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International audience; The segmented RNA genome of influenza A viruses (IAVs) enables viral evolution through genetic reassortment after multiple IAVs coinfect the same cell, leading to viruses harboring combinations of eight genomic segments from distinct parental viruses. Existing data indicate that reassortant genotypes are not equiprobable; however, the low throughput of available virology techniques does not allow quantitative analysis. Here, we have developed a high-throughput single-cell droplet microfluidic system allowing encapsulation of IAV-infected cells, each cell being infected by a single progeny virion resulting from a coinfection process. Customized barcoded primers for targeted viral RNA sequencing enabled the analysis of 18,422 viral genotypes resulting from coinfection with two circulating human H1N1pdm09 and H3N2 IAVs. Results were highly reproducible, confirmed that genetic reassortment is far from random, and allowed accurate quantification of reassortants including rare events. In total, 159 out of the 254 possible reassortant genotypes were observed but with widely varied prevalence (from 0.038 to 8.45%). In cells where eight segments were detected, all 112 possible pairwise combinations of segments were observed. The inclusion of data from single cells where less than eight segments were detected allowed analysis of pairwise cosegregation between segments with very high confidence. Direct coupling analysis accurately predicted the fraction of pairwise segments and full genotypes. Overall, our results indicate that a large proportion of reassortant genotypes can emerge upon coinfection and be detected over a wide range of frequencies, highlighting the power of our tool for systematic and exhaustive monitoring of the reassortment potential of IAVs.

Disaster planning is a core facet of modern health care practice. Owing to complex infrastructure requirements, radiology departments are vulnerable to system failures that may occur in isolation or during a disaster event when the urgency for and volume of imaging examinations increases. Planning for systems failures helps ensure continuity of service provision and patient care during an adverse event. Hazards to which a radiology department is vulnerable can be identified by applying a systematic approach with recognized tools such as the Hazard, Risk, and Vulnerability Analysis. Potential critical weaknesses within the department are highlighted by the Failure Mode and Effects Analysis tool. Recognizing the potential latent conditions and active failures that may impact systems allows implementation of strategies to prevent failure or to build resilience and mitigate the effects if they happen. Inherent system resilience to an adverse event can be estimated, and the ability of a department to operate during a disaster and the subsequent recovery can be predicted. The main systems at risk in a radiology department are staff, structure, stuff (supplies and/or equipment), and software, although individual issues and solutions within these are department specific. When medical imaging or examination interpretation needs cannot be met in the radiology department, the use of portable imaging modalities and teleradiology can augment the disaster response. All phases of disaster response planning should consider both sustaining operations and the transition back to normal function.

OBJECTIVE To describe the development and implementation of a Peer Curbside Consult Service (PCCS) for a pediatric hospital medicine (PHM) division. METHODS We developed a pilot intervention with hospitalists at a freestanding children’s hospital to provide peer consultation services for challenging clinical cases. Postconsultation surveys collected from both the requesting and consulting hospitalists provided feedback about the program. The 12-point Template for Intervention Description and Replication (TIDieR) checklist is used to describe the process for program creation and implementation. RESULTS The PCCS has provided 60 consultations in the first 2 years since implementation in April 2020 and supports a large PHM division with >75 members who practice at a tertiary care, freestanding children’s hospital and 7 affiliate sites. Hospitalists request peer consultation for challenging clinical cases. The consultations were typically conducted in person or via telephone. Currently, 11 PHM faculty members within the division volunteer as consultants, with 2 assigned per week. Electronic postconsultation experience surveys were received from 70% of requesting and 89% of consultant hospitalists. We also provide preliminary data from this pilot intervention in the Supplemental Information. CONCLUSIONS We successfully established a peer consult service that provided just-in-time clinical decision support across the various practice sites. Through transparent reporting using the TIDieR checklist, other divisions may be able to replicate and adapt their own peer consult program.

