EEG alpha and theta signatures of socially and non-socially cued working memory in virtual reality

In this preregistered study (https://osf.io/s4rm9) we investigated the behavioural and neurological [electroencephalography; alpha (attention) and theta (effort)] effects of dynamic non-predictive social and non-social cues on working memory. In a virtual environment realistic human-avatars dynamically looked to the left or right side of a table. A moving stick served as a non-social control cue. Kitchen items were presented in the valid cued or invalid un-cued location for encoding. Behavioural findings showed a similar influence of the cues on working memory performance. Alpha power changes were equivalent for the cues during cueing and encoding, reflecting similar attentional processing. However, theta power changes revealed different patterns for the cues. Theta power increased more strongly for the non-social cue compared to the social cue during initial cueing. Furthermore, while for the non-social cue there was a significantly larger increase in theta power for valid compared to invalid conditions during encoding, this was reversed for the social cue, with a significantly larger increase in theta power for the invalid compared to valid conditions, indicating differences in the cues’ effects on cognitive effort. Therefore, while social and non-social attention cues impact working memory performance in a similar fashion, the underlying neural mechanisms appear to differ.     

基于无尺度网络法的4 116 张胃癌中医处方研究

本研究借助临床科研信息共享系统,使用无尺度网络挖掘方法,分析了江苏省中医院门诊994 例胃癌患者中医治疗的4 116 张处方,以图示化直观展示了核心药物及配伍,揭示出该院胃癌的中医治疗处方用药特点。该方法具有较高的可信度,对于中医处方的研究具有一定的意义和价值。     

Mental health,financial, and social outcomes among older adults with probable COVID-19 infection: A longitudinal cohort study

We investigated the immediate and longer-term impact (over 4-6 months) of probable COVID-19 infection on mental health, wellbeing, financial hardship, and social interactions among older people living in England. Data were analysed from 5146 older adults participating in the English Longitudinal Study of Ageing who provided data before the pandemic (2018-19) and at two COVID-19 assessments in 2020 (June-July and November-December). The associations of probable COVID-19 infection (first COVID-19 assessment) with depression, anxiety, poor quality of life (QoL), loneliness, financial hardship, and social contact with family/friends at the first and second COVID-19 assessments were tested using linear/logistic regression and were adjusted for pre-pandemic outcome measures. Participants with probable infection had higher levels of depression and anxiety, poorer QoL, and greater loneliness scores compared with those without probable infection at both the first (OR_depression = 1.62, P-value = 0.005; OR_anxiety = 1.59, P-value = 0.049; b_poorQoL = 1.34, P < 0.001; b_loneliness = 0.49, P < 0.001) and second (OR_depression = 1.56, P-value = 0.003; OR_anxiety = 1.55, P-value = 0.041; b_poorQoL = 1.38, P-value < 0.001; b_loneliness = 0.31, P-value = 0.024) COVID-19 assessments. Participants with probable infection also experienced greater financial difficulties than those without infection at the first assessment (OR = 1.50, P-value = 0.011). Probable COVID-19 infection is associated with longer-term deterioration of mental health and wellbeing and short-term increases in financial hardship among older adults. It is important to monitor the mental health of older people affected by COVID-19 and provide additional support to those in need.

