Chain Reduction of CHCl3 Photocatalyzed by SPEEK/PVA Films Swollen in Air-Saturated HCO2Na Solutions.

Thin cross-linked films containing sulfonated poly(ether etherketone), SPEEK, and poly(vinyl alcohol), PVA, served as efficient photocatalysts for the reduction of CHCl3 when swollen in air-saturated solutions of formate buffers were photolyzed with 350 nm photons. The phototransformation generated CH2Cl2, CO2 and Cl- as products. The utilization of the continuous extraction method coupled with in situ potentiometry enabled kinetic determinations of the reaction progress. Quantum yields of halide ion formation, ϕ(Cl-), larger than 1 were obtained in the presence of air. These findings, together with the occurrence of a post-irradiation Cl- formation, indicated that the photoreduction took place via a chain process. Reductions photoinitiated by swollen films exhibited ϕ(Cl-) values between 3 and 20 times higher than the reactions induced in solutions containing the two polymers. Also, the dependencies of ϕ(Cl-) on CHCl3 or HCO2- concentration diverged significantly from the trends observed using solutions. Most findings are consistent with the occurrence of a reaction mechanism involving SPEEK radicals, •CO2- and •CHCl2 as chain carriers.

MiniBooNE and MicroBooNE Combined Fit to a 3+1 Sterile Neutrino Scenario.

This Letter presents the results from the MiniBooNE experiment within a full "3+1" scenario where one sterile neutrino is introduced to the three-active-neutrino picture. In addition to electron-neutrino appearance at short baselines, this scenario also allows for disappearance of the muon-neutrino and electron-neutrino fluxes in the Booster Neutrino Beam, which is shared by the MicroBooNE experiment. We present the 3+1 fit to the MiniBooNE electron-(anti)neutrino and muon-(anti)neutrino data alone and in combination with MicroBooNE electron-neutrino data. The best-fit parameters of the combined fit with the exclusive charged-current quasielastic analysis (inclusive analysis) are Δm^{2}=0.209 eV^{2}(0.033 eV^{2}), |U_{e4}|^{2}=0.016(0.500), |U_{µ4}|^{2}=0.500(0.500), and sin^{2}(2θ_{µe})=0.0316(1.0). Comparing the no-oscillation scenario to the 3+1 model, the data prefer the 3+1 model with a Δχ^{2}/d.o.f.=24.7/3(17.3/3), a 4.3σ(3.4σ) preference assuming the asymptotic approximation given by Wilks's theorem.

Autonomous control for miniaturized mobile robots in unknown pipe networks.

Despite recent advances in robotic technology, sewer pipe inspection is still limited to conventional approaches that use cable-tethered robots. Such commercially available tethered robots lack autonomy, and their operation must be manually controlled via their tethered cables. Consequently, they can only travel to a certain distance in pipe, cannot access small-diameter pipes, and their deployment incurs high costs for highly skilled operators. In this paper, we introduce a miniaturised mobile robot for pipe inspection. We present an autonomous control strategy for this robot that is effective, stable, and requires only low-computational resources. The robots used here can access pipes as small as 75 mm in diameter. Due to their small size, low carrying capacity, and limited battery supply, our robots can only carry simple sensors, a small processor, and miniature wheel-legs for locomotion. Yet, our control method is able to compensate for these limitations. We demonstrate fully autonomous robot mobility in a sewer pipe network, without any visual aid or power-hungry image processing. The control algorithm allows the robot to correctly recognise each local network configuration, and to make appropriate decisions accordingly. The control strategy was tested using the physical micro robot in a laboratory pipe network. In both simulation and experiment, the robot autonomously and exhaustively explored an unknown pipe network without missing any pipe section while avoiding obstacles. This is a significant advance towards fully autonomous inspection robot systems for sewer pipe networks.

Evaluating Palin Stammering Therapy for School Children (Palin STSC 8-14): protocol for a feasibility randomised controlled trial comparing Palin STSC(8-14) with usual treatment.

