bluuebunny/crossref_metadata_2025 huggingface dataset:
Stapes and Stapes Revision Surgery: Preoperative Air-Bone Gap Is a Prognostic Marker
Authors: Sharaf Kariem , Grueninger Ivo , Hilpert Annalena , Polterauer Daniel , Volgger Veronika , Manz Kirsi , Canis Martin , Hempel John Martin , Müller Joachim
Published: April 2021

Objective:

Stapes surgery is considered an effective treatment in otosclerosis, but controversy remains regarding predictors of surgical outcome.

Study Design:

Retrospective cohort study.

Setting:

Tertiary referral center.

Patients:

One hundred sixty three cases of stapes surgery between 2012 and 2019 were reviewed.

Main Outcome Measures:

Primary outcome measures were relative hearing improvement (relHI), defined as preoperative minus postoperative air conduction divided by preoperative air-bone gap (ABG), as well as relative ABG closure (relABGc), defined as preoperative ABG minus postoperative ABG divided by preoperative ABG. Univariate and multivariate linear regression analyses were performed to determine independent predictors for these outcomes.

Results:

Higher preoperative bone conduction (BC) and primary surgery (compared with revision) were independently associated with increased relHI (p = 0.001 and p = 0.004, respectively). Lower preoperative BC, higher preoperative ABG, primary surgery, and age were independently associated with increased relABGc (p = 0.0030, p < 0.001, p = 0.0214, and p = 0.0099, respectively). Sex did not predict surgical outcome. In patients with less than 20 dB preoperative ABG, likelihood of negative relABGc was increased (compared with 20–30 dB or >30 dB preoperative ABG, p = 0.0292, Fisher's exact test). This tendency was not significant for relHI (p = 0.074).

Conclusions:

Our findings demonstrate that calculating HI and ABGc in relation to preoperative ABG can reliably predict outcomes of stapes surgery. Both primary and revision stapes surgery are effective treatment options, but relative improvement is higher in primary cases. Preoperative BC, preoperative ABG, and age predict surgical outcomes as well. Otosclerosis patients with low preoperative ABG, especially less than 20 dB, should be counseled and selected cautiously regarding stapes surgery.
Evaluation of Long-term Cholesteatoma Recidivism: Using the JOS, EAONO-JOS, and STAMCO Cholesteatoma Staging Systems
Authors: Eggink Maura C. , de Wolf Maarten J.F. , Ebbens Fenna A. , Dikkers Frederik G. , van Spronsen Erik
Published: April 2021

Objective:

To assess the prognostic value of the Japanese Otological Society (JOS), EAONO-JOS, and STAMCO classifications in predicting the severity of acquired cholesteatoma and to identify other factors that could influence residual and recurrent cholesteatoma, as well as adverse events (AE).

Method:

A retrospective chart review of patients undergoing primary cholesteatoma surgery in our tertiary referral center. Primary outcome measures were based on three groups of follow-up (FU): Group A, studying residual cholesteatoma, FU > 52 weeks of last-look surgery or magnetic resonance imaging, diffusion-weighted imaging; group B, studying recurrent disease, FU > 52 weeks of last outpatient clinic visit; and group C, studying AE, FU > 12 weeks after surgery. Cholesteatomata were staged according to the JOS, EAONO-JOS, and STAMCO classifications. Kaplan–Meier curves were used to determine the prognostic value of the various classifications and to identify other determining factors, while correcting for FU.

Results:

FU was found to be a significant confounder. No correlation was found between staging and the occurrence of residual or recurrent disease, nor the occurrence of AE. Type of surgery was a significant determinant of all three primary outcome measures. A higher age was associated with a lower risk of residual disease.

Conclusion:

In our population the JOS, EAONO-JOS, and STAMCO classifications have limited prognostic value. Three main confounders were identified that pose a challenge in developing a universal classification: FU, surgery type, and age. Cholesteatoma staging should be postponed until a system is developed which significantly correlates cholesteatoma stage to cholesteatoma severity, to have implications for management strategies.
Delayed Facial Palsy After Resection of Vestibular Schwannoma: An Analysis of Long-term Facial Nerve Outcomes
Authors: Tawfik Kareem O. , Coulter Michael , Alexander Thomas H. , Saliba Joe , Mastrodimos Bill , Cueva Roberto A.
Published: April 2021

Objectives:

1) Identify clinical factors associated with delayed facial palsy (DFP) after microsurgical resection of vestibular schwannoma. 2) Determine whether DFP predicts worse facial nerve (FN) outcomes.

Methods:

Adult patients (≥18 yrs) who underwent vestibular schwannoma resection between February 2008 and December 2017 were retrospectively reviewed. Postoperative House-Brackmann (HB) FN function was assessed on the day of surgery, daily during patients’ inpatient admissions, and at postoperative clinic visits. Follow-up exceeded ≥12 months for all patients. DFP was defined as a decline (≥1 HB grade) in FN function (relative to the preoperative state) occurring between postoperative days 1 and 30.

Results:

Two hundred ninety-one patients were analyzed. Mean age was 51.5 years (±12.3) and mean tumor size 20.6 mm (±10.8). Immediate FP occurred in 61 (21%) patients, and DFP occurred in 112 (38%) patients. Tumor size was largest in patients with immediate FP (p < 0.0001). On univariate analysis, DFP was associated with better final FN outcomes (OR 0.447, p = 0.0101) compared with immediate FP. Multivariate analysis, however, showed that timing of FP was no longer significant, whereas larger tumor size and preoperative HB2 function predicted worse FN outcomes (OR 2.718, p < 0.0001 and OR 9.196, p = 0.0039, respectively). In patients with DFP, longer time to onset of palsy predicted more favorable FN outcomes.