The coronavirus disease 2019 (COVID-19) pandemic has affected several aspects of people’s lives, including physical and mental health, employment and financial security, social connections, and access to healthcare (1). Despite a large body of research documenting the adverse psychosocial effects of the pandemic and its containment measures across the population, little is currently known regarding the impact that contracting COVID-19 itself may have on the individual’s mental health, personal finances, and social relationships.Several longitudinal studies have reported increases in depression, anxiety, and general psychological distress in the adult population during the COVID-19 pandemic compared with prepandemic levels (2, 3). People who have contracted COVID-19 might be particularly vulnerable to the psychological impact of the pandemic. Indeed, initial evidence suggests that the experience of COVID-19 symptoms is associated not only with adverse physical consequences, but also with long-term effects on mental health (4, 5). Various mechanisms could underlie the psychological effects of COVID-19 infection, including the potential neurotropic properties of the virus (6, 7); the presence of elevated proinflammatory cytokines (e.g., interleukin-6) in patients with severe COVID-19 symptoms (8), which are implicated in the development of psychiatric disorders such as depression (9); and the exposure to prolonged periods of social isolation and physical inactivity in people affected by COVID-19 (10), which in turn can increase mental distress and feelings of loneliness. Compounded by the widespread psychosocial effects of the pandemic across the population, these factors might further exacerbate the risk of mental health problems among individuals recovering from COVID-19 infection.Data from previous coronavirus epidemics demonstrate the potential psychiatric consequences of the virus in both the acute and postacute phases of the illness (11). Further, studies across different countries have found that individuals reporting COVID-19 symptoms and patients recovering from acute COVID-19 illness exhibit increased levels of anxiety, depression, suicidal ideation, loneliness, and poor quality of life (QoL) compared with healthy people (5, 12–19). Studies using data from electronic health records in the United States have also shown that COVID-19 patients with no previous psychiatric history are at increased risk of first-time diagnosis of psychiatric disorders compared with those affected by other health events (e.g., influenza) or healthy controls (20, 21). However, most studies to date are limited by small, nonrepresentative samples and short follow-up periods, and they lack longitudinal data on the participants’ mental health before COVID-19, as well as data on confounding factors. Since individuals with preexisting mental disorders seem particularly susceptible to COVID-19 infection (20, 22), it is unclear the extent to which reverse causality and confounding bias might contribute to the association between COVID-19 infection and psychological distress. In addition, studies involving electronic health records or clinical samples may not capture individuals with moderate COVID-19 symptoms and those with less severe mental health problems who do not present to health services.Longitudinal cohort studies are well suited to study the immediate and longer-term psychosocial consequences of COVID-19 infection in the general population, as they include comprehensive information on mental health before the infection and other confounding factors (e.g., sex, age, socioeconomic position). Results from the United Kingdom suggest that people with probable COVID-19 symptoms experience greater psychological distress up to 7 months following the start of the infection (23). In contrast, an online study in the United States found evidence only for short-term psychological effects that diminish as the symptoms subside (24). Notably, these studies have only focused on general psychological distress; therefore, the impact of COVID-19 infection on specific mental health and wellbeing outcomes (e.g., depression, anxiety, loneliness, and QoL) in the general population is unclear.Numerous studies have also highlighted the financial impact of the pandemic—including job losses, pay cuts, reductions in household income, fluctuations in stock markets and wealth held in risky assets, and widespread financial worries (25–27)—as well as its adverse consequences for various domains of social relationships, including social networks, social support, and social interaction (28, 29). However, these studies relate to the whole population rather than to people with COVID-19 infection. Empirical evidence regarding the impact that COVID-19 infection may have on a person’s financial situation and social relationships is limited. For instance, cross-sectional results suggest that adults who have experienced COVID-19 are more likely to report that their social relationships, work, and household finances have been adversely affected by the pandemic, compared with those who have not had COVID-19 (30). However, this analysis did not account for preexisting trends in social connections and economic outcomes, and it was unable to disentangle short-term versus longer-term psychosocial consequences of the infection.Older adults are at increased risk of social isolation and serious illness following COVID-19 infection (31), and they also are particularly vulnerable to the effects of chronic stress on the brain (32). A recent analysis of data from the English Longitudinal Study of Aging (ELSA) also demonstrates that the mental health and wellbeing of the older population deteriorated significantly as the pandemic progressed in 2020, compared with prepandemic levels (33). Given these factors, older people might be disproportionally affected by the psychosocial effects of COVID-19 infection. However, little research on COVID-19 has involved older adults who are also often unable to access online surveys (34). In addition, care-seeking behaviors changed considerably in the early stages of the pandemic, with large numbers of older adults with care needs not actively contacting health services and not seeking help (35). Therefore, older adults’ experiences of COVID-19 might be underrepresented in earlier studies.In the present analysis, we investigated the immediate and longer-term impact (over 4 to 6 months) of probable COVID-19 infection on mental health (i.e., depression and anxiety), wellbeing (i.e., QoL and loneliness), financial hardship, and social interactions in a large, representative sample of older adults from ELSA. In addition, we assessed whether the psychosocial impact of probable COVID-19 infection might vary across different sociodemographic groups. All outcomes were assessed before the pandemic began (i.e., 2018/2019) and on two occasions during the pandemic, which enabled us to test both short-term and longer-term associations. The data were collected online and by telephone interview to ensure coverage of those without internet access.     

