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This study aimed to highlight the key studies that have led to the current understanding and treatment of head and neck cancer.
The Thomson Reuters Web of Science database was used to identify relevant manuscripts. The results were ranked according to the number of citations. The 100 most cited papers were analysed.
A total of 63 538 eligible papers were returned. The median number of citations was 626. The most cited paper compared radiotherapy with and without cetuximab (3205 citations). The New England Journal of Medicine had the most citations (23 514), and the USA had the greatest number of publications (n = 66). The most common topics of publication were the treatment (n = 45) and basic science (n = 19) of head and neck cancer, followed by the role of human papillomavirus (n = 16).
This analysis highlighted key articles that influenced head and neck cancer research and treatment. It serves as a guide as to what makes a ‘citable’ paper in this field.
We undertook a quality improvement project to address challenges with pulmonary artery catheter (PAC) line maintenance in a setting of low-baseline central-line infection rates. We observed a subsequent reduction in Staphylococcal PAC line infections and a trend toward a reduction in overall PAC infection rates over 1 year.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Agents that block the renin–angiotensin system (RAS) improve glucoregulation in the metabolic syndrome disorder. We evaluated the effects of egg white hydrolysate (EWH), previously shown to modulate the protein abundance of RAS component in vivo, on glucose homeostasis in diet-induced insulin-resistant rats. Sprague–Dawley rats were fed a high-fat diet (HFD) for 6 weeks to induce insulin resistance. They were then randomly divided into four groups receiving HFD or HFD supplemented with different concentrations of EWH (1, 2 and 4 %) for another 6 weeks in the first trial. In the second trial, insulin-resistant rats were divided into two groups receiving only HFD or HFD+4 % EWH for 6 weeks. Glucose homeostasis was assessed by oral glucose tolerance and insulin tolerance tests. Insulin signalling and protein abundance of RAS components, gluconeogenesis enzymes and PPARγ were evaluated in muscle, fat and liver. Adipocyte morphology and inflammatory markers were evaluated. In vivo administration of EWH increased insulin sensitivity, improved oral glucose tolerance (P < 0·0001) and reduced systemic inflammation (P < 0·05). EWH potentiated insulin-induced Akt phosphorylation in muscle (P = 0·0341) and adipose tissue (P = 0·0276), but minimal differences in the protein abundance of tissue RAS components between the EWH and control groups were observed. EWH treatment also reduced adipocyte size (P = 0·0383) and increased PPARγ2 protein abundance (P = 0·0237). EWH treatment yielded positive effects on the inflammatory profile, glucose tolerance, insulin sensitivity and adipocyte differentiation in HFD-induced insulin resistance rats. The involvement of local RAS activity requires further investigation.
We present Phantom, a fast, parallel, modular, and low-memory smoothed particle hydrodynamics and magnetohydrodynamics code developed over the last decade for astrophysical applications in three dimensions. The code has been developed with a focus on stellar, galactic, planetary, and high energy astrophysics, and has already been used widely for studies of accretion discs and turbulence, from the birth of planets to how black holes accrete. Here we describe and test the core algorithms as well as modules for magnetohydrodynamics, self-gravity, sink particles, dust–gas mixtures, H2 chemistry, physical viscosity, external forces including numerous galactic potentials, Lense–Thirring precession, Poynting–Robertson drag, and stochastic turbulent driving. Phantom is hereby made publicly available.
TiO2 nanomaterials with platelet or nanosheet morphologies can offer improved properties for photocatalytic applications, but established methods to produce them typically require structure-directing agents since anatase-phase TiO2 does not have a layered structure. In the present work, the preparation of TiO2 nanosheets by the chemical oxidation of TiS2 nanosheets is demonstrated. Electrochemical exfoliation of bulk TiS2 into TiS2 nanosheets, followed by the hydrothermal treatment at 180 °C for 14 h is performed. The results show that polycrystalline TiO2 nanosheets with the anatase structure are formed, and that the nanosheet morphology can still be maintained after the hydrothermal treatment. The TiO2 nanosheets show good photocatalytic activity for the degradation of methylene blue, but the performance is negatively affected by the residual carbon black that was needed in the TiS2 electrode to enable electrochemical exfoliation. These results show that conversion of TiS2 nanosheets to TiO2 nanosheets is a promising synthetic strategy but highlights how the interfacial properties of the obtained materials could be affected by ancillary components in the preparation method.