BACKGROUND: Having a stammer can have a significant effect on a child's social, emotional and educational development. With approximately 66,000 children in the UK having a stammer, there is a need to establish an adequate evidence base to inform clinical practice. We describe a feasibility trial to explore the effectiveness of a new therapy programme for children aged 8-14: Palin Stammering Therapy for School Children (Palin STSC(8-14)). Preliminary data from the Michael Palin Centre, where the programme was developed, indicate that Palin STSC(8-14) is effective in reducing stammering frequency and impact for children, with beneficial effects for parents too. We will investigate the feasibility of the methods required for a definitive randomised controlled trial to investigate the application of this therapy by NHS speech and language therapists (SLTs), compared with 'treatment as usual' (TAU), beyond the specialist context in which it was developed. METHODS: This is a two-arm feasibility cluster-randomised controlled trial of Palin STSC(8-14) with TAU control arm, and randomisation at the level of the SLT. Quantitative and qualitative data will be collected to examine the following: the recruitment and retention of therapists and families, the acceptability of the research processes and the therapeutic intervention and the appropriateness of the therapy outcome measures. Assessments will be completed by children and parents at baseline and 6 months later, including measures of stammering severity; the impact of child's stammering on both children and parents; child temperament, behaviour and peer relations, anxiety; quality of life; and economic outcomes. There will also be a qualitative process evaluation, including interviews with parents, children, SLTs and SLT managers to explore the acceptability of both the research and therapy methods. Treatment fidelity will be examined through analysis of therapy session records and recordings. DISCUSSION: The findings of this feasibility trial will inform the decision as to whether to progress to a full-scale randomised controlled trial to explore the effectiveness of Palin STSC(8-14) when compared to Treatment as Usual in NHS SLT services. There is a strong need for an evidence-based intervention for school age children who stammer. TRIAL REGISTRATION: ISRCTN. ISRCTN17058884 . Registered on 18 December 2019.

The PRO-ACTIVE trial protocol: a randomized study comparing the effectiveness of PROphylACTic swallow InterVEntion for patients receiving radiotherapy for head and neck cancer.

BACKGROUND: Swallowing therapy is commonly provided as a treatment to lessen the risk or severity of dysphagia secondary to radiotherapy (RT) for head and neck cancer (HNC); however, best practice is not yet established. This trial will compare the effectiveness of prophylactic (high and low intensity) versus reactive interventions for swallowing in patients with HNC undergoing RT. METHODS: This multi-site, international randomized clinical trial (RCT) will include 952 adult patients receiving radiotherapy for HNC and who are at high risk for post-RT dysphagia. Participants will be randomized to receive one of three interventions for swallowing during RT: RE-ACTIVE, started promptly if/when dysphagia is identified; PRO-ACTIVE EAT, low intensity prophylactic intervention started before RT commences; or, PRO-ACTIVE EAT+EXERCISE, high intensity prophylactic intervention also started before RT commences. We hypothesize that the PRO-ACTIVE therapies are more effective than late RE-ACTIVE therapy; and, that the more intensive PRO-ACTIVE (EAT + EXERCISE) is superior to the low intensive PRO-ACTIVE (EAT). The primary endpoint of effectiveness is duration of feeding tube dependency one year post radiation therapy, selected as a pragmatic outcome valued equally by diverse stakeholders (e.g., patients, caregivers and clinicians). Secondary outcomes will include objective measures of swallow physiology and function, pneumonia and weight loss, along with various patient-reported swallowing-related outcomes, such as quality of life, symptom burden, and self-efficacy. DISCUSSION: Dysphagia is a common and potentially life-threatening chronic toxicity of radiotherapy, and a priority issue for HNC survivors. Yet, the optimal timing and intensity of swallowing therapy provided by a speech-language pathologist is not known. With no clearly preferred strategy, current practice is fraught with substantial variation. The pragmatic PRO-ACTIVE trial aims to specifically address the decisional dilemma of when swallowing therapy should begin (i.e., before or after a swallowing problem develops). The critical impact of this dilemma is heightened by the growing number of young HNC patients in healthcare systems that need to allocate resources most effectively. The results of the PRO-ACTIVE trial will address the global uncertainty regarding best practice for dysphagia management in HNC patients receiving radiotherapy. TRIAL REGISTRATION: The protocol is registered with the US Patient Centered Outcomes Research Institute, and the PRO-ACTIVE trial was prospectively registered at ClinicalTrials.gov , under the identifier NCT03455608 ; First posted: Mar 6, 2018; Last verified: Jun 17, 2021. Protocol Version: 1.3 (January 27, 2020).