Duties, fears and physicians

This article deals with the physician's fear of contagion using AIDS as a paradigm. It deals with this in four ways: it examines the concepts of duty, fear and courage in their medical setting; it deals with the historical aspects of the problem; it analyzes the role of social contract and professionalism; and it develops a viewpoint of the physician's obligation based on these considerations and predicated on a view of professionalism and social contract.     

Association of social determinants of health with late diagnosis and survival of patients with pancreatic cancer

BackgroundPancreatic cancer disparities have been described. However, it is unknown if they contribute to a late diagnosis and survival of patients with metastatic disease. Identifying their role is important as it will open the door for interventions. We hypothesize that social determinants of health (SDH) such as income, education, race, and insurance status impact (I) stage of diagnosis of PC (Stage IV vs. other stages), and (II) overall survival (OS) in Stage IV patients.MethodsUsing the National Cancer Database, we evaluated a primary outcome of diagnosis of Stage IV PC and a secondary outcome of OS. Primary predictors included race, income, education, and insurance. Covariates included age, sex and Charlson-Deyo comorbidity score. Univariate, multivariable logistic regression models evaluated risk of a late diagnosis. Univariate, multivariable Cox proportional hazards model examined OS. 95% confidence intervals were used.Results230,877 patients were included, median age of 68 years (SD 12.1). In univariate analysis, a better education, higher income, and insurance decreased the odds of Stage IV PC, while Black race increased it. In multivariable analysis, education [>93% high-school completion (HSC) vs. <82.4%, OR 0.96 (0.93–0.99)] and insurance [private vs. no, OR 0.72 (0.67–0.74)] significantly decreased the risk of a late diagnosis, whereas Black race increased the odds [vs. White, OR 1.09 (1.07–1.12)]. In univariate Cox analysis, having a higher income, insurance and better education improved OS, while Black race worsened it. In multivariable Cox, higher income [>$63,333 (vs. <$40,277), HR 0.87 (0.85–0.89)] and insurance [private vs. no, HR 0.77 (0.74–0.79)] improved OS.ConclusionsSDH impacted the continuum of care for patients with advanced pancreatic cancer, including stage at diagnosis and overall survival.     

肺癌免疫治疗中分离反应的研究进展

肺癌是世界上最常见的恶性肿瘤之一,也是全球癌症死亡的主要原因[1]。近年来,随着免疫检查点抑制剂(immune checkpoint inhibitors,ICIs) 的应用、发展与兴起,一小部分晚期非小细胞肺癌(non-small cell lung cancer,NSCLC) 患者可从中获益。随着对ICIs药物应用后治疗效果的观察,与化疗药物及靶向药物可引起的典型反应,包括完全缓解(complete response,CR)、部分缓解(partial response,PR)、疾病稳定(stable disease,SD)、疾病进展(progressive disease,PD)比较,ICIs可引起另一种非典型反应模式,包括超进展、假性进展、分离反应等。与前两种非典型反应模式比较,目前的研究数据对分离反应的研究报道相对较少。本文回顾一些分离反应的研究,探讨其意义并思考其后续治疗方法。     

Experimental evidence of physician social preferences

Physicians’ professional ethics require that they put patients’ interests ahead of their own and that they should allocate limited medical resources efficiently. Understanding physicians’ extent of adherence to these principles requires understanding the social preferences that lie behind them. These social preferences may be divided into two qualitatively different trade-offs: the trade-off between self and other (altruism) and the trade-off between reducing differences in payoffs (equality) and increasing total payoffs (efficiency). We experimentally measure social preferences among a nationwide sample of practicing physicians in the United States. Our design allows us to distinguish empirically between altruism and equality–efficiency orientation and to accurately measure both trade-offs at the level of the individual subject. We further compare the experimentally measured social preferences of physicians with those of a representative sample of Americans, an “elite” subsample of Americans, and a nationwide sample of medical students. We find that physicians’ altruism stands out. Although most physicians place a greater weight on self than on other, the share of physicians who place a greater weight on other than on self is twice as large as for all other samples—32% as compared with 15 to 17%. Subjects in the general population are the closest to physicians in terms of altruism. The higher altruism among physicians compared with the other samples cannot be explained by income or age differences. By contrast, physicians’ preferences regarding equality–efficiency orientation are not meaningfully different from those of the general sample and elite subsample and are less efficiency oriented than medical students.

