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While we would like agents that can coordinate with humans, current algorithms such as self-play and population-based training create agents that can coordinate with themselves. Agents that assume their partner to be optimal or similar to them can converge to coordination protocols that fail to understand and be understood by humans. To demonstrate this, we introduce a simple environment that requires challenging coordination, based on the popular game Overcooked, and learn a simple model that mimics human play. We evaluate the performance of agents trained via self-play and population-based training. These agents perform very well when paired with themselves, but when paired with our human model, they are significantly worse than agents designed to play with the human model. An experiment with a planning algorithm yields the same conclusion, though only when the human-aware planner is given the exact human model that it is playing with. A user study with real humans shows this pattern as well, though less strongly. Qualitatively, we find that the gains come from having the agent adapt to the human's gameplay. Given this result, we suggest several approaches for designing agents that learn about humans in order to better coordinate with them. Code is available at https://github.com/HumanCompatibleAI/overcooked_ai.

Cigarette smoking increases the risk of numerous health problems, including cancer, cardiovascular and pulmonary disorders, making smoking the leading cause of preventable death in the world. Nicotine is primarily responsible for the highly addictive properties of cigarettes. Although the majority of smokers express a desire to quit, few are successful in doing so. Twin and family studies have indicated substantial genetic contributions to smoking behaviors. One major research focus has been to elucidate the specific genes involved; this has been accomplished primarily through genome-wide linkage analyses and candidate gene association studies. Much attention has focused on genes involved in the neurotransmitter pathways for the brain reward system and genes altering nicotine metabolism. This paper reviews the current state of knowledge for genetic factors implicated in smoking behaviors, and examines how genetic variations may affect therapeutic outcomes for drugs used to assist smoking cessation.The Pharmacogenomics Journal (2007) 7, 81–98. doi:10.1038/sj.tpj.6500436; published online 16 January 2007 [ABSTRACT FROM AUTHOR]

Board, card or video games have been played by virtually every individual in the world. Games are popular because they are intuitive and fun. These distinctive qualities of games also make them ideal for studying the mind. By being intuitive, games provide a unique vantage point for understanding the inductive biases that support behaviour in more complex, ecological settings than traditional laboratory experiments. By being fun, games allow researchers to study new questions in cognition such as the meaning of 'play' and intrinsic motivation, while also supporting more extensive and diverse data collection by attracting many more participants. We describe the advantages and drawbacks of using games relative to standard laboratory-based experiments and lay out a set of recommendations on how to gain the most from using games to study cognition. We hope this Perspective will lead to a wider use of games as experimental paradigms, elevating the ecological validity, scale and robustness of research on the mind., (© 2024. Springer Nature Limited.)

All biological and artificial agents must act given limits on their ability to acquire and process information. As such, a general theory of adaptive behavior should be able to account for the complex interactions between an agent's learning history, decisions, and capacity constraints. Recent work in computer science has begun to clarify the principles that shape these dynamics by bridging ideas from reinforcement learning , Bayesian decision-making , and rate-distortion theory . This body of work provides an account of capacity-limited Bayesian reinforcement learning , a unifying normative framework for modeling the effect of processing constraints on learning and action selection. Here, we provide an accessible review of recent algorithms and theoretical results in this setting, paying special attention to how these ideas can be applied to studying questions in the cognitive and behavioral sciences., Competing Interests: Competing Interests: The authors declare no conflict of interests., (© 2024 Massachusetts Institute of Technology.)

Resolving lineage relationships between cells in an organism provides key insights into the fate of individual cells and drives a fundamental understanding of the process of development and disease. A recent rapid increase in experimental and computational advances for detecting naturally occurring somatic nuclear and mitochondrial mutation at single-cell resolution has expanded lineage tracing from model organisms to humans. This review discusses the advantages and challenges of experimental and computational techniques for cell lineage tracing using somatic mutation as endogenous DNA barcodes to decipher the relationships between cells during development and tumour evolution. We outlook the advantages of spatial clonal evolution analysis and single-cell lineage tracing using endogenous genetic markers., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

People use language to influence others' beliefs and actions. Yet models of communication have diverged along these lines, formalizing the speaker's objective in terms of either the listener's beliefs or actions. We argue that this divergence lies at the root of a longstanding controversy over the Gricean maxims of truthfulness and relevance. We first bridge the divide by introducing a speaker model which considers both the listener's beliefs (epistemic utility) and their actions (decision-theoretic utility). We show that formalizing truthfulness as an epistemic utility and relevance as a decision-theoretic utility reconciles the tension between them, readily explaining puzzles such as context-dependent standards of truthfulness. We then test a set of novel predictions generated by our model. We introduce a new signaling game which decouples utterances' truthfulness and relevance, then use it to conduct a pair of experiments. Our first experiment demonstrates that participants jointly maximize epistemic and decision-theoretic utility, rather than either alone. Our second experiment shows that when the two conflict, participants make a graded tradeoff rather than prioritizing one over the other. These results demonstrate that human communication cannot be reduced to influencing beliefs or actions alone. Taken together, our work provides a new foundation for grounding rational communication not only in what we believe , but in what those beliefs lead us to do. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Planning underpins the impressive flexibility of goal-directed behavior. However, even when planning, people can display surprising rigidity in how they think about problems (e.g., "functional fixedness") that lead them astray. How can our capacity for behavioral flexibility be reconciled with our susceptibility to conceptual inflexibility? We propose that these tendencies reflect avoidance of two cognitive costs: the cost of representing task details and the cost of switching between representations. To test this hypothesis, we developed a novel paradigm that affords participants opportunities to choose different families of simplified representations to plan. In two preregistered, online studies ( N s = 377 and 294 adults), we found that participants' optimal behavior, suboptimal behavior, and reaction time were explained by a computational model that formalized people's avoidance of representational complexity and switching. These results demonstrate how the selection of simplified, rigid representations leads to the otherwise puzzling combination of flexibility and inflexibility observed in problem solving.

