Quasiparticle Poisoning of Superconducting Qubits from Resonant Absorption of Pair-Breaking Photons.

The ideal superconductor provides a pristine environment for the delicate states of a quantum computer: because there is an energy gap to excitations, there are no spurious modes with which the qubits can interact, causing irreversible decay of the quantum state. As a practical matter, however, there exists a high density of excitations out of the superconducting ground state even at ultralow temperature; these are known as quasiparticles. Observed quasiparticle densities are of order 1 µm^{-3}, tens of orders of magnitude greater than the equilibrium density expected from theory. Nonequilibrium quasiparticles extract energy from the qubit mode and can induce dephasing. Here we show that a dominant mechanism for quasiparticle poisoning is direct absorption of high-energy photons at the qubit junction. We use a Josephson junction-based photon source to controllably dose qubit circuits with millimeter-wave radiation, and we use an interferometric quantum gate sequence to reconstruct the charge parity of the qubit. We find that the structure of the qubit itself acts as a resonant antenna for millimeter-wave radiation, providing an efficient path for photons to generate quasiparticles. A deep understanding of this physics will pave the way to realization of next-generation superconducting qubits that are robust against quasiparticle poisoning.

Plasmoid Formation and Strong Radiative Cooling in a Driven Magnetic Reconnection Experiment.

We present the first experimental study of plasmoid formation in a magnetic reconnection layer undergoing rapid radiative cooling, a regime relevant to extreme astrophysical plasmas. Two exploding aluminum wire arrays, driven by the Z machine, generate a reconnection layer (S_{L}≈120) in which the cooling rate far exceeds the hydrodynamic transit rate (τ_{hydro}/τ_{cool}>100). The reconnection layer generates a transient burst of >1 keV x-ray emission, consistent with the formation and subsequent rapid cooling of the layer. Time-gated x-ray images show fast-moving (up to 50 km s^{-1}) hotspots in the layer, consistent with the presence of plasmoids in 3D resistive magnetohydrodynamic simulations. X-ray spectroscopy shows that these hotspots generate the majority of Al K-shell emission (around 1.6 keV) prior to the onset of cooling, and exhibit temperatures (170 eV) much greater than that of the plasma inflows and the rest of the reconnection layer, thus providing insight into the generation of high-energy radiation in radiatively cooled reconnection events.

Multi-Modal Digital Impressions For Palatal Defects.

INTRODUCTION: This in-vitro study investigated limitations of intra-oral scanners (IOS) in capturing palatal defects at decreased mouth openings. The trueness and precision of composite 3D-printed models from Cone-Beam Computed Tomography (CBCT) and IOS were measured. METHODS: A partially dentate palatal defect model was scanned with IOS (3M™TrueDefinition) at various simulated mouth openings. Five silicone impressions were poured in gypsum. Scans were taken using 3M™TrueDefinition; Planmeca Planscan®, n=5 each. Model was scanned on two CBCT (PlanmecaProFace®; Accuitomo170®CBCT, n=5 each). Geomagic®Control2014™ was used to create composite-models merging CBCT with IOS. Thirty composite-models were 3D-printed. Trueness and precision were measured. Pearson Correlation Coefficients measured correlation between mouth opening and data capture. Data analysed using Kruskal-Wallis, Wilcoxon rank-sum, and ANOVA. Statistical significance inferred when p⟨0.05. RESULTS: Mouth openings ⟨20mm, IOS didn't capture information of soft tissue. Increased mouth opening positively correlated with increased data capture(r=0.93, p=0.001). AccuitomoCBCT and TrueDefinition IOS composite-models had the highest (trueness) and [precision](median (IQR) 0.172 mm(0.062-0.426)); [mean [SD] 0.080 mm [0.008]]. Casts had the lowest results (median (IQR) 0.289 mm(0.119-1.565));[mean [SD] 0.338 mm [0.089]](p⟨0.001). CONCLUSION: Mouth opening ⟨20mm resulted in insufficient data capture by IOS for clinical applications. Composite digital models showed promising trueness and precision results.

The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade.

Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology and is the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant genetic variants in the alternative pathway of complement have been strongly linked to disease. More recently, a rare variant in the terminal pathway of complement has been associated with increased risk, Complement component 9 (C9) P167S. To assess the functional consequence of this variant, C9 levels were measured in two independent cohorts of AMD patients. In both cohorts, it was demonstrated that the P167S variant was associated with low C9 plasma levels. Further analysis showed that patients with advanced AMD had elevated sC5b-9 compared to those with non-advanced AMD, although this was not associated with the P167S polymorphism. Electron microscopy of membrane attack complexes (MACs) generated using recombinantly produced wild type or P167S C9 demonstrated identical MAC ring structures. In functional assays, the P167S variant displayed a higher propensity to polymerize and a small increase in its ability to induce hemolysis of sheep erythrocytes when added to C9-depleted serum. The demonstration that this C9 P167S AMD risk polymorphism displays increased polymerization and functional activity provides a rationale for the gene therapy trials of sCD59 to inhibit the terminal pathway of complement in AMD that are underway.

A comparison of self-reported risk and protective factors and the death implicit association test in the prediction of future suicide attempts in adolescent emergency department patients.

BACKGROUND: Concerns have been raised about the utility of self-report assessments in predicting future suicide attempts. Clinicians in pediatric emergency departments (EDs) often are required to assess suicidal risk. The Death Implicit Association Test (IAT) is an alternative to self-report assessment of suicidal risk that may have utility in ED settings. METHODS: A total of 1679 adolescents recruited from 13 pediatric emergency rooms in the Pediatric Emergency Care Applied Research Network were assessed using a self-report survey of risk and protective factors for a suicide attempt, and the IAT, and then followed up 3 months later to determine if an attempt had occurred. The accuracy of prediction was compared between self-reports and the IAT using the area under the curve (AUC) with respect to receiver operator characteristics. RESULTS: A few self-report variables, namely, current and past suicide ideation, past suicidal behavior, total negative life events, and school or social connectedness, predicted an attempt at 3 months with an AUC of 0.87 [95% confidence interval (CI), 0.84-0.90] in the entire sample, and AUC = 0.91, (95% CI 0.85-0.95) for those who presented without reported suicidal ideation. The IAT did not add significantly to the predictive power of selected self-report variables. The IAT alone was modestly predictive of 3-month attempts in the overall sample ((AUC = 0.59, 95% CI 0.52-0.65) and was a better predictor in patients who were non-suicidal at baseline (AUC = 0.67, 95% CI 0.55-0.79). CONCLUSIONS: In pediatric EDs, a small set of self-reported items predicted suicide attempts within 3 months more accurately than did the IAT.

Prediction of plan adaptation in head and neck cancer proton therapy using clinical, radiographic, and dosimetric features.

PURPOSE: Because proton head and neck (HN) treatments are sensitive to anatomical changes, plan adaptation (re-plan) during the treatment course is needed for a significant portion of patients. We aim to predict re-plan at plan review stage for HN proton therapy with a neural network (NN) model trained with patients' dosimetric and clinical features. The model can serve as a valuable tool for planners to assess the probability of needing to revise the current plan. METHODS AND MATERIALS: Mean beam dose heterogeneity index (BHI), defined as the ratio of the maximum beam dose to the prescription dose, plan robustness features (clinical target volume (CTV), V100 changes, and V100 > 95% passing rates in 21 robust evaluation scenarios), as well as clinical features (e.g., age, tumor site, and surgery/chemotherapy status) were gathered from 171 patients treated at our proton center in 2020, with a median age of 64 and stages from I-IVc across 13 HN sites. Statistical analyses of dosimetric parameters and clinical features were conducted between re-plan and no-replan groups. A NN was trained and tested using these features. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the prediction model. A sensitivity analysis was done to determine feature importance. RESULTS: Mean BHI in the re-plan group was significantly higher than the no-replan group (p < .01). Tumor site (p < .01), chemotherapy status (p < .01), and surgery status (p < .01) were significantly correlated to re-plan. The model had sensitivities/specificities of 75.0%/77.4%, respectively, and an area under the ROC curve of .855. CONCLUSION: There are several dosimetric and clinical features that correlate to re-plans, and NNs trained with these features can be used to predict HN re-plans, which can be used to reduce re-plan rate by improving plan quality.

