Electrostatic sensor arrays (ESAs) are promising in industrial applications related to charged particle monitoring. Sensitivity is a fundamental and commonly-used sensing characteristic of an ESA. However, the usually used spatial sensitivity, which is called static sensitivity here, is not proper for moving particles or capable of reflecting array signal processing algorithms integrated in an ESA. Besides, reports on ESAs for intermittent particles are scarce yet, especially lacking suitable array signal processing algorithms. To solve the problems, the dynamic sensitivity of ESA is proposed, and a hemisphere-shaped electrostatic sensors’ circular array (HSESCA) along with its application in intermittent particle monitoring are taken as an example. In detail, a sensing model of the HSESCA is built. On this basis, its array signals are analyzed; the dynamic sensitivity is thereupon defined by analyzing the processing of the array signals. Besides, a component extraction-based array signal processing algorithm for intermittent particles is proposed, and the corresponding dynamic sensitivity is analyzed quantitatively. Moreover, simulated and experimental results are discussed, which validate the accuracy of the models and the effectiveness of the relevant approaches. The proposed dynamic sensitivity of ESA, as well as the array signal processing algorithm are expected to provide references in modeling, designing and using ESAs. Electrostatic monitoring systems (EMSs) are featured with the advantages of robustness and low cost ,2, makinThe sensing principle of an electrostatic sensor is electrostatic induction. It determines that even if a particle carries a constant charge, the corresponding induced charge on an electrostatic sensor probe will reduce sharply when the distance between the particle and the probe gets larger. As a result, a near particle with quite weak charge can generate similar signals as a far particle with great charge. That is to say, the charge quantity of a particle can hardly be accurately monitored by a single electrostatic sensor if the position of the particle is not provided. In view of the sensitivity, this means that most electrostatic sensors have the drawback of inhomogeneous and quite localized sensitivity; thus, only particles near the probe can be effectively detected ,10. In aCircular ESA is a kind of representative hardware structure, which is made up by placing some identical electrostatic sensors uniformly around a circular pipeline in one cross-section ,16,17,18In the aspect of application, a circular ESA is usually used to detect the particle distribution over the cross-section of a pipeline and further infer gas-solid flow parameters, such as particle density and flow regime. In these cases, the particles to be monitored are continuous in the time domain. That is to say, there are always numerous particles passing a cross-section simultaneously, thus forming an obvious profile of the solid-phase, which can be imaged by tomography-based methods ,11,14. ETo solve the problems above, the dynamic sensitivity of ESA is proposed to describe the sensitivity of ESAs in a systemic perspective. An ESA called the hemisphere-shaped electrostatic sensors’ circular array (HSESCA) along with its application in intermittent particle monitoring are taken as an example. In detail, a sensing model of the HSESCA, as well as that of the sensor units is built in This section builds a quantitative relationship between a charged particle and the induced charge of an HSESCA, which provides a theoretical foundation for this paper.An HSESCA with eight sensor units is installed on a grounded pipeline, as shown in K whose unit is V/C. A hemispherical probe and its signal conditioner channel compose an independent sensor unit of the HSESCA. The array signal analyzer is composed of a signal acquisition card and a computer. Some specially-designed array signal processing algorithms are usually integrated in the computer to calculate the monitoring parameters (denoted as M) of the whole HSESCA.The hemispherical probes are uniformly installed in a cross-section around the pipeline. It is called the observation cross-section. Once the charged particles pass, the induced charge will be generated on each probe and then converted into voltage array signals immediately by the multi-channel signal conditioner for post-processing. Every channel of the conditioner is designed as an identical proportional two-stage amplifier as in As the sensitivity characteristics of an electrostatic sensor are quite localized ,9,10 andx-axis and the z-axis, respectively. Then, the y-axis is determined by the right-hand rule automatically. Accordingly, a point in the pipeline is denoted as P.As shown in −19 s), the interaction between the probe and charged particles in the pipeline can be described by a pure electrostatic field [1 is the hemispherical surface of the probe and Γ2 is the inner wall of the pipeline. tρ(P) is the volume charge density in the pipeline at time t, and tφ(P) is the corresponding potential distribution. Besides, const(t) is a constant function of t, describing the equipotential surface of the probe. ε is the permittivity of free space, and Because electrostatic equilibrium states are reached instantaneously  is firstly solved using the Green function and the method of image charges. Then, the sensing model at P is obtained according to the relationship between the induced charge and the potential distribution on a conductor surface [Q is the total induced charge on the probe, a is the radius of the probe and On account of the pipeline being much bigger than the probe, the electrostatic field on the inner wall is simplified as that on one infinite plane ,6,17. Inq ,10, φt and those of the point charge denoted as P in the new coordinate system; as shown in In order to build a sensing model for all of the sensor units in the same coordinate system, firstly, according to the symmetry of the probe, Equation (2) is transformed into:  one see  to the ci-th sensor unit is derived from Equation (3) as: ib is the distance from the charged particle to the i-th probe and iβ is the included angle between the point charge and the axis of the i-th probe. They are determined by geometrical relationships: O and the bottom face of a probe.Thereupon, the sensing model of the Further, the sensing model of the HSESCA is obtained by making a superposition of sensing models of all of the sensor units. That is: D = −0.0188 iβ + 0.0444 is the calibration boundary that is determined according to the variation trend of the relative error [ib < D, the relative error is negligible; thus, the sensing model is only calibrated where ib ≥ D. The calibration parameters are obtained using fitting methods; they are: In addition, an FEM-based calibration method was proposed as a supplement to consider the actual boundary conditions . It is uve error . In the It is obvious that Equation (7) is calibrated as In order to make a comparison with the dynamic sensitivity of ESA, the static sensitivity of ESA is defined here. The static sensitivity of an electrostatic sensor is defined as the absolute induced charge on the probe generated by a unit charge ,8,21. Anq are of opposite signs. As for an HSESCA, its static sensitivity model is derived from Equations (9) and (10): The minus indicates that the induced charge and the point charge When actual boundary conditions are considered, the model in the observation cross-section can also be calibrated in a similar way as Equation (8), that is Array signal processing algorithms are included in the definition of the dynamic sensitivity of ESA. In order to find effective array signal processing algorithms for an HSESCA, the characteristics of its array signal shave to be analyzed.x-coordinates of the particle are denoted with velocity v and time t, while the y-coordinates and z-coordinates are regarded as constants. In this way, induced charge on the i-th probe is expressed by iQ, where x0 is the initial x-coordinate. After that, the induced charge is transformed and amplified into voltage according to the amplification coefficient K of the signal conditioner  and (12), one can get: K = −1, q = 1C, and the time when the particle reaches the observation cross-section is set as the zero time . The radius of the hemispherical probes is set to 12 mm, and the motion path is set to y = 100 mm and z = 70 mm  occur on gas path components of gas turbines, some fault-related particles will be produced and charged. Thus, the condition information of the gas path components can be obtained by monitoring the particles ,6,7,28. i-th sensor unit of the HSESCA, its dynamic sensitivity model builds a relationship between moving charged particles and its out-put voltage signals, as Equation (14). This is expressed by As for a single electrostatic sensor, for example the q and position . They codetermine the signal peak uimax, according to the unit’s dynamic sensitivity model SiD,, that is uimax, = qSiD,. However, the relationship is irreversible in practical applications. This is because the position information is difficult to obtain by using a single electrostatic sensor; thus, the value of SiD, is not determined. As a result, the charge quantity q cannot be calculated backward for the lack of position information. This is the basic reason for the low monitoring accuracy of a single electrostatic sensor.This means that a charged particle