Colorectal cancer (CRC) has been proven to be highly reliant on arginine availability. Limiting arginine-rich foods or treating patients with arginine-depleting enzymes arginine deiminase (ADI) or arginase can suppress colon cancer. However, arginase and ADI are not the best drug candidates for CRC. Ornithine, the product of arginase, can enhance the supply of polyamine, which favors CRC cell growth, while citrulline, the product of ADI, faces the problem of arginine recycling due to the overexpression of argininosuccinate synthetase (ASS). Biosynthetic arginine decarboxylase (ADC), an enzyme that catalyzes the conversion of arginine to agmatine and carbon dioxide, may be a better choice as it combines both arginine depletion and suppression of intracellular polyamine synthesis via its product agmatine. ADC has anti-tumor potential yet has received much less attention than the other two arginine-depleting enzymes. In order to gain a better understanding of ADC, the preparation and the anti-cancer properties of this enzyme were explored in this study. When tested in vitro, ADC inhibited the proliferation of three colorectal cancer cell lines regardless of their ASS cellular expression. In contrast, ADC had a lesser cytotoxic effect on the human foreskin fibroblasts and rat primary hepatocytes. Further in vitro studies revealed that ADC induced S and G2/M phase cell-cycle arrest and apoptosis in HCT116 and LoVo cells. ADC-induced apoptosis in HCT116 cells followed the mitochondrial apoptotic pathway and was caspase-3-dependent. With all results obtained, we suggest that arginine is a potential target for treating colorectal cancer with ADC, and the anti-cancer properties of ADC should be more deeply investigated in the future.

Background: Currently, surgical resection is the mainstay for colorectal liver metastases (CRLM) management and the only potentially curative treatment modality. Prognostication tools can support patient selection for surgical resection to maximize therapeutic benefit. This study aimed to develop a survival prediction model using machine learning based on a multicenter patient sample in Hong Kong., Methods: Patients who underwent hepatectomy for CRLM between 1 January 2009 and 31 December 2018 in four hospitals in Hong Kong were included in the study. Survival analysis was performed using Cox proportional hazards (CPH). A stepwise selection on Cox multivariable models with Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to a multiply-imputed dataset to build a prediction model. The model was validated in the validation set, and its performance was compared with that of Fong Clinical Risk Score (CRS) using concordance index., Results: A total of 572 patients were included with a median follow-up of 3.6 years. The full models for overall survival (OS) and recurrence-free survival (RFS) consist of the same 8 established and novel variables, namely colorectal cancer nodal stage, CRLM neoadjuvant treatment, Charlson Comorbidity Score, pre-hepatectomy bilirubin and carcinoembryonic antigen (CEA) levels, CRLM largest tumor diameter, extrahepatic metastasis detected on positron emission-tomography (PET)-scan as well as KRAS status. Our CRLM Machine-learning Algorithm Prognostication model (CMAP) demonstrated better ability to predict OS (C-index =0.651), compared with the Fong CRS for 1-year (C-index =0.571) and 5-year OS (C-index =0.574). It also achieved a C-index of 0.651 for RFS., Conclusions: We present a promising machine learning algorithm to individualize prognostications for patients following resection of CRLM with good discriminative ability., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-21-453/coif). CML serves as the unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2023 Hepatobiliary Surgery and Nutrition. All rights reserved.)

