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Oxide ion conductors are technologically relevant for applications in electrochemical devices such as sensors, separation membranes and fuel cells. Magnesium doping in Na 0.5 Bi 0.5 TiO 3 —a piezoelectric material that suffers from high leakage conductivity—now results in a family of ionic conductors that could prove significant not only for dielectric-based applications but also for intermediate-temperature solid-oxide fuel cells. Oxide ion conductors find important technical applications in electrochemical devices such as solid-oxide fuel cells (SOFCs), oxygen separation membranes and sensors 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 . Na 0.5 Bi 0.5 TiO 3 (NBT) is a well-known lead-free piezoelectric material; however, it is often reported to possess high leakage conductivity that is problematic for its piezo- and ferroelectric applications 10 , 11 , 12 , 13 , 14 , 15 . Here we report this high leakage to be oxide ion conduction due to Bi-deficiency and oxygen vacancies induced during materials processing. Mg-doping on the Ti-site increases the ionic conductivity to ~0.01 S cm −1 at 600 °C, improves the electrolyte stability in reducing atmospheres and lowers the sintering temperature. This study not only demonstrates how to adjust the nominal NBT composition for dielectric-based applications, but also, more importantly, gives NBT-based materials an unexpected role as a completely new family of oxide ion conductors with potential applications in intermediate-temperature SOFCs and opens up a new direction to design oxide ion conductors in perovskite oxides.

Future optical clock networks will require free-space optical time-frequency transfer between flying clocks. However, simple one-way or standard two-way time transfer between flying clocks will completely break down because of the time-of-flight variations and Doppler shifts associated with the strongly time-varying link distances. Here, we demonstrate an advanced, frequency comb-based optical two-way time-frequency transfer (O-TWTFT) that can successfully synchronize the optical timescales at two sites connected via a time-varying turbulent air path. The link between the two sites is established using either a quadcopter-mounted retroreflector or a swept delay line at speeds up to 24 ms −1 . Despite 50-ps breakdown in time-of-flight reciprocity, the sites’ timescales are synchronized to < 1 fs in time deviation. The corresponding sites’ frequencies agree to ~ 10 −18 despite 10 −7 Doppler shifts. This work demonstrates comb-based O-TWTFT can enable free-space optical networks between airborne or satellite-borne optical clocks for precision navigation, timing and probes of fundamental science. Optical clock networks have many applications from precision time keeping, sensing to fundamental physics. Here the authors demonstrate robust and free-space femtosecond time synchronization of optical clocks via a moving quadcopter.

Cities impose unique selection pressures on wildlife and generate clines in phenotypic traits along urban–rural gradients. Roads are a widespread feature of human‐dominated landscapes and are known to cause direct wildlife mortality; however, whether they act as a selective force influencing phenotypic trait variation along urban–rural gradients remains unclear. This study tested the hypothesis that roads influence natural selection of coat color in the eastern gray squirrel (Sciurus carolinensis), a species with two distinct coat colors: a gray morph that is common in all areas and a melanic morph more prevalent in urban areas than in rural ones. Vehicular collisions are a significant cause of mortality in eastern gray squirrels, with the melanic morph more visually conspicuous on roads and more easily detected and avoided by drivers than the gray morph. Standardized road cruise surveys along an urbanization gradient in Syracuse, New York, USA, revealed that the prevalence of melanism among living squirrels in Syracuse was negatively related to distance from the city center, whereas there was no urban–rural cline in melanism among road‐killed individuals, with the melanic morph underrepresented among road‐killed squirrels by up to 30% along the urbanization gradient. An examination of the prevalence of each color morph on and off road surfaces in a range‐wide compilation of > 100,000 photographs of S. carolinensis also indicated that the melanic morph was underrepresented among road‐killed squirrels imaged. Our study highlights vehicular collisions as an important source of natural selection on phenotypic traits, suggesting a potential role in shaping patterns of urban evolution and contributing to the maintenance of urban–rural clines.

