The requiem reinvented: Brahms‘s Ein deutsches Requiem and the transformation from literal to symbolic.

Johannes Brahms was the first composer to claim the requiem genre without utilizing the Catholic Missa pro defunctis text. Brahms compiled passages from Luther‘s Bible for his 1868 Ein deutsches Requiem, texts that focused on comfort for the living rather than judgment and pleas for mercy on behalf of the deceased. The absence of the traditional text and the change in message created a discrepancy between the genre named in the title and the language and content of the text, and engendered debate concerning the work‘s genre classification. This unresolved debate affects understanding about the development of the genre after 1868. This study applied semiotic theory to the question of genre classification for Ein deutsches Requiem. Marcel Danesi‘s The Quest for Meaning: A Guide to Semiotic Theory and Practice (2007) outlined a method for organizing information relevant to encoded meaning in signifiers such as signs, symbols, and icons. This theory was applied to Ein deutsches Requiem in order to uncover and document encoded meaning behind the word "requiem" in Brahms‘s title. Robert Chase‘s Dies Irae: A Guide to Requiem Music (2003) and Memento Mori: A Guide to Contemporary Memorial Music (2007) provided data from the earliest requiem manuscripts to twenty-first century requiems. Analysis of these data resulted in clearly defined systems of convention related to the genre over time. Identification of the specific practices of requiem composers by era was foundational for an accurate description of the genre both before and after Ein deutsches Requiem. This semiotic study examined "requiem" as a literal term and as a signifier, and defined its moment of signification as it relates to the musical genre. Consideration of historical, comparative, and cultural contexts described how communication through "requiem" as a symbol was achieved. Further analysis outlined the impact of this symbolic requiem on the genre after 1868. The question of genre classification was resolved, enabling a new understanding of the evolution of the requiem genre

High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines.

Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control. Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo

Changes in health-related behaviours and mental health in a UK public sample during the first set of COVID-19 public health restrictions

Public health restrictions, in response to the COVID-19 pandemic, have had potentially wide-ranging, unintended effects on health-related behaviours such as diet and physical activity and also affected mental health due to reduced social interactions. This study explored how health-related behaviours and mental health were impacted in a sample of the UK public during the COVID-19 pandemic. Two online surveys were administered in the UK, one within the first three months of the restrictions (Timepoints 1 (involving pre-pandemic recall) and 2) and another ten weeks later (Timepoint 3). Moderate-vigorous physical activity (MVPA), sitting time, screen time and sexual activity were self-reported. Diet was assessed using the Dietary Instrument for Nutri-tion Education questionnaire. Mental health was measured using the short-form Warwick-Edinburgh Mental Well-being Scale and Becks’ Anxiety and Depression Inventories. Differences between timepoints were explored using the Friedman, Wilcoxon signed-rank, McNemar and McNemar-Bowker tests. 296 adults (74% under 65 years old; 65% female) provided data across all timepoints. Between T1 and T2, MVPA, time outdoors and sexual activity decreased while sitting and screen time increased (p<0.05). Between T2 and T3, saturated fat intake, MVPA, time out-doors, and mental wellbeing increased while sitting, screen time and anxiety symptoms decreased (p<0.05). This study found that depending on the level of COVID-19 public health restrictions in place, there appeared to be a varying impact on different health-related behaviours and mental health. As countries emerge from restrictions, it will be prudent to direct necessary resources to address these important public health issues

Does the mind map learning strategy facilitate information retrieval and critical thinking in medical students?

