The relationship between cognitive functioning and psychopathology in patients with psychiatric disorders: a transdiagnostic network analysis.

BACKGROUND: Patients with psychiatric disorders often experience cognitive dysfunction, but the precise relationship between cognitive deficits and psychopathology remains unclear. We investigated the relationships between domains of cognitive functioning and psychopathology in a transdiagnostic sample using a data-driven approach. METHODS: Cross-sectional network analyses were conducted to investigate the relationships between domains of psychopathology and cognitive functioning and detect clusters in the network. This naturalistic transdiagnostic sample consists of 1016 psychiatric patients who have a variety of psychiatric diagnoses, such as depressive disorders, anxiety disorders, obsessive-compulsive and related disorders, and schizophrenia spectrum and other psychotic disorders. Psychopathology symptoms were assessed using various questionnaires. Core cognitive domains were assessed with a battery of automated tests. RESULTS: Network analysis detected three clusters that we labelled: general psychopathology, substance use, and cognition. Depressive and anxiety symptoms, verbal memory, and visual attention were the most central nodes in the network. Most associations between cognitive functioning and symptoms were negative, i.e. increased symptom severity was associated with worse cognitive functioning. Cannabis use, (subclinical) psychotic experiences, and anhedonia had the strongest total negative relationships with cognitive variables. CONCLUSIONS: Cognitive functioning and psychopathology are independent but related dimensions, which interact in a transdiagnostic manner. Depression, anxiety, verbal memory, and visual attention are especially relevant in this network and can be considered independent transdiagnostic targets for research and treatment in psychiatry. Moreover, future research on cognitive functioning in psychopathology should take a transdiagnostic approach, focusing on symptom-specific interactions with cognitive domains rather than investigating cognitive functioning within diagnostic categories.

The impact of pace of life on pedestrian heat stress: A computational modelling approach.

Elevated walking speed is an indicator of increased pace of life in cities, caused by environmental pressures inherent to urban environments, which lead to short- and long-term consequences for health and well-being. In this paper we investigate the effect of walking speed on heat stress. We define the heat-stress-optimal walking speed and estimate its values for a wide range of air temperatures with the use of computational modelling of metabolic heat production and thermal regulation. The heat-stress-optimal walking speed shows three distinct phases in relation to air temperature, determined by different modes of interaction between the environment and physiology. Simulation results suggest that different temperature regimes require walking speed adaptation to preserve heat balance. Empirical data collected for Singapore reveals elevated average walking speed, which is not responsive to slight changes in microclimate (4-5 °C). The proposed computational model predicts the amount of additional heat produced by an individual due to the high pace of life. We conclude that there are direct implications of the high pace of life in cities on the immediate heat stress of people, and we show how a lower walking speed significantly reduces self-overheating and improves thermal comfort.

Identification of risk factors for patients with diabetes: diabetic polyneuropathy case study.

BACKGROUND: Methods of data mining and analytics can be efficiently applied in medicine to develop models that use patient-specific data to predict the development of diabetic polyneuropathy. However, there is room for improvement in the accuracy of predictive models. Existing studies of diabetes polyneuropathy considered a limited number of predictors in one study to enable a comparison of efficiency of different machine learning methods with different predictors to find the most efficient one. The purpose of this study is the implementation of machine learning methods for identifying the risk of diabetes polyneuropathy based on structured electronic medical records collected in databases of medical information systems. METHODS: For the purposes of our study, we developed a structured procedure for predictive modelling, which includes data extraction and preprocessing, model adjustment and performance assessment, selection of the best models and interpretation of results. The dataset contained a total number of 238,590 laboratory records. Each record 27 laboratory tests, age, gender and presence of retinopathy or nephropathy). The records included information about 5846 patients with diabetes. Diagnosis served as a source of information about the target class values for classification. RESULTS: It was discovered that inclusion of two expressions, namely "nephropathy" and "retinopathy" allows to increase the performance, achieving up to 79.82% precision, 81.52% recall, 80.64% F1 score, 82.61% accuracy, and 89.88% AUC using the neural network classifier. Additionally, different models showed different results in terms of interpretation significance: random forest confirmed that the most important risk factor for polyneuropathy is the increased neutrophil level, meaning the presence of inflammation in the body. Linear models showed linear dependencies of the presence of polyneuropathy on blood glucose levels, which is confirmed by the clinical interpretation of the importance of blood glucose control. CONCLUSION: Depending on whether one needs to identify pathophysiological mechanisms for one's prospective study or identify early or late predictors, the choice of model will vary. In comparison with the previous studies, our research makes a comprehensive comparison of different decisions using a large and well-structured dataset applied to different decision support tasks.