In a classic article, Kenneth Arrow (1) argued that asymmetric information pervades the health-care market. Patients rely on physicians’ expert knowledge in planning their medical care. Health insurers and government agencies (Medicare and Medicaid) largely rely on physicians to decide which treatments are appropriate for their patients. This deference to physicians’ authority may be justified given their superior expertise and informational advantages (2). However, the dual role of recommending and providing treatments creates opportunities for physicians to place their interests ahead of their patients’ interests, for example by recommending profitable tests and treatments that offer little or no health benefits. A second risk is more subtle. Physicians must trade off their individual patients’ interests in getting care, even if the benefit is likely to be small, against society’s interest in allocating limited medical resources efficiently, in order to generate the greatest benefits for the overall health of a population.The norms of physician professionalism—including, in particular, the patient-centered norms that constitute physicians’ traditional professional ethic—are intended to address the risk of selfishness. Arrow argues that due to information asymmetry, the principle of“buyer beware” that governs ordinary consumer markets should be replaced, in health care, by the physicians’ professional responsibility to put patients’ interests ahead of their own (1). Physician leaders publicly promote the importance of professionalism, while exhorting physicians to act altruistically. For example, the editors of the New England Journal of Medicine have asserted that “medicine is one of the few spheres of human activity in which the purposes are unambiguously altruistic” (3), while the American Board of Internal Medicine similarly asserts that “altruism is the essence of professionalism … the best interest of patients, not self-interest, is the rule” (4). On the other hand, empirical studies have suggested that, at least in some situations, some physicians create “supplier-induced demand,” which influences a patient’s demand for care “against the physician’s interpretation of the best interest of the patient” (5), contributing to skepticism about whether physicians do in fact behave altruistically. [Such skepticism is not limited to medicine. Legal ethics, for example, has long sought to control lawyers’ abuse of discretion through professional norms of client loyalty and care (6). But skeptics have cast these norms as self-serving, and the law governing lawyers increasingly subjects them to elaborate institutionalized mechanisms of bureaucratic control.]While the effects of professional norms on physician behavior are difficult to measure directly, a clearer understanding of physicians’ social preferences can help to illuminate whether professional norms and physicians’ individual preferences are oppositional or aligned. Our study therefore helps to evaluate the likely effectiveness of both professional norms and the turn to bureaucracy. While altruism and related professional norms are important in many other professions (7), the distinct characteristics of the market for medical care, namely information asymmetry and uncertainty in the relationship between medical treatments and patient outcomes (1), render it especially critical to study these issues among physicians.Health care systems in the US and elsewhere address the second risk—concerning efficiency—in more complex ways. Although professional ethics give physicians a responsibility to conserve scarce medical resources (8), the norm that directs individual physicians to put their patients first may render a norm-based approach inadequate to the problem of efficiency (9). Health insurers therefore use bureaucratic mechanisms and financial incentives to manage the information asymmetry between a physician who knows the specific patient’s situation and the insurer which does not (9).^*We deploy an incentivized economic experiment to investigate both altruism (the trade-off between self and other) and equality–efficiency orientation (the trade-off between reducing self–other differences in payouts and increasing payout totals) in practicing US physicians, and we compare our results with analogous experiments that measure parallel behaviors in other populations. A vast literature considers social preferences, and laboratory experiments have been very fruitful in both establishing the empirical reliability of such preferences and directing theoretical attention to them. [We will not attempt to review the enormous body of work in behavioral and experimental economics on social preferences. Camerer (10) provides a comprehensive discussion, if now somewhat dated, of the vast body of experimental and theoretical research in economics focusing on dictator, ultimatum, and trust games. Engel (11) provides the most comprehensive meta-study of dictator games.] After presenting our results, we relate them to the results from prior work that are particularly relevant to our study (Discussion). We note that the social preferences of physicians and professionals more generally remain relatively understudied, and our discussion of the relationship between our study and prior work explains the specific contributions that we make.Our sample consists of 284 physicians from 36 medical groups around the United States, including physicians in primary care (internal medicine and family medicine) and cardiology, and physicians in private practices and employed by hospitals. Our experiment gives subjects broad discretion to implement their preferences, free from bureaucratic control or even surveillance. Our results therefore inform the question whether norms are likely to affect physician choices along both dimensions of behavior. Our study measures altruism in a large multisite sample of practicing physicians and measures both dimensions of social preferences.Our experiment asked subjects to make trade-offs between their own self-interest and the interest of an anonymous other and, at the same time, between equality and efficiency. These two aspects of social preferences often operate together, but they remain conceptually distinct. [Social preferences can be weighted toward equality (reducing differences in payoffs) or weighted toward efficiency (increasing total payoffs) and range from pure utilitarian