The effects of smoking on pregnancy risks in women with polycystic ovary syndrome: a population-based study.

STUDY QUESTION: Is there is an association between smoking and pregnancy complications in pregnant women with polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER: There is an increased risk of developing gestational diabetes mellitus (GDM) among women with PCOS who smoke. WHAT IS KNOWN ALREADY: Smokers are at increased risk of developing Type 2 Diabetes Mellitus (DM). Given the common pathophysiology and shared risk factors between type 2 DM and GDM, we sought to assess whether an association between smoking and the development of GDM exists. STUDY DESIGN, SIZE, DURATION: This is a retrospective population-based study utilizing data from the HCUP-NIS over 11 years from 2004 to 2014. Pregnant women with PCOS who did smoke were compared to pregnant women with PCOS who did not smoke. A second comparison was made between pregnant smokers with and without PCOS. Of the 443 590 women who smoked during pregnancy and the 14 882 women with PCOS, 631 women were both smokers and diagnosed with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: The Healthcare Cost and Utilization Project-Nationwide Inpatient Sample (HCUP-NIS) is the largest inpatient sample database in the USA and is composed of hospital inpatient stays submitted by hospitals throughout the entire country. Each year, the database provides information relating to 7 million inpatient stays, including patient characteristics, diagnosis and procedures. The data are representative of ∼20% of admissions to US hospitals across 48 states and the District of Columbia. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in the risks of preterm delivery (aOR1.2; CI 0.8-1.9), placental abruption (aOR1.1; CI 0.4-3.2), pregnancy induced hypertension (aOR1.0; CI 0.7-1.5), rate of operative vaginal delivery (aOR1.5; CI 0.9-2.5) and rates of cesarean section (C/S) (aOR1.0; CI 0.7-1.3) between smoking and non-smoking women with PCOS. A significant association between smoking and GDM was observed in women with PCOS (aOR1.5; CI1.01-2.1). LIMITATIONS, REASONS FOR CAUTION: The limitations of our study are its retrospective nature and the fact that it relies on an administrative database. Data regarding smoking and PCOS diagnosis could be skewed due to patients' underreporting, lack of documentation and documentation differences. WIDER IMPLICATIONS OF THE FINDINGS: The public health implications of confirming smoking as a risk for GDM among women with PCOS are many. This can lead to earlier screening in pregnancy of smokers for GDM. Earlier initiation of interventions could decrease fetal complications and possibly have an impact on the life and long-term health of the offspring. Future studies are needed in order to assess whether smoking cessation during pregnancy decreases the risk of GDM in that gestation. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

The impact of green spaces on mental health in urban settings: a scoping review.

BACKGROUND: Our planet is currently experiencing the largest wave of urban growth in history, with 55% of the world's population (4.2 billion people) currently living in urban areas, a figure set to rise to 70% by 2050. Primary care is the first point of treatment for most mental health disorders. Since the urban environment and health are intrinsically linked, it is useful to examine the effectiveness of Nature-Based Solutions in addressing mental health. AIMS: The aim of this scoping review was to examine "How urban green spaces can improve mental health and wellbeing among patients attending general practice and primary care?" METHODS: The scoping review framework comprised a five-stage process developed by Arksey and O'Malley. RESULTS: Twenty-five studies were included in the review, mostly cross-sectional studies. A wide range of mental health outcomes were identified. Out of the 25 included studies, 23 showed positive associations between mental health and green space characteristics. CONCLUSION: Our findings suggest that while green spaces are associated with positive mental health outcomes, most studies were cross-sectional in nature and provided limited evidence for association. Furthermore, the population samples used in most of the studies were taken from national survey data and were not specifically primary care patients. Further studies that assess primary care patients specifically are warranted.