Ferric derisomaltose (FDI; Monofer) is used in clinical practice to treat iron deficiency, but the safety and efficacy of FDI has not been robustly evaluated in a large real-world study. This retrospective, multicentre, audit-based, observational study provides pragmatic information about safety and clinical responses with FDI across therapy areas and patient populations, helping to facilitate treatment decisions. Participating sites provided data from the medical records of adults who had received ≥ 1 FDI infusion. The primary outcome was the incidence of adverse reactions within 24 hours of the FDI infusion. Secondary outcomes included the change from baseline in haemoglobin and ferritin up to 12 months post infusion. In total, 19 sites provided data for a total of 7354 FDI-treated patients; 64.3% of patients were female, and 42.2% were aged ≥ 70 years. Surgery was the main hospital specialty (34.5%). The incidence of any recorded adverse reactions, hypersensitivity reactions, and anaphylaxis were 1.7%, 0.4%, and < 0.1%, respectively, regardless of baseline anaemia status. Statistically significant increases in haemoglobin and ferritin were observed between baseline and Month 4 following FDI treatment (p < 0.0001). Improvements in haemoglobin were more pronounced for hospital specialties where operative blood loss is expected (surgery/obstetrics) compared with those where blood loss is not expected. This study provides real-world clinical evidence for the low risk of adverse reactions with FDI across diverse patient populations, providing reassurance that intravenous iron is not associated with serious toxicity. These findings may inform changes in intravenous iron delivery to provide effective therapy to more patients in need.

The use of optical clocks or oscillators in future ultraprecise navigation, gravitational sensing, coherent arrays, and relativity experiments will require time comparison and synchronization over terrestrial or satellite free-space links. Here, we demonstrate full unambiguous synchronization of two optical time scales across a free-space link. The time deviation between synchronized time scales is below 1 fs over durations from 0.1 to 6500 s, despite atmospheric turbulence and kilometer-scale path length variations. Over 2 days, the time wander is 40 fs peak to peak. Our approach relies on the two-way reciprocity of a single-spatial-mode optical link, valid to below 225 attoseconds across a turbulent 4-km path. This femtosecond level of time-frequency transfer should enable optical networks using state-of-the-art optical clocks or oscillators.

Background Evidence for the longer-term benefits of online mindfulness training for medical students, including in the reduction of stress and improved wellbeing, is limited. This study aimed to evaluate the impact of a novel online mindfulness training program on trait mindfulness, wellbeing and study engagement of medical students at program completion and 6-month follow-up. Methods This was a randomised waitlist control study of an 8-week, online, mindfulness-based intervention versus normal curriculum alone for medical students ( N  = 114). The primary outcome measures were the changes from baseline to program completion at Week 8 for self-reported trait mindfulness (Freiburg Mindfulness Inventory), perceived stress (Perceived Stress Scale), self-compassion (Self-Compassion Scale) and study engagement scores (Utrecht Work Engagement Scale for Students). The secondary outcome measures were these score changes from baseline to 6-month follow up. Intervention and control students completed surveys at all three time points. Program adherence (Mindfulness Adherence Questionnaire) was also measured in the intervention group. Results The intervention group experienced modest but statistically significant improvements in mindfulness (9%, p  = 0.0002), self-compassion (5%, p  = 0.026), and study engagement (4%, p  = 0.035) from baseline to Week 8. They also reported a sustained improvement of 5% ( p  = 0.017) in mindfulness scores at 6 months. The control group reported no significant changes at Week 8 or 6 Months. Between-group comparisons showed that compared to the control group, the intervention group improved significantly more in mindfulness ( p  = 0.0076), and statistically marginally more in study engagement ( p  = 0.0534) at Week 8. No statistically significant between-group differences were observed at 6 months. Conclusions These results add to the small but growing body of evidence suggesting that online mindfulness-based interventions with minimal contact can improve, albeit in modest magnitude, mindfulness and possibly study engagement in medical students for the duration of a mindfulness program. Further refinements to the program may be important to maintain improvements in the longer-term. Trial registration Registration number ACTRN12624000783527.

Retinal visual prostheses (\"bionic eyes\") have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. Clinicaltrials.gov NCT01603576.