Background Recent evidence suggests a role for lung microbiome in occurrence of chronic lung allograft dysfunction (CLAD). However, the mechanisms linking the microbiome to CLAD are poorly delineated. We investigated a possible mechanism involved in microbial modulation of mucosal response leading to CLAD with the hypothesis that a Proteobacteria dominant lung microbiome would inhibit N-myc-interactor (NMI) expression and induce epithelial to mesenchymal transition (EMT). Methods Explant CLAD, non-CLAD, and healthy nontransplant lung tissue were collected, as well as bronchoalveolar lavage from 14 CLAD and matched non-CLAD subjects, which were followed by 16S rRNA amplicon sequencing and quantitative polymerase chain reaction (PCR) analysis. Pseudomonas aeruginosa (PsA) or PsA-lipopolysaccharide was cocultured with primary human bronchial epithelial cells (PBEC). Western blot analysis and quantitative reverse transcription (qRT) PCR was performed to evaluate NMI expression and EMT in explants and in PsA-exposed PBECs. These experiments were repeated after siRNA silencing and upregulation (plasmid vector) of EMT regulator NMI. Results 16S rRNA amplicon analyses revealed that CLAD patients have a higher abundance of phyla Proteobacteria and reduced abundance of the phyla Bacteroidetes . At the genera level, CLAD subjects had an increased abundance of genera Pseudomonas and reduced Prevotella . Human CLAD airway cells showed a downregulation of the N-myc-interactor gene and presence of EMT. Furthermore, exposure of human primary bronchial epithelial cells to PsA resulted in downregulation of NMI and induction of an EMT phenotype while NMI upregulation resulted in attenuation of this PsA-induced EMT response. Conclusions CLAD is associated with increased bacterial biomass and a Proteobacteria enriched airway microbiome and EMT. Proteobacteria such as PsA induces EMT in human bronchial epithelial cells via NMI, demonstrating a newly uncovered mechanism by which the microbiome induces cellular metaplasia .

Objectives We present a full autopsy with a focused radiology and pathologic review of the coronary arteries. We hope that the results described in this article will help create better diagnostic measures and prevent future coronary artery vasculitis misdiagnosis. Methods A full autopsy was performed on the body of Dr Myung Choong Yoon, with full consent from the family, within the department of pathology and laboratory medicine at Vancouver General Hospital. Tissue samples from the heart, brain, lungs, and spinal cord were submitted to specialist pathologists for histologic processing. Results Cardiac gated computed tomography coronary angiography suggested periarteritis. Coexistent calcified coronary atherosclerosis with linear calcifications was present along the luminal wall, along with coronary artery ectasia. Histologic assessment confirmed features of dense adventitial fibrosis around the coronary arteries, with an exuberant lymphoplasmacytic infiltrate and numerous plasma cells consistent with IgG4-related disease. The media of the coronary arteries was markedly attenuated or completely absent, which likely contributed to the coronary arterial ectasia noted microscopically. These findings confirmed IgG4-related coronary arteritis. Conclusions Coronary periarteritis is an uncommon manifestation of IgG4-related disease established radiographically and later by autopsy.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but M. tb biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the recalcitrance of TB infections. Here, we used M. tb experimental evolution to investigate this complex phenotype and identify candidate loci controlling biofilm formation. We identified novel candidate loci, adding to our understanding of the genetic architecture underlying M. tb biofilm development. Under selective pressure to grow as a biofilm, regulatory mutations rapidly swept to fixation and were associated with changes in multiple traits, including extracellular matrix production, cell size, and growth rate. Genetic and phenotypic paths to enhanced biofilm growth varied according to the genetic background of the parent strain, suggesting that epistatic interactions are important in M. tb adaptation to changing environments.

In the current cultural climate, gender disparity is a topical and contentious issue. In academic medicine, there is an underrepresentation of female faculty in leadership positions with lower research output and fewer grant awards. We study the gender differences in faculty rank, leadership positions, and research output among chest radiologists in North America.A list of clinical faculty at radiology programs in North America was obtained using the FREIDA database and program websites. Demographic information and data pertaining to academic rank, peer-reviewed publications, and research productivity of each chest radiologist was obtained from Doximity and SCOPUS databases.Four hundred ten (281 male:129 female) academic chest radiologists were included. Females were underrepresented at senior faculty level accounting for 18.8% (n = 21) of full, 29.2% (n = 21) of associate and 40.7% (n = 61) of assistant professors. 23.1% (n = 14) of department chiefs were women. Women were more likely to occupy a faculty position in chest radiology in Canada than in US (P 0.05). The median H-index, and numbers of publications and citations were lower for females than male faculty (P 0.05). Male faculty had more years of experience - median of 19 years, 16.5 years for females (P 0.05).Gender disparity exists in chest radiology with similar male predominance in terms of senior faculty rank, leadership roles, and research productivity to other medical specialties. The observed deficiency of research and scholarly output among female chest radiologists and the paucity of aspirational female radiologists in senior academic/leadership positions are factors which perpetuate this gender disparity and contribute to persistence of the gender pay gap.

Functionalization of semiconductors by metallic nanoparticle is considered to be one of the most effective procedure to improve photocatalytic hydrogen production. Photodeposition is frequently used for functionalization but particle sizes and dispersions are still difficult to control. Here, Pt functionalization is achieved in a one-pot synthesis. The as-prepared samples are compared to reference materials prepared by conventional photodeposition and our results confirm that small and well-dispersed nanoparticles with superior stability are obtained by one-pot synthesis. The enhanced stability is attributed to a limited leaching of Pt nanoparticles during illumination likely caused by the preferable interaction of small, well dispersed Pt nanoparticles with the TiO2 support material. In addition, our results demonstrate that Na-residues are detrimental for the photocatalytic performance and washing in acidic solution is mandatory to effectively reduce the sodium contamination.