Conclusions:

When accounting for tumor size, the timing of onset of postoperative facial palsy does not predict final FN outcomes. In patients who develop DFP, the longer the interval between surgery and onset of weakness, the better the chances of good long-term FN function.
Feasibility of semiquantitative 18F-fluorodeoxyglucose PET/computed tomography in patients with advanced lung cancer for interim treatment evaluation of combining immunotherapy and chemotherapy
Authors: Ke Linping , Wu Leilei , Yu Jinming , Meng Xue
Published: April 2021

Objective

This study aimed to investigate the prognosis value of 18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) in advanced lung cancer patients with immunotherapy combined with chemotherapy.

Methods

Fifty-one advanced lung cancer patients were included in this retrospective study, who underwent 18F-FDG PET/CT imaging before four cycles of immunotherapy combined with chemotherapy at our institution between January 2018 and January 2020. The following PET/CT parameters were calculated: standardized uptake value SUVmax, SUVmean, SUVpeak, SUVsd, metabolic tumor volume (MTV), total lesion glycolysis (TLG), MTV25%, MTV42%, MTV50%, MTV75%, global lung glycolysis (GLG), target-to-background ratio (TBR), SUVpeakwb, MTVwb, TLGwb, SUVmeanwb, SUVmaxwb. Logistics regression analyses were used for assessing the association between baseline metabolic parameters and response to treatment. Kaplan–Meier estimator curves and the log-rank test were constructed for survival analyses.

Results

According to RECIST, nine patients (18%) showed partial response, 25 (49%) had SD, and 17 (33%) had progressive disease. The mean ± SD of SUVmax, SUVpeak, MTV were lower in clinical benefit (CB) group than no-clinical benefit (no-CB) group (all P < 0.05). Median PFS was 3.7 months in no-CB group and 9.9 months in CB group (P < 0.001). Multivariate logistic analysis indicated that SUVmax and histology were independent factors significantly related to the evaluation of therapeutic efficiency. Furthermore, SUVmax is an independent predictor of efficacy in non-small cell lung cancer.

Conclusion

SUVmax can be used to predict interim treatment response of immunotherapy combination with chemotherapy for advanced lung cancer. Moreover, the combination of SUVmax and histology may predict treatment response with acceptable reliability. However, a large prospective multicenter trial is still needed to examine the above finding for lacking limited evidence.
Polygenic risk scores: how much do they add?
Authors: Christoffersen Mette , Tybjærg-Hansen Anne
Published: April 2021

Purpose of review

Current methods to assess genetic risk of familial hypercholesterolemia and coronary artery disease (CAD) focus on testing monogenic mutations in well known genes. Here we review recent developments in polygenic risk scores (PRSs) for LDL cholesterol and for CAD, and how they may add to current risk prediction algorithms.

Recent findings

PRSs can identify 10–20 times as many individuals at high polygenic risk compared with monogenic mutations, and PRSs can modulate the effect of a monogenic variant on risk. Current risk factor prediction tools for prevention of CAD incompletely capture polygenic susceptibility, and PRSs may identify subgroups of patients who are likely to benefit more from lipid-lowering therapy. Finally, PRSs can be quantified already at birth, long before other risk factors used to predict CAD, and before clinical manifestations of disease.

PRSs for CAD may soon be incorporated into clinical practice. Therefore, there is an urgent need to establish both analytical and clinical reporting standards for PRSs, and for validating scores in different ethnicities. Thresholds for intervention need to be established for PRSs and integrated into established risk scores. Training programs are needed for clinical staff to learn to communicate polygenic risk in a comprehensive way to the patient.
Enhancing the learning and supervision framework for training in flexible endoscopic evaluation of swallowing
Authors: Robinson H. Fiona
Published: April 2021

Purpose of review

This article reviews the literature on the development of competency-based training and assessment in endoscopy, comparing gastrointestinal endoscopy and flexible endoscopic evaluation of swallowing (FEES). The discussion focusses on how a robust and explicit learning framework can be translated to the delivery of training in FEES to optimize trainee outcomes and supervisor skill.

Recent findings

Specialist Speech and Language Therapists (SLT) carry out FEES to inform the diagnosis and management of swallowing and voice disorders. Taught courses are generally followed by local workplace-based supervised practice to attain the competencies identified in the relevant professional guidelines. However, the curriculum for the workplace-based FEES training lacks a learning and assessment framework and little direction for the workplace-based supervisor. In gastrointestinal endoscopy training, this previously led to less than optimal outcomes for trainees and patients and so new models of training were developed.