<p>Abstract</p> <p>Background</p> <p>A learning strategy underutilized in medical education is mind mapping. Mind maps are multi-sensory tools that may help medical students organize, integrate, and retain information. Recent work suggests that using mind mapping as a note-taking strategy facilitates critical thinking. The purpose of this study was to investigate whether a relationship existed between mind mapping and critical thinking, as measured by the Health Sciences Reasoning Test (HSRT), and whether a relationship existed between mind mapping and recall of domain-based information.</p> <p>Methods</p> <p>In this quasi-experimental study, 131 first-year medical students were randomly assigned to a standard note-taking (SNT) group or mind map (MM) group during orientation. Subjects were given a demographic survey and pre-HSRT. They were then given an unfamiliar text passage, a pre-quiz based upon the passage, and a 30-minute break, during which time subjects in the MM group were given a presentation on mind mapping. After the break, subjects were given the same passage and wrote notes based on their group (SNT or MM) assignment. A post-quiz based upon the passage was administered, followed by a post-HSRT. Differences in mean pre- and post-quiz scores between groups were analyzed using independent samples <it>t</it>-tests, whereas differences in mean pre- and post-HSRT total scores and subscores between groups were analyzed using ANOVA. Mind map depth was assessed using the Mind Map Assessment Rubric (MMAR).</p> <p>Results</p> <p>There were no significant differences in mean scores on both the pre- and post-quizzes between note-taking groups. And, no significant differences were found between pre- and post-HSRT mean total scores and subscores.</p> <p>Conclusions</p> <p>Although mind mapping was not found to increase short-term recall of domain-based information or critical thinking compared to SNT, a brief introduction to mind mapping allowed novice MM subjects to perform similarly to SNT subjects. This demonstrates that medical students using mind maps can successfully retrieve information in the short term, and does not put them at a disadvantage compared to SNT students. Future studies should explore longitudinal effects of mind-map proficiency training on both short- and long-term information retrieval and critical thinking.</p

The role of chemotherapeutic drugs in the evaluation of breast tumour response to chemotherapy using serial FDG-PET

INTRODUCTION: The aims of this study were to investigate whether drug sequence (docetaxel followed by anthracyclines or the drugs in reverse order) affects changes in the maximal standard uptake volume (SUVmax) on [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) during neoadjuvant chemotherapy in women with locally advanced breast cancer. METHODS: Women were randomly assigned to receive either drug sequence, and FDG-PET scans were taken at baseline, after four cycles and after eight cycles of chemotherapy. Tumour response to chemotherapy was evaluated based on histology from a surgical specimen collected upon completion of chemotherapy. RESULTS: Sixty women were enrolled into the study. Thirty-one received docetaxel followed by anthracyclines (Arm A) and 29 received drugs in the reverse order (Arm B). Most women (83%) had ductal carcinoma and 10 women (17%) had lobular or lobular/ductal carcinoma. All but one tumour were downstaged during therapy. Overall, there was no significant difference in response between the two drug regimens. However, women in Arm B who achieved complete pathological response had mean FDG-PET SUVmax reduction of 87.7% after four cycles, in contrast to those who had no or minor pathological response. These women recorded mean SUVmax reductions of only 27% (P < 0.01). Women in Arm A showed no significant difference in SUVmax response according to pathological response. Sensitivity, specificity, accuracy and positive and negative predictive values were highest in women in Arm B. CONCLUSIONS: Our results show that SUVmax uptake by breast tumours during chemotherapy can be dependent on the drugs used. Care must be taken when interpreting FDG-PET in settings where patients receive varied drug protocols

Early metabolic response using FDG PET/CT and molecular phenotypes of breast cancer treated with neoadjuvant chemotherapy