Since the advent of multidetecter computed tomography (CT), radiologist sensitivity in detection of traumatic bowel and mesenteric abnormalities has significantly improved. Although several CT signs have been described to identify intestinal injury, accurate interpretation of these findings can remain challenging. Early detection of bowel and mesenteric injury is important as it alters patient management, disposition, and follow-up. This article reviews the common imaging findings of traumatic small bowel and mesenteric injury.

A mass casualty incident (MCI) is an event that generates more patients at one time than locally available resources can manage using routine procedures. By their nature, many of these incidents have no prior notice but result in large numbers of casualties with injuries that range in severity. They can happen anywhere and at any time and regional hospitals and health-care providers have to mount a response quickly and effectively to save as many lives as possible. Radiologists must go from passenger to pilot when it comes to MCI planning. When involved at the hospital-wide planning stage, they can offer valuable expertise on how radiology can improve triage accuracy and at what cost in terms of time and resources and thereby contribute a pragmatic understanding of radiology’s role and value during MCIs. By taking ownership of MCI planning in their own departments, radiologists can ensure that the radiology department can respond quickly and effectively to unforeseen emergencies. Well-designed radiology protocols will save lives in an MCI setting.

Aim This study evaluated the use of Lumbar Puncture (LP) in a general paediatric unit over a 3-year period. Methods Index patients, who had a successful LP, were identified from the microbiology database and failed LP procedures were identified from a chart review of the serum PCR database. Data abstracted included 1) patient age, 2) LP indication, 3) LP procedure outcome; classified as atraumatic, traumatic or failed, 4) grade of doctor undertaking the procedure and 5) the final diagnosis. Results We identified 104 paediatric patients, of whom 29(27.9%) were neonates. LP was indicated for the evaluation of acute undifferentiated illnesses, with 33 (31.7%) patients having fever without source beyond the neonatal period and 16 (15.4%) being neonates with fever. A CSF sample was obtained in 96 (92.4%) patients, with 71 (73.9%) being atraumatic. Successful LP was undertaken by Consultants in 4 (4.1%), Registrars in 83 (86.5%) and SHOs in 9 (9.4%) patients. 14 (14.6%) patients had positive CSF cultures with an additional 23 having positive cultures or serology (9 blood cultures, 11 urine cultures and 3 positive serum PCR). Conclusion Skill in LP performance is still required, to evaluate acute undifferentiated illness, in general paediatric units and ancillary methods to aid SHOs with LP skill development is desirable.

New infrastructure corridors within the Slave Geological Province could provide transportation, electric, and communications links to mineral-rich areas of northern Canada, and connect southern highway systems and Arctic shipping routes. Relatively little information on permafrost and ground ice is available compared to other regions, particularly in the north of the corridor. Improved knowledge of permafrost and ground ice conditions is required to inform planning and management of infrastructure. Work within the Geological Survey of Canada's (GSC) GEM-GeoNorth program includes mapping periglacial terrain features, synthesizing existing permafrost and surficial data, and modelling ground ice conditions along the Yellowknife-Grays Bay corridor. Here we present initial modelling of ground ice abundance in the region using a methodology developed for the national scale Ground ice map of Canada (GIMC), and higher resolution surficial geology mapping. The results highlight the increased estimated abundance of potentially ice-rich deposits compared to the GIMC when using more detailed surficial geology as model inputs.

Thermokarst results from thawing of excess ground ice in permafrost sediments. Thermokarst processes and landforms are controlled by ground ice type, amount and distribution, as well as the patterns of ground ice loss over time. Recent acceleration of varied thermokarst processes across diverse Canadian permafrost terrains make for a challenging task in predicting landscape-scale thaw trajectories. Using existing ground ice models, we examined the modelled amounts and spatial extent of ground ice loss relative to ground ice maxima in the last ca. 16 ka BP for relict, segregated and wedge ice. We relate observed thermokarst features to the nature of ground ice development and loss in different environments (cold continuous permafrost, discontinuous permafrost, and no current permafrost). In cold, continuous permafrost areas where ground ice loss has been limited over the last 16 ka BP, thermokarst processes include active layer detachments and slumps in segregated and relict ice, gullying and ponding in ice wedge troughs, and the cyclical development of shallow thermokarst ponds in segregated ice. With ground ice loss in discontinuous permafrost, thermokarst processes are wide-ranging. Slumps, subsidence, and collapse of lithalsas, palsas and peat plateaus occur from thawing of segregated ice, thermokarst ponds from melting wedge and segregated ice, and involuted terrain from melting and creep of relict or segregated ice. In former permafrost terrain, evidence of thermokarst includes former ice wedge polygons, collapsed lithalsas, and irregular hummocky terrain. The relations between modelled ground ice loss and observed thermokarst landscapes assist in understanding present-day processes and in predicting future thermokarst landform evolution with a changing climate.