contains two kinds of information, charge quantity It has been mentioned that the array signals of an HSESCA contain the position information of a monitored particle see , which cq and position . They codetermine the signal peak uimax, of each sensor unit according to its dynamic sensitivity model SiD,. Then, the peaks are processed by a certain array signal processing algorithm to calculate the monitoring parameter M. In this process, the estimated position information  of the particle is usually obtained and used. Therefore, valves of SiD, are determined by the position information, making it possible to calculate the charge quantity q backward. In fact, the monitoring parameters of many applications are just the charge quantity or some derivative values of it. As a result, by using an HSESCA and corresponding array signal processing algorithms, the monitoring accuracy can be improved.This means that a charged particle contains two kinds of information, charge quantity FD is proposed to denote the array signal processing algorithms. It builds the relationship between the array signals and monitoring parameters of an ESA  is the vector of the signal peaks and SD is the vector of dynamic sensitivity values of the sensor units. The q is reducible because FD has to be designed as a linear operator of q.Further, the dynamic sensitivity of ESA is defined in the observation cross-section as the absolute value of a monitoring parameter when a unit charge passes. As for intermittent particle monitoring, the dynamic sensitivity model of an HSESCA is expressed as: It is seen from Equation (15) that the essence of the dynamic sensitivity of ESA is a recombination of the dynamic sensitivity of the sensor units according to a dynamic operator, which builds a direct relationship between moving charged particles and the system monitor values of an ESA. In other words, the dynamic sensitivity of ESA reflects the monitoring accuracy of an ESA directly by taking array signal processing algorithms into consideration. The concept of dynamic sensitivity has been used by Zhou et al. , but theA proper array signal processing algorithm is significant to ensuring the monitoring accuracy of an ESA. As for intermittent particle monitoring , it has been mentioned that the accurate charge quantity of any monitored particle is desired; thus, the position information of the particle should be used. In addition, the demand for real-time monitoring should be met to avoid missing momentary faults; thus, the corresponding array signal processing algorithms have to be fast enough.To meet the conditions above, a component extraction-based array signal processing algorithm is designed. It is based on a simple idea that a monitored particle is located near the sensor units that produce larger signal peaks. According to this idea, a set of common components is extracted from the peaks of the array signals. The components are considered to be generated by a set of imaginary point charges. They have fixed positions, but their imaginary charge quantities vary with the position of the monitored particle. In this way, the position information of the monitored particle can be used according to different charge quantities of the imaginary point charges. It is worth noting that the accurate position of a particle is not needed in the algorithm, but it is made use of by introducing a component extraction-based method. As a result, the algorithm only contains some simple steps, which are convenient for computer processing. More details are provided as follows.y = 100 mm and z = 70 mm.As shown in Umax. Then, Umax is re-sorted into Ur incrementally according to the absolute values of the signal peaks. That is to say, the i-th absolute smallest peak is denoted as riu; thus, the new vector is Ur{ru1, ru2, ru3, ru4, ru5, ru6, ru7, ru8}. For example, the No. 2 probe is the nearest one to the point charge, while the No. 6 probe is the farthest one to the point charge . In detail, the absolute smallest signal peak ru1 is firstly denoted as c1; it is a common signal component contained in every signal peak. Then, the second absolute smallest peak ru2 is denoted as the sum of c1 and c2. It is obvious that c2 is a common signal component contained in every signal peak, except ru1, and so on; a vector of eight common signal components is extracted from Ur, that is C{c1,c2, c3, c4, c5, c6, c7, c8}. The second step is component extraction. It is clear that a monitored particle is located near the sensor units that produce larger signal peaks. Thus, if a signal component is only contained in one signal peak, its value implies how close the particle is to the corresponding sensor probe. Analogously, if a signal component is contained in every signal peak, its value implies how close the particle is to the central point. Accordingly, a set of common signal components is extracted from q1 located in the central point is firstly assumed to generate c1. Then, because c2 is contained in every signal peak, except that of the No. 6 sensor unit, an imaginary point charge q2 is located in the connection line between the origin, and the No. 2 probe is assumed to generate c2. Analogously, as c3 is produced by every sensor unit except the No. 5 and No. 6 sensor units, q3 located in the bisector of the No. 1 and the No. 2 probes is assumed to generate c3, and so on; eight imaginary point charges are decomposed from the charged particle q, as shown in q8 should be quite close to the No. 2 probe, because its relevant signal component is only produced by that probe. The positions of the imaginary point charges are considered to be fixed due to the symmetry of the HSESCA. However, their imaginary charge quantities, which are determined by the values of the extracted components, vary with the position of the monitored particle. In other words, the charge quantities of the imaginary point charges imply the position information of the monitored particle.The third step is weighting and summation. First of all, the extracted signal components are considered to be generated by a set of imaginary point charges. In detail, based on the symmetry of the circular array and the idea that a charged particle is located near the sensor units that produce larger signal peaks, an imaginary point charge i-th imaginary point charge is expressed as iq = ic/is, where is is the dynamic sensitivity of the No. 2 sensor unit at the position of iq. By recording: iq = iciw, where iw is just the weight coefficient of ic.Next, the charge quantities of the imaginary point charges are calculated, which can be regarded as a process of weighting the extracted components according to the position information. According to the dynamic sensitivity model of the sensor units as Equation (14), the M is obtained by summing up the imaginary point charges: W is the vector of the weight coefficients and C is the vector of the extracted signal components. When q is in some symmetric lines of the HSESCA, some components could be zero, but it does not affect the computing process.Finally, the monitoring parameter W is determined in the pre-step  at the grid points shown in As mentioned above, an HSESCA with eight sensor units is installed on a grounded pipeline. The pipeline has an inner radius of 200 mm; the hemispherical probes have a radius of 12 mm with their button faces 2 mm far from the inner wall of the pipeline. For the sake of simplicity, the amplification coefficient of the signal conditioner is set to The simulated results are shown by the surface diagrams in The static sensitivity of the HSESCA in the observation cross-section is calculated by using Equation (11) and the calibration method. The results are shown in It is seen from K = −1. Then, by placing a point charge q = 1 C in turn at each grid point shown in For the sake of simplicity, here, we set the amplification coefficient It is seen from Experimental results were obtained by using an eight-channel HSESCA experiment apparatus. As shown in In the experiment, the particles were released at different test points, as shown in P1, P2, P3, P4 and P5, respectively , the experimental value at each test point was obtained by dividing the summation of all of the signal peaks by the charge quantity of the corresponding particle, followed by a scaling to suppose K = −1. The results are shown in To make a comparison between the theoretical and experimental results of the static sensitivity of the HSESCA, the theoretical values in Line 1 and Line 2 were firstly calculated by using Equation (11) and the calibration method when It can be seen that the experimental values show fine consistencies with the theoretical ones. Further analysis shows that the mean absolute value of relative error from all of the test points in Line 1 is 2.2544%, and that in Line 2 is 1.3516%. The errors are acceptable and can be explained by the errors in controlling the particles’ falling positions and measuring their charge quantities. Therefore, the sensing model of the HSESCA, as well as that of the sensor units are validated.K = −1, the theoretical values in Line 1 and Line 2 were firstly calculated (see K = −1. The results are shown in Theoretical and experimental results of the dynamic sensitivity of the HSESCA were also compared. When the amplification coefficient was set to ated see . After tIt is observed that the experimental values match well with the theoretical ones. Further analysis shows that the mean absolute