to maxmin or Rawlsianism. As the dispute between Harsanyi (12, 13) and Rawls (14) shows, fair-minded people (who are all perfectly impartial between self and other) can disagree about how to trade off equality and efficiency. The work of Harsanyi and Rawls, and of the many others who have followed them, has had broad-reaching influence across many disciplines, including philosophy, economics, and law.] To capture both of these features in our experiment, we employ a modified dictator game (15–17) in which we ask physicians to allocate real money between themselves and an anonymous other drawn from a broadly representative sample of the US population. Our experiment presents subjects with allocation decisions in which the “price of giving” varies across decision problems—sometimes the subject may need to sacrifice more than a token (the experimental currency)—to give a single token to other (the recipient); in other decisions, it may cost only a fraction of a token. These decisions are made through an intuitive “point-and-click” graphical interface in which the choices are represented as a budget line where each point represents a possible allocation. The slope of the line captures the price of giving tokens to other.^†Intuitively, this method allowed us to collect a rich dataset capable of measuring both altruism and equality–efficiency orientation at the level of the individual subject. [The importance of studying individual heterogeneity in social preferences is emphasized by Andreoni and Miller (17). Because of this heterogeneity, it is necessary to investigate behavior at an individual level. Our experimental design allows subjects to make numerous choices over a wide range of budget lines, and this yields a rich dataset that is well-suited to analysis at the individual level. It is clearly advantageous to estimate individual-level parameters and then generate individual-level distributions of the estimations rather than to pool data and then estimate population-level parameters.] The degree of altruism is reflected in the amount subjects give on average, whereas equality–efficiency orientation is captured by how subjects respond to the price of giving. Increasing the fraction of the budget spent on other as the price of giving increases indicates social preferences weighted toward equality (reducing the difference in payoffs between self and other), whereas decreasing it when the price of giving increases indicates social preferences weighted toward efficiency (increasing the total payoffs to self and other). We rely on techniques developed in our prior work (15, 16, 18) to evaluate the consistency of physicians’ choices (i.e., whether they reflect a complete and transitive preference ordering) and to explore the structure of the social utility functions that rationalize the observed data.We further compare physicians’ preferences with preferences previously measured in three other populations using equivalent experiments: 1) a broadly representative sample of US adults (18), 2) an “elite” subsample of those who hold a graduate degree and have an annual household income over $100,000 (15, 18), and 3) a sample of medical students from nine schools around the United States (19, 20). The social preferences of these populations provide important benchmarks against which physicians’ social preferences can be assessed; furthermore, the comparison with medical students may shed light on whether physicians’ distinctive social preferences reflect a “selection effect” based on who enters medicine or a “treatment effect” of practicing medicine.^‡We begin our analysis of the experimental data by using classical revealed preference theory (21–23) to test whether subjects’ choices are consistent with the essence of all traditional models of economic decision-making—utility maximization.^§ Our physician subjects exhibit a remarkably high degree of consistency when compared with other populations, including medical students and also students from Yale Law School (YLS), the population that had exhibited the highest degree of consistency in prior experiments (15). [In our subsequent analysis, we do not draw detailed comparisons between our physician sample and the sample YLS students (15). The experimental design in Fisman et al. (15) differs from the current one in that the YLS student subjects were asked to allocate money between themselves and another student, rather than an individual drawn from a sample broadly representative of the US adults.] This result reveals that our physician subjects are highly adept at implementing a consistent, well-behaved social preference ordering. This makes it natural to estimate—at the level of the individual subject—the substantive social preferences that physicians display.We then estimate social preferences at the level of the individual physician using a constant elasticity of substitution (CES) utility function commonly employed by economists in demand analysis. The CES functional form is appealing because the degree of altruism and equality–efficiency orientation are each independently represented in a precise and transparent manner through its two parameters, which we estimate separately for each subject (further details on the CES specification and estimation are provided in Empirical Framework).We find that physicians are more altruistic than any other population, while physicians’ preferences concerning the trade-off between equality and efficiency are almost indistinguishable graphically from the preferences of the American Life Panel (ALP) elites and also the broader ALP sample. These findings on physicians’ distinctive social preferences have direct and concrete implications for professionalism, incentives, and bureaucratic rules directed at physicians. Insofar as physicians are altruistic, they may be more likely to live up to the professional ideal of putting patients’ interests ahead of their own. At the same time, altruism as captured in our experiment is far from ubiquitous, even among physicians and, furthermore, physicians’ efficiency orientation is indistinguishable from than that of the general population. Taken together, our findings suggest that the ideal of physician professionalism—putting the patient first—is not merely a self-serving myth but that other mechanisms may be required to support the quality of medical care and to promote efficient allocation of medical resources.     