This thesis primarily focuses on photophysics of charge and energy transfer in plasmonic structures. After an initial study of photothermal catalysis using silver bromide for methane activation which found the process to be unsuitable at 1 bar, the focus pivoted towards plasmonic nanostructures for photothermal applications. Charge transfer across a 4-mercaptobenzoic acid linker between silver nanocubes and cerium dioxide was examined using Raman spectroscopy, this found an increase in charge transfer with thicker shells and higher energy light. The photophysics of a similar system were then probed, using time-resolved spectroscopy and gold nanoparticles embedded in a cerium praseodymium mixed metal oxide. That study indicated that charge and energy transfer could occur and were influenced by the composition: with ballistic charge transfer dominating in cerium oxide, chemical interfacial damping being prevalent with low levels of praseodymium, and plasmon induced resonant energy transfer occurring with higher loadings of praseodymium. A final study is, at first glance, somewhat of a non-sequitur and examines the photophysics of hafnium nitride. In existing literature there was a discrepancy between theoretical and experimental work regarding the lifetime of photo-excited electrons in hafnium nitride, in this study this discrepancy is resolved and shows that the photo-excited electrons rapidly (

The Cancer Genome Atlas study in thyroid cancer exposed the genomic landscape of ~500 PTCs and revealed BRAFV600E-mutant tumors as having different prognosis, contrasting indolent cases and those with more invasive disease. Here, we describe the generation and characterization of six novel BRAFV600E-driven papillary thyroid cancer (PTC) cell lines established from a BrafV600E+/−/Pten+/−/TPO-Cre mouse model that spontaneously develop thyroid tumors. The novel cell lines were obtained from animals representing a range of developmental stages and both sexes, with the goal of establishing a heterogeneous panel of PTC cell lines sharing a common driver mutation. These cell lines recapitulate the genetics and diverse histopathological features of BRAFV600E-driven PTC, exhibiting differing degrees of growth, differentiation, and invasive potential that may help define mechanisms of pathogenesis underlying the heterogeneity present in the patient population. We demonstrate that these cell lines can be used for a variety of in vitro applications and can maintain the potential for in vivo transplantation into immunocompetent hosts. We believe that these novel cell lines will provide powerful tools for investigating the molecular basis of thyroid cancer progression and will lead to the development of more personalized diagnostic and treatment strategies for BRAFV600E-driven PTC.

There is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use single-cell RNA-sequencing to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. We show widespread inter-individual variability in the percentage of IAV-infected monocytes. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such as IFITM3, MX1 and OAS3. Upon IAV challenge, we find that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. We also uncover a stronger resistance of CD16+ monocytes to IAV infection, together with CD16+-specific mRNA expression of IL6 and TNF in response to IAV. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number of CD16+ monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Based on these data, we hypothesize that higher basal monocyte activation, driven by environmental factors and/or weak-effect genetic variants, underlies the lower cellular susceptibility to IAV infection of individuals of African ancestry relative to those of European ancestry. Further studies are now required to investigate how such cellular differences in IAV susceptibility translate into population differences in clinical outcomes and susceptibility to severe influenza.

There is great interest in the development of alternatives to noble metals for plasmonic nanostructures. Transition metal nitrides are promising due to their robust refractory properties. However, the photophysics of these nanostructures, particularly the hot carrier dynamics and photothermal response on ultrafast timescales, are not well understood. This limits their implementation in applications such as photothermal catalysis or solar thermophotovoltaics. In this study, the light-induced relaxation processes in water-dispersed HfN nanoparticles are, for the first time, elucidated by fs transient absorption, Lumerical FDTD and COMSOL Multiphysics simulations, and temperature-dependent ellipsometry. It is unequivocally demonstrated that HfN nanoparticles convert absorbed photons into heat within

Objectives: This study is an evaluation of the emergency department (ED) satisfaction with the current radiologic reporting system used at a major Northeastern academic medical center. The radiology reports are the main form of communication and usually the final product of any radiological investigation delivered to clinicians. The aim of this study was to improve current radiology reporting practices and to better tailor reports to match the needs and expectations of ED clinicians. Methods: A 9-question online survey was sent to ED residents, fellows, faculty, and nurse practitioners/advanced practice providers at a major Northeastern academic medical center in the United States. For the open-ended section, coding and emergent theme categorization was conducted for quantification of responses. The survey was designed to evaluate the attitudes toward the structure, style, form, and wording used in reports. Results: The response rate was 48.6% (68/140). The ED respondents were generally satisfied with radiology reports, their language, vocabulary, and clarity. They preferred the impression section to be before the findings in simple examinations and to stratify the reports according to emergency status for complex examinations. They did not like extended differential, hedge terms, and delayed reporting. Additionally, ED respondents recommended focused, fast reporting with considerable changes toward a more standardized report. Conclusions: This evaluation delivered a list of actionable recommendations. The top recommendation is to standardize reporting structure, style, and lexicon, in addition to being focused, timely, and brief.