This study reports on the synthesis of Fe 3+ -activated Sr 9 Al 6 O 18 nanophosphors (SAO:Fe NPs) using a simple solution combustion process, which emits a pale green light and possesses excellent fluorescence properties. An in-situ powder dusting method was utilized to extract unique ridge features of latent fingerprints (LFPs) on various surfaces using ultra-violet 254 nm excitation. The results showed that SAO:Fe NPs possess high contrast, high sensitivity, and no background interference, enabling the observation of LFPs for longer periods. Poroscopy, which is the examination of sweat pores on the skin's papillary ridges, is important in the identification process, and the YOLOv8x program based on deep convolutional neural networks was used to study the features visible in FPs. The potential of SAO:Fe NPs to ameliorate oxidative stress and thrombosis was analyzed. The results showed that SAO:Fe NPs have antioxidant properties by scavenging 2,2-diphenylpicrylhydrazyl (DPPH) and normalized the stress markers in NaNO 2 -induced oxidative stress in Red Blood Cells (RBC). In addition, SAO:Fe inhibited platelet aggregation induced by adenosine diphosphate (ADP). Therefore, SAO:Fe NPs may have potential applications in advanced cardiology and forensic sciences. Overall, this study highlights the synthesis and potential applications of SAO:Fe NPs, which can enhance the sensitivity and specificity of fingerprint detection and provide insights into developing novel treatments for oxidative stress and thrombosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Human behavior emerges from planning over elaborate decompositions of tasks into goals, subgoals, and low-level actions. How are these decompositions created and used? Here, we propose and evaluate a normative framework for task decomposition based on the simple idea that people decompose tasks to reduce the overall cost of planning while maintaining task performance. Analyzing 11,117 distinct graph-structured planning tasks, we find that our framework justifies several existing heuristics for task decomposition and makes predictions that can be distinguished from two alternative normative accounts. We report a behavioral study of task decomposition (N = 806) that uses 30 randomly sampled graphs, a larger and more diverse set than that of any previous behavioral study on this topic. We find that human responses are more consistent with our framework for task decomposition than alternative normative accounts and are most consistent with a heuristic-betweenness centrality-that is justified by our approach. Taken together, our results suggest the computational cost of planning is a key principle guiding the intelligent structuring of goal-directed behavior., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Correa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

People use a wide range of communicative acts across different modalities, from concrete demonstrations to abstract language. While these modalities are typically studied independently, we take a comparative approach and ask when and why one modality might outperform another. We present a series of real-time, multi-player experiments asking participants to teach concepts using either demonstrations or language. Our first experiment (N=416) asks when language might outperform demonstration. We manipulate the complexity of the concept being taught and find that language communicates complex concepts more effectively than demonstration. We then ask why language succeeds in this setting. We hypothesized that language allowed teachers to reference abstract object features (e.g., shapes and colors), while demonstration teachers could only provide concrete examples (specific positive or negative objects). To test this hypothesis, our second experiment (N=568) ablated object features from the teacher's interface. This manipulation severely impaired linguistic (but not demonstrative) teaching. Our findings suggest that language communicates complex concepts by directly transmitting abstract rules. In contrast, demonstrations transmit examples, requiring the learner to infer the rules., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The cadmium tungstate rods have been given much attention due to their potential for usage in numerous luminescent applications. We have prepared single crystalline Sn-doped Cd 1-x Sn x WO 4 (where x = 0, 1, 3, and 5%) nanorods (NRDs) and characterized them using refined X-ray diffraction and TEM analysis, revealing a monoclinic phase and a crystallite size that decreased from 62 to 38 nm as Sn concentration increased. Precise Sn doping modulation in CdWO 4 NRDs causes surface recombination of electrons and holes, which causes the PL intensity to decrease as the Sn content rises. The chromaticity diagram shows that an increase in the Sn content caused a change in the emission color from sky blue to light green, which was attributed to the increased defect density. The photoluminescence time decay curve of all samples fit well with double-order exponential decay, and the average decay lifetime was found to be 1.11, 0.93, and 1.16 ns for Cd 1-x Sn x WO 4 , x = 0, 1, and 5%, respectively. This work provides an understanding of the behavior of Sn-doped CdWO 4 NRDs during electron transitions and the physical nature of emission that could be used in bio-imaging, light sources, displays, and other applications.

Understanding Theory of Mind should begin with an analysis of the problems it solves. The traditional answer is that Theory of Mind is used for predicting others' thoughts and actions. However, the same Theory of Mind is also used for planning to change others' thoughts and actions. Planning requires that Theory of Mind consists of abstract structured causal representations and supports efficient search and selection from innumerable possible actions. Theory of Mind contrasts with less cognitively demanding alternatives: statistical predictive models of other people's actions, or model-free reinforcement of actions by their effects on other people. Theory of Mind is likely used to plan novel interventions and predict their effects, for example, in pedagogy, emotion regulation, and impression management., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