value of relative error from all of the test points in Line 1 is 3.3233%, and that in Line 2 is 0.5936%. Just as the results in the static sensitivity test, the errors here are acceptable and can be explained by the errors in controlling the particles’ falling positions and measuring their charge quantities. In addition, by making a comparison between The experimental results match well with the theoretical ones, which has validated the accuracy of the theoretical models and effectiveness of the corresponding methods.Compared with static sensitivity, the dynamic sensitivity of the HSESCA has much greater values in most of the observation cross-section. This demonstrates that the component extraction-based array signal processing algorithm is effective at overcoming the defect of inhomogeneous and localized static sensitivity, thus making a significant improvement on the monitoring accuracy for intermittent particles.There still exist relatively less sensitive zones near the inner wall of the pipeline after adopting the proposed algorithm. This is caused by the influence of the pipeline on the electrostatic field. A strategy to optimize the number of sensor units combined with optimizations on the proposed algorithm is likely to alleviate the drawback, which deserves further studies.Ill-conditioning and noise may impact the results of the proposed array signal processing algorithm. This is of great significance, to be discussed in further studies.By taking the processing of the array signals into consideration, the dynamic sensitivity of ESA has been defined to describe the sensitivity characteristics of ESAs in a systemic perspective. It builds a direct relationship between the monitored particles and the monitoring parameters of a whole ESA, thus reflecting the monitoring accuracy directly. An HSESCA along with its application in intermittent particle monitoring has been taken as an example. Its dynamic sensitivity in accordance with a proposed component extraction-based array signal processing algorithm has been analyzed quantitatively. Relevant numerical simulations have been made, and experimental validations have been carried out on an eight-channel HSESCA experiment apparatus. Detailed results have been provided, compared and discussed, which are summarized as follows:


MicroRNA are major regulators of neuronal gene expression at the post-transcriptional and translational levels. This layer of control is critical for spatially and temporally restricted gene expression, facilitating highly dynamic changes to cellular structure and function associated with neural plasticity. Investigation of microRNA function in the neural system, however, is at an early stage, and many aspects of the mechanisms employing these small non-coding RNAs remain unclear. In this article, we critically review current knowledge pertaining to microRNA function in neural activity, with emphasis on mechanisms of microRNA repression, their subcellular remodelling and functional impacts on neural plasticity and behavioural phenotypes. Neurons are characterized by their ability to rapidly integrate, store and transmit synaptic stimuli received from a multiplicity of sources. This complex nature is thought to be underpinned by the inherent plasticity of neuronal structure and excitability, both of which are intrinsically linked and associated with modulation of neuronal communication and information storage in complex organisms ,2. In reThe regulation of mRNA translation, in particular, has been subject to increasing focus due to its intricate nature and extensive potential for fine-tuning of neuronal remodelling. Since the discovery of active ribosomes in dendritic spines ,5, it haMounting evidence supports a major regulatory role for brain-enriched non-coding microRNA (miRNA) at the post-transcriptional and translational levels through target-specific repression of mRNA . RecentlmiRNA are a family of ∼22nt non-coding RNAs initially characterized in 1993 as negative regulators of gene expression ,17. SincmiRNA genes are typically transcribed by RNA polymerase II and processed by the Drosha-DGCR8  nuclear microprocessor complex to yield ∼70nt hairpin precursor miRNAs (pre-miRs) ,21. NewlmiRNA and the RISC have been traditionally characterized as mediators of transcript degradation, which has been observed in multiple eukaryotic systems ,31. In pThe majority of human miRNA tend to engage in imperfect base-pairing with targets to promote degradation via the 5′ to 3′ mRNA decay pathway . In contet al.  mRNA without triggering degradation, causing these cells to exhibit decreased responsiveness to nicotine stimulation  and facilitation (Aplysia) . P-bodies are thought to act as cytoplasmic foci of miRNA-mediated mRNA repression, which form upon the aggregation of 5′ to 3′ decay machinery, RISC components and translationally arrested mRNAs ,63. AlthAplysia) . Taken tGiven the capacity of miRNA to precisely regulate the stability and translation of mRNA, further investigation of their subcellular localisation in neurons provides important insight into their function. Early tissue profiling studies identified the CNS as a source of miRNA enrichment ,75, withet al.  receptors, resulting in dendritic outgrowth which bears strong functional relevance for neuronal miRNA localisation in activity-dependent neuronal plasticity  transcription of its host gene after pharmacological stimulation of hippocampal neurons ,86. Thiset al.  demonstret al. .et al.  or spared nerve injury (in vivo)  . Interesin vivo) . ThereinTarget RNA-directed miRNA degradation (TDMD) has also recently emerged as a novel mechanism of neuronal miRNA downregulation, whereby extensive complementarity with a target RNA leads to miRNA destabilisation and decay through 3′ trimming or the untemplated addition of A residues . Complemet al. —a protein kinase which regulates translational control pathways—from functional repression . The resin vivo in brain regions such as the hippocampus has been shown strongly influence performance in behavioural paradigms associated with memory. This concept was demonstrated in a study by Konopka et al (Dicer1 knockout mouse to investigate the effects of total miRNA ablation. Subsequent remodelling of dendritic spine structure and increased expression of synapse-associated proteins were, in part, thought to contribute to an enhancement of spatial and fear-associated memory after Morris water maze and fear conditioning paradigms (et al. (Patterns of miRNA expression, and the resultant changes to gene expression evidently play a major role in maintaining and dynamically modulating neural plasticity. Many of the resultant modifications to neuronal excitability and morphology have been directly observed in models of synaptic plasticity, the hypothesised biological mechanism behind the phenomena of learning and memory . Accordika et al , who devaradigms . These r (et al. , wherebySeveral specific miRNA species have been implicated in the regulation of neurocognitive functions associated with synaptic plasticity. These studies suggest that aberrant regulation of a subset of genes may result in overall abnormal neurobehavioural phenotypes. For example, overexpression of miR-134 in the CA1 region of the hippocampus results in contextual fear learning deficits in mice, indicative of the role miR-134 plays in negative regulation of dendritic spine size . SimilarFrom the discussed evidence, it is clear that miRNA regulation of gene expression has particularly distinct complexity and biological significance in the neuronal context. Although investigating the interactions and physiological impacts associated with individual miRNA has been an essential aspect of research effort, the mechanistic details associated with miRNA expression and the discrete decision-making processes involved, is of key importance to fully appreciate how these molecules operate. One dimension of miRNA function which will likely form key focus in coming years with regards to the neuron is the modulation of mRNA translational competency, which presents an especially interesting and seemingly logical system by which subcellular neuronal compartments such as dendritic spines could express genes in a semi-autonomous manner. Recent reports of miRNA acting as translational regulators supports the existence of such a system ,52,58–60Our understanding of miRNA in the regulation of neural plasticity is slowly emerging and likely to expand further in coming years as new miRNA are implicated and characterized. While over 3700 mammalian miRNA are currently supported by evidence , and a lPost-transcriptional gene regulation is vital to organizing the intricate patterns of intracellular protein synthesis that supports complex cellular morphology, cellular networks and systems. The vertebrate brain has optimized these systems by incorporating small non-coding RNA as the universal guide to mediate the highest specificity of interactions at the lowest biological cost. In this review we have summarized what is known about this remarkable system, as there is increasing evidence that post-transcriptional regulation of gene expression is critical for neuronal plasticity and its neurobehavioural manifestations. We are currently just scratching the surface of this mechanism, and further investigation of miRNA in particular is likely to reveal significant new insights into the complexity of neuronal gene expression and function.


Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations.Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan  in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding.Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications. Levosimendan was developed in the early 1990s in Finland and became available for prescription starting in 2001. It has been used since then in more than 60 countries. The unique pharmacological properties of this drug raised a major interest among physicians in charge of patients with heart failure, both in the medical and the surgical environments. Initial studies were most often positive, attesting for improvement in hemodynamics and/or organ function, and even suggested a reduced mortality . ShortlyLevosimendan has a pharmacodynamic profile combining inotropic and vasodilating effects (inodilator), and a nearly unique (among inotropes) myocardial protective effect. The inotropic effect results, in part, from an increased affinity of troponin C for calcium when the drug is present, which in turn prolongs the duration of actin/myosin cross-bridges –12. ThisFrom the pharmacokinetic point of view, levosimendan has a fast onset of action and a half-life of 1 h. The drug undergoes hepatic metabolism (acetylation) followed by renal excretion. Quite uniquely, it has an active metabolite with a very long half-life 70–80 h) responsible for a prolonged effect , 23. All0–80 h reThe “classical” inotropic drugs (catecholamines and phosphodiesterase III inhibitors) are widely used in the perioperative setting, particularly in patients undergoing cardiac surgery. While they can provide life-sustaining support in circumstances of severe right and/or left cardiac ventricular failure and improve both clinical symptoms experienced by patients and systemic end-organ perfusion, the benefits of these inotropes on medium- and long-term survival have never been documented . To dateThe catecholamines  are the most frequently used during the perioperative period. With an elimination half-life of just a few minutes, their on/off properties are quite appreciated at the bedside. The infusion of dobutamine produces a dose-dependent rise in cardiac output, mainly by increasing heart rate rather than stroke volume . Major an = 52) of patients with acute or chronic heart failure and treated with beta-blockers, a prospective randomized double-blind international study found that levosimendan, as opposed to dobutamine, increased cardiac index and decreased pulmonary capillary wedged pressure, but failed to improve clinical symptoms and mixed venous oxygen saturation [Patients receiving beta-blockers (BB) in an acute or chronic setting have an altered beta-adrenergic receptor function and are therefore unlikely to respond optimally to catecholamines. The relevant clinical contexts are as follows: (i) patients with acute myocardial infarction given BB prophylactically who subsequently develop cardiogenic shock and require inotropic support, (ii) patients with chronic heart failure who are under chronic BB therapy and have acute on chronic cardiac decompensation, and (iii) patients with accidental/intentional BB intoxication. When beta-adrenergic receptors number and/or function are decreased, levosimendan appears as the drug of choice because its mechanisms of action are independent of this receptor. This is supported by a few experimental and clinical studies. In an animal model of acute intoxication with propranolol, Leppikangas et al. demonstrated that levosimendan, but not dobutamine or placebo, was able to increase stroke volume, inotropism, heart rate, and mean arterial pressure . This waturation . In addituration , 34. Basturation , 36.Fig−1 min−1) over 6 h at 2-week intervals in 120 advanced heart failure patients [p = 0.069). The LION-HEART study, another multicenter RCT involving 69 patients with chronic advanced heart failure, compared the effect of 6-h levosimendan infusions (0.2 μg kg−1 min−1) repeated every 2 weeks for 12 weeks with placebo infusions on NT-proBNP levels at 12 weeks [P < 0.001) and attenuated the decline in quality of life . The incidence of serious adverse events was not different between treatment and placebo groups, reflecting the safety of repetitive infusions of levosimendan. However, it is important to mention that although mortality and readmission rates decreased with levosimendan, they remained much higher in comparison to those observed when heart transplantation or mechanical circulatory assist devices could be carried out. Therefore, the strategy of repetitive infusions cannot be considered as an alternative to them, but alleviates the symptoms and improves the quality of life in patients awaiting transplantation or in those who are ineligible for more invasive approaches. A new RCT  is currently under way to try to confirm the usefulness of repeated infusions of levosimendan in this patient population [Patients with symptomatic advanced heart failure despite optimal medical treatment are sometimes unable to be discharged because they are dependent on dobutamine infusions that cannot be weaned off. Such patients are at high-risk of death and may be waiting for a heart transplantation or a long-term mechanical assist device or, in contrast, may not be eligible for these therapeutic options. In such situations, repetitive infusions of levosimendan may offer the advantage of a prolonged inotropic effect with the possibility of improving the clinical symptomatology and allowing hospital discharge. Very limited data exists regarding the effectiveness of repetitive infusions of levosimendan –41. A repatients . The imp12 weeks . The autpulation .Although the classical hemodynamic profile of cardiogenic shock associates low cardiac output, low arterial pressure, elevated left/right ventricular diastolic pressure, and elevated systemic vascular resistance, other phenotypes can be encountered. Some shock states related to ischemia-reperfusion injury lead to a sepsis-like syndrome with low systemic vascular resistance , 47, whiUnlike dobutamine, levosimendan increases moderately myocardial oxygen consumption, does not alter diastolic function, and has less direct pro-arrhythmic effects . Moreove2 [There is currently no high-quality study dealing with the use of levosimendan in cardiogenic shock. The most recent meta-analysis performed using a few studies with a high risk of bias, reports that, when compared to dobutamine, levosimendan did not affect short and long-term mortality, ischemic events, acute kidney injury, dysrhythmias, or hospital length of stay . Levosim2 . The nee2 , 50. Cur2 . A new RTakotsubo syndrome is a form of acute myocardial stunning in which catecholamines appear to have a central role in the pathophysiology, as there is no occlusive coronary artery disease to explain the pattern of temporary LV dysfunction observed. To date, there have been no randomized trials to define the optimal management of patients with suspected Takotsubo syndrome. Levosimendan has been advocated as the first choice inotropic support when mechanical circulatory assist devices are not available –54. ThisThere is experimental evidence attesting for the ability of levosimendan to reverse, in part, pulmonary vasoconstriction and improve right ventricular function in various animal models of pulmonary hypertension –58. Pati. To avoid this complication, low doses of positive inotropic drugs are commonly administered in order to maintain left ventricular ejection and avoid upstream congestion. Moreover, since the duration of VA ECMO is directly correlated to complications, the weaning of the device should be attempted as soon as possible. Although dobutamine is currently the first-line drug used for patients in cardiogenic shock [Veno-arterial extra-corporeal membrane oxygenation (VA ECMO) is used to restore adequate perfusion to vital organs in patients suffering from refractory cardiogenic shock . Howeveric shock , 66, theic shock –70. Howeic shock , 71. In Experimentally, in septic rabbits, levosimendan yields a similar improvement in left ventricular systolic function, when compared to dobutamine or milrinone, but improves diastolic function to a greater extent . A largeAlthough two large randomized controlled trials failed to show a reduction in composite endpoints reflecting low cardiac output syndrome and mortality in a mixed population of CABG, valvular, or combined surgery with LVEF< 40% , 8, a reDue to a very interesting pharmacological profile, levosimendan has raised a lot of interest in the field of heart failure management. Unfortunately, all the large randomized controlled trials have failed to demonstrate a clear superiority of this drug over placebo, when used on top of usual catecholamines, in the populations that they have tested. Even if the initial enthusiasm for this drug has somewhat been reconsidered, there are still good reasons to believe that it might be useful in specific subgroups. These include patients with acute heart failure receiving beta-blockers and Takotsubo syndrome, patients awaiting heart transplant or left ventricular assist device implantation, and patients under VA ECMO to facilitate weaning. In addition, there may still be room for levosimendan in the management of some patients with cardiogenic shock, and as a prophylactic treatment prior to CABG surgery in patients with low LVEF. Additional studies are still required to support these potential indications with a higher level of evidence.