Purpose Prospective radiology fellows often rely on the internet to obtain information with regard to the application process for and the unique qualities of different fellowship programs. The aim of this study was to analyze the content of websites of the United States' and Canadian cardiothoracic radiology fellowships. Methods All active Cardiothoracic Radiology fellowship websites as of July 2019 were evaluated and compared using 25 criteria in the following domains: Application, Recruitment, Clinical Training, Education/Research, and Incentives. Program website information availability was compared by geographic region. Results There were 60 active cardiothoracic radiology fellowships, and 59 of these fellowships had a dedicated fellowship website. Websites, on average, had 9.3 of the 25 criteria (37.2%). The mean number of schools that satisfied the criterion in the "Incentives" domain ([7.75/59] 10.5%±2.8%) was significantly lower than that for the "Application Process" domain ([40.50/59]; 68.7%±40.6%) (P=0.01). There was no significant difference in the information content of programs in different geographic regions (P=0.246). Conclusion Most cardiothoracic radiology fellowship websites were lacking content relevant to prospective fellows. Provision of more relevant and easily accessible online content may support programs to better inform and recruit residents and to promote the specialty of cardiothoracic radiology.

Plasmonic sensitization of semiconductors is an attractive approach to increase light-induced photocatalytic performance; one method is to use plasmonic nanostructures in core@shell geometry. The occurrence and mechanism of synergetic effects in photocatalysis of such geometries are under intense debate and proposed to occur either through light-induced charge transfer (CT) or through thermal effects. This study focuses on the relation between the dimensions of Ag@CeO2 nanocubes, the wavelength-dependent efficiency, and the mechanism of light-induced direct CT. A 4-mercaptobenzoic acid (4-MBA) linker between core and shell acts as a Raman probe for CT. For all Ag@CeO2 nanocubes, CT increases with decreasing excitation wavelength, with notable increase at and below 514 nm. This is fully explainable by CT from silver to the 4-MBA LUMO, with the increase for excitation wavelengths that exceed the Ag/4-MBA LUMO gap of 2.28 eV (543 nm). A second general trend observed is an increase in CT yield with ceria shell thickness, which is assigned to relaxation of the excited electron further into the ceria conduction band, potentially producing defects.

Objectives Experienced physicians must rapidly identify ill pediatric patients. We evaluated the ability of an illness rating score (IRS) to predict admission to a pediatric hospital and explored the underlying clinical reasoning of the gestalt assessment of illness. Methods We used mixed-methods to study pediatric emergency medicine physicians at an academic children’s hospital emergency department (ED). Physicians rated patients’ illness severity with the IRS, anchored by 0 (totally well) and 10 (critically ill), and shared their rationale with concurrent think-aloud responses. The association between IRS and need for hospitalization, respiratory support, parenteral antibiotics, and resuscitative intravenous (IV) fluids were analyzed with mixed effects linear regression. Area under the curve (AUC) receiver operator characteristic (ROC) curve and test characteristics at different cut-points were calculated for IRS as a predictor of admission. Think-aloud responses were qualitatively analyzed via inductive process. Results A total of 141 IRS were analyzed (mean 3.56, SD 2.30, range 0–9). Mean IRS were significantly higher for patients requiring admission (4.32 vs. 3.13, p Conclusions Rapid assessments as captured by the IRS differentiated pediatric patients who required admission and medical interventions. Think-aloud responses for the rationale for rapid assessments may form the basis for teaching the skill of identifying ill pediatric patients.

Introduction We assessed management of patients with de novo metastatic rectal cancer, referred for radiotherapy to the rectum, who were candidates for short-course radiotherapy (SCRT) and chemotherapy, followed by resection of all disease. We assessed surgical outcomes, overall survival (OS) and progression-free survival (PFS). Methods Retrospective review of patients meeting criteria: (i) treatment with SCRT to rectum; (ii) locally advanced primary rectal cancer; and (iii) resectable distant metastases at diagnosis. Data were collected from charts, correspondence and electronic patient records. OS and PFS were calculated using the Kaplan-Meier method. Results Between 2016 and 2020, 48 patients with stage IV rectal cancer at diagnosis were treated with SCRT. Only 15 patients (31%) had resectable metastatic disease and were intended for SCRT (25 Gy/5#), then chemotherapy, followed by resection of all sites of disease and are included in our study. 12 of the 15 surgical candidates (80%) had rectal surgery as planned, and 11 of the 15 (73%) had resection of the rectal primary and all metastatic disease. One patient had a pathological complete response (pCR), and 50% of surgical patients had a Mandard TRG of 1 or 2. Median PFS and OS for the 15 surgical candidates were 12.6 and 25.2 months, respectively, with a median FU of 21.2 months. Conclusion For this cohort of patients, our treatment paradigm is pragmatic and results in excellent pathological response. However, the effectiveness of this approach should be the subject of future prospective studies.

How adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Using cells adhering to deformable micropillar arrays, we demonstrate that traction force and FAK localization as well as traction force and Y397-FAK phosphorylation are linearly coupled at individual FAs on stiff, but not soft, substrates. Similarly, FAK phosphorylation increases linearly with external forces applied to FAs using magnetic beads. This mechanosignaling coupling requires actomyosin contractility, talin-FAK binding, and full-length vinculin that binds talin and actin. Using an in vitro 3D biomimetic wound healing model, we show that force-FAK signaling coupling coordinates cell migration and tissue-scale forces to promote microtissue repair. A simple kinetic binding model of talin-FAK interactions under force can recapitulate the experimental observations. This study provides insights on how talin and vinculin convert forces into FAK signaling events regulating cell migration and tissue repair., How adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Here authors show that force- FAK signaling coupling coordinates cell migration and tissue-scale forces to promote microtissue repair.

There is considerable inter-individual and inter-population variability in response to viruses. The potential of monocytes to elicit type-I interferon responses has attracted attention to their role in viral infections. Here, we use an ex vivo model to characterize the role of cellular heterogeneity in human variation of monocyte responses to influenza A virus (IAV) exposure. Using single-cell RNA-sequencing, we show widespread inter-individual variability in the percentage of IAV-infected monocytes. We show that cells escaping viral infection display increased mRNA expression of type-I interferon stimulated genes and decreased expression of ribosomal genes, relative to both infected cells and those never exposed to IAV. While this host defense strategy is shared between CD16+/CD16- monocytes, we also uncover CD16+-specific mRNA expression of IL6 and TNF in response to IAV, and a stronger resistance of CD16+ monocytes to IAV infection. Notably, individuals with high cellular susceptibility to IAV are characterized by a lower activation at basal state of an IRF/STAT-induced transcriptional network, which includes antiviral genes such as IFITM3, MX1, and OAS3. Finally, using flow cytometry and bulk RNA-sequencing across 200 individuals of African and European ancestry, we observe a higher number of CD16+ monocytes and lower susceptibility to IAV infection among monocytes from individuals of African-descent. Collectively, our results reveal the effects of IAV infection on the transcriptional landscape of human monocytes and highlight previously unappreciated differences in cellular susceptibility to IAV infection between individuals of African and European ancestry, which may account for the greater susceptibility of Africans to severe influenza.Significance StatementMonocytes may play a critical role during severe viral infections. Our study tackles how heterogeneity in monocyte subsets and activation contributes to shape individual differences in the transcriptional response to viral infections. Using single-cell RNA-sequencing, we reveal heterogeneity in monocyte susceptibility to IAV infection, both between CD16+/CD16- monocytes and across individuals, driven by differences in basal activation of an IRF/STAT-induced antiviral program. Furthermore, we show a decreased ability of IAV to infect and replicate in monocytes from African-ancestry individuals, with possible implications for antigen presentation and lymphocyte activation. These results highlight the importance of early cellular activation in determining an individuals’ innate immune response to viral infection.

POINTS CLES Un homme de 76 ans s’est presente dans un centre hospitalier de soins quaternaires en raison de symptomes respiratoires, de fatigue et d’un episode d’evanouissement dans les 6 jours precedents. Le patient presentait une toux seche post-infectieuse en voie de resolution

IntroductionDNA methylation data facilitate the development of accurate molecular estimators of chronological age, or ‘epigenetic clocks.’ We present a robust epigenetic clock for the beluga whale, Delphinapterus leucas, developed for an endangered population in Cook Inlet, Alaska, USA.Methods and ResultsWe used a custom methylation array to measure methylation levels at 37,491 cytosine-guanine sites (CpGs) from skin samples of dead whales (n = 67) whose chronological ages were estimated based on tooth growth layer groups. Using these calibration data, a penalized regression model selected 23 CpGs, providing an R2 = 0.92 for the training data; and an R2 = 0.74 and median absolute age error = 2.9 years for the leave one out cross-validation. We applied the epigenetic clock to an independent data set of 38 skin samples collected with a biopsy dart from living whales between 2016 and 2018. Age estimates ranged from 11 to 27 years. We also report sex correlations in CpG data and describe an approach of identifying the sex of an animal using DNA methylation.DiscussionThe epigenetic estimators of age and sex presented here have broad applications for conservation and management of Cook Inlet beluga whales and potentially other cetaceans.