One of the most striking features of human cognition is the ability to plan. Two aspects of human planning stand out-its efficiency and flexibility. Efficiency is especially impressive because plans must often be made in complex environments, and yet people successfully plan solutions to many everyday problems despite having limited cognitive resources 1-3 . Standard accounts in psychology, economics and artificial intelligence have suggested that human planning succeeds because people have a complete representation of a task and then use heuristics to plan future actions in that representation 4-11 . However, this approach generally assumes that task representations are fixed. Here we propose that task representations can be controlled and that such control provides opportunities to quickly simplify problems and more easily reason about them. We propose a computational account of this simplification process and, in a series of preregistered behavioural experiments, show that it is subject to online cognitive control 12-14 and that people optimally balance the complexity of a task representation and its utility for planning and acting. These results demonstrate how strategically perceiving and conceiving problems facilitates the effective use of limited cognitive resources., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: Cardiovascular diseases (CVD) are a long-term sequela of diabetes. Better individual-based continuity of care has been reported to reduce the risk of chronic complications among patients with diabetes. Maintaining a one-to-one patient-physician relationship is often challenging, especially in public health care settings. This study aimed to evaluate the relationship between higher team-based continuity of care, defined as consultations provided by the same physician team, and CVD risks in patients with diabetes from public primary care clinics., Research Design and Methods: This was a retrospective cohort study in Hong Kong of 312,068 patients with type 2 diabetes and without any history of CVD at baseline (defined as the earliest attendance at a doctor's consultation in a public-sector clinic between 2008 and 2018). Team-based continuity of care was measured using the usual provider continuity index (UPCI), calculated by the proportion of consultations provided by the most visited physician team in the 2 years before baseline. Patients were divided into quartiles based on their UPCI, and the characteristics of the quartiles were balanced using propensity score fine stratification weights. Multivariable Cox regression was applied to assess the effect of team-based continuity of care on CVD incidence. Patient demographics, smoking status, physiological measurements, number of attendances, comorbidities, and medications were adjusted for in the propensity weightings and regression analyses., Results: After an average follow-up of 6.5 years, the total number of new CVD events was 52,428. Compared with patients in the 1st quartile, patients in the 2nd, 3rd, and 4th quartiles of the UCPI had a CVD hazard ratio (95% CI) of 0.95 (0.92-0.97), 0.92 (0.89-0.94), and 0.87 (0.84-0.89), respectively, indicating that higher continuity of care was associated with lower CVD risks. The subtypes of CVD, including coronary heart disease and stroke, also showed a similar pattern. Subgroup analyses suggested that patients <65 years of age had greater benefits from higher team-based continuity of care., Conclusions: Team-based continuity of care was associated with lower CVD risk among individuals with type 2 diabetes, especially those who were younger. This suggests a potential flexible alternative implementation of continuity of care in public clinics., (© 2022 by the American Diabetes Association.)

Introduction: Cardiometabolic risk factors and renal function are monitored regularly for patients with diabetes mellitus (DM)/ hypertension (HT). In addition to risk factor levels at a single time point, their trajectory (changes over time) can also be differentially related to the risk of cardiovascular diseases (CVD) and mortality. This study aimed to systematically examine the evidence regarding the association between risk factor trajectories and risk of CVD/mortality in patients with DM/HT., Method: PubMed, MEDLINE, and Embase were searched for articles from January 1963 to April 2021. Inclusion criteria: studies that 1) analyzed trajectories of risk factors including haemoglobin A1c (HbA1c), blood pressure, estimated glomerular filtration rate (eGFR), body mass index (BMI), and blood lipids; 2) were performed in the DM/HT population and, 3) included risk of CVD/mortality as outcomes. Study quality was assessed using the Newcastle-Ottawa quality assessment scale., Results: A total of 22,099 articles were identified. After screening by title and abstract, 22,027 articles were excluded by irrelevant outcomes, exposure, population, or type of articles. Following full-text screening, 11 articles investigating the trajectories of HbA1c (N = 7), systolic blood pressure (SBP) (N = 3), and eGFR (N = 1) were included for data extraction and analysis. No studies were identified examining the association of BMI or lipid trajectories with CVD/mortality. All included studies were of good quality based on the NOS criteria. In general, stable trajectories within optimal ranges of the risk factors (HbA1c: <7%, SBP: 120-139mmHg, eGFR: >60mL/min/1.73m2) had the lowest CVD/mortality risk compared to an increasing HbA1c trajectory (from 8% to 10%), an increasing SBP trajectory (from 120-139 to ≥140mmHg), or a decreasing eGFR trajectory (from 90 to 70mL/min/1.73m2)., Conclusion: A relatively stable and well-controlled trajectory for cardiometabolic risk factors was associated with the lowest risk of CVD/mortality. Risk factor trajectories have important clinical implications in addition to single time point measurements. More attention should be given to patients with suboptimal control and those with unstable trends of cardiometabolic risk factors., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Eric Wan has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, and the Hong Kong Research Grant Council, outside the submitted work. Esther Yu has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, outside the submitted work. Professor Cindy Lam has received research grants from the Food and Health Bureau of the Government of the Hong Kong SAR, the Hong Kong Research Grant Council, the Hong Kong College of Family Physicians, and Kerry Group Kuok Foundation, outside the submitted work.