A new learning framework for FEES underpinned by medical pedagogy has shown early promise in supporting the acquisition of competence. Incorporating a new FEES-specific systematic assessment, the framework provides direction for the supervisor and evidence of trainee progression, which subsequently enhances supervisor confidence to determine trainee competence.
Associations of Attachment and Coping Styles With Social Functioning in Patients With Bipolar Disorder I
Authors: Karaş Hakan , Çarpar Elif , Küçükgöncü Suat , Kaşer Muzaffer
Published: April 2021

The aim of this study was to investigate the relationship of attachment and coping mechanisms with social functioning in patients with bipolar disorder (BD). Sixty-three patients with BD type I and 63 healthy controls were evaluated. Structured Clinical Interview for DSM-IV Axis I Disorders, Hamilton Depression Rating Scale, Young Mania Rating Scale, Experiences in Close Relationships Questionnaire II, Coping Orientation to Problems Experienced (COPE) inventory, and Social Functioning Scale were used. In the BD group, adaptive coping style scores and attachment avoidance scores were significantly lower than the control group, but mean scores of maladaptive coping styles were higher than the control group. Regression analysis showed that positive reinterpretation and growth, active coping, use of emotional social support, planning, religious activities, and mental disengagement subscales of COPE were significantly associated with social functioning. Psychosocial interventions to strengthen adaptive coping mechanisms may help improve the social functioning in patients with BD.
Nursing Orientation During the COVID-19 Pandemic
Authors: Dale-Tam Jennifer , Thompson Kristin
Published: April 2021

Traditional in-person delivery of nursing orientation programs at a large academic hospital could not occur because of the COVID-19 pandemic, with the need to limit group sizes and adhere to physical distancing guidelines. A nurse educator team pivoted the orientation program to a virtual model combined with the review of select clinical skills and buddy shifts. This model effectively met the nurses’ needs required to practice safely on an inpatient environment.
Rare Complete Hydatidiform Mole With p57 Expression in Villous Mesenchyme: Case Report and Review of Discordant p57 Expression in Hydatidiform Moles
Authors: Murphy Kathleen M. , Carrick Kelley , Gwin Katja , Rogers Vanessa , Koduru Prasad , Ronnett Brigitte M. , Castrillon Diego H.
Published: April 2021

Complete hydatidiform mole (CHM) is a premalignant proliferative disease of the placenta characterized by misexpression of imprinted gene products, most notably p57. The majority of CHM exhibit immunohistochemical absence of p57 protein in villous mesenchyme (VM) and cytotrophoblast (CT) and are thus p57 VM/CT concordant. However, some gestations show loss of p57 in only VM or CT, either in all chorionic villi or a subset thereof (VM/CT discordant). Here, we present a rare case of a p57 VM/CT-discordant CHM with diffuse retention of p57 expression in VM but complete absence in CT. Histologically, the case exhibited typical features of CHM including trophoblast hyperplasia and severe nuclear atypia, but was unusual in the presence of gestational membranes identified ultrasonographically and histologically. Ploidy determination by FISH and genotyping by short tandem repeat analyses showed that this was a diploid gestation with variable allelic ratios and with an androgenetic lineage, similar to previously reported p57 VM/CT-discordant cases.
De Novo Radiomics Approach Using Image Augmentation and Features From T1 Mapping to Predict Gleason Scores in Prostate Cancer
Authors: Makowski Marcus R. , Bressem Keno K. , Franz Luise , Kader Avan , Niehues Stefan M. , Keller Sarah , Rueckert Daniel , Adams Lisa C.
Published: April 2021

Objectives

The aims of this study were to discriminate among prostate cancers (PCa's) with Gleason scores 6, 7, and ≥8 on biparametric magnetic resonance imaging (bpMRI) of the prostate using radiomics and to evaluate the added value of image augmentation and quantitative T1 mapping.

Materials and Methods

Eighty-five patients with subsequently histologically proven PCa underwent bpMRI at 3 T (T2-weighted imaging, diffusion-weighted imaging) with 66 patients undergoing additional T1 mapping at 3 T. The PCa lesions as well as the peripheral and transition zones were segmented pixel by pixel in multiple slices of the 3D MRI data sets (T2-weighted images, apparent diffusion coefficient, and T1 maps). To increase the size of the data set, images were augmented for contrast, brightness, noise, and perspective multiple times, effectively increasing the sample size 10-fold, and 322 different radiomics features were extracted before and after augmentation. Four different machine learning algorithms, including a random forest (RF), stochastic gradient boosting (SGB), support vector machine (SVM), and k-nearest neighbor, were trained with and without features from T1 maps to differentiate among 3 different Gleason groups (6, 7, and ≥8).

Results

Support vector machine showed the highest accuracy of 0.92 (95% confidence interval [CI], 0.62–1.00) for classifying the different Gleason scores, followed by RF (0.83; 95% CI, 0.52–0.98), SGB (0.75; 95% CI, 0.43–0.95), and k-nearest neighbor (0.50; 95% CI, 0.21–0.79). Image augmentation resulted in an average increase in accuracy between 0.08 (SGB) and 0.48 (SVM). Removing T1 mapping features led to a decline in accuracy for RF (−0.16) and SGB (−0.25) and a higher generalization error.

Conclusions

When data are limited, image augmentations and features from quantitative T1 mapping sequences might help to achieve higher accuracy and lower generalization error for classification among different Gleason groups in bpMRI by using radiomics.
Robot-assisted Treatment of Epigastric Hernias With a Suprapubic Approach
Authors: Pini Ramon , Di Giuseppe Matteo , Toti Johannes M.A. , Mongelli Francesco , Marcantonio Maria , Spampatti Sebastiano , La Regina Davide
Published: April 2021

Background:

Robot-assisted ventral hernia repair has shown itself to be feasible and safe in abdominal wall surgery. Presently, the ports are placed laterally to meet the distance from the fascial defect. The aim of our study is to report our experience of epigastric hernia treatment with trocar insertion in the suprapubic region.

Materials and Methods:

On a prospectively collected dataset on robot-assisted surgery, patients treated for epigastric hernias with suprapubic approach were identified. Demographic and clinical data were collected and analyzed.