Postgraduate medical training incorporates education, both formal and informal, combined with clinical service. This study explored the early training experience of pediatricians in Ireland and its potential impact on patient safety.We sought to identify factors that contribute to the patient safety experience of new entrant pediatric trainees.Trainees, or senior house officers (SHOs), in their first year of postgraduate training, participated in an interview conducted using a critical interview technique (CIT). They described an adverse event where the medical care delivered to the patient was not ideal. Thematic analysis identified themes that influenced the described event.Thirteen trainees participated in the interviews. This study identified influences on the relationship between the SHO and patient safety, including the SHO themselves, teamwork and communication. Colleagues within the workplace, including consultants, registrars, and nurses, also affect this relationship. The registrar is described as a central figure holding an active role in clinical care in 11 of the 13 stories told. In the participants' experience, the registrar was the senior decision-maker, teacher, team builder, and communication intermediary within the teams' hierarchical structure. The registrars' previous clinical experience, communication style, along with their ability to supervise and provide feedback shaped the SHO experience.Through a process designed to focus on exploring patient safety, it emerged that the registrar plays a crucial role in the working experience of their junior colleagues. The influence of the registrar needs to be recognized within clinical teams and by postgraduate training bodies.

Mass casualty incidents, by nature of their scale and unpredictability, can rapidly overwhelm health infrastructure. Preparation is the key to managing these crises with the lowest risk to emergency and health personnel, while providing maximal life saving measures. We present an overview of the multitiered planning that should go into forming a well set out emergency response plan and one that is capable of being adapted to a wide range of mass casualty scenarios. We highlight the ethical implications that a healthcare team faces while making challenging decisions rapidly in a high-pressure environment. Radiology trainees should be aware of the response systems in place at their institutions and the role that is expected of them in mass casualty incidents.

Background/objectives Little research has compared clinician acne severity assessment with either adolescent- or parent-rated scales of acne severity or impact on quality of life (QOL). We sought to assess how adolescents and their parents perceive the severity and impact of acne on the adolescent's QOL and correlate this with clinical severity. Methods Each adolescent and a parent completed a validated QOL survey regarding the adolescent's acne and rated the adolescent's acne severity and QOL impact using a Likert scale. Clinicians assessed the adolescent's acne using a standardized acne severity scale. Statistical analysis compared adolescent scores with respective parent scores or with clinician assessment using a paired t test or Spearman rank-order correlation test. Results The Likert impact score more accurately reflected acne impact on QOL for adolescents than for parents when considering the validated QOL survey as the gold standard (r2 = .56 vs r2 = .36). Likert scores for adolescents and parents were weakly correlated for acne severity but not for acne QOL impact (r2 = .36 vs r2 = .18). Correlations of acne severity scores between clinician and either adolescent or parent were weak. Conclusions Parents and adolescents are in relative agreement regarding acne severity and QOL impact. However, parent and adolescent perceptions are disparate from clinician acne assessment. It is important that physicians identify and consider adolescent and parent perceptions in addition to clinical assessment to better inform the approach to acne management.

Standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT), followed by surgical resection. However, &gt, 70% of patients do not achieve a complete pathological response and have higher rates of relapse and death. There are no validated pre- or on-treatment factors that predict response to NACRT besides tumour stage and size. We characterised the response of 33 LARC patients to NACRT, collected tumour samples from patients prior to, during and after NACRT, and performed whole exome, transcriptome and high-depth targeted sequencing. The pre-treatment LARC genome was not predictive of response to NACRT. However, in line with the increasing recognition of microbial influence in cancer, RNA analysis of pre-treatment tumours suggested a greater abundance of Fusobacteria in intermediate and poor responders. In addition, we investigated tumour heterogeneity and evolution in response to NACRT. While matched pre-treatment, on-treatment and post-treatment tumours revealed minimal genome evolution overall, we identified cases in which microsatellite instability developed or was selected for during NACRT. Recent research has suggested a role for adaptive mutability to targeted therapy in colorectal cancer cells. We provide preliminary evidence of selection for mismatch repair deficiency in response to NACRT. Furthermore, pre-NACRT genomic landscapes do not predict treatment response but pre-NACRT microbiome characteristics may be informative.