Synchronous pancreatic and scrotal tuberculosis: Double jeopardy.

We describe a patient who presented with scrotal swelling followed by non-healing and discharging scrotal sinuses, following local trauma and was initially suspected to have an infected scrotal hematoma. An evaluation revealed it to be scrotal tuberculosis. He also complained of upper abdominal pain and on transabdominal ultrasonography was detected to have a mass in the head of the pancreas. Evaluation of the pancreatic mass revealed it to be pancreatic tuberculosis. Both lesions responded well to anti-tubercular therapy. This is an unusual case of two rare sites of extrapulmonary tuberculosis presenting simultaneously in the same individual. Care needs to be exercised while evaluating any non-healing ulcers or sinuses and mass lesions in countries endemic for tuberculosis as this disease can be a great masquerader.

Accelerating Solutions for the Overdose Crisis: an Effectiveness-Implementation Hybrid Protocol for the HEAL Prevention Cooperative.

Given increasing opioid overdose mortality rates in the USA over the past 20 years, accelerating the implementation of prevention interventions found to be effective is critical. The Helping End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is a consortium of research projects funded to implement and test interventions designed to prevent the onset or escalation of opioid misuse among youth and young adults. The HPC offers a unique opportunity to synthesize and share lessons learned from participating research projects' varied implementation experiences, which can facilitate quicker integration of effective prevention interventions into practice. This protocol paper describes our hybrid approach to collecting and analyzing information about the implementation experiences of nine of the HPC research projects while they maintain their focus on assessing the effectiveness and cost-effectiveness of prevention interventions. To better understand implementation within this context, we will address five research questions: (1) What were the context and approach for implementing the prevention interventions, and how was the overall implementation experience? (2) How representative of the target population are the participants who were enrolled and retained in the research projects' effectiveness trials? (3) For what purposes and how were stakeholders engaged by the research projects? (4) What are the adaptable components of the prevention interventions? And finally, (5) how might implementation of the prevention interventions vary for non-trial implementation? This work will result in intervention-specific and general practical dissemination resources that can help potential adopters and deliverers of opioid misuse prevention make adoption decisions and prepare for successful implementation.

Cavity-Enhanced 2D Material Quantum Emitters Deterministically Integrated with Silicon Nitride Microresonators.

Optically active defects in 2D materials, such as hexagonal boron nitride (hBN) and transition-metal dichalcogenides (TMDs), are an attractive class of single-photon emitters with high brightness, operation up to room temperature, site-specific engineering of emitter arrays with strain and irradiation techniques, and tunability with external electric fields. In this work, we demonstrate a novel approach to precisely align and embed hBN and TMDs within background-free silicon nitride microring resonators. Through the Purcell effect, high-purity hBN emitters exhibit a cavity-enhanced spectral coupling efficiency of up to 46% at room temperature, exceeding the theoretical limit (up to 40%) for cavity-free waveguide-emitter coupling and demonstrating nearly a 1 order of magnitude improvement over previous work. The devices are fabricated with a CMOS-compatible process and exhibit no degradation of the 2D material optical properties, robustness to thermal annealing, and 100 nm positioning accuracy of quantum emitters within single-mode waveguides, opening a path for scalable quantum photonic chips with on-demand single-photon sources.

A Retrospective Service- Evaluation of Implant Success, Survival, Periimplant Health and Prosthetic Complications in a Cohort of Head and Neck Cancer Patients.

OBJECTIVES: To determine the success, survival, peri-implant health and prosthetic complications in head and neck cancer patients receiving oral rehabilitation utilising dental implants between 2008 and the present day. MATERIALS AND METHODS: Service evaluation. Survival Group: Retrospective review of records to determine implant survival and prosthetic complications. Success Group: Examination to determine implant success and health. RESULTS: Survival Group: 260 implants in 81 individuals, median follow up 49.2 months. 89.3% implant survival at 96 months, no further failures up to 133 months. 40.9% individuals required repair or remake of prosthesis by 72 months - mostly denture re-lines. Success group: 164 implants in 48 individuals, median follow up 56 months. Peri-implant mucositis detected in 22% of fixtures (37.5% individuals); peri-implantitis in 12.8% (25% individuals); 33.3% fixtures exhibiting periimplantitis at 120 months. Previous smoking significantly associated with development of peri-implantitis (HR 2.372, p=0.032, 95CI:1.232, 93.317). Compromised survival (e.g. peri-implantitis), absolute (not in mouth) or clinical failure estimated to occur in 28.1% fixtures at 101 months, mostly due to peri-implantitis. CONCLUSIONS: There is a large burden of ongoing care in this cohort, requiring interventions to improve peri-implant health and maintain complex prostheses. Oral rehabilitation and ongoing maintenance in this cohort is complex and multi-disciplinary.