Results:

Twelve patients were selected. Median age was 58.5 years [interquartile range (IQR): 47.8 to 67.3 y]; 4 patients were male (33.3%) and the median body mass index was 23.9 kg/m2 (IQR: 22.3 to 26.2 kg/m2). All patients were referred to surgery because of pain. The median measure of the hernia defect was 30 mm (IQR: 13.75 to 31.0 mm); median larger mesh diameter was 13.5 cm (IQR: 9.5 to 15.0 cm); and median operative time was 136.5 minutes (IQR: 120.0 to 186.5 min). No intraoperative complication or conversion to open surgery occurred. Postoperatively, 2 patients presented a seroma and median length of hospital stay was 2.0 days (IQR: 1.75 to 3 d). No case of hernia recurrence was recorded at a mean follow-up of 11.2 months (range: 4 to 29 mo).

Conclusions:

In the robot-assisted treatment of hernias of the epigastric region, a suprapubic port placement can be considered instead of a lateral one to have a better field overview, especially in subxiphoid hernias. Further studies are needed to assess the benefits and limitations of such technique.
Robotic General Surgery Resident Training Curriculum: A Pilot Experience
Authors: Grannan Hailee R. , Hetzel Emily , Goldblatt Matthew I. , Gould Jon C. , Higgins Rana M.
Published: April 2021

Background:

The purpose of this study was to report the impact of a pilot robotic general surgery resident training curriculum.

Materials and Methods:

A single institution pilot robotic general surgery training curriculum was instituted in 2016. Accreditation Council for Graduate Medical Education operative case log trends, resident simulation performance, and surveys were analyzed.

Results:

Forty-three general surgery residents participated in the robotic surgery training curriculum, 2016 to 2019. In total, 161 robotic cases were logged, increasing each academic year. Residents acted as bedside assistant in 42.9% (n=69) and as console surgeon in 57.1% (n=92). Fifteen first-year residents were surveyed on the training curriculum. On the postcurriculum survey, 100% found the curriculum to be very helpful, notably the hands-on in-service and skills simulator.

Conclusions:

Since the curriculum onset, residents participated in an increasing number of robotic operative cases and were actively engaged in simulation exercises. The establishment of this curriculum has facilitated the integration of resident education into the utilization of robotic technology. This study highlights the value of a formal robotic surgery curriculum for general surgery residency training.
Analysis and Augmentation of Small Datasets with Unsupervised Machine Learning
Authors: Dolgikh Serge
Published: April 2021

Analysis of small datasets presents a number of essential challenges not in the least due to insufficient sampling of characteristic patterns in the data making confident conclusions about the unknown distribution elusive and resulting in lower statistical confidence and higher error. In this work, a novel approach to augmentation of small datasets is proposed based on an ensemble of neural network models of unsupervised generative self-learning. Applying generative learning with an ensemble of individual models allowed to identify stable clusters of data points in the latent representations of the observable data. Several techniques of augmentation based on identified latent cluster structure were applied to produce new data points and enhance the dataset. The proposed method can be used with small and extremely small datasets to identify characteristics patterns, augment data and in some cases, improve accuracy of classification in the scenarios with strong deficit of labels.
Efficacy of universal masking for source control and personal protection from simulated cough and exhaled aerosols in a room
Authors: Lindsley William G. , Beezhold Donald H. , Coyle Jayme , Derk Raymond C. , Blachere Francoise M. , Boots Theresa , Reynolds Jeffrey S. , McKinney Walter G. , Sinsel Erik , Noti John D.
Published: April 2021

Face masks reduce the spread of infectious respiratory diseases such as COVID-19 by blocking aerosols produced during coughs and exhalations (“source control”). Masks also slow and deflect cough and exhalation airflows, which changes the dispersion of aerosols. Factors such as the directions in which people are facing (orientation) and separation distance also affect aerosol dispersion. However, it is not clear how masking, orientation, and distance interact. We placed a respiratory aerosol simulator (“source”) and a breathing simulator (“recipient”) in a 3 m x 3 m chamber and measured aerosol concentrations for different combinations of masking, orientation, and separation distance. When the simulators were front-to-front during coughing, masks reduced the 15-minute mean aerosol concentration at the recipient by 92% at 0.9 and 1.8 m separation. When the simulators were side-by-side, masks reduced the concentration by 81% at 0.9 m and 78% at 1.8 m. During breathing, masks reduced the aerosol concentration by 66% when front-to-front and 76% when side-by-side at 0.9 m. Similar results were seen at 1.8 m. When the simulators were unmasked, changing the orientations from front-to-front to side-by-side reduced the cough aerosol concentration by 59% at 0.9 m and 60% at 1.8 m. When both simulators were masked, changing the orientations did not significantly change the concentration at either distance during coughing or breathing. Increasing the distance between the simulators from 0.9 m to 1.8 m during coughing reduced the aerosol concentration by 25% when no masks were worn but had little effect when both simulators were masked. During breathing, when neither simulator was masked, increasing the separation reduced the concentration by 13%, which approached significance, while the change was not significant when both source and recipient were masked. Our results show that universal masking reduces exposure to respiratory aerosol particles regardless of the orientation and separation distance between the source and recipient.
An emerging role of microplastics in the etiology of lung ground glass nodules
Authors: Chen Qiqing , Gao Jiani , Yu Hairui , Su Hang , Yang Yan , Cao Yajuan , Zhang Qun , Ren Yijiu , Shi Huahong , Chen Chang , Liu Haipeng
Published: April 2021

