveguide circuits based on voltage-controlled phase shifters. The observed results demonstrate the robustness of our schemes to imperfections and statistical noise. This new approach is likely to have important applications in both fundamental science and in quantum technologies, including device independent quantum key distribution.Comment: 7 pages, 7 figure