There's a difference between someone instantaneously saying "Yes!" when you ask them on a date compared to "…yes." Psychologists and economists have long studied how people can infer preferences from others' choices. However, these models have tended to focus on what people choose and not how long it takes them to make a choice. We present a rational model for inferring preferences from response times, using a drift diffusion model to characterize how preferences influence response time, and Bayesian inference to invert this relationship. We test our model's predictions for three experimental questions. Matching model predictions, participants inferred that a decision-maker preferred a chosen item more if the decision-maker spent less time deliberating (Experiment 1), participants predicted a decision-maker's choice in a novel comparison based on inferring the decision-maker's relative preferences from previous response times and choices (Experiment 2), and participants could incorporate information about a decision-maker's mental state of cautious or careless (Experiments 3, 4A, and 4B)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Theory of mind enables an observer to interpret others' behavior in terms of unobservable beliefs, desires, intentions, feelings, and expectations about the world. This also empowers the person whose behavior is being observed: By intelligently modifying her actions, she can influence the mental representations that an observer ascribes to her, and by extension, what the observer comes to believe about the world. That is, she can engage in intentionally communicative demonstrations . Here, we develop a computational account of generating and interpreting communicative demonstrations by explicitly distinguishing between two interacting types of planning. Typically, instrumental planning aims to control states of the environment, whereas belief-directed planning aims to influence an observer's mental representations. Our framework extends existing formal models of pragmatics and pedagogy to the setting of value-guided decision-making, captures how people modify their intentional behavior to show what they know about the reward or causal structure of an environment, and helps explain data on infant and child imitation in terms of literal versus pragmatic interpretation of adult demonstrators' actions. Additionally, our analysis of belief-directed intentionality and mentalizing sheds light on the sociocognitive mechanisms that underlie distinctly human forms of communication, culture, and sociality. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction: COVID-19 pandemic has resulted in significant changes in pedagogy for undergraduate medical curriculum. Many physical clinical teachings have been replaced by online pedagogy. This study aims to evaluate the relation between medical students' stress during COVID-19 pandemic and their academic performance at the final examination., Methods: This is a cross-sectional questionnaire-based study. Student's stress level were evaluated by the COVID-19 Student Stress Questionnaire (CSSQ). Correlation of stress level and students' performance at the final examination was performed., Results: 110 out of 221 (49.8%) final-year medical students responded to the questionnaire, 13 students failed in the final examination (case) while 97 students passed in the final MBBS examination (control).Baseline demographic data between case and control were comparable. The median age for both cases and controls were 24 years.Compared to controls, cases reported higher levels of stress in all domains, namely in relation to risk of contagion, social isolation, interpersonal relationships with relatives, university colleagues and professors, academic life, and sexual life. Notably, a significantly higher proportion of cases reported academic-related stress compared to controls (p < 0.01), with 100% of cases perceiving their academic studying experience during the COVID-19 pandemic to be "very" or "extremely" stressful, compared to 35.1% of controls., Conclusion: Increased stress to academic and study during COVID-19 was associated with worse examination outcome at the final examination. Extra academic support will be needed to cater students' need during the pandemic., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Background: The rising prevalence of non-communicable diseases (NCDs) such as diabetes mellitus (DM) and hypertension (HT) has placed a tremendous burden on healthcare systems around the world, resulting in a call for more effective service delivery models. Better continuity of care (CoC) has been associated with improved health outcomes. This review examines the association between CoC and health outcomes in patients with DM and/or HT., Methods: This was a systematic review with searches carried out on 13 March 2021 through PubMed, Embase, MEDLINE and CINAHL plus, clinical trials registry and bibliography reviews. Eligibility criteria were: published in English; from 2000 onwards; included adult DM and/or HT patients; examined CoC as their main intervention/exposure; and utilised quantifiable outcome measures (categorised into health indicators and service utilisation). The study quality was evaluated with Critical Appraisal Skills Programme (CASP) appraisal checklists., Results: Initial searching yielded 21,090 results with 42 studies meeting the inclusion criteria. High CoC was associated with reduced hospitalisation (16 out of 18 studies), emergency room attendances (eight out of eight), mortality rate (six out of seven), disease-related complications (seven out of seven), and healthcare expenses (four out of four) but not with blood pressure (two out of 13), lipid profile (one out of six), body mass index (zero out of three). Six out of 12 studies on diabetic outcomes reported significant improvement in haemoglobin A1c by higher CoC. Variations in the classification of continuity of care and outcome definition were identified, making meta-analyses inappropriate. CASP evaluation rated most studies fair in quality, but found insufficient adjustment on confounders, selection bias and short follow-up period were common limitations of current literatures., Conclusion: There is evidence of a strong association between higher continuity of care and reduced mortality rate, complication risks and health service utilisation among DM and/or HT patients but little to no improvement in various health indicators. Significant methodological heterogeneity in how CoC and patient outcomes are assessed limits the ability for meta-analysis of findings. Further studies comprising sufficient confounding adjustment and standardised definitions are needed to provide stronger evidence of the benefits of CoC on patients with DM and/or HT.

Humans use punishment to influence each other's behavior. Many current theories presume that this operates as a simple form of incentive. In contrast, we show that people infer the communicative intent behind punishment, which can sometimes diverge sharply from its immediate incentive value. In other words, people respond to punishment not as a reward to be maximized, but as a communicative signal to be interpreted. Specifically, we show that people expect harmless, yet communicative, punishments to be as effective as harmful punishments (Experiment 1). Under some situations, people display a systematic preference for harmless punishments over more canonical, harmful punishments (Experiment 2). People readily seek out and infer the communicative message inherent in a punishment (Experiment 3). And people expect that learning from punishment depends on the ease with which its communicative intent can be inferred (Experiment 4). Taken together, these findings demonstrate that people expect punishment to be constructed and interpreted as a communicative act., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Competing Interests: The author has no conflicts of interest to disclose.