Pulmonary ground glass nodules (GGNs) have been increasingly identified in past decades and is becoming an important clinical dilemma in oncology. Meanwhile, humans persistently inhale microplastics which are dominant in the air. However, the retention of “non-self” microplastics in human lung and its correlation with pulmonary GGNs remains elusive. In this study, we firstly demonstrated the presence of microfibers and microplastics in human lung, with higher detection rates in GGNs in comparison to those in normal tissue. Moreover, both types and colors of microfibers in tumor were richer than those in normal tissues. Intriguingly, high risk of microfibers exposure predisposes the formation of pulmonary GGN. Further, increased roughness surface was observed in microfibers isolated in human lung, indicating the possible link of surface roughness to the formation of pulmonary GGN. Collectively, our findings reveal an emerging role of environmental microplastics exposure in the etiology of pulmonary GGN.

One Sentence Summary

The exposure of environmental microplastics is a risk factor of pulmonary GGN.
Point of Care Testing using rapid automated Antigen Testing for SARS-COV-2 in Care Homes – an exploratory safety, usability and diagnostic agreement evaluation
Authors: Micocci Massimo , Buckle Peter , Hayward Gail , Allen A. Joy , Davies Kerrie , Kierkegaard Patrick , Spilsbury Karen , Thompson Carl , Astle Anita , Heath Ros , Sharpe Claire , Akrill Cyd , Lasserson Dan , Perera Rafael , Body Richard , Gordon Adam L
Published: April 2021

Introduction

Successful adoption of POCTs (Point-of-Care tests) for COVID-19 in care homes requires the identification of ideal use cases and a full understanding of contextual and usability factors that affect test results and minimise biosafety risks. This paper presents findings from a scoping-usability and test performance study of a microfluidic immunofluorescence assay for COVID-19 in care homes.

Methods

A mixed-methods evaluation was conducted in four UK care homes to scope usability and to assess the agreement with qRT-PCR. A dry run with luminescent dye was carried out to explore biosafety issues.

Results

The agreement analysis was carried out on 227 asymptomatic participants (159 staff and 68 residents) and 14 symptomatic participants (5 staff and 9 residents). Asymptomatic specimens showed 50% (95% CI: 1.3%-98.7%) positive agreement and 96% (95% CI: 92.5%-98.1%) negative agreement with overall prevalence and bias-adjusted Kappa (PABAK) of 0.911 (95% CI: 0.857-0.965). Symptomatic specimens showed 83.3% (95% CI: 35.9%-99.6%) positive agreement and 100% (95% CI: 63.1%-100%) negative agreement with overall prevalence and bias-adjusted Kappa (PABAK) of 0.857 (95% CI: 0.549-1).

The dry run showed four main sources of contamination that led to the modification of the standard operating procedures. Simulation after modification showed no further evidence of contamination.

Conclusion

Careful consideration of biosafety issues and contextual factors associated with care home are mandatory for safe use the POCT. Whilst POCT may have some utility for ruling out COVID-19, further diagnostic accuracy evaluations are needed to promote effective adoption.
Optimal health and economic impact of non-pharmaceutical intervention measures prior and post vaccination in England: a mathematical modelling study
Authors: Tildesley Michael J. , Vassall Anna , Riley Steven , Jit Mark , Sandmann Frank , Hill Edward M. , Thompson Robin N. , Atkins Benjamin D. , Edmunds John , Dyson Louise , Keeling Matt J.
Published: April 2021

Background

Even with good progress on vaccination, SARS-CoV-2 infections in the UK may continue to impose a high burden of disease and therefore pose substantial challenges for health policy decision makers. Stringent government-mandated physical distancing measures (lockdown) have been demonstrated to be epidemiologically effective, but can have both positive and negative economic consequences. The duration and frequency of any intervention policy could, in theory, could be optimised to maximise economic benefits while achieving substantial reductions in disease.

Methods

Here we use a pre-existing SARS-CoV-2 transmission model to assess the health and economic implications of different strengths of control through time in order to identify optimal approaches to non-pharmaceutical intervention stringency in the UK, considering the role of vaccination in reducing the need for future physical distancing measures. The model is calibrated to the COVID-19 epidemic in England and we carry out retrospective analysis of the optimal timing of precautionary breaks in 2020 and the optimal relaxation policy from the January 2021 lockdown, considering the willingness to pay for health improvement.

Results

We find that the precise timing and intensity of interventions is highly dependent upon the objective of control. As intervention measures are relaxed, we predict a resurgence in cases, but the optimal intervention policy can be established dependent upon the willingness to pay (WTP) per QALY loss avoided. Our results show that establishing an optimal level of control can result in a reduction in net monetary loss of billions of pounds, dependent upon the precise WTP value.