Precision Constraints for Three-Flavor Neutrino Oscillations from the Full MINOS+ and MINOS Dataset.

We report the final measurement of the neutrino oscillation parameters Δm_{32}^{2} and sin^{2}θ_{23} using all data from the MINOS and MINOS+ experiments. These data were collected using a total exposure of 23.76×10^{20} protons on target producing ν_{µ} and ν[over ¯]_{µ} beams and 60.75 kt yr exposure to atmospheric neutrinos. The measurement of the disappearance of ν_{µ} and the appearance of ν_{e} events between the Near and Far detectors yields |Δm_{32}^{2}|=2.40_{-0.09}^{+0.08}(2.45_{-0.08}^{+0.07})×10^{-3} eV^{2} and sin^{2}θ_{23}=0.43_{-0.04}^{+0.20}(0.42_{-0.03}^{+0.07}) at 68% C.L. for normal (inverted) hierarchy.

Laser-Assisted Delivery of Molecules in Fungal Cells.

Fungal infections are becoming a global health problem. A major limiting factor for the development of antifungals is the high impermeability of the rigid and thick fungal cell wall. Compared to mammalian cells, fungal cells are more resilient to perforation due to the presence of this carbohydrate armor. While a few methods have been reported to penetrate the fungal cell wall, such as electroporation, biolistics, glass beads, and the use of monovalent cations, such methods are generally time-consuming, compromise cell viability, and often lead to low permeation rates. In addition, their use remains limited to in vitro applications due to the collateral damage that these techniques could cause to healthy living tissues. Presented in this study is a delivery approach based on the generation of transient breaks, or pores, in the cell wall. Breaks are generated by cavitation and shock waves resulting from the irradiation of gold nanoparticles with a femtosecond infrared laser. Such an approach enabled the delivery of membrane impermeable molecules (i.e., calcein and plasmid DNA) into Saccharomyces cerevisiae, a fungal model organism. This method is expected to exhibit high biocompatibility and holds potential for clinical applications for the treatment of fungal infections given that neither the laser irradiation nor the nanoparticles have been found to damage cells. Mechanistical aspects of photoporation, such as the proximity needed between the nanoparticle and the cell membrane for these processes to take place, are also discussed. Hence, the laser-assisted drug delivery approach described here is suitable for further preclinical evaluation in oral, vaginal, and skin mycoses where current treatments are insufficient due to host-related adverse reactions, poor fungal cell penetration, or risk of developing antifungal resistance.

Expanded analysis of secondary germline findings from matched tumor/normal sequencing identifies additional clinically significant mutations.