Background: Palliative care aims to improve the quality of life for patients and their families, by helping them to cope with problems associated with illness. It targets four aspects of health: physical, psychological, social, and spiritual. Most of the current literature on palliative care is limited to the perspectives of health professionals. This study aims to investigate the views of outpatients receiving palliative care at the Hong Kong Queen Mary Hospital Hospice Centre (HKQMHHC), which offers palliative care services to cancer patients., Methods: This observational cross-sectional study was performed with the completion of a single paper- based original questionnaire over 18 afternoon clinic sessions on Thursdays and Fridays from December 2017 to February 2018 at the HKQMHHC. The questionnaire was designed to examine patients' perspectives; in particular, the Edmonton Symptom Assessment Scale (ESAS) was used to assess their symptoms. Descriptive and univariate analyses were performed., Results: One hundred patients attending HKQMHHC were included in the study. The study revealed that all the mean scores for aspects of care offered at the centre were above 8, on a scale of 0-10 with 0 being extremely inadequate and 10 being extremely adequate. Each respondent was able to identify an average of 1.82 of the 4 aspects of palliative care. Eighty-seven percent of respondents perceived the physical aspect of this care to be of the highest priority. A negative correlation (P<0.05) was found between the extent of symptoms experienced by the patient and their satisfaction towards the services offered., Conclusions: Patients generally held very positive attitudes, reflecting that the services sufficiently met their needs. However, owing to their rather limited knowledge, this may have restricted their perspectives to a largely superficial level, as many discerned palliative care to be simply targeting physical health with medical consultations. Considering the implications of the results, the addition of accessibility and education components to Hong Kong's current system of palliative care is crucial in the betterment of such services for patients. There should also be increased local coverage of palliative care services to facilitate convenience of access. With reference to the World Health Organisation (WHO) palliative care model, the inclusion of a continued spectrum of services, such as physical and mental health activities and psychosocial counselling, should be reinforced throughout the progression of disease so as to better help patients to cope with illness. The discovery of the relationship between extent of symptoms experienced and patients' satisfaction towards services provided is a new direction for further study.

Astrocytes are increasingly recognized as active contributors to the disease process in multiple sclerosis (MS), rather than being merely reactive. We investigated the expression of a selected microRNA (miRNA) panel that could contribute both to the injury and to the recovery phases of the disease. Individual astrocytes were laser microdissected from brain sections. We then compared the miRNAs' expressions in MS and control brain samples at different lesional stages in white versus grey matter regions. In active MS lesions, we found upregulation of ischemia-related miRNAs in white but not grey matter, often with reversion to the normal state in inactive lesions. In contrast to our previous findings on MS macrophages, expression of 2 classical inflammatory-related miRNAs, miRNA-155 and miRNA-146a, was reduced in astrocytes from active and chronic active MS lesions in white and grey matter, suggesting a lesser direct pathogenetic role for these miRNAs in astrocytes. miRNAs within the categories regulating aquaporin4 (-100, -145, -320) and glutamate transport/apoptosis/neuroprotection (-124a, -181a, and -29a) showed some contrasting responses. The regional and lesion-stage differences of expression of these miRNAs indicate the remarkable ability of astrocytes to show a wide range of selective responses in the face of differing insults and phases of resolution., (© 2019 American Association of Neuropathologists, Inc. All rights reserved.)

Background: BOAST (British Orthopaedic Association Standards for Trauma) and NICE (National Institute of Clinical Excellence) guidelines recommend clinical photography of all open fractures on admission and at key stages of patient care for objective wound documentation and to avoid repeated examination. Recording and handling photographs in a compliant and confidential manner in the setting of acute trauma management can prove challenging. To facilitate clinical photography at our Major Trauma Centre (MTC) institution, a smartphone-based Secure Clinical Image Transfer (SCIT) app was introduced and integrated with the existing clinical photography database to allow clinicians to take photographs, which are saved directly to patient records., Objectives: To compare rates of information governance (IG)-compliant clinical photography of wounds of patients with open fractures before and after introduction of departmental smartphones loaded with the clinical photography app SCIT., Methods: Admission lists were inspected retrospectively for patients admitted with open fractures between August and October 2016, before SCIT was introduced. The Trust clinical photography database was searched for corresponding patient images and where present, graded out of three for clarity, comprehensiveness and context. The procedure was repeated prospectively from August to October 2017 after rollout of SCIT. The uptake and quality of photography were statistically compared (Fisher's exact test, significance level p < 0.05)., Results: 42 open fractures were identified in the 2016 period and 40 in the 2017 period. None of the 42 patients in the 2016 cohort had records of IG-compliant clinical photography on admission. 16 of 40 patients in the 2017 cohort had IG-compliant clinical photography on admission. This was statistically significant (p < 0.0001). 5 of 42 patients in the 2016 cohort and 8 of 40 patients in the 2017 cohort had photographs after first debridement. This was statistically insignificant (p = 0.375). All five photographs in the 2016 cohort scored 3/3. 18 of 21 photographs in the 2017 cohort scored 3/3, one scored 2/3 and two scored 1/3., Conclusions: Integrating commonplace smartphone technology with a secure platform for taking and storing photographs can improve rates of IG-compliant clinical photography of open fractures. This may improve documentation, communication and patient care., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Folate is an important B vitamin required for methylation reactions, nucleotide and neurotransmitter synthesis, and maintenance of homocysteine at nontoxic levels. Its metabolism is tightly linked to that of choline, a precursor to acetylcholine and membrane phospholipids. Low folate intake and genetic variants in folate metabolism, such as the methylenetetrahydrofolate reductase (MTHFR) 677 C>T polymorphism, have been suggested to impact brain function and increase the risk for cognitive decline and late-onset Alzheimer's disease. Our study aimed to assess the impact of genetic and nutritional disturbances in folate metabolism, and their potential interaction, on features of cognitive decline and brain biochemistry in a mouse model. Wild-type and Mthfr +/- mice, a model for the MTHFR 677 C>T polymorphism, were fed control or folate-deficient diets from weaning until 8 and 10 months of age. We observed short-term memory impairment measured by the novel object paradigm, altered transcriptional levels of synaptic markers and epigenetic enzymes, as well as impaired choline metabolism due to the Mthfr +/- genotype in cortex or hippocampus. We also detected changes in mRNA levels of Presenillin-1, neurotrophic factors, one-carbon metabolic and epigenetic enzymes, as well as reduced levels of S-adenosylmethionine and acetylcholine, due to the folate-deficient diet. These findings shed further insights into the mechanisms by which genetic and dietary folate metabolic disturbances increase the risk for cognitive decline and suggest that these mechanisms are distinct.

