Erratum to: Single cell analysis of CD4+ T cell differentiation reveals three major cell states and progressive acceleration of proliferation.

Background: Differentiation of lymphocytes is frequently accompanied by cell cycle changes, interplay that is of central importance for immunity but is still incompletely understood. Here, we interrogate and quantitatively model how proliferation is linked to differentiation in CD4+ T cells. Results: We perform ex vivo single-cell RNA-sequencing of CD4+ T cells during a mouse model of infection that elicits a type 2 immune response and infer that the differentiated, cytokine-producing cells cycle faster than early activated precursor cells. To dissect this phenomenon quantitatively, we determine expression profiles across consecutive generations of differentiated and undifferentiated cells during Th2 polarization in vitro. We predict three discrete cell states, which we verify by single-cell quantitative PCR. Based on these three states, we extract rates of death, division and differentiation with a branching state Markov model to describe the cell population dynamics. From this multi-scale modelling, we infer a significant acceleration in proliferation from the intermediate activated cell state to the mature cytokine-secreting effector state. We confirm this acceleration both by live imaging of single Th2 cells and in an ex vivo Th1 malaria model by single-cell RNA-sequencing. Conclusion: The link between cytokine secretion and proliferation rate holds both in Th1 and Th2 cells in vivo and in vitro, indicating that this is likely a general phenomenon in adaptive immunity

Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China

<div><p>Background</p><p>Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system.</p><p>Methods</p><p>Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed.</p><p>Results</p><p>Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and$13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to$-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy.</p><p>Conclusions</p><p>The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.</p></div

Parameters of Weibull models fitted to the Kaplan-Merier survival curve in the trial.

<p>Parameters of Weibull models fitted to the Kaplan-Merier survival curve in the trial.</p

The median survival time of icotinib and gefitinib as second-line therapy for advanced NSCLC patients.

<p>(month).</p

Incremental cost-effective ratio (ICUR) tornado diagram.

<p>Incremental cost-effective ratio (ICUR) tornado diagram.</p

Markov decision tree model structure of icotinib and gefitinib strategies for the treatment of advanced NSCLC.

<p>Markov decision tree model structure of icotinib and gefitinib strategies for the treatment of advanced NSCLC.</p

Baseline costs, risks and utility values of icotinib and gefitinib in advanced NSCLC patients in China.

<p>Data are in 2014 US dollars.</p

Prevalence and factors associated with occupational burnout among HIV/AIDS healthcare workers in China: a cross-sectional study

Abstract Background Burnout is a psychosomatic syndrome characterized by three dimensions (emotional exhaustion [EE], feelings of depersonalization [DP], and reduced personal accomplishment [PA]). We determined the prevalence of burnout and mental health status between HIV/AIDS healthcare workers and other healthcare workers, and determined the factors associated with burnout of HIV/AIDS healthcare workers. Methods All participants were asked to complete a self-administered questionnaire. The participants were recruited from the departments of infectious diseases in four hospitals which treated HIV/AIDS. The questionnaire included demographics, the Maslach Burnout Inventory-General Survey (MBI-GS), the Symptom Checklist 90 (SCL-90), the Eysenck Personality Questionnaire (EPQ), and the Trait Coping Style Questionnaire (TCSQ). Results A total of 512 questionnaires were distributed; 501 questionnaires were completed and collected (the response rate was 97.9 %). After eliminating nine invalid questionnaires (1.80 %), 264 physicians and nurses caring for HIV/AIDS and 228 physicians and nurses caring for other infectious diseases provided valid responses (98.2 %). The HIV/AIDS healthcare workers’ scores on the emotional exhaustion (F = 6.350, p = 0.012) and depersonalization dimensions (F = 8.533, p = 0.004) were significantly higher than other healthcare workers. The HIV/AIDS healthcare workers had higher total scores and positive items on the Symptom Checklist 90 (SCL-90) compared with other healthcare workers. Low job satisfaction, serious somatization, interpersonal sensitivity, poor quality of sleep, high psychoticism scores, and use of negative coping styles were frequently associated with burnout. Conclusions Burnout was shown to be highly prevalent in HIV/AIDS healthcare workers, 76.9 % of whom met the accepted criteria for burnout. In addition, compared with other healthcare workers, HIV/AIDS healthcare workers experienced lower levels of psychological health. Interventions should be targeted at reducing the occurrence of burnout and alleviating psychological pressure amongst HIV/AIDS healthcare workers

A plague on both your houses

Book synopsis: Given the centrality of sexuality to theories of psychoanalysis, it is striking how little it is actually taught in institutes. This unique and creatively organized book seeks to remedy this lack, by creating a layered dialogue between academics writing queer and sexuality theories, practicing clinicians, and psychoanalytic theorists. The chapters pull the reader into an exciting liminal space where cultural, societal, and clinical discourses intermingle, creating embodied experiences of gender, sexualities, and sex. As editors, Giffney and Watson curate an encounter between queer theorists, clinicians and psychoanalytic theorists. But the experience of the encounter includes the reader, who has the invaluable opportunity to be a fly on the wall as these cross-disciplininary conversations unfold chapter by chapter. Reading this book is not a passive experience but one requiring active participation in an examination of the ways cultural discourses of sexuality shape transferences and clinical engagement. Most exciting was the historical register, where established theorists glance back to their own individual romances with psychoanalysis, sharing their initial hopes for the radical potentials of clinical theory and practice to transform our experiences. This radical potential of psychoanalysis is rekindled through the layered dialogues and passionate encounters captured in Clinical Encounters in Sexuality