CIC, or Capicua, encodes a transcriptional repressor that is itself repressed by RAS/MAPK signalling. CIC is a recurrent target of somatic mutation in type 1 low grade gliomas (LGG), with at least half of the alterations predicted to be deleterious. Type 1 LGGs are a cohort of tumours that are molecularly defined by the loss of heterozygosity of chromosome arms 1p and 19q and the presence of neomorphic IDH1/2 mutations. Despite the high frequency of mutations in CIC within this tumour type, CIC’s putative tumour suppressive role remains to be elucidated. It is also unclear how CIC may cooperate with neomorphic IDH1/2 to promote gliomagenesis. To comprehensively characterize the molecular consequences of CIC loss, we performed RNA-seq, Whole Genome Bisulfite Sequencing, and ChIP-seq on 6 different histone modifications on isogenic CIC-wildtype (WT) and CIC-knockout (KO) normal human astrocytes. To also investigate the collective effects of CIC deficiency and neomorphic IDH1 on the transcriptome and epigenome, we generated the same dataset in isogenic CIC-WT and CIC-KO astrocytes possessing the IDH1 R132H mutation. Analysis of differentially expressed genes illustrates the enrichment of oncogenic pathways in specifically the CIC-KO, IDH1-R132H cells, supporting a synergistic relationship between CIC loss and IDH1-R132H in driving tumour progression. Integrative analyses are ongoing to unveil the epigenetic mechanisms underpinning the regulatory changes in these isogenic cell line models.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Introduction: The management of patient flow in the emergency department (ED) is crucial for the practice of emergency medicine (EM). However, this skill is difficult to teach didactically and is learned implicitly in the latter half of residency training. To help expedite the learning process, we developed the GridlockED board game as an educational tool to simulate ED patient flow. By having junior medical trainees play this game, we believe that they will develop a greater understanding of patient flow and resource management in the ED. Additionally, since GridlockED is a cooperative game, players may also benefit by improving their communication and teamwork skills. Methods: GridlockED was developed over twenty months of iterative gameplay and review. Feedback from attending emergency physicians, residents, and medical students was integrated into the game through a Plan-Do-Study-Act (PDSA) model. Emergency medicine nurses, physicians and residents at McMaster University were recruited to play GridlockED. Each player completed a pre-survey to collect demographic data and to assess their prior experience with playing board games. All play sessions were recorded for data collection purposes. Following each game session, a member of the research team conducted an exit interview with the players to gather information about their play experience and the educational value of the game. A post-survey was also sent to each participant for further feedback. Results: Eighteen gameplay sessions were conducted from June to August 2017. A total of thirty-two participants played the game (13 emergency physicians, 15 residents, and four nurses). Overall responses to the post-gameplay survey showed that players endorsed GridlockED as a useful potential teaching tool (75%, n=24/32) and the majority felt that it had the potential to improve patient flow in the ED (56%, n=18/32). Most participants found that the game was easy to play (91%, n=27/29), and that the instructions were clear (87.5%, n=28/32). Respondents also felt that the game reflected real life scenarios (56%, n=18) and that cases reflected the types of patients that they saw in the ED (78%, n=25). Conclusion: Our results have shown an overall positive response to GridlockED, with most participants supporting it as both an engaging board game and potential teaching tool. We believe that future studies with larger sample sizes and medical students will further validate the use of serious games in medical education.