Healthy eating and fitness mobile apps are designed to promote healthier living. However, for young people, body dissatisfaction is commonplace, and these types of apps can become a source of maladaptive eating and exercise behaviors. Furthermore, such apps are designed to promote continuous engagement, potentially fostering compulsive behaviors.The aim of this study was to identify potential risks around healthy eating and fitness app use and negative experience and behavior formation among young people and to inform the understanding around how current commercial healthy eating and fitness apps on the market may, or may not, be exasperating such behaviors.Our research was conducted in 2 phases. Through a survey (n=106) and 2 workshops (n=8), we gained an understanding of young people’s perceptions of healthy eating and fitness apps and any potential harm that their use might have; we then explored these further through interviews with experts (n=3) in eating disorder and body image. Using insights drawn from this initial phase, we then explored the degree to which leading apps are preventing, or indeed contributing to, the formation of maladaptive eating and exercise behaviors. We conducted a review of the top 100 healthy eating and fitness apps on the Google Play Store to find out whether or not apps on the market have the potential to elicit maladaptive eating and exercise behaviors.Participants were aged between 18 and 25 years and had current or past experience of using healthy eating and fitness apps. Almost half of our survey participants indicated that they had experienced some form of negative experiences and behaviors through their app use. Our findings indicate a wide range of concerns around the wider impact of healthy eating and fitness apps on individuals at risk of maladaptive eating and exercise behavior, including (1) guilt formation because of the nature of persuasive models, (2) social isolation as a result of personal regimens around diet and fitness goals, (3) fear of receiving negative responses when targets are not achieved, and (4) feelings of being controlled by the app. The app review identified logging functionalities available across the apps that are used to promote the sustained use of the app. However, a significant number of these functionalities were seen to have the potential to cause negative experiences and behaviors.In this study, we offer a set of responsibility guidelines for future researchers, designers, and developers of digital technologies aiming to support healthy eating and fitness behaviors. Our study highlights the necessity for careful considerations around the design of apps that promote weight loss or body modification through fitness training, especially when they are used by young people who are vulnerable to the development of poor body image and maladaptive eating and exercise behaviors. There was a sense that apps should send positive notifications regardless of whether the daily goal was achieved:Apps that implemented a positive approach to encourage users for their effort were seen to be more appealing. Participants noted that receiving “little badges” (W2-P2) or a simple message such as “nice one, you’ve done that well” (W1-P5) could be [On Fitbit] at the end of the day if you don’t hit your daily step target [...] it just goes back to the next day, but then if you do hit it, it goes green and it’s like “woohoo”. But MyFitnessPal, I think it’s like addictive methods of trying to get you to use it to reach your goals.W2-P2However, this concept of achieving set goals was not always seen to be a positive thing. Participants described how fixating around the attainment of a goal could lead to obsessive behaviors: “You don’t want to do badly, so it makes you more obsessive of reaching your goals” (W1-P1) and how not reaching a specific goal could lead to feelings of distress and guilt: “The worst features of the apps are that he [the persona character] feels guilty if he goes over calories and that can cause further restriction and it’s made him obsessive” (W1-P4), which could in turn lead to negative counter-behaviors, such as meal skipping: “you could reach your calories at like 3pm and then you don’t feel like you could eat anything else for that day” (W1-P1).E-3 described how the prescription of goals—such as hitting 10,000 steps a day—may overshadow any intrinsic motivations for exercising :The monitoring apps can make you think about physical activity in quite a sad way, or quite a compulsive way. If you have a step counter actually you think “I’m going to go for a walk to get my step count up” and your motivation behind doing it is quite external, it’s not about enjoying the walk for example, it’s not about getting some fresh air or just clearing your head for a minute, actually suddenly that walk is all about “well this is going to get me about 3000 steps if I do this 20 minute walk at lunch time” for example.E-3E-1 discussed how a focus on these aspects of quantification and goal attainment could become a potential risk for the emergence of maladaptive eating and exercise behavior, if paired with obsessive personality traits or perfectionism:People who tend to have an obsessive personality and also high levels of perfectionism will sustain their use of fitness apps and count every calorie, count every step, count every episode that they go to the gym and all their exercise and use a mobile platform to collect that data.He noted how, in clinical care, “we actively discouraged [people with eating disorders] from using those apps and various wrist monitors that count the steps and activity levels” as they can become “triggering” as well as sustaining “obsessional and restrictive and rigid behaviors”. E-2 further highlighted this point by describing his own personal experience of using healthy eating and fitness apps to track his food intake and exercise levels:I got to this point where I felt like I was really in control and I found the counting of the calories wasreally empowering...especially running and walking [...] you can put it on and it tracks you and it gives you your speed, and I was really fixated on how far I was going and how fast I was going.E-2E-2 also highlighted how this eventually led to him losing a sense of control:I no longer felt in control, it sort of started spiraling and I was losing like five pounds, six pounds.At this point, he realized that he has established an unhealthy relationship with healthy eating and fitness apps:It all had to sort of go because I just realized how unhealthy it was and I know that I can’t really use those kind of apps in a healthy way.Participants discussed how heavy dieting and exercise regimes could have a negative impact on maintaining a good social life; many social gatherings focus on food, and often, a lot of time is required to maintain a heavy gym regime. W2-P1 described how, for some people, socializing becomes challenging because of the need to make dietary sacrifices:If you’re very religiously logging it and then you think oh I can’t go out to that restaurant or I don’t want to go out for drinks.The concept of religiously monitoring caloric intake in an attempt to lose weight was highlighted by E-1 as a key challenge that could ultimately lead to social isolation and impact of the psycho-social development of a young person:For a lot of people it becomes an obsessive, all-consuming pursuit and therefore all energy is invested in that and there is no space left to do other things like invest time in social relationships, in social gatherings, education, family, friends and other sorts of developmental aspects of growing up.It was noted how engagement with apps on a mobile phone is largely, by design, a personal and private experience, which could in fact intensify negative experiences and behaviors, as it is easy to hide from family and friends:...by the time you’ve noticed it they’re probably already obsessive, because apps are actually very easy to hide that you’re using itW1-P1W2-P2 also described how easy it is for young people to engage in secretive behaviors without anyone finding out:It’s on a phone where you’ve got a password. Sure, people can have visibility of it but they may not even know you have it. So say if it’s a young, like a teenager, their parents may not even know they’re using it, why would they, it’s on a locked phone [...] I think you can quite easily start to like manipulate your calories in a negative way and nobody would know you’re doing it.Participants discussed the issue of under logging calorie intake and how an app may respond in such cases:It comes up in red basically giving you a warning that you’re not eating as much, or, if you carry on like this you’ll be losing two pounds in a week.W1-P2However, they discussed that providing such weight loss projection could motivate users to eat less to lose weight faster within the estimated time frame. Participants explained how, when the user underlogs, apps currently only respond with a warning notification, instead of taking any actions to prevent this from happening. For example, W2-P2 described how she restricted her calorie intake to 1200 calories per day for 7 months without any guidance from the app to re-evaluate her goals:It didn’t come up like “you’re doing this and you should not be doing it” kind of thing, so I think it is negative, it should prompt you to re-evaluate your weight and your goals but it doesn’t, it automatically recalculates your weight, but you can keep changing your end goal and then I’m not sure it brings up like well this is in an underweight category of [Body Mass Index] BMI.Our health experts also envisioned apps taking more responsibility to protect users, particularly those at risk, by not just focusing on sending notifications to encourage achieving the daily goal but also by notifying when overuse happens:I think apps could be more intelligent and could give feedback about over-use [...] if you spend too much time on your fitness app or on your diet app or too much time in the gym if you are monitoring all your activities, one could have a warning come up that this might not be the most healthy thing to do.E-1gentle approach to encourage engagement was also seen as beneficial:On the contrary, the need for a If someone’s not doing as much physical activity, having an app which kind of brings you back in gently rather than saying “you haven’t exercised for five days, what are you doing,” actually that could be really helpful, so trying to think about encouraging people to do those healthy activities rather than worrying too much about what those outcomes are going to be.E-3listen to your body and gain the power to switch off when needed. They discussed the notion of feeling controlled, or being driven, by apps and how one should have a period of detox if this happens. E-1 highlighted the need for a psycho-educational component about the harms and benefits of healthy eating and fitness apps, explaining that young people in recovery learn to disconnect themselves from their phones:Each of the experts highlighted the importance of being able to ...trying to live with the anxiety of not knowing the detail of their activity levels and input and outputs; that is something pretty much promoted in recovery.He further explained how they aim to teach young people to trust their own bodies and themselves, to look after themselves:It’s natural for one to allow your body to find its own equilibrium and its own input and output in terms of food and activity levels, and to rest when you feel the need to rest and to exercise when you feel the need to exercise.E-1This view was also shared by E-2 who explained the need to be mindful around logging behaviors:Am I checking this because of anxiety and habit or because I want to use it? How autonomous am I in doing this? [...] whether you feel compelled to use it, I think people need to work out whether that’s the case for them or not, like having that awareness is really important and that’s what gives people the power.E-2This was echoed by E-3:I try to think about what am I doing, why am I doing this, what’s this app encouraging me to do, is it actually doing what I want it to be making me do or is it making me do something negative.E-3It was acknowledged by E-2 that this can be counter-intuitive to the way healthy eating and fitness apps are currently designed, with users often being actively encouraged to log and monitor themselves constantly: “if you don’t [log] then you mess up your statistics”. He explained how, on one occasion, forgetting his phone at home and not having the ability to track his steps made him feel anxious:I felt more anxious because I didn’t know how much I’d done and I needed the steps, like the app to tell me that I’d done enough