KEY POINTS A 76-year-old man presented to a quaternary care hospital with a 6-day history of respiratory symptoms, fatigue and a fainting episode. The patient had a resolving postinfectious dry cough from an upper respiratory infection that occurred 3 months before presentation. He had hypertension

Preoperative radiotherapy or combined chemoradiotherapy for locally advanced rectal cancer (LARC) can cause acute and late gastrointestinal (GI) side-effects. There is thought to be a dose-volume relationship between small bowel irradiation and the development of these effects. A planning study was undertaken to compare small bowel sparing for a range of 3D conformal and dynamic arc planning solutions. A planning study was carried out for 20 LARC patients. Organs at risk (OAR) contoured included bowel loops and peritoneal space (PS). For each of the 20 patients, 5 plans were created: (1) standard 3D conformal plan; (2) standard dual dynamic arc plan; (3) dual dynamic arc plan with 90° avoidance sector through the anterior portion of the patient; (4) dual dynamic arc plan with an anterior avoidance structure in the optimizer; (5) dual dynamic arc plan with both an anterior avoidance structure and an avoidance sector. The prescription was 50.4 Gy in 28 fractions to the planning target volume (PTV). Five Dose Volume Levels (DVLs; V15 Gy, V20 Gy, V25 Gy, V35 Gy, V40 Gy, and V50.4 Gy) for bowel and PS were selected. The DVLs were compared between the plans using Friedman Tests and Wilcoxon Signed Rank Tests. Comparison of the 5 plans revealed that a dual dynamic arc plan containing both an anterior avoidance sector and structure significantly improved the dose to the bowel compared to a standard 3D conformal plan and to a standard dual dynamic arc plan. This improvement was achieved while maintaining PTV coverage. This novel dual dynamic arc planning technique that uses both an avoidance sector and structure reduces the dose to the bowel and PS, which may lead to a reduction in GI toxicity.

BackgroundComputed tomography (CT), by its nature, imparts a high dose of ionising radiation to patients being imaged. Diagnostic Reference Levels (DRLs) are used extensively in research but are also used in practice to establish if local imaging protocols have been optimised.AimTo audit effective dose (ED) at CT for four commonly performed examinations performed with a modern multidectector 64 slice CT (MDCT) system at large tertiary care centre by comparison with current international reference standardsMethods800 consecutive studies of CT brain, cervical spine, thorax and abdomen-pelvis were examined. All patients were imaged on 64-slice MDCT with study-specific protocols. Dose descriptors were extracted from image dose reports. ED was calculated using dose-length product conversion coefficients for all patients. Data was collated with Irish national and local DRLs, and published international point values.ResultsED range at CT abdomen-pelvis of 2.03-26.04 mSv (mean 8.041 mSv) was 28.5% above the national DRL (9 mSv) and 26% above the local DRL (9.75 mSv). ED at CT thorax of 2.46-10.09 mSv (5.061 mSv) was 3.5% greater than local DRL (8.4mSv) and 42.5% greater than the national DRL (5.46 mSv). ED at CT brain of 2.25-8.08 mSv (3.075 mSv) was 100% above both the local (1.98 mSv) and national (2.06 mSv) DRLs. CT cervical spine ED of 1.49-21.94 mSv (5.14 mSv) was 79% greater than the local (3.07 mSv) and 100% greater than the national DRL (1.42 mSv).ConclusionsAll studies exceed national DRLs. A significant optimisation potential is noted, in particular, for studies involving the head and cervical spine. A further review of study protocols is necessary to facilitate optimisation of total study radiation dose.

This review aims to examine the challenges facing radiologists interpreting trauma computed tomography (CT) images in this era of a changing approach to management of solid organ trauma. After reviewing the pearls and pitfalls of CT imaging protocols for detection of traumatic solid organ injuries, we describe the key changes in the 2018 American Association for the Surgery of Trauma Organ Injury Scales for liver, spleen, and kidney and their implications for management strategies. We then focus on the important imaging findings in observed in patients who undergo nonoperative management and patients who are imaged post damage control surgery.

BACKGROUND Neoadjuvant chemo-radiotherapy is utilized for locally advanced rectal cancer to optimize local control. A subset of patients form mucin pools following radiotherapy but the association between mucin pools and pathological and oncological outcomes following curative proctectomy for rectal cancer remains unknown. OBJECTIVE The aim of this study was to determine the significance of mucin pool formation after neoadjuvant chemoradiotherapy for rectal cancer. METHODS This is a retrospective analysis of a prospectively maintained rectal cancer database. Patients who underwent curative proctectomy for rectal cancer following long course chemoradiotherapy between January 2007 and December 2016 were eligible for inclusion. RESULTS A total of 297 patients were eligible for inclusion; of these 36 (12.1%) had mucin pools on final histopathology. Tumors with mucin pools were less likely to be ypT3/T4 (25.0 vs 51.0%, P = 0.003), were more likely to have a good response (83.3 vs 53.6%, P