Introduction: Competency-based workplace assessments are important in clinical training. However, feedback and assessment are still often perceived as unsatisfactory, particularly in busy settings such as emergency departments. Currently, little is known about how attending staff physicians sense of self may interface with the processes they use to assess and give feedback to trainees. We aimed to understand how attendings perceive their roles when tasked with conducting assessments and providing feedback to trainees. Methods: We conducted semi-structured, individual interviews with attendings (n=16) who used McMAP (McMaster Modular Assessment Program), a workplace-based assessment system at McMaster Universitys Royal College Emergency Medicine program. Attendings were recruited using snowball sampling. Data were interpreted using thematic analysis, sensitized to the dramaturgical lens and rater cognition frameworks. Results: Attendings identified themselves using three distinct but intimately connected roles when assessing trainee performance: the doctor that ensures the safety and well-being of patients; the coach (educator) that empowers, guides, and supports the next generation of medical doctors; and the assessor that formally assesses a trainees progression through the residency program. These roles are influenced by clinical training and experience, teaching experience and context. Conclusion: The ways in which attendings assess and provide feedback to trainees involve a complex and dynamic process that is influenced by their perceived roles as a doctor, coach, and assessor. Understanding the way attendings view and juggle their roles may provide insight into potentially new approaches to assessment and feedback. Results and implications will be discussed.
Introduction: Emergency medicine clinicians (physicians, nurses, paramedics, physician assistants) utilize podcasts for learning. However, their versatility produces variability in the ways they are used (e.g. their speed can be increased or decreased, unrelated activities can be performed simultaneously, or they can be accompanied by active learning methods). This study investigated how and why podcasts are used by an international cohort of clinicians. Methods: An international sample of medical students, residents, physicians, nurses, physician assistants, and paramedics was recruited to complete a survey hosted on FluidSurveys software using social media (Twitter and Facebook), direct contact from our international authorship group, infographics, and a study website (https://METRIQstudy.org/). Participants who indicated interest in the study were sent an email containing the study survey. Reminder emails were sent every 5-10 days a maximum of three times. Results: 462 clinicians expressed interest and 397 completed the survey (86.0% completion rate). Participants hailed from 34 countries (38.8% Canada, 30% United States, 31.2% outside of North America) and a majority (61.9%) were physicians. Approximately half (45.8%) of the participants listened to podcasts weekly. Podcasts were used to learn core material (75.1%), refresh memory (72.3%), or review new literature (75.8%). Most listened on iPhones (61%) and the native Apple App (66.1%). The preferred Android apps were Pocket Casts (22.8%) and Google Play (18.5%). Many listened to podcasts while driving (72.3%). Active learning techniques such as pausing, repeating segments, taking notes, or listening to a podcast more than once were rarely used (1/4 of the time or less) by the majority of participants. Conclusion: This study describes how and why medical education podcasts are used by emergency medicine clinicians and should inform both podcast producers and future research investigating the impact of various listening habits on retention. Further analysis of the data will elucidate differences in listening habits
To describe the transmission dynamics of the emergence and persistence of vanA vancomycin-resistant enterococcus (VRE) in an intensive care unit (ICU) using whole-genome sequencing of patient and environmental isolates.
Retrospective cohort study.
ICU in a tertiary referral center.
Patients admitted to the ICU over an 11-month period.
VanA VRE isolated from patients (n=31) were sequenced using the Illumina MiSeq platform. Environmental samples from bed spaces, equipment, and waste rooms were collected. All vanA VRE-positive environmental samples (n=14) were also sequenced. Data were collected regarding patient ward and bed movements.
The 31 patient vanA VRE isolates were from screening (n=19), urine (n=4), bloodstream (n=3), skin/wound (n=3), and intra-abdominal (n=2) sources. The phylogeny from sequencing data confirmed several VRE clusters, with 1 group accounting for 38 of 45 isolates (84%). Within this cluster, cross-transmission was extensive and complex across the ICU. Directionality indicated that colonized patients contaminated environmental sites. Similarly, environmental sources not only led to patient colonization but also to infection. Notably, shared equipment acted as a conduit for transmission between different ICU areas. Infected patients, however, were not linked to further VRE transmission.