exercise, rather than listening to my body, which I think is a big thing with these apps and social media—they’re prescribed—I think that sort of disconnects people from their bodies a little bit.E-2In summary, survey results showed that almost half of our respondents had some form of negative experience using healthy eating and fitness apps. Approximately one-third of respondents reported that they had stopped engaging with healthy eating and fitness apps, typically citing that they found them too demanding or that they lacked the motivation for long-term use. Workshops and interviews further explored personal and professional perspectives on the impact of healthy eating and fitness apps on young people. Participants described how the pressure of attaining health goals, set through the app, could lead to negative experiences and behaviors. There was much consensus that healthy eating and fitness apps can bring feelings of guilt leading to negative experiences and behaviors such as meal skipping. The quantification element of the healthy eating and fitness apps was also seen as a contributing factor for development of maladaptive eating and exercise behaviors, particularly for those with obsessive personalities. Participants concerningly discussed the possible impact of obsession with logging behaviors on social isolation. This was backed up by experts highlighting the importance of being mindful around logging behaviors.The next stage of our research then focused on exploring the specific features of healthy eating and fitness apps that are currently available on the market, including the ability to log behaviors of interest and how the app responds to user engagement and behavior logging. We wanted to understand the potential of the top 100 healthy eating and fitness apps to elicit the negative experiences and behaviors reported in the first stage.Data from the reviews were collated into a spreadsheet. For review responses that resulted in qualitative data, we performed a qualitative content analysis . As follFor reviews that resulted in quantitative data, responses were summed to produce scores that reflect the number of apps belonging to each possible category. Interrater reliability of this coding had already been determined in the previous review phase see .Descriptions of apps were coded according to the health behavior targeted by the app. The vast majority of the apps focused on exercise promotion (n=62) and exercise and diet combined (n=24). A total of 3 apps were found to not focus on either diet or exercise. This included 1 app that focused on editing the body to assess how one would look like with various bodily enhancements  and 2 that focused on weight monitoring . Around two-thirds of the apps included the ability to set appearance-related goals, such as weight loss and enhancement in muscle tone (n=65).The majority of apps collected some form of data pertaining to physical activity (n=84). This included data such as daily steps, cycling, and the completion of workouts specified by the app. A much smaller percentage of apps collected dietary data pertaining to food consumption (n=23). More than half requested user data pertaining to weight (n=56).In total, 21 apps allowed the setting of underweight body goals (corresponding to a BMI<18.5). Qualitative responses to other questions highlighted how this could include setting extremely low BMI targets in some apps: “I still can set a BMI goal<13”.Around two-thirds of the apps that facilitated the recording of dietary intake allowed the reporting of calorie consumption that was 50% more or 50% less than the recommended daily amount for the average individual (n=16). Some apps responded differently to the entering of low-calorie consumption (n=8), for example, highlighting that a goal had not been met or not allowing the calories to be logged. Others had a minimum calorie entry threshold and would not allow calories to be logged under this target. Some apps treated the under logging of calories the same as logging calorie content in line with their goals (n=8), including those that praised under logging calories in the same way that they praised calorie entry consistent with goals . A small proportion of apps also responded differently to logging calories that exceeded the daily target (n=8). Example responses to exceeding calorie goals included numeric feedback, reminders about goals, and visual feedback such as turning the calorie counter red or sad face emoji. Furthermore, some apps had a more questioning approach, for example, asking if the calorie entry is correct.A fifth of the apps responded to failure to meet exercise goals (n=20). The nature of these responses varied and included reminders, numerical feedback. Similar to when logging a high calorie intake, some apps adopted a questioning approach (“Wanna give up? Think about why you started?”). Two-thirds of the apps offered praise and rewards for continuous use (n=60). Qualitative responses as to the nature of this praise varied. Many offered direct messages of praise such as congratulations messages or fireworks. Elements of gamification were present in some apps, with trophies, badges, and the unlocking of levels being used to reward continuous use.Apps were coded according to whether positive or negative feedback was used to motivate users’ engagement with the app. The majority focused on positive feedback (n=72), whereas a minority of apps were felt to focus on negative feedback (n=19). The remainder of apps either provided neutral feedback (n=8) or provided both positive and negative feedback to the extent that the reviewers could not differentiate between which was being used more in the app (n=1).Examples of both positive and negative feedback were provided in qualitative responses to other questions . Some apps sent positive feedback to encourage users to keep up with their initial goal “Hey [user name]! You’ll feel great after a workout. Strive for progress, not perfection” or suggested that the user adjust their personal goal so that it was more in line with their lifestyle “You haven't been active lately, do you want to adjust your goal”. An example of negative feedback included users being punished for not reaching their personal target “if you miss a day you'll get punished by losing a heart”.Furthermore, apps were coded as to whether they focus on what the user has achieved or what they have not achieved. Just under half of the apps were positively focused on achievements (n=49), highlighting what the user had done, whereas around one quarter were negatively focused on achievements (n=26), highlighting what the user had not done. The remainder did not focus on achievements (n=25) and included apps that did not involve goal setting or targets and those with predetermined reminders not linked to user behavior.Around one-third of apps facilitated the sharing of data with other app users (n=32). The remaining apps either did not facilitate this (n=66) or did not collect any user data (n=2). A much higher proportion of apps facilitated the sharing of app-related achievements through social media sites (n=59), whereas the remainder did not (n=39) or did not collect any data (n=2).A small proportion of apps automatically ranked users among others (n=6) but all of these apps allowed this feature to be deactivated. This ranking approach was evident in the qualitative responses about app feedback. For example, a push-up workout app compared user reports about their workouts with other users in similar categories : “you did X push-ups, this is better than XX% of users today”.In summary, we wanted to identify the logging functionalities available in the top 100 healthy eating and fitness apps that have the potential to elicit negative experiences and behaviors captured in the first stage. We found that apps responded differently to data-logging behaviors, for example, some allowing users to under log their calorie consumption whereas others using guilt-inducing techniques when calories exceed the daily goal. Alarmingly, 21% of the apps we reviewed allowed underweight goal setting (BMI<18.5). In addition, one quarter of the apps focused on negative reinforcement for maintaining health goals. A substantial number of apps facilitate sharing data with other users (n=32) and across social media (n=59).The aim of this research was to understand the potential role of healthy eating and fitness apps in the development of maladaptive body-related attitudes and eating and exercise behaviors in young people. Drawing on the findings from Phase 1 and Phase 2, we have identified 5 important ways in which healthy eating and fitness apps may potentially exert negative impacts on users. In this section, we reflect on these themes and how future research may mitigate against these issues.Calorie counting is a prominent feature of many currently available healthy eating and fitness apps and a key reason why many of the survey respondents, both male and female, reported using healthy eating and fitness apps. However, participants in both the survey and workshops also described how obsessive thoughts and behaviors around calorie counting and logging could emerge. For example, not achieving a calorie count within a certain boundary could cause feelings of failure and guilt, often then leading to restrictive eating or excessive exercising behaviors , simply because the app indicated that they had already reached their caloric intake for the day. This tendency to engage in purge behaviors echoes findings from previous research examining the consequences of healthy eating and fitness app use  and foodself-knowledge through numbers [numbers game for the young people in our study, becoming a law for them to live their lives by. In the workshops, participants describe how self-tracking led them to over focus on the calories contained in food at the expense of nutrition . Furthermore, some survey respondents described cheating the app by not accurately logging their food consumption. Although healthy eating and fitness apps offer new ways of monitoring, measuring, and representing the human body [the numbers over physical observations [In addition to calorie counting, there were other aspects of self-tracking evident in the apps reviewed . The primary objective of self-tracking is around obtaining  numbers , and the numbers . Howeverman body , they alrvations . This obReflecting on these points, we need to think about better ways to log food and exercise. For example,  have useFurthermore, our experts highlighted a need for approaches that promote listening to one’s own body, and its nutritional needs and physical limitations, rather than becoming reliant on the attainment of what are often arbitrary numerical goals. Such an approach is consistent with newly emerged evidence-based psychological approaches to improving exercise and eating behavior that are focused on the development of embodied and mindful approaches to eating and exercise . ReframiA high percentage of healthy eating and fitness apps  currently available on the market focus on the achievement of appearance-related goals rather