Carrots and sticks motivate behavior, and people can teach new behaviors to other organisms, such as children or nonhuman animals, by tapping into their reward learning mechanisms. But how people teach with reward and punishment depends on their expectations about the learner. We examine how people teach using reward and punishment by contrasting two hypotheses. The first is evaluative feedback as reinforcement, where rewards and punishments are used to shape learner behavior through reinforcement learning mechanisms. The second is evaluative feedback as communication, where rewards and punishments are used to signal target behavior to a learning agent reasoning about a teacher's pedagogical goals. We present formalizations of learning from these 2 teaching strategies based on computational frameworks for reinforcement learning. Our analysis based on these models motivates a simple interactive teaching paradigm that distinguishes between the two teaching hypotheses. Across 3 sets of experiments, we find that people are strongly biased to use evaluative feedback communicatively rather than as reinforcement. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Osteochondroma is the most common benign bone tumor, but it rarely arises from the scapula. Scapulothoracic bursitis is quite rare and osteochondroma is one of the unusual causes of this condition. Synovial chondromatosis may occur extremely uncommonly in this bursa. We reported an unusual case of scapulothoracic bursitis with synovial chondromatosis, which is caused by osteochondroma. To the best of our knowledge, there is no defined chondromatosis in the scapulothoracic bursa secondary to scapular osteochondroma in the literature.

Percutaneous cholecystostomy (PC) is a well-established treatment for acute cholecystitis. We investigate the performance and role of PC in managing acute cholangitis.Retrospective review on all patients who underwent PC for acute cholangitis between January 2012 and June 2017 at a major regional hospital in Hong Kong.Thirty-two patients were included. The median age was 84 years and median American Society of Anaesthesiologists (ASA) physical status was Class III (severe systemic disease). All fulfilled Tokyo Guidelines 2013 (TG13) diagnostic criteria for moderate or severe cholangitis. Eighty-four percent of the patients were shown to have lower common bile duct stones on imaging. The majority had previously failed intervention by endoscopic retrograde cholangiopancreatography (38%), percutaneous transhepatic biliary drainage (38%), or both (13%)The technical success rate for PC was 100% with no procedure-related mortality. The overall 30-day mortality was 9%. Rest of the patients (91%) had significant improvement in clinical symptoms and could be discharged with median length of stay of 14 days. Significant postprocedural biochemical improvement was observed in terms of white cell count (P < .001), serum bilirubin (P < .001), alkaline phosphatase (P = .001), and alanine transaminase levels (P < .001). Time from admission to PC was associated with excess mortality (P = .002).PC is an effective treatment for acute cholangitis in high-risk elderly patients. Early intervention is associated with lower mortality. PC is particularly valuable as a temporising measure before definitive treatment in critical patients or as salvage therapy where other methods endoscopic retrograde cholangiopancreatography/percutaneous transhepatic biliary drainage (ERCP/PTBD) have failed.

Humans often attempt to influence one another's behavior using rewards and punishments. How does this work? Psychologists have often assumed that "evaluative feedback" influences behavior via standard learning mechanisms that learn from environmental contingencies. On this view, teaching with evaluative feedback involves leveraging learning systems designed to maximize an organism's positive outcomes. Yet, despite its parsimony, programs of research predicated on this assumption, such as ones in developmental psychology, animal behavior, and human-robot interaction, have had limited success. We offer an explanation by analyzing the logic of evaluative feedback and show that specialized learning mechanisms are uniquely favored in the case of evaluative feedback from a social partner. Specifically, evaluative feedback works best when it is treated as communicating information about the value of an action rather than as a form of reward to be maximized. This account suggests that human learning from evaluative feedback depends on inferences about communicative intent, goals and other mental states-much like learning from other sources, such as demonstration, observation and instruction. Because these abilities are especially developed in humans, the present account also explains why evaluative feedback is far more widespread in humans than non-human animals., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Methylenetetrahydrofolate reductase (MTHFR) generates methyltetrahydrofolate for methylation reactions. Severe MTHFR deficiency results in homocystinuria and neurologic impairment. Mild MTHFR deficiency (677C > T polymorphism) increases risk for complex traits, including neuropsychiatric disorders. Although low dietary folate impacts brain development, recent concerns have focused on high folate intake following food fortification and increased vitamin use. Our goal was to determine whether high dietary folate during pregnancy affects brain development in murine offspring. Female mice were placed on control diet (CD) or folic acid-supplemented diet (FASD) throughout mating, pregnancy and lactation. Three-week-old male pups were evaluated for motor and cognitive function. Tissues from E17.5 embryos, pups and dams were collected for choline/methyl metabolite measurements, immunoblotting or gene expression of relevant enzymes. Brains were examined for morphology of hippocampus and cortex. Pups of FASD mothers displayed short-term memory impairment, decreased hippocampal size and decreased thickness of the dentate gyrus. MTHFR protein levels were reduced in FASD pup livers, with lower concentrations of phosphocholine and glycerophosphocholine in liver and hippocampus, respectively. FASD pup brains showed evidence of altered acetylcholine availability and Dnmt3a mRNA was reduced in cortex and hippocampus. E17.5 embryos and placentas from FASD dams were smaller. MTHFR protein and mRNA were reduced in embryonic liver, with lower concentrations of choline, betaine and phosphocholine. Embryonic brain displayed altered development of cortical layers. In summary, high folate intake during pregnancy leads to pseudo-MTHFR deficiency, disturbed choline/methyl metabolism, embryonic growth delay and memory impairment in offspring. These findings highlight the unintended negative consequences of supplemental folic acid., (© The Author 2017. Published by Oxford University Press.)