Genomic sequencing confirmed a predominantly clonal outbreak of VRE with complex transmission dynamics. The environmental reservoir, particularly from shared equipment, played a key role in ongoing VRE spread. This study provides evidence to support the use of multifaceted strategies, with an emphasis on measures to reduce bacterial burden in the environment, for successful VRE control.
In Hong Kong, universal varicella vaccination started in July 2014. Before this, children could receive varicella vaccine via the private market. We analysed the epidemiology of varicella and zoster before universal vaccination. We estimated varicella vaccination coverage through surveys in preschool children. We estimated the burden of varicella and zoster with varicella notifications from 1999/00 to 2013/14, Accident and Emergency Department (A&E) attendance and inpatient admissions to public hospitals from 2004/05 to 2013/14. We fitted a catalytic model to serological data on antibodies against varicella-zoster virus to estimate the force of infection. We found that varicella vaccination coverage gradually increased to about 50% before programme inception. In children younger than 5 years, the annual rate of varicella notifications, varicella admission and zoster A&E attendance generally declined. The annual notification, A&E attendance and hospitalisation rate of varicella and zoster generally increased for individuals between 10 and 59 years old. Varicella serology indicated an age shift during the study period towards a higher proportion of infections in slightly older individuals, but the change was most notable before vaccine licensure. In conclusion, we observed a shift in the burden of varicella to slightly older age groups with a corresponding increase in incidence but it cannot necessarily be attributed to private market vaccine coverage alone. Increasing varicella vaccination uptake in the private market might affect varicella transmission and epidemiology, but not to the level of interrupting transmission.
Polygenic risk scores (PRS) for depression correlate with depression status and chronicity, and provide causal anchors to identify depressive mechanisms. Neuroticism is phenotypically and genetically positively associated with depression, whereas psychological resilience demonstrates negative phenotypic associations. Whether increased neuroticism and reduced resilience are downstream mediators of genetic risk for depression, and whether they contribute independently to risk remains unknown.
Moderating and mediating relationships between depression PRS, neuroticism, resilience and both clinical and self-reported depression were examined in a large, population-based cohort, Generation Scotland: Scottish Family Health Study (N = 4166), using linear regression and structural equation modelling. Neuroticism and resilience were measured by the Eysenck Personality Scale Short Form Revised and the Brief Resilience Scale, respectively.
PRS for depression was associated with increased likelihood of self-reported and clinical depression. No interaction was found between PRS and neuroticism, or between PRS and resilience. Neuroticism was associated with increased likelihood of self-reported and clinical depression, whereas resilience was associated with reduced risk. Structural equation modelling suggested the association between PRS and self-reported and clinical depression was mediated by neuroticism (43–57%), while resilience mediated the association in the opposite direction (37–40%). For both self-reported and clinical diagnoses, the genetic risk for depression was independently mediated by neuroticism and resilience.
Findings suggest polygenic risk for depression increases vulnerability for self-reported and clinical depression through independent effects on increased neuroticism and reduced psychological resilience. In addition, two partially independent mechanisms – neuroticism and resilience – may form part of the pathway of vulnerability to depression.
Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free). Cancer and TNFi exposure were time-dependent, and independent risk factors of mycobacterial diseases were assessed by Cox regression. Among 1344 RA patients diagnosed during 2000–2013, 68 (5·1%) developed cancer before their end points. The incidence rates of mycobacterial diseases in the cancer-positive (n = 56), TNFi-exposure (n = 290), cancer-TNFi-comb (n = 12), and cancer-TNFi-free (n = 986) subgroups were 6·7, 2·0, 7·6, and 1·3 per 1000 person-years, respectively. As compared with the cancer-TNFi-free group, the risk for mycobacterial diseases increased for the TNFi-exposure group (adjusted HR = 3·6, 95% confidence interval (95% CI) 1·1–11·5, P = 0·032) and remained high for cancer-positive (adjusted HR = 14·6, 95% CI 3·3–63·7, P < 0·001) after adjustment. This study suggested that cancer development increased the risk of mycobacterial diseases in RA patients, and risk assessment for this subgroup should be considered.