Poly(I:C) transfection induces a pro-inflammatory cascade in murine mammary carcinoma and fibrosarcoma cells.

Germline-encoded pattern recognition receptors [PRRs] in mammalian cells function in the detection of molecular patterns associated with pathogen invasion or cellular damage. A PRR subset is activated by the atypical presence and location of double-stranded RNA [dsRNA] or its synthetic analogue polyinosinic-polycytidylic acid [poly(I:C)], triggering pro-inflammatory signalling and death in many cell types. Poly(I:C) has been tested as a sole or combination cancer therapy in preclinical studies and clinical trials. The purpose of this study was to evaluate the effects of poly(I:C) transfection via electroporation on cell lines from a cancer of epithelial origin, 4T1 mammary carcinoma, and a cancer of mesenchymal origin, WEHI 164 fibrosarcoma. The effects of the poly(I:C) delivery on cell metabolism implicate the induction of cell death. A pro-inflammatory response was demonstrated by mRNA upregulation and the secretion of Type I interferon and several cytokines and chemokines. The mRNAs of dsRNA sensor DExD/H-box helicase 58/retinoic acid-inducible gene I protein [Ddx58/RIG-I] and sensor/co-sensor DEAH-box helicase 9 [Dhx9] were not regulated, but the mRNAs of RNA sensors toll-like receptor 3 [TLR3], interferon-induced with helicase C domain 1/melanoma differentiation-associated protein 5 [Ifih1/MDA5] and Z-DNA binding protein 1 [Zbp1] and co-sensors DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 [Ddx60] and interferon-inducible protein 204 [Ifi204] were upregulated in both cell lines. The mRNAs encoding signalling pathways components were present or upregulated in both cell types. These data demonstrate that RNA sensing effects can be amplified by electroporation delivery, potentially expanding the practicality of this immunotherapeutic approach.

Solitary fibrous tumor of the caruncle: a solitary location.

A 78-year-old Caucasian male presented with diplopia and decreased vision in the left eye for 1 month, in addition to a painless fleshy lesion in the inner corner of the left eye for 3-month duration. His best-corrected visual acuity was 20/40 and 20/50. Slit lamp examination revealed a left medial conjunctival and caruncular lesion, measuring 6 mm by 4 mm. Histology of the excised mass showed a cellular submucosal spindle cell neoplasm without cytologic atypia and rare mitoses, immunohistologically diffusely positive for CD34 and STAT6, and negative for SMA. Based on these findings, solitary fibrous tumor was diagnosed. With the combined diagnostic power of light microscopy and immunohistochemistry, SFTs are diagnosed increasingly and more accurately in the orbit. With this first case report of a caruncular SFT, we believe that SFTs should remain on the differential for mesenchymal tumors of the conjunctiva and caruncle.

First-line atezolizumab plus nab-paclitaxel for unresectable, locally advanced, or metastatic triple-negative breast cancer: IMpassion130 final overall survival analysis.