Conclusions

It is vital, as the UK emerges from lockdown, but continues to face an on-going pandemic, to accurately establish the overall health and economic costs when making policy decisions. We demonstrate how some of these can be quantified, employing mechanistic infectious disease transmission models to establish optimal levels of control for the ongoing COVID-19 pandemic.
Estimation of local time-varying reproduction numbers in noisy surveillance data
Authors: Li Wenrui , Bulekova Katia , Gregor Brian , White Laura F. , Kolaczyk Eric D.
Published: April 2021

1

A valuable metric in understanding local infectious disease dynamics is the local time-varying reproduction number, i.e. the expected number of secondary local cases caused by each infected individual. Accurate estimation of this quantity requires distinguishing cases arising from local transmission from those imported from elsewhere. Realistically, we can expect identification of cases as local or imported to be imperfect. We study the propagation of such errors in estimation of the local time-varying reproduction number. In addition, we propose a Bayesian framework for estimation of the true local time-varying reproduction number when identification errors exist. And we illustrate the practical performance of our estimator through simulation studies and with outbreaks of COVID-19 in Hong Kong and Victoria, Australia.
Increased Interregional Travel to Shopping Malls and Restaurants in Response to Differential COVID-19 Restrictions in the Greater Toronto Area
Authors: Soucy Jean-Paul R. , Ghasemi Amir , Sturrock Shelby L. , Berry Isha , Buchan Sarah A. , MacFadden Derek R. , Daneman Nick , Gibb Nicholas , Brown Kevin A.
Published: April 2021

Background

In the fall of 2020, the government of Ontario, Canada adopted a 5-tier, regional framework of public health measures for the COVID-19 pandemic. During the second wave of COVID-19 in Ontario, the urban core of the Greater Toronto Area (Toronto and Peel) were the first regions in the province to enter the highest restriction tier (“lockdown”) on November 23, 2020, which closed restaurants to in-person dining and limited non-essential businesses, including shopping malls, to curbside pickup. The peripheral regions of the Greater Toronto Area (York, Durham, Halton) would not enter lockdown until later the following month. In this analysis, we examine whether the implementation of differentially timed restrictions in a highly interconnected metropolitan area led to increased interregional travel, potentially driving further transmission of SARS-CoV-2.

Methods

We used anonymized smartphone data to estimate the number of visits by residents of regions in the urban core to shopping malls and restaurants in peripheral regions in the week before compared to the week after the November 23 lockdown.

Results

Residents of Toronto and Peel took fewer trips to shopping malls and restaurants in the week following lockdown. This was entirely driven by reductions in visits within the locked down regions themselves, as there was a significant increase in trips to shopping malls in peripheral regions by these residents in the same period (Toronto: +40.7%, Peel: +65.5%). Visits to restaurants in peripheral regions also increased slightly (Toronto: +6.3%, Peel: +11.8%).

Discussion

Heterogeneous restrictions may undermine lockdowns in the urban core as well as driving residents from zones of higher transmission to zones of lower transmission. These concerns are likely generalizable to other major metropolitan areas, which often comprise interconnected but administratively independent regions.
Detection of SARS-CoV-2 infection by saliva and nasopharyngeal sampling in frontline healthcare workers: an observational cohort study
Authors: Walker Naomi F. , Byrne Rachel L. , Howard Ashleigh , Nikolaou Elissavet , Farrar Madlen , Glynn Sharon , Cheliotis Katerina S. , Cubas Atienzar Ana I. , Davies Kelly , Reine Jesus , Rashid-Gardner Zalina , German Esther L. , Solórzano Carla , Blandamer Tess , Hitchins Lisa , Myerscough Christopher , Gessner Brad , Biegner Elizabeth , Collins Andrea M. , Beadsworth Mike , Todd Stacy , Hill Helen , Houlihan Catherine F. , Nastouli Eleni , Adams Emily R. , Mitsi Elena , Ferreira Daniela M.
Published: April 2021

Background

The SARS-CoV-2 pandemic has caused an unprecedented strain on healthcare systems worldwide, including the UK National Health Service (NHS). During the first wave of SARS-CoV-2 transmission in UK, SARS-CoV-2 NHS diagnostic test availability was limited to self-isolating symptomatic staff. The burden of symptomatic and asymptomatic infection in healthcare workers (HCW) attending work was unknown.

Methods

We conducted an observational cohort study of SARS-CoV-2 infection in HCW working in an acute NHS Trust during the first wave of the COVID-19 pandemic, using serial self-collected saliva and nasopharyngeal (NP) samples. We also collected self-assessed symptom profiles and isolation behaviours. We retrospectively compared SARS-CoV-2 detection by RT-PCR from saliva (weekly) and NP swabs (twice weekly) from 85 individuals in this cohort and evaluated the association with symptoms.

Findings

Over a 12-week period from 30th March 2020, 40% (n=34/85, CI95% 31.3-51.8%) HCWs had evidence of SARS-CoV-2 infection by surveillance NP swab and/or saliva RT-qPCR. Agreement between paired saliva and NP swabs was poor (28.6%, CI95% 13.2-48.7%) with both methods detecting symptomatic and asymptomatic infections. Symptoms were reported by 47.1% (n=40) and self-isolation by 25.9% participants (n=22). Only 41.2% (n=14/34) participants with SARS-CoV-2 infection reported any symptoms within 14 days of the infection.