than health goals. This finding is consistent with research conducted around other health and fitness media, such as magazines .Focusing on appearance-related goals in eating and exercise settings has been linked to negative body image and maladaptive eating and exercise behavior . In contthinspiration . However, it is possible that these types of responses might serve as munities ), motivaThe literature on behavior change, and the roles of notifications in supporting change, is extensive ,75,76. IIn our study, young people openly discussed the negative emotions they have experienced when interacting with healthy eating and fitness apps. They expressed feelings of guilt, disappointment, and pressure. This echoes findings from ,63, wherextreme measure behaviors , instead promoting better coping mechanisms . Consequently, engaging users in the creation of preplanned statements that mitigate negative feelings such as guilt triggered by not meeting goals might be a useful way of supporting users.Although the aim of notifications is to encourage engagement, previous research suggests that these are not always effective and can instead cause additional stress on young people . Rather compete toward weekly step counts. Research suggests that perceived social norms can be a powerful motivator of behavior change in relation to eating and exercise, in that individuals are more likely to engage in behavior if they perceive others to be doing it [Healthy eating and fitness apps offer the opportunity to enhance the social life of the user by giving access to group memberships and opportunities to find like-minded people or friends on the internet (sharing and comparing data through the app) and offline  . Many apdoing it . Howeverdoing it .Our app review indicates that the majority of apps facilitated social features, that is, data sharing with other app users (n=32) or through social media (n=59). However, although healthy eating and fitness apps are seen as socially mediated experiences to connect people with common interests and goals for healthy eating and physical activity , our quaMost healthy eating and fitness apps are designed to reinforce continuous use. Typically, this is achieved through gamification features that render daily routines into games . GamificAlthough the aim of gamifications is to promote sustained use, studies have shown that long-term engagement is not always achievable, for example, only 11.6% of app users in Great Britain are still engaging with an app a week after installing it on their phones (findings from other countries are similar) . Our surperiod of detox when unusual patterns of use are detected, as part of the gamification model. In addition, providing a framework within the app that encourages users to self-reflect on their use patterns and to re-evaluate their goals regularly may help users who might be struggling to re-gain a sense of much needed control.One possible option for the future app developer would be to consider encouraging more long-term behavior change, rather than focusing on engagement . FurtherThis research adopted a mixed-methods approach to develop a holistic understanding of the potential negative impact of healthy eating and fitness app use among young people. Though we aimed to recruit both male and female participants to engage in our qualitative research, we struggled to recruit individuals identifying as male to engage in workshop activities. That said, male perspectives are still represented in the survey data and in fact made up the majority of respondents. One reason for this could be that we recruited largely from computer science, which is a predominantly male field; however, for future work, a gender balance would be preferable. We also did recruit a male eating disorder campaigner, activist, and writer with a personal experience of eating disorder who advocates for greater recognition of eating disorder service delivery and the male experience to participate in the interviews. However, future research should aim to more deeply explore the male experience of healthy eating and fitness app use further. Similarly, it may be important for future research in this field to consider how other individual difference variables, such as race, class, body size, and disability, affect participants’ engagement with healthy eating and fitness apps and their potential for misuse.Through our study, we have offered a deepened understanding of young people’s experiences of healthy eating and fitness apps and the potential harm that their use might have. We have offered a set of guidelines for future apps that can be responsibly developed to prevent the formation of maladaptive eating and exercise behaviors. Although we understand that an app developer would never set out to meaningfully bring about negative emotional responses in their users, we must also be mindful of the fact that these responses are happening. Through this study, we hope to open a dialogue around how use of these apps could have the potential to become the seed that develops into a more serious issue. As the target user demographic for these types of apps, young people are most vulnerable to the development of poor body image and maladaptive eating and exercise patterns. As such, we need to take care in the type of language we are using and the type of sustained behaviors we are promoting.


The relationships between several Hofstede’s cultural dimensions and prosocial behavior at national level have been investigated by some studies. Yet the roles of indulgence versus restraint (IVR) and long-term versus short-term orientation (LTO), two newly established cultural dimensions, have received insufficient interest. This study aimed to investigate whether the World Giving Index (WGI), a national level measure of prosocial behavior  provided by Gallup, was affected by IVR and LTO. The results suggested a positive link between IVR and WGI, and a negative link between LTO and helping a stranger. Culture values can in a great extend account for why prosocial behavior varies across countries. Further analysis revealed interactions among IVR, LTO, and individualism versus collectivism (IND). Simple slope analyses found that: (1) a higher level of IND could enhance the positive influence of IVR on prosocial behavior; (2) a lower level of IND could weaken the negative impact of LTO on prosocial behavior; (3) a higher level of IVR could weaken the negative effect of LTO on prosocial behavior. People are willing to sacrifice their own interests, including time, energy, money, and even physical health, to benefit others or the society as a whole. These behaviors are called prosocial behavior, which includes sharing, formal and informal helping, charitable donation, and volunteering . In the Confucian Work Dynamism. LTO indicates the time-orientation of a society. Societies located at the long-term pole prefer virtues oriented toward future reward, particularly perseverance, thrift, order of relation by status, and a sense of shame. In contrast, societies located at the short-term pole prefer virtues related to the past and present, in particular respecting for tradition, protecting one’s “face,” and fulfilling social obligations. East Asian countries mostly have a long-term orientation, while Australia, United States, some Latin American, African, and Muslim countries can be identified as short-term orientated societies  and the sixth dimension  were added to Hofstede’s model . LTO oriocieties .Indulgence versus restraint was originally extracted from the World Values Survey and adopted by Hofstede in his model . IVR refCulture values are important factors in determining an individual’s social behavior . CountryThe reasons why national cultural values influence prosocial behavior have also been addressed by previous researchers. Culture is a collective level phenomenon containing variable values, beliefs, and practices across societies . Individ1. Furthermore, the cultural values of a country may change over time  the relationship between LTO and prosocial behavior was moderated by IVR.2 using data gathered by Gallup. Three components of WGI  were measured each by an item asking the participants if they have given money to charity/volunteered for an organization/helped a stranger in the month previous to the survey. For each of these three questions, a percentage of participants who said yes were calculated. Then these three percentages were averaged within a country to form an aggregate score representing prosocial behavior at national level. If a country had missing data in the 2016 WGI, the missing value was replaced by the average score of the years available during 2010–2015. Previous studies showed that WGI can be used as a reliable and valid measure of prosocial behavior  as that country.Based on previous findings that religion and economic factors  also infTable 1. Power distance, uncertainty avoidance, and masculinity versus femininity were also included in the correlation analysis in order to make a comparison with the results of previous studies. As Table 2 illustrated, IVR was positively correlated with three indicators of prosocial behavior , while LTO was only significantly negatively correlated with helping a stranger . And IND was significantly positively correlated with donating  and volunteering . This indicated that IVR may be the most important predictor of prosocial behavior among the three cultural dimensions. Among the three cultural dimensions, the correlation between IVR and LTO was negative , and the correlation of LTO with IND was positive , while the relationship between IVR and IND was insignificant. These results suggested that these three cultural dimensions are essentially different constructs that may each contribute uniquely to prosocial behavior.Pearson correlations between IVR, IND, LTO, and WGI  were shown in r = -0.50; for volunteering, r = -0.28; for helping, r = -0.21; for WGI, r = -0.44, ps < 0.01; uncertainty avoidance: for donating, r = -0.44; for volunteering, r = -0.25; for helping, r = -0.23; for WGI, r = 0.40; ps < 0.01), while masculinity versus femininity was not associated with prosocial behavior.Consistent with Table 2). This method enables us to find the variables whose predictive values cannot be substituted by other variables. Table 2 showed that (1) when WGI, donating, and volunteering were outcomes, the effects of uncertainty avoidance and IVR were significant , with other four cultural dimensions providing no more predictive power; (2) when helping a stranger was the outcome, the effects of LTO, uncertain avoidance, and power distance were significant . These findings suggested that the two newly developed cultural dimensions  in Hofstede’s model are useful in predicting country-level prosociality. Uncertainty avoidance was the only cultural dimension that was predictive of WGI and its three components above other cultural dimensions, showing that it has particular importance in influencing prosocial behavior. Surprisingly, IND and religion did not exert significant influence on prosocial behavior. This is inconsistent with Hierarchical