Weekly Nowcasting of New COVID-19 Cases Using Past Viral Load Measurements

The rapid spread of the coronavirus disease COVID-19 has imposed clinical and financial burdens on hospitals and governments attempting to provide patients with medical care and implement disease-controlling policies. The transmissibility of the disease was shown to be correlated with the patient’s viral load, which can be measured during testing using the cycle threshold (Ct). Previous models have utilized Ct to forecast the trajectory of the spread, which can provide valuable information to better allocate resources and change policies. However, these models combined other variables specific to medical institutions or came in the form of compartmental models that rely on epidemiological assumptions, all of which could impose prediction uncertainties. In this study, we overcome these limitations using data-driven modeling that utilizes Ct and previous number of cases, two institution-independent variables. We collected three groups of patients (n = 6296, n = 3228, and n = 12,096) from different time periods to train, validate, and independently validate the models. We used three machine learning algorithms and three deep learning algorithms that can model the temporal dynamic behavior of the number of cases. The endpoint was 7-week forward number of cases, and the prediction was evaluated using mean square error (MSE). The sequence-to-sequence model showed the best prediction during validation (MSE = 0.025), while polynomial regression (OLS) and support vector machine regression (SVR) had better performance during independent validation (MSE = 0.1596, and MSE = 0.16754, respectively), which exhibited better generalizability of the latter. The OLS and SVR models were used on a dataset from an external institution and showed promise in predicting COVID-19 incidences across institutions. These models may support clinical and logistic decision-making after prospective validation.     

Spindle–slow oscillation coupling correlates with memory performance and connectivity changes in a hippocampal network after sleep

After experiences are encoded, post‐encoding reactivations during sleep have been proposed to mediate long‐term memory consolidation. Spindle–slow oscillation coupling during NREM sleep is a candidate mechanism through which a hippocampal‐cortical dialogue may strengthen a newly formed memory engram. Here, we investigated the role of fast spindle‐ and slow spindle–slow oscillation coupling in the consolidation of spatial memory in humans with a virtual watermaze task involving allocentric and egocentric learning strategies. Furthermore, we analyzed how resting‐state functional connectivity evolved across learning, consolidation, and retrieval of this task using a data‐driven approach. Our results show task‐related connectivity changes in the executive control network, the default mode network, and the hippocampal network at post‐task rest. The hippocampal network could further be divided into two subnetworks of which only one showed modulation by sleep. Decreased functional connectivity in this subnetwork was associated with higher spindle–slow oscillation coupling power, which was also related to better memory performance at test. Overall, this study contributes to a more holistic understanding of the functional resting‐state networks and the mechanisms during sleep associated to spatial memory consolidation.