Interpretation

HCWs are a potential source of SARS-CoV-2 transmission in hospitals and symptom screening will identify the minority of infections in HCW. Saliva is an easily accessible fluid sample for screening for SARS-CoV-2 infection and in addition to NP swab, facilitated ascertainment of symptomatic and asymptomatic cases in this setting. Combined saliva and NP testing would improve detection of SARS-CoV-2 for surveillance. Better understanding of transmissibility from asymptomatic staff using transmission-based infection precautions, is required to inform policy.
Bayesian, Universal COVID Testing
Authors: Meyer Christian T. , Kralj Joel M.
Published: April 2021

During the SARS-COV2 pandemic, there has been a persistent call for universal testing to better inform policy decisions. However, a little considered aspect of this call is the relationship between a test’s accuracy and the tested demographic. What are the implications of frequent, universal testing in otherwise asymptomatic demographics? By applying Bayesian statistics, it becomes clear that as the odds of having COVID decreases, there is a non-linear increase in the odds that each positive test is, in fact, a false positive. This phenomenon has precedence in the historical narrative surrounding universal mammogram screening which is no longer recommended due to the unacceptably high rate of false positives. The solution to combat the inflation of false positives is also suggested by Bayesian statistics: intelligently integrating multiple COVID diagnostic tests and symptoms via Bayes’ Theorem, an approach conceptually similar to pre-screening for mammograms. This extra information is readily available (e.g. olfactory function and fever) and will minimize the economic and emotional costs incurred by false positives while simultaneously improving the information available for policy-makers. In summary, along with the push for universal testing should be an equally rigorous approach to interpreting the test results.
Depression and Anxiety Symptoms in Young Adults Before and During the COVID-19 Pandemic: Evidence from a Canadian Population-Based Cohort
Authors: Watkins-Martin Kia , Orri Massimiliano , Pennestri Marie-Hélène , Castellanos-Ryan Natalie , Larose Simon , Gouin Jean-Philippe , Ouellet-Morin Isabelle , Chadi Nicholas , Philippe Frederick , Boivin Michel , Tremblay Richard E. , Côté Sylvana , Geoffroy Marie-Claude
Published: April 2021

Objectives

Concerns have been raised that the COVID-19 pandemic could increase risk for adverse mental health outcomes, especially in young adults, a vulnerable age group. We investigated changes in depression and anxiety symptoms (overall and severe) from before to during the pandemic, as well as whether these changes are linked to COVID-19 related stressors and pre-existing vulnerabilities in young adults followed in the context of a population-based cohort.

Method

Participants (n=1039) from the Quebec Longitudinal Study of Child Development reported on their depression and anxiety symptoms and completed a COVID-19 questionnaire during the first wave of the COVID-19 pandemic in the summer of 2020 (age 22 years). Assessments at age 20 (2018) were used to estimate pre-pandemic depression and anxiety symptom severity.

Results

While overall levels of depression and anxiety symptoms did not change, there was an increase in rates of severe depression (but not severe anxiety) from before (6.1%) to during (8.2%) the pandemic. Depressive and anxiety symptoms increased from before to during the COVID-19 pandemic among young adults with the lowest levels of symptoms before the pandemic, while they decreased among those with the highest levels of pre-existing symptoms. Youth who were living alone experienced an increase in depressive symptoms. Other COVID-19 related variables (e.g., loss of education/occupation, frequent news-seeking) and pre-existing vulnerabilities (e.g., low SES, low social support) were not associated with changes in depression or anxiety symptoms.

Conclusion

Depression and anxiety symptoms in young adults from Québec in Summer 2020 were comparable to symptoms reported in 2018. Most COVID-19 related stressors and pre-existing vulnerabilities were not associated with changes in symptoms. However, the increased rate of severe depression and the increase in depression and anxiety symptoms among young adults with the least mental health symptoms before the COVID-19 pandemic are concerning.
Comparison of structural MRI brain measures between 1.5T and 3T: data from the Lothian Birth Cohort 1936
Authors: Buchanan Colin R. , Muñoz Maniega Susana , Valdés Hernández Maria C. , Ballerini Lucia , Barclay Gayle , Taylor Adele M. , Russ Tom C. , Tucker-Drob Elliot M. , Wardlaw Joanna M. , Deary Ian J. , Bastin Mark E. , Cox Simon R.
Published: April 2021

Multi-scanner MRI studies are reliant on understanding the apparent differences in imaging measures between different scanners. We provide a comprehensive analysis of T1-weighted and diffusion MRI (dMRI) structural brain measures between a 1.5T GE Signa Horizon HDx and a 3T Siemens Magnetom Prisma using 91 community-dwelling older participants (aged 82 years). Although we found considerable differences in absolute measurements (global tissue volumes were measured as ∼6—11% higher and fractional anisotropy was 33% higher at 3T than at 1.5T), between-scanner consistency was good to excellent for global volumetric and dMRI measures (intraclass correlation coefficient [ICC] range: 0.612—0.993) and fair to good for 68 cortical regions (FreeSurfer) and cortical surface measures (mean ICC: 0.504—0.763). Between-scanner consistency was fair for dMRI measures of 12 major white matter tracts (mean ICC: 0.475—0.564), and the general factors of these tracts provided excellent consistency (ICC ≥ 0.769). Whole-brain structural networks provided good to excellent consistency for global metrics (ICC ≥ 0.612). Although consistency was poor for individual network connections (mean ICCs: 0.275 – 0.280), this was driven by a large difference in network sparsity (0.599 versus 0.334), and consistency was improved when comparing only the connections present in every participant (mean ICCs: 0.533—0.647). Regression-based k-fold cross-validation showed that, particularly for global volumes, between-scanner differences could be largely eliminated (R2range 0.615—0.991). We conclude that low granularity measures of brain structure can be reliably matched between the scanners tested, but caution is warranted when combining high granularity information from different scanners.
A Mobile App for Prolonged Grief among Bereaved Parents: Study Protocol for a Randomized Controlled Trial
Authors: Eklund Rakel , Eisma Maarten C. , Boelen Paul A. , Arnberg Filip , Sveen Josefin
Published: April 2021

Introduction

Bereaved parents have elevated risk to develop mental health problems, yet, few studies have evaluated the effect of psychosocial interventions developed for bereaved parents. Cognitive behavioral therapy (CBT), both face-to-face or digitally delivered, has shown to be an effective intervention for prolonged grief symptoms. Self-help mobile apps offer various advantages and studies show improved mental health after app interventions. No app has yet been evaluated targeting prolonged grief in bereaved parents. Therefore, the aim of this planned study is to develop and examine the effectiveness of a CBT-based mobile app, called My Grief, in reducing symptoms of prolonged grief, as well as other psychological symptoms, in bereaved parents. Another aim is to assess users’ experiences and adverse events of My Grief.