BACKGROUND: Guidelines recommend atezolizumab plus nab-paclitaxel (A + nP) for first-line treatment of unresectable, locally advanced, or metastatic triple-negative breast cancer expressing programmed death-ligand 1 (PD-L1) on tumor-infiltrating immune cells (IC), based on IMpassion130. We report the final overall survival (OS) and safety of that study as per the prespecified analysis plan. PATIENTS AND METHODS: Patients were randomized to nP 100 mg/m2 (days 1, 8, and 15 of a 28-day cycle) with atezolizumab 840 mg (A + nP) or placebo (P + nP; days 1 and 15), until progression or unacceptable toxicity. Coprimary endpoints were progression-free survival [intention-to-treat (ITT) and PD-L1 IC-positive populations] and OS (tested hierarchically in the ITT population and, if significant, in the PD-L1 IC-positive population). RESULTS: Each arm comprised 451 patients; 666 (73.8%) had died by the final OS analysis cut-off (median follow-up, 18.8 months; interquartile range, 8.9-34.7 months). Median OS in the ITT population was 21.0 months [95% confidence interval (CI), 19.0-23.4 months] with A + nP, and 18.7 months (95% CI, 16.9-20.8 months) with P + nP [stratified hazard ratio (HR), 0.87; 95% CI, 0.75-1.02; P = 0.077]. Exploratory analysis in the PD-L1 IC-positive population showed a median OS of 25.4 months (95% CI, 19.6-30.7 months) with A + nP (n = 185) and 17.9 months (95% CI, 13.6-20.3 months) with P + nP (n = 184; stratified HR, 0.67; 95% CI, 0.53-0.86). Safety outcomes were consistent with previous analyses and the known toxicity profiles of each agent. Immune-mediated adverse events of special interest were reported in 58.7% and 41.6% of patients treated with A + nP and P + nP, respectively. CONCLUSION: Although the OS benefit in the ITT population was not statistically significant, precluding formal testing, clinically meaningful OS benefit was observed with A + nP in PD-L1 IC-positive patients, consistent with prior interim analyses. This combination remained safe and tolerable with longer follow-up.

Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer.

BACKGROUND: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-bound-paclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumab-paclitaxel in aTNBC. PATIENTS AND METHODS: Eligible patients [no prior systemic therapy or ≥12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression ≥1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. RESULTS: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P = 0.20; median PFS 6.0 months with atezolizumab-paclitaxel versus 5.7 months with placebo-paclitaxel]. In the PD-L1-positive population, atezolizumab-paclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placebo-paclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumab-paclitaxel versus 28.3 months with placebo-paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. CONCLUSION: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. CLINICALTRIALS.GOV: NCT03125902.

Medical care disruptions during the first six months of the COVID-19 pandemic: the experience of older breast cancer survivors.

PURPOSE: Older cancer survivors required medical care during the COVID-19 pandemic, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors aged 60-98 from five US regions (n = 321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included interruptions in seeing or speaking to doctors, receiving medical treatment or supportive therapies, or filling prescriptions since the pandemic began. Logistic regression models evaluated associations between care disruptions and education, medical, psychosocial, and COVID-19-related factors. Multivariate models included age, county COVID-19 death rates, comorbidity, and post-diagnosis time. RESULTS: There was a high response rate (n = 262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were higher with each year of education (OR 1.22, 95% CI 1.08-1.37, p = < 0.001) and increased depression by CES-D score (OR 1.04, CI 1.003-1.08, p = 0.033) while increased tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99, p = 0.012). There was a trend between disruptions and comorbidities (unadjusted OR 1.13 per comorbidity, 95% CI 0.99-1.29, p = 0.07). Adjusting for covariates, higher education years (OR1.23, 95% CI 1.09-1.39, p = 0.001) and tangible social support (OR 0.98 95% CI 0.97-1.00, p = 0.006) remained significantly associated with having care disruptions. CONCLUSION: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions. CLINICALTRIALS. GOV IDENTIFIER: NCT03451383.

Fetal endoscopic tracheal occlusion reverses the natural history of right-sided congenital diaphragmatic hernia: European multicenter experience.