Game of neutrophils: modeling the balance between apoptosis and necrosis.

BACKGROUND: Neutrophils are one of the key players in the human innate immune system (HIIS). In the event of an insult where the body is exposed to inflammation triggering moieties (ITMs), neutrophils are mobilized towards the site of insult and antagonize the inflammation. If the inflammation is cleared, neutrophils go into a programmed death called apoptosis. However, if the insult is intense or persistent, neutrophils take on a violent death pathway called necrosis, which involves the rupture of their cytoplasmic content into the surrounding tissue that causes local tissue damage, thus further aggravating inflammation. This seemingly paradoxical phenomenon fuels the inflammatory process by triggering the recruitment of additional neutrophils to the site of inflammation, aimed to contribute to the complete neutralization of severe inflammation. This delicate balance between the cost and benefit of the neutrophils' choice of death pathway has been optimized during the evolution of the innate immune system. The goal of our work is to understand how the tradeoff between the cost and benefit of the different death pathways of neutrophils, in response to various levels of insults, has been optimized over evolutionary time by using the concepts of evolutionary game theory. RESULTS: We show that by using evolutionary game theory, we are able to formulate a game that predicts the percentage of necrosis and apoptosis when exposed to various levels of insults. CONCLUSION: By adopting an evolutionary perspective, we identify the driving mechanisms leading to the delicate balance between apoptosis and necrosis in neutrophils' cell death in response to different insults. Using our simple model, we verify that indeed, the global cost of remaining ITMs is the driving mechanism that reproduces the percentage of necrosis and apoptosis observed in data and neutrophils need sufficient information of the overall inflammation to be able to pick a death pathway that presumably increases the survival of the organism.

Time-frequency methods for structural health monitoring.

Detection of early warning signals for the imminent failure of large and complex engineered structures is a daunting challenge with many open research questions. In this paper we report on novel ways to perform Structural Health Monitoring (SHM) of flood protection systems (levees, earthen dikes and concrete dams) using sensor data. We present a robust data-driven anomaly detection method that combines time-frequency feature extraction, using wavelet analysis and phase shift, with one-sided classification techniques to identify the onset of failure anomalies in real-time sensor measurements. The methodology has been successfully tested at three operational levees. We detected a dam leakage in the retaining dam (Germany) and "strange" behaviour of sensors installed in a Boston levee (UK) and a Rhine levee (Germany).

Behavioural thermal regulation explains pedestrian path choices in hot urban environments.

Due to phenomena such as urban heat islands, outdoor thermal comfort of the cities' residents emerges as a growing concern. A major challenge for mega-cities in changing climate is the design of urban spaces that ensure and promote pedestrian thermal comfort. Understanding pedestrian behavioural adaptation to urban thermal environments is critically important to attain this goal. Current research in pedestrian behaviour lacks controlled experimentation, which limits the quantitative modelling of such complex behaviour. Combining well-controlled experiments with human participants and computational methods inspired by behavioural ecology and decision theory, we examine the effect of sun exposure on route choice in a tropical city. We find that the distance walked in the shade is discounted by a factor of 0.86 compared to the distance walked in the sun, and that shadows cast by buildings have a stronger effect than trees. The discounting effect is mathematically formalised and thus allows quantification of the behaviour that can be used in understanding pedestrian behaviour in changing urban climates. The results highlight the importance of assessment of climate through human responses to it and point the way forward to explore scenarios to mitigate pedestrian heat stress.

A unifying model to estimate the effect of heat stress in the human innate immunity during physical activities.