This study aimed to investigate the genetic causes of vestibular dysfunction. We used vestibular sensory-evoked potentials (VsEPs) to characterize the vestibular function of 35 inbred mouse strains selected from the Hybrid Mouse Diversity Panel and demonstrated strain-dependent phenotypic variation in vestibular function. Using these phenotypic data, we performed the first genome-wide association study controlling for population structure that has revealed two highly suggestive loci, one of which lies within a haplotype block containing five genes (Stard6, 4930503L19Rik, Poli, Mbd2, Dcc) on Chr. 18 (peak SNP rs29632020), one gene, deleted in colorectal carcinoma (Dcc) has a well-established role in nervous system development. An in-depth analysis of Dcc-deficient mice demonstrated elevation in mean VsEP threshold for Dcc (+/-) mice (-11.86 dB) compared to wild-type (-9.68 dB) littermates. Synaptic ribbon studies revealed Dcc (-/-) (P0) and Dcc (+/-) (6-week-old) mice showed lower density of the presynaptic marker (CtBP2) as compared to wild-type controls. Vestibular ganglion cell counts of Dcc (-/-) (P0) was lower than controls. Whole-mount preparations showed abnormal innervation of the utricle, saccule, and crista ampullaris at E14.5, E16.5, and E18.5. Postnatal studies were limited by the perinatal lethality in Dcc (-/-) mice. Expression analyses using in situ hybridization and immunohistochemistry showed Dcc expression in the mouse vestibular ganglion (E15.5), and utricle and crista ampullaris (6-week-old), respectively. In summary, we report the first GWAS for vestibular functional variation in inbred mice and provide evidence for the role of Dcc in the normal innervation of the peripheral vestibular system.

Anatomic distribution and age are variables linked to functions of astrocytes under physiologic and pathologic conditions. We measured the relative expression of a panel of microRNAs (miRNAs) in astrocytes captured by laser micro-dissection from normal human adult white and grey matter, human fetal white matter and germinal matrix samples. Although expression of most miRNAs was comparable between adult and fetal samples, regional differences were observed. In the adult cerebral cortex, expression of miRNAs in morphologically distinct inter-laminar astrocytes underlying the glial limitans differed from those in deeper cortical layers, suggesting functional specialization possibly related to structural stability and defense from potentially harmful factors in the cerebrospinal fluid. Differences between adult white and grey matter miRNA expression included higher expression of pro-inflammatory miRNAs in the former, potentially contributing to differences in inflammation between grey and white matter plaques in multiple sclerosis. Lower expression of miRNAs in fetal versus adult white matter astrocytes likely reflects the immaturity of these migrating cells. Highly expressed miRNAs in the fetal germinal matrix are probably relevant in development and also recapitulate some responses to injury. Future studies can address regional alterations of miRNA expression in pathological conditions.

The myelin g-ratio, defined as the ratio between the inner and the outer diameter of the myelin sheath, is a fundamental property of white matter that can be computed from a simple formula relating the myelin volume fraction to the fiber volume fraction or the axon volume fraction. In this paper, a unique combination of magnetization transfer, diffusion imaging and histology is presented, providing a novel method for in vivo magnetic resonance imaging of the axon volume fraction and the myelin g-ratio. Our method was demonstrated in the corpus callosum of one cynomolgus macaque, and applied to obtain full-brain g-ratio maps in one healthy human subject and one multiple sclerosis patient. In the macaque, the g-ratio was relatively constant across the corpus callosum, as measured by both MRI and electron microscopy. In the human subjects, the g-ratio in multiple sclerosis lesions was higher than in normal appearing white matter, which was in turn higher than in healthy white matter. Measuring the g-ratio brings us one step closer to fully characterizing white matter non-invasively, making it possible to perform in vivo histology of the human brain during development, aging, disease and treatment., (Copyright © 2015 Elsevier Inc. All rights reserved.)