BackgroundEsophagectomy is associated with a high rate of morbidity and mortality. Preoperative cardiopulmonary fitness has been correlated with outcomes of major surgery. Variables derived from cardiopulmonary exercise testing (CPET) have been associated with postoperative outcomes. It is unclear whether preoperative cardiorespiratory fitness of patients undergoing esophagectomy is associated with long-term survival. This study aimed to evaluate whether any of the CPET variables routinely derived from patients with esophageal cancer may aid in predicting long-term survival after esophagectomy.MethodsPatients undergoing CPET followed by trans-thoracic esophagectomy for esophageal cancer with curative intent between January 2013 and January 2017 from single high-volume center were retrospectively analyzed. The relationship between predictive co-variables, including CPET variables and survival, was studied with a Cox proportional hazard model. Receiver operation curve (ROC) analysis was performed to find cutoff values for CPET variables predictive of 3-year survival.ResultsThe study analyzed 313 patients. The ventilatory equivalent for carbon dioxide (VE/VCO2) at the anerobic threshold was the only CPET variable independently predictive of long-term survival in the multivariable analysis (hazard ratio [HR], 1.049; 95% confidence interval [CI], 1.011–1.088; p = 0.011). Pathologic stages 3 and 4 disease was the other co-variable found to be independently predictive of survival. An ROC analysis of the VE/VCO2 failed to demonstrate a predictive cutoff value of 3-year survival (area under the curve, 0.564; 95% CI, 0.499–0.629; p = 0.056).ConclusionsA high VE/VCO2 before esophagectomy for malignant disease is an independent predictor of long-term survival and may be an important variable for clinicians to consider when counseling patients.

ObjectivesPreoperative exercise training can improve cardiorespiratory fitness before major surgery. However, little is known about what influences participation and adherence in high-risk patient groups. We identified barriers and facilitators to uptake, engagement and adherence to a presurgical, home-based physical activity and exercise intervention called ChemoFit delivered during chemotherapy and before major oesophagogastric surgery.DesignA qualitative study using focus group discussions and individual semi-structured interviews was conducted. All were audio-recorded, transcribed verbatim and data thematically analysed.SettingNorthern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Hospitals Foundation Trust.ParticipantsPatients with oesophagogastric cancer who participated in the ChemoFit intervention recruited between March 2020 and January 2021.InterventionA home-based physical activity and exercise intervention involving cardiovasular and strength exercise using resistance bands and pedometers to monitor step count. Weekly telephone calls provided feedback, support and positive reinforcement.ResultsTwenty-two participants (18 men, 4 women; aged 67±8 years old) took part in a focus group discussion (n=17) or a semi-structured interview (n=5). Fifteen themes were identified from the data generated. Participants reported that the intervention was physically and mentally beneficial, and data highlighted features of the intervention that influenced uptake and adherence. An opportunity to increase the likelihood of surviving the pending operation was reported by participants as the most salient factor to engagement, and using the intervention as a distraction from illness and taking steps to positively influence the situation were the most salient factors to adherence.ConclusionsUptake to the ChemoFit intervention was encouraged by provision of information that participation could reduce surgical risk and that participants could play an active role in risk reduction. Adherence was facilitated by the intervention being considered a positive distraction and participants being able to do something that could ultimately provide benefit. While participants reported difficulties and avoidance with some of the exercises recommended, understanding the importance of physical activity and exercise as part of their treatment regimen led to individual adaptations to intervention components to reach individual goals.Trial registration numberNCT04194463

Measurements of the cross sectional area of the sciatic nerve are described in a group of 10 patients with genetically confirmed Charcot–Marie–Tooth disease type 1A (CMT1A), nine patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 10 healthy controls using MRI. One mid-thigh of each individual was imaged using a short tau inversion recovery sequence and the nerve appearance evaluated radiologically with respect to the signal intensity and visibility of the internal neural structure. The cross sectional area of the sciatic nerve of each individual was measured by defining irregular enclosing regions of interest on the MRI images. The sciatic nerve area was enlarged in both CMT1A (p<0.001) and CIDP (p=0.008) compared with controls and in CMT1A compared with CIDP (p<0.001). Median (interquartile range) areas were 67.6 (16.2) mm2 for the CIDP group, 135.9 (46.5) mm2 for the CMT1A group and 43.3 (19.9) mm2 for the control group. The critical upper value for discriminating pathologically enlarged nerves from normal controls with p<0.05 was 64.4 mm2. Quantification of sciatic nerve hypertrophy on MRI may be of assistance in cases where the diagnosis is still in doubt, providing an objective pathological marker complimenting other clinical investigations.