Methods and analysis

We will conduct a two-armed randomized waitlist-controlled trial. Parents living in Sweden, who lost a child to cancer between one and ten years ago, with elevated symptoms of prolonged grief, will be recruited to participate in the trial. The content of My Grief covers four main domains (Learn; Self-monitoring; Exercises; Get support) and builds on principles of CBT and the proven-effective PTSD Coach app. Participants in the intervention group will fill out online questionnaires at baseline and at 3-, 6- and 12-months follow-ups, and the waitlist-controls at baseline and at 3 months. The primary outcome will be prolonged grief symptoms at the 3 months follow-up. Secondary outcomes are posttraumatic stress and depression symptoms, quality of life, and cognitive behavioral variables (i.e., avoidance, rumination, negative cognitions).

Ethics and dissemination

Ethical approval has been received from the Swedish Ethical Review Authority (project no. 2021-00770). If the app is shown to be effective, the app will be made publicly accessible on app stores, so that it can benefit other bereaved parents.

Trial registration

Clinicaltrials.gov, identifier: NCT04552717.

STRENGTHS AND LIMITATIONS

This is the first study to examine whether access of a self-help app can have beneficial effect on bereaved parent’s mental health, quality of life

This study will examine the effect of the app on cognitive-behavioral processes proposed to underlie the development of prolonged grief.

Generalizability of findings from this study may be limited as parents who want to participate in such study may experience fewer barriers to talk about the loss and seek help for their grief.

This study includes parents who have lost a child to cancer, hence the findings may not be generalizable to other causes.

This study uses self-report questionnaires, hence we do not establish formal diagnosis of prolonged grief disorder.
Network controllability mediates the relationship between rigid structure and flexible dynamics
Authors: Gu Shi , Fotiadis Panagiotis , Parkes Linden , Xia Cedric H. , Gur Ruben C. , Gur Raquel E. , Roalf David R. , Satterthwaite Theodore D. , Bassett Danielle S.
Published: April 2021

Precisely how the anatomical structure of the brain supports a wide range of complex functions remains a question of marked importance in both basic and clinical neuroscience. Progress has been hampered by the lack of theoretical frameworks explaining how a structural network of relatively rigid inter-areal connections can produce a diverse repertoire of functional neural dynamics. Here, we address this gap by positing that the brain’s structural network architecture determines the set of accessible functional connectivity patterns according to predictions of network control theory. In a large developmental cohort of 823 youths aged 8 to 23 years, we found that the flexibility of a brain region’s functional connectivity was positively correlated with the proportion of its structural links extending to different cognitive systems. Notably, this relationship was mediated by nodes’ boundary controllability, suggesting that a region’s strategic location on the boundaries of modules may underpin the capacity to integrate information across different cognitive processes. Broadly, our study provides a mechanistic framework that illustrates how temporal flexibility observed in functional networks may be mediated by the controllability of the underlying structural connectivity.

AUTHOR SUMMARY

Precisely how the relatively rigid white matter wiring of the human brain gives rise to a diverse repertoire of functional neural dynamics is not well understood. In this work, we combined tools from network science and control theory to address this question. Capitalizing on a large developmental cohort, we demonstrated that the ability of a brain region to flexibly change its functional module allegiance over time (i.e., its modular flexibility), was positively correlated with its proportion of anatomical edges projecting to multiple cognitive networks (i.e., its structural participation coefficient). Moreover, this relationship was strongly mediated by the region’s boundary controllability, a metric capturing its capacity to integrate information across multiple cognitive domains.
Binding mechanism of neutralizing Nanobodies targeting SARS-CoV-2 Spike Glycoprotein
Authors: Golcuk Mert , Hacisuleyman Aysima , Erman Burak , Yildiz Ahmet , Gur Mert
Published: April 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human cells upon binding of its spike (S) glycoproteins to ACE2 receptors. Several nanobodies neutralize SARS-CoV-2 infection by binding to the receptor-binding domain (RBD) of S protein, but the underlying mechanism is not well understood. Here, we identified an extended network of pairwise interactions between RBD and nanobodies H11-H4, H11-D4, and Ty1 by performing all-atom molecular dynamics (MD) simulations. Simulations of the nanobody-RBD-ACE2 complex revealed that H11-H4 more strongly binds to RBD without overlapping with ACE2 and triggers dissociation of ACE2 due to electrostatic repulsion. In comparison, Ty1 binding results in dissociation of ACE2 from RBD due to an overlap with the ACE2 binding site, whereas H11-D4 binding does not trigger ACE2 dissociation. Mutations in SARS-CoV-2 501Y.V1 and 501.V2 variants resulted in a negligible effect on RBD-ACE2 binding. However, the 501.V2 variant weakened H11-H4 and H11-D4 binding while strengthening Ty1 binding to RBD. Our simulations indicate that all three nanobodies can neutralize 501Y.V1 while Ty1 is more effective against the 501.V2 variant.