BACKGROUND: Next-generation sequencing (NGS) for tumor molecular profiling can reveal secondary germline pathogenic and likely pathogenic variants (LPV/PV). The American College of Medical Genetics (ACMG) recommends return of secondary results for a subset of 59 genes, but other genes with evidence of clinical utility are emerging. We previously reported that 4.3% of patients who underwent NGS of a targeted panel of 201 genes had LPV/PV based on the ACMG list. Here we report the frequency of additional germline cancer-related gene variants and discuss their clinical utility. PATIENTS AND METHODS: Matched tumor and germline DNA NGS of a targeted panel of 201 genes was performed in a research laboratory on samples from 1000 patients with advanced or metastatic solid tumors enrolled in a molecular testing protocol (NCT01772771). The frequency of germline LPV/PV in 54 cancer-related genes, beyond the genes in ACMG list, were analyzed. RESULTS: Among 1000 patients who underwent tumor/normal DNA sequencing, 46 (4.6%) were found to have a germline LPV/PV in the following genes: AR-(5), ATM-(4), BAP1-(1), CDH1-(1), CDKN2A-(1), CHEK1-(2), CHEK2-(10), EGFR-(1), ERCC3-(4), ERCC5-(1), HNF1B-(1), HRAS-(1), MITF-(4), MLL3-(1), NF1-(3), PKHD1-(4), PTCH1-(1), and SMARCA4-(1). Thus, a total 8.7% of patients had an LPV/PV with 2 patients having 2 concomitant germline LPV/PV. Five mutations in high-penetrance hereditary cancer predisposition genes were selected to be returned to patients or their representatives: BAP1, CDH1, CDKN2A, EGFR, and SMARCA4. CONCLUSIONS: Broader genomic testing is likely to identify additional secondary pathogenic germline alterations, some with potential clinical utility for return to patients and their relatives. The recommended genes for which germline results should be returned are continually changing, warranting continued study.

First Measurement of the Total Neutron Cross Section on Argon between 100 and 800 MeV.

We report the first measurement of the neutron cross section on argon in the energy range of 100-800 MeV. The measurement was obtained with a 4.3-h exposure of the Mini-CAPTAIN detector to the WNR/LANSCE beam at LANL. The total cross section is measured from the attenuation coefficient of the neutron flux as it traverses the liquid argon volume. A set of 2631 candidate interactions is divided in bins of the neutron kinetic energy calculated from time-of-flight measurements. These interactions are reconstructed with custom-made algorithms specifically designed for the data in a time projection chamber the size of the Mini-CAPTAIN detector. The energy averaged cross section is 0.91±0.10(stat)±0.09(syst) b. A comparison of the measured cross section is made to the GEANT4 and FLUKA event generator packages, where the energy averaged cross sections in this range are 0.60 and 0.68 b, respectively.

Measurements of Nonsinglet Moments of the Nucleon Structure Functions and Comparison to Predictions from Lattice QCD for Q

We present extractions of the nucleon nonsinglet moments utilizing new precision data on the deuteron F_{2} structure function at large Bjorken-x determined via the Rosenbluth separation technique at Jefferson Lab Experimental Hall C. These new data are combined with a complementary set of data on the proton previously measured in Hall C at similar kinematics and world datasets on the proton and deuteron at lower x measured at SLAC and CERN. The new Jefferson Lab data provide coverage of the upper third of the x range, crucial for precision determination of the higher moments. In contrast to previous extractions, these moments have been corrected for nuclear effects in the deuteron using a new global fit to the deuteron and proton data. The obtained experimental moments represent an order of magnitude improvement in precision over previous extractions using high x data. Moreover, recent exciting developments in lattice QCD calculations provide a first ever comparison of these new experimental results with calculations of moments carried out at the physical pion mass, as well as a new approach that first calculates the quark distributions directly before determining moments.

Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial.

Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain. Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP. Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018. Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight. Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute). Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001). Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.

Correction to: Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial.

After publication of the original article [1], the authors have notified us that two of the collaborator first and last names have been inverted in the "PROTHOR Investigators" table.

Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPC) may result in longer duration of in-hospital stay and even mortality. Both thoracic surgery and intraoperative mechanical ventilation settings add considerably to the risk of PPC. It is unclear if one-lung ventilation (OLV) for thoracic surgery with a strategy of intraoperative high positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM) reduces PPC, compared to low PEEP without RM. METHODS: PROTHOR is an international, multicenter, randomized, controlled, assessor-blinded, two-arm trial initiated by investigators of the PROtective VEntilation NETwork. In total, 2378 patients will be randomly assigned to one of two different intraoperative mechanical ventilation strategies. Investigators screen patients aged 18 years or older, scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV, with a maximal body mass index of 35 kg/m2, and a planned duration of surgery of more than 60 min. Further, the expected duration of OLV shall be longer than two-lung ventilation, and lung separation is planned with a double lumen tube. Patients will be randomly assigned to PEEP of 10 cmH2O with lung RM, or PEEP of 5 cmH2O without RM. During two-lung ventilation tidal volume is set at 7 mL/kg predicted body weight and, during OLV, it will be decreased to 5 mL/kg. The occurrence of PPC will be recorded as a collapsed composite of single adverse pulmonary events and represents the primary endpoint. DISCUSSION: PROTHOR is the first randomized controlled trial in patients undergoing thoracic surgery with OLV that is adequately powered to compare the effects of intraoperative high PEEP with RM versus low PEEP without RM on PPC. The results of the PROTHOR trial will support anesthesiologists in their decision to set intraoperative PEEP during protective ventilation for OLV in thoracic surgery. TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov ( NCT02963025 ) on 15 November 2016.

Ultra-deep next-generation sequencing of plasma cell-free DNA in patients with advanced lung cancers: results from the Actionable Genome Consortium.

BACKGROUND: Noninvasive genotyping using plasma cell-free DNA (cfDNA) has the potential to obviate the need for some invasive biopsies in cancer patients while also elucidating disease heterogeneity. We sought to develop an ultra-deep plasma next-generation sequencing (NGS) assay for patients with non-small-cell lung cancers (NSCLC) that could detect targetable oncogenic drivers and resistance mutations in patients where tissue biopsy failed to identify an actionable alteration. PATIENTS AND METHODS: Plasma was prospectively collected from patients with advanced, progressive NSCLC. We carried out ultra-deep NGS using cfDNA extracted from plasma and matched white blood cells using a hybrid capture panel covering 37 lung cancer-related genes sequenced to 50 000× raw target coverage filtering somatic mutations attributable to clonal hematopoiesis. Clinical sensitivity and specificity for plasma detection of known oncogenic drivers were calculated and compared with tissue genotyping results. Orthogonal ddPCR validation was carried out in a subset of cases. RESULTS: In 127 assessable patients, plasma NGS detected driver mutations with variant allele fractions ranging from 0.14% to 52%. Plasma ddPCR for EGFR or KRAS mutations revealed findings nearly identical to those of plasma NGS in 21 of 22 patients, with high concordance of variant allele fraction (r = 0.98). Blinded to tissue genotype, plasma NGS sensitivity for de novo plasma detection of known oncogenic drivers was 75% (68/91). Specificity of plasma NGS in those who were driver-negative by tissue NGS was 100% (19/19). In 17 patients with tumor tissue deemed insufficient for genotyping, plasma NGS identified four KRAS mutations. In 23 EGFR mutant cases with acquired resistance to targeted therapy, plasma NGS detected potential resistance mechanisms, including EGFR T790M and C797S mutations and ERBB2 amplification. CONCLUSIONS: Ultra-deep plasma NGS with clonal hematopoiesis filtering resulted in de novo detection of targetable oncogenic drivers and resistance mechanisms in patients with NSCLC, including when tissue biopsy was inadequate for genotyping.

Correction: Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer.

The original version of this article contained error in Figure 2e. In Figure 2e, the 6th colony image of T47D cells treated with shMSI2 was inadvertently replaced with a duplicate of 7th colony image. However, the conclusions reported in the manuscript are not affected by figure replacement. The authors regret that these errors were made and apologize for the confusion and inconvenience. The correct version of this figure panel appears in the Author Correction associated with this Article.

Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications.

BACKGROUND: The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative pulmonary complications (PPCs). METHODS: LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during 'daytime' when induction of anaesthesia was between 8:00 AM and 7:59 PM, and as 'night-time' when induction was between 8:00 PM and 7:59 AM. RESULTS: Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P=0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P=0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P=0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09-1.90; P=0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89-1.90; P=0.15). CONCLUSIONS: Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients' clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events. CLINICAL TRIAL REGISTRATION: NCT01601223.