OBJECTIVE: To evaluate the neonatal outcome of fetuses with isolated right-sided congenital diaphragmatic hernia (iRCDH) based on prenatal severity indicators and antenatal management. METHODS: This was a retrospective review of prospectively collected data on consecutive cases diagnosed with iRCDH before 30 weeks' gestation in four fetal therapy centers, between January 2008 and December 2018. Data on prenatal severity assessment, antenatal management and perinatal outcome were retrieved. Univariate and multivariate logistic regression analysis were used to identify predictors of survival at discharge and early neonatal morbidity. RESULTS: Of 265 patients assessed during the study period, we excluded 40 (15%) who underwent termination of pregnancy, two cases of unexplained fetal death, two that were lost to follow-up, one for which antenatal assessment of lung hypoplasia was not available and six cases which were found to have major associated anomalies or syndromes after birth. Of the 214 fetuses with iRCDH included in the neonatal outcome analysis, 86 were managed expectantly during pregnancy and 128 underwent fetal endoscopic tracheal occlusion (FETO) with a balloon. In the expectant-management group, lung size measured by ultrasound or by magnetic resonance imaging was the only independent predictor of survival (observed-to-expected lung-to-head ratio (o/e-LHR) odds ratio (OR), 1.06 (95% CI, 1.02-1.11); P = 0.003). Until now, stratification for severe lung hypoplasia has been based on an o/e-LHR cut-off of 45%. In cases managed expectantly, the survival rate was 15% (4/27) in those with o/e-LHR ≤ 45% and 61% (36/59) for o/e-LHR > 45% (P = 0.001). However, the best o/e-LHR cut-off for the prediction of survival at discharge was 50%, with a sensitivity of 78% and specificity of 72%. In the expectantly managed group, survivors with severe pulmonary hypoplasia stayed longer in the neonatal intensive care unit than did those with mildly hypoplastic lungs. In fetuses with an o/e-LHR ≤ 45% treated with FETO, survival rate was higher than in those with similar lung size managed expectantly (49/120 (41%) vs 4/27 (15%); P = 0.014), despite higher prematurity rates (gestational age at birth: 34.4 ± 2.7 weeks vs 36.8 ± 3.0 weeks; P < 0.0001). In fetuses treated with FETO, gestational age at birth was the only predictor of survival (OR, 1.25 (95% CI, 1.04-1.50); P = 0.02). CONCLUSIONS: Antenatal measurement of lung size can predict survival in iRCDH. In fetuses with severe lung hypoplasia, FETO was associated with a significant increase in survival without an associated increase in neonatal morbidity. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide.

Membrane-active peptides have been extensively studied to probe protein-membrane interactions, to act as antimicrobial agents and cell-penetrating peptides (CPPs) for the delivery of therapeutic agents to cells. Hundreds of membrane-active sequences acting as CPPs have now been described including bioportides that serve as single entity modifiers of cell physiology at the intracellular level. Translation of promising CPPs in pre-clinical studies have, however, been disappointing as only few identified delivery systems have progressed to clinical trials. To search for novel membrane-active peptides a sequence from the EGFR juxtamembrane region was identified (named EJP18), synthesised, and examined in its L- and D-form for its ability to mediate the delivery of a small fluorophore and whole proteins to cancer cell lines. Initial studies identified the peptide as being highly membrane-active causing extensive and rapid plasma membrane reorganisation, blebbing, and toxicity. At lower, non-toxic concentrations the peptides outperformed the well-characterised CPP octaarginine in cellular delivery capacity for a fluorophore or proteins that were associated with the peptide covalently or via ionic interactions. EJP18 thus represents a novel membrane-active peptide that may be used as a naturally derived model for biophysical protein-membrane interactions or for delivery of cargo into cells for therapeutic or diagnostic applications.

Challenges and visions for managing pain-related insomnia in primary care using the hybrid CBT approach: a small-scale qualitative interview study with GPs, nurses, and practice managers.