Schizotypal traits are considered a phenotypic-indicator of schizotypy, a latent personality organization reflecting a putative liability for psychosis. To date, no previous study has examined the comparability of factorial structures across samples originating from different countries and cultures. The main goal was to evaluate the factorial structure and reliability of the Schizotypal Personality Questionnaire (SPQ) scores by amalgamating data from studies conducted in 12 countries and across 21 sites.
The overall sample consisted of 27 001 participants (37.5% males, n = 4251 drawn from the general population). The mean age was 22.12 years (s.d. = 6.28, range 16–55 years). The SPQ was used. Confirmatory factor analysis (CFA) and Multilevel CFA (ML-CFA) were used to evaluate the factor structure underlying the SPQ scores.
At the SPQ item level, the nine factor and second-order factor models showed adequate goodness-of-fit. At the SPQ subscale level, three- and four-factor models displayed better goodness-of-fit indices than other CFA models. ML-CFA showed that the intraclass correlation coefficients values were lower than 0.106. The three-factor model showed adequate goodness of fit indices in multilevel analysis. The ordinal α coefficients were high, ranging from 0.73 to 0.94 across individual samples, and from 0.84 to 0.91 for the combined sample.
The results are consistent with the conceptual notion that schizotypal personality is a multifaceted construct and support the validity and utility of SPQ in cross-cultural research. We discuss theoretical and clinical implications of our results for diagnostic systems, psychosis models and cross-national mental health strategies.
A method has been devised and tested for measuring the c-axis orientation of crystal grains in thin sections of glacier ice. The crystal orientation and grain size of ice are of great interest to glaciologists since these parameters contain information on the prior thermal and flow history of the ice. The traditional method of determining c-axis orientation involves a transmission measurement through an ice sample, a process that is time-consuming and therefore impractical for obtaining a continuous record. A reflection- or backscatter-based method could potentially be used inside boreholes, with bubbles as reflectors to avoid such drawbacks. The concept demonstration of this paper is performed on ice slices, enabling a direct comparison of accuracy with traditional methods. Measurements of the crystal orientations (θ, ϕ) in 11 grains showed an average error of ±0.8° in ϕ, with no grain error >1.4°. Measurements of θ showed an average error of ±8.2° on ten grains, with unexplained disagreement on the remaining grain. Although the technique is applied specifically to glacier ice, it should be generally applicable to any transparent birefringent polycrystalline material.
Background: Oligodendroglioma (ODG), a molecularly defined subtype of glioma, is a treatment responsive, slow growing tumour strongly associated with IDH mutation and 1p19q co-deletion. Mutations in Capicua (CIC), located on chromosome 19q, have been found in up to 70% of IDH mutated, 1p19q co-deleted ODGs; suggesting that loss or altered function of CIC may be crucially associated with ODG’s unique biology. CIC and ATXN1L have previously been implicated in neurodegeneration, however, this interaction has not been studied in cancer. Methods: Transcriptome profiling of CIC knockout HEK293 cell lines generated using CRISPR was performed using microarray. CIC and ATXN1L interaction was confirmed using immunoprecipitation and immunofluorescence. Transcript and protein changes of CIC targets were tested using RT-qPCR and Western blot following ATXN1L siRNA knockdown. Results: Transcriptomic profiling of CIC knockout cell lines resulted in a list of candidate CIC target genes validated against clinical samples. Immunoprecipitation and immunofluorescence confirmed CIC and ATXN1L interaction. Derepression of candidate CIC targets at transcript and protein levels was seen upon siRNA knockdown of ATXN1L. Conclusions: The interaction between CIC and ATXN1L is necessary for the repression of CIC target genes, including known oncogenes. Further research into the relationship between CIC and ATXN1L may lead potentially novel avenues of therapeutic approaches for less favorable gliomas.