Background: This study was aimed 1) to investigate the predictive value of FDG PET/CT (fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography) for histopathologic response and 2) to explore the results of FDG PET/CT by molecular phenotypes of breast cancer patients who received neoadjuvant chemotherapy. Methods: Seventy-eight stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. FDG PET/CTs were acquired before chemotherapy and after the first cycle of chemotherapy for evaluating early metabolic response. Results: The mean pre- and post-chemotherapy standard uptake value (SUV) were 7.5 and 3.9, respectively. The early metabolic response provided by FDG PET/CT after one cycle of neoadjuvant chemotherapy was correlated with the histopathologic response after completion of neoadjuvant chemotherapy (P = 0.002). Sensitivity and negative predictive value were 85.7% and 95.1%, respectively. The estrogen receptor negative phenotype had a higher pre-chemotherapy SUV (8.6 vs. 6.4, P = 0.047) and percent change in SUV (48% vs. 30%, P = 0.038). In triple negative breast cancer (TNBC), the pre-chemotherapy SUV was higher than in non-TNBC (9.8 vs. 6.4, P = 0.008). Conclusions: The early metabolic response using FDG PET/CT could have a predictive value for the assessment of histopathologic non-response of stage II/III breast cancer treated with neoadjuvant chemotherapy. Our findings suggest that the initial SUV and the decline in SUV differed based on the molecular phenotype

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

A Phenotypic Mouse Model of Basaloid Breast Tumors

Chemotherapeutic strategies that target basal-like breast tumors are difficult to design without understanding their cellular and molecular basis. Here, we induce tumors in mice by carcinogen administration, creating a phenocopy of tumors with the diagnostic and functional aspects of human triple negative disease (including EGFR expression/lack of erbB, estrogen-independent growth and co-clustering of the transcriptome with other basaloid models). These tumor strains are a complement to established mouse models that are based on mutations in Brca1 and/or p53. Tumors comprise two distinct cell subpopulations, basal and luminal epithelial cells. These cell fractions were purified by flow cytometry, and only basal cell fractions found to have tumor initiating activity (cancer stem cells). The phenotype of serially regenerated tumors was stable, and irrespective of tumor precursor cell. Tumors were passaged entirely in vivo and serial generations tested for their phenotypic stability. The relative chemo-sensitivity of basal and luminal cells were evaluated. Upon treatment with anthracycline, tumors were effectively de-bulked, but recurred; this correlated with maintenance of a high rate of basal cell division throughout the treatment period. Thus, these tumors grow as robust cell mixtures of basal bipotential tumor initiating cells alongside a luminal majority, and the cellular response to drug administration is dominated by the distinct biology of the two cell types. Given the ability to separate basal and luminal cells, and the discovery potential of this approach, we propose that this mouse model could be a convenient one for preclinical studies

Protocol for a randomised controlled trial of risk screening and early intervention comparing child- and family-focused cognitive-behavioural therapy for PTSD in children following accidental injury

Background: Accidental injury represents the most common type of traumatic event to which a child or adolescent may be exposed, with a significant number of these children going on to experience posttraumatic stress disorder (PTSD). However, very little research has examined potential interventions for the treatment of PTSD in these children. The present trial aims to evaluate and compare child- and family-focused versions of a cognitive-behavioural early intervention for PTSD following accidental injury.Methods/Design: The principal clinical question under investigation is the efficacy of an early, trauma-focused cognitive-behavioural intervention for the treatment of PTSD in children following accidental injury. Specifically, we compare the efficacy of two active treatments (child-focused and family-focused CBT) and a waitlist control (no therapy) to determine which is associated with greater reductions in psychological and health-related outcome measures over time. The primary outcome will be a reduction in trauma symptoms on a diagnostic interview in the active treatments compared to the waitlist control and greater reductions in the family-compared to the child-focused condition. In doing so, this project will also trial a method of stepped screening and assessment to determine those children requiring early intervention for PTSD following accidental injury.Discussion: The present trial will be one of the first controlled trials to examine a trauma-focused CBT, early intervention for children experiencing PTSD following accidental injury (as opposed to other types of traumatic events) and the first within a stepped care approach. In addition, it will provide the first evidence comparing the efficacy of child and family-focused interventions for this target group. Given the significant number of children and adolescents exposed to accidental injury, the successful implementation of this protocol has considerable implications. If efficacious, this early intervention will assist in reducing symptoms of traumatic stress as well as preventing chronic disorder and disability in children experiencing acute PTSD following accidental injury