Public health is threatened by climate change and extreme temperature events worldwide. Differences in health predispositions, access to cooling infrastructure and occupation raises an issue of heat-related health inequality in those vulnerable and disadvantaged demographic groups. To address these issues, a comprehensive understanding of the effect of elevated body temperatures on human biological systems and overall health is urgently needed. In this paper we look at the inner workings of the human innate immunity under exposure to heat stress induced through exposure to environment and physical exertion. We couple two experimentally validated computational models: the innate immune system and thermal regulation of the human body. We first study the dynamics of critical indicators of innate immunity as a function of human core temperature. Next, we identify environmental and physical activity regimes that lead to core temperature levels that can potentially compromise the performance of the human innate immunity. Finally, to take into account the response of innate immunity to various intensities of physical activities, we utilise the dynamic core temperatures generated by a thermal regulation model. We compare the dynamics of all key players of the innate immunity for a variety of stresses like running a marathon, doing construction work, and leisure walking at speed of 4 km/h, all in the setting of a hot and humid tropical climate such as present in Singapore. We find that exposure to moderate heat stress leading to core temperatures within the mild febrile range (37, 38][Formula: see text], nudges the innate immune system into activation and improves the efficiency of its response. Overheating corresponding to core temperatures beyond 38[Formula: see text], however, has detrimental effects on the performance of the innate immune system, as it further induces inflammation, which causes a series of reactions that may lead to the non-resolution of the ongoing inflammation. Among the three physical activities considered in our simulated scenarios (marathon, construction work, and walking), marathon induces the highest level of inflammation that challenges the innate immune response with its resolution. Our study advances the current state of research towards understanding the implications of heat exposure for such an essential physiological system as the innate immunity. Although we find that among considered physical activities, a marathon of 2 h and 46 min induces the highest level of inflammation, it must be noted that construction work done on a daily basis under the hot and humid tropical climate, can produce a continuous level of inflammation triggering moieties stretched at a longer timeline beating the negative effects of running a marathon. Our study demonstrates that the performance of the innate immune system can be severely compromised by the exposure to heat stress and physical exertion. This poses significant risks to health especially to those with limited access to cooling infrastructures. This is due in part to having low income, or having to work on outdoor settings, which is the case for construction workers. These risks to public health should be addressed through individual and population-level measures via behavioural adaptation and provision of the cooling infrastructure in outdoor environments.

Supplemented Alkaline Phosphatase Supports the Immune Response in Patients Undergoing Cardiac Surgery: Clinical and Computational Evidence.

Alkaline phosphatase (AP) is an enzyme that exhibits anti-inflammatory effects by dephosphorylating inflammation triggering moieties (ITMs) like bacterial lipopolysaccharides and extracellular nucleotides. AP administration aims to prevent and treat peri- and post-surgical ischemia reperfusion injury in cardiothoracic surgery patients. Recent studies reported that intravenous bolus administration and continuous infusion of AP in patients undergoing coronary artery bypass grafting with cardiac valve surgery induce an increased release of liver-type "tissue non-specific alkaline phosphatase" (TNAP) into the bloodstream. The release of liver-type TNAP into circulation could be the body's way of strengthening its defense against a massive ischemic insult. However, the underlying mechanism behind the induction of TNAP is still unclear. To obtain a deeper insight into the role of AP during surgery, we developed a mathematical model of systemic inflammation that clarifies the relation between supplemented AP and TNAP and describes a plausible induction mechanism of TNAP in patients undergoing cardiothoracic surgery. The model was validated against clinical data from patients treated with bovine Intestinal AP (bIAP treatment) or without AP (placebo treatment), in addition to standard care procedures. We performed additional in-silico experiments adding a secondary source of ITMs after surgery, as observed in some patients with complications, and predicted the response to different AP treatment regimens. Our results show a strong protective effect of supplemented AP for patients with complications. The model provides evidence of the existence of an induction mechanism of liver-type tissue non-specific alkaline phosphatase, triggered by the supplementation of AP in patients undergoing cardiac surgery. To the best of our knowledge this is the first time that a quantitative and validated numerical model of systemic inflammation under clinical treatment conditions is presented.