BACKGROUND: Chronic pain and insomnia have a complex, bidirectional relationship - addressing sleep complaints alongside pain may be key to alleviating patient-reported distress and disability. Healthcare professionals have consistently reported wanting to offer psychologically informed chronic pain management at the primary care level. Research in secondary care has demonstrated good treatment efficacy of hybrid CBT for chronic pain and insomnia. However, primary care is typically the main point of treatment entry, hence may be better situated to offer treatments using a multidisciplinary approach. In this study, primary care service providers' perception of feasibility for tackling pain-related insomnia in primary care was explored. METHODS: The data corpus originates from a feasibility trial exploring hybrid CBT for chronic pain and insomnia delivered in primary care. This formed three in-depth group interviews with primary care staff (n = 9) from different primary care centres from the same NHS locale. All interviews were conducted on-site using a semi-structured approach. Verbal data was recorded, transcribed verbatim and analysed using the thematic analysis process. RESULTS: Eight themes were identified - 1) Discrepant conceptualisations of the chronic pain-insomnia relationship and clinical application, 2) Mismatch between patients' needs and available treatment offerings, 3) Awareness of psychological complexities, 4) Identified treatment gap for pain-related insomnia, 5) Lack of funding and existing infrastructure for new service development, 6) General shortage of psychological services for complex health conditions, 7) Multidisciplinary team provision with pain specialist input, and 8) Accessibility through primary care. These mapped onto four domains - Current understanding and practice, Perceived facilitators, Perceived barriers, Ideal scenarios for a new treatment service - which reflected the focus of our investigation. Taken together these provide key context for understanding challenges faced by health care professionals in considering and developing a new clinical service. CONCLUSIONS: Primary care service providers from one locale advocate better, multidisciplinary treatment provision for chronic pain and insomnia. Findings suggest that situating this in primary care could be a feasible option, but this requires systemic support and specialist input as well as definitive trials for success.

Guidelines for reporting on CBCT scans.

The aim of a radiographic report is to provide an accurate interpretation of images to facilitate the diagnostic process, and when indicated prompt the appropriate management for the patient. It is part of the patient's clinical records. This paper describes the imaging chain involved in the cone beam computed tomography (CBCT) workflow from referring to reporting on a CBCT scan. It provides guidelines on the essential information required before and immediately after a CBCT scan is taken, and optimizing the viewing conditions. Finally, it describes a framework for a systematic, comprehensive and tailored CBCT radiographic report. It is aimed at endodontists, clinicians and radiologists reporting on CBCT scans of the dentoalveolar region.

Preferred Reporting Items for Diagnostic Accuracy Studies in Endodontics (PRIDASE) guidelines: a development protocol.

Diagnostic accuracy studies play an important role in informing clinical practice and patient management, by evaluating the ability of diagnostic testing and imaging to identify the presence or absence of a disease or condition. These studies compare the relative diagnostic strength of the test or device with a reference standard, therefore, guiding clinical decisions on the reliability of the test, the need for further tests, and whether to monitor or treat a particular condition. Inadequate and incomplete reporting of diagnostic accuracy studies can disguise methodological deficiencies and ultimately result in study bias and the inability to translate research findings into daily clinical practice. The Preferred Reporting Items for Diagnostic Accuracy Studies in Endodontics (PRIDASE) guidelines are being developed in order to improve the accuracy, transparency, completeness and reproducibility of diagnostic accuracy studies in the speciality of Endodontology. The aim of this paper is to report the process used to develop the PRIDASE guidelines based on a well-established consensus process. The project leaders (PD, VN) formed a steering committee of nine members (PD, VN, PA, AF, DR, SP, CK, MP, HD) to oversee and manage the project. The PRIDASE steering committee will develop the initial draft of the PRIDASE guidelines by adapting and modifying the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 guidelines, adding new items related specifically to the nature of Endodontics and incorporate the Clinical and Laboratory Images in Publication (CLIP) principles. The initial guidelines will consist of a series of domains and individual items and will be validated by the members of a PRIDASE Delphi Group (PDG) consisting of a minimum of 30 individuals who will evaluate independently the individual items based on two parameters: 'clarity' using a dichotomous scoring (yes/no) and 'suitability' for inclusion using a 9-point Likert Scale. The scores awarded by each member and any suggestions for improvement will be shared with the PDG to inform an iterative process that will result in a series of items that are clear and suitable for inclusion in the new PRIDASE guidelines. Once the PDG has completed its work, the steering committee will create a PRIDASE Meeting Group (PMG) of 20 individuals from around the world. Members of the PDG will be eligible to be the part of PMG. The draft guidelines and flowchart approved by the PDG will then be presented for further validation and agreement by the PMG. As a result of these discussions, the PRIDASE guidelines will be finalized and then disseminated to relevant stakeholders through publications and via the Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (http://pride-endodonticguidelines.org). Periodic updates to the PRIDASE guidelines will be made based on feedback from stakeholders and end-users.