multiple regression was used to analyze the unique contribution of each cultural dimension. Religion and HDI as the controls were entered in Step 1, and six cultural dimensions were added in the regression model using a stepwise method in Step 2  IVR did not influence WGI , whereas in high IND societies the influence of IVR on WGI was significant , see Figure 1. Simple slope analysis revealed similar findings when the outcomes were donating , and helping a stranger . Furthermore, the influence of IND on the relationship of volunteering with IVR is stronger in high IND countries  than in Low IND countries . These results suggested that indulgence in a society generally has a positive effect on prosocial behavior, but this effect is much stronger in individualist societies than in collectivist societies.As shown in Table 4, the significant interaction between LTO and IND showed that the relationship between LTO and donating can be influenced by IND. Simple slope analysis showed that in low IND societies LTO did not influence donating , while in high IND societies the influence of LTO on donating was significantly negative ], see Figure 2.In Table 5 showed that the interaction effect of LTO and IVR in predicting prosocial behavior was also significant, showing that the relationship between LTO and prosocial behavior (excepting volunteering) was moderated by IVR. Simple slope analysis showed that LTO had a negative influence on WGI in low IVR societies , while the influence of LTO on WGI is insignificant in high IVR societies , see Figure 3. Similar results were found when the outcome was helping a stranger . But both in low and high IVR societies, influences of LTO on donating money were not significant .It has been suggested that the fundamental psychological processes of an individual, such as cognition, judgment, evaluation, emotion, etc, can be systematically influenced by the culture values of a society . ConsistLong-term versus short-term orientation is also an important cultural dimension in influencing prosocial behavior. In this study, the negative association between LTO and helping a stranger was rather strong, which is partly consistent with Hypothesis 1b. A possible explanation is that, in short-term orientated societies service to others is considered as an important goal, while in long-term orientated societies thrift and perseverance are considered as important goals . Luria eIn this study the effect of IND on prosocial behavior was partialed out by IVR, LTO, religion, and HDI, though it has been revealed by previous studies . The dimThe results showed that IND played a moderating role in the relationship between IVR and prosocial behavior. High IND in a country could strengthen the relationship of IVR with WGI and its components. That is, the IVR-prosociality association was stronger in high IND countries than in low IND countries. This may be explained by the fact that components of WGI are prosocial behavior primarily directed toward out-groups/strangers. In collectivist societies, IVR may promote prosocial behavior toward in-groups, while in individualist societies IVR may promote prosocial behavior toward out-groups or strangers .Individualism versus collectivism also played a moderating role in the relationship between LTO and prosocial behaviors. A significant interaction between LTO and IND in predicting money donation indicated that the negative LTO-donation association tended to be stronger in individualist societies than in collectivist societies. Collectivism emphasizes interpersonal relatedness and commitment to groups or the society . The negFurthermore, a moderating effect of IVR in the LTO-prosociality relationship also was found. The effect of LTO on prosocial behavior was significant in low IVR societies, but insignificant in high IVR societies. Long-term orientated societies encourage thrift and perseverance and discourage service to others. One manifestation of LTO is a conservative attitude toward money that may deter prosocial behavior . These nDrawing on the newly published datasets and a relatively larger sample size, this study explored the effects of two newly established cultural dimensions in Hofestede’s model (IVR and LTO) on prosocial behavior that have received little interest in previous studies. We found that the effects of LTO and IVR on prosocial behavior were moderated by IND. These findings have made a significant progress in explaining why prosocial behavior varies across cultures. However, this study also has limitations.Previous literature suggests that WGI is a reliable measure of prosocial behavior , but whaIncreasing prosocial behavior in a society is beneficial not only for social harmony and solidarity , but alsThis study showed that the interactions among IVR, LTO, and IND also have significant effects on prosocial behavior. Nevertheless, we have not provided sound explanations for these interactions. For example, why the relationship between IVR and prosocial behavior is stronger in high versus low IND countries? These questions are expected to be addressed elaborately by future research.In this study IVR was the only cultural dimension contributing to all three types of prosocial behavior. Its influence remained robust after the effects of other cultural dimensions were controlled. This is consistent with previous findings that prosocial behavior is mainly motivated by emotion . SurprisLong-term versus short-term orientation has exerted a strong negative influence on helping a stranger, suggesting that devaluing the importance of serving others and endorsement of thrift and perseverance in a society can have a negative impact on building prosocial ethos. Moderation analyses have also revealed several valuable findings: (1) IVR is more strongly conductive to prosocial behavior in individualist societies than in collectivist societies; (2) low IND in a society  could weaken the negative effect of LTO on donating; (3) high IVR in a society  could attenuate the negative effect of LTO on prosocial behavior.QG designed the study and wrote the manuscript. ZL and XL wrote the manuscript and collected the data. ZL and XQ collected and analyzed the data under the supervision of QG. QG, ZL, and XQ revised the manuscript, and replied to comments.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The interface interactions between the two components and the resultant optoelectronic properties of the composite are demonstrated. According to transmission electron microscopy and X-ray absorption spectroscopy, the dispersion of CeO2 nanoparticles in the polymer matrix strongly depends on the CeO2 nanoparticle concentration and results in different degrees of charge transfer. The photo-induced charge transfer and recombination processes were studied using steady-state optical spectroscopy, which shows a significant fluorescence quenching and red shifting in the composite. The higher photo-activity of the composite as compared to the single components was observed and explained. Unexpected room temperature ferromagnetism was observed in both components and all composites, of which the origin was attributed to the topology and defects.This study presents the preparation, characterization, and properties of a new composite containing cerium oxide nanoparticles and a conjugated polymer. CeO Composites containing nanoparticles have received much attention due to their synergistic and hybrid properties derived from their corresponding components. The composite properties depend on the properties of their individual components and also on their morphologies and interfacial characteristics. For instance, Bellucci et al. demonstrated that the optical properties changes were correlated to nanoparticle-driven interface modulations . The pot2) is one of the most used metal oxides because cerium is the most abundant element among the rare earths and is environmentally friendly  thiadiazole, two equivalents of 2,7-bis-9,9’-spirobifluorene and one equivalent of N,N’-bis(2-ethylhexyl)-2,6-dibromonaphtalene-1,4,5,8-tetracarboxylic acid diimide. 2,7-Bis-9,9’-spirobifluorene , 4,7-dibromobenzo[c] thiadiazole , N,N’-bis(2-ethylhexyl)-2,6-dibromonaphtalene-1,4,5,8-tetracarboxylic acid diimide  and aqueous K2CO3  were mixed in 1,4-dioxane (20 mL). After degassing for 10 min, tetrakis(-triphenylphosphine) palladium  was added under an argon atmosphere. The reaction mixture was heated at 110 °C for 48 h before cooling to room temperature. The reaction mixture was extracted with dilute aqueous hydrochloric acid and dichloromethane. The organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate. After filtration, the residue was concentrated and poured into methanol and then the precipitate was collected by filtration. The solid was washed by a Soxhlet extraction with methanol and acetone for 24 h, respectively before being dissolved in hot chloroform. The product was dried under a vacuum to give a yield of 65%. The detailed synthetic process of the polymer is shown in The conjugated polymer was synthesized by the modification procedures reported previously . All che3)3·6H2O; 434.23 g/mol, 99.5% purity) was purchased from Alfa Aesar. Ammonium hydroxide  was purchased from Avantor . Ethylene glycol (99.5% purity) was purchased from Sigma-Aldrich. These chemicals were used without further purification. Distilled water was used in the synthesis process for nanoparticles.Cerium (III) nitrate hexahydrate (Ce(NO2 nanoparticles were synthesized by the co-precipitation method. The Ce(NO3)3·6H2O is dissolved in 80% ethylene glycol (EG)/water mixture by stirring at 600 rpm at room temperature. When all the nitrate precursors are dissolved, ammonium hydroxide (3 M) is added dropwise while the solution is kept in the same condition. After the addition of the precipitating agent , the mixture was stirred at 30 °C for 21 h. The precipitate was separated by centrifugation at 6000 rpm for 10 min and washed three times with ethanol. The separated solid was dried for 24 h and crushed with mortar and pistil, the CeO2 nanoparticles were obtained as powders.CeO2 nanoparticle powders with a 20, 40 and 50 weight percent were added into the polymer solution and the mixture was sonicated for 30 min. The composites were left in the oil bath for 72 h.Polymer is dissolved in tetrahydrofuran (THF) with a concentration of 0.001 g/mL and sonicated for 30 min. Different amounts of CeO3L-edge were performed at room temperature on a Wiggler beamline 17C at the National Synchrotron Radiation Research Center (NSRRC), Taiwan. The monochromator Si (111) crystals were used in Wiggler beamline 17 C. The energy resolution at the Ce 3L-edge (5723 eV) was about 0.4 eV. The XANES spectra at the C K-edge were recorded at beamline 20A using total electron yield (TEY) mode at the National Synchrotron Radiation Research Center (NSRRC), Taiwan. The magnetization was measured at room temperature using a vibrating sample magnetometer (VSM) at the Institute of Physics, Academia Sinica, Taiwan.The NPs were characterized by using the X-ray diffractometer (XRD) with Cu Kα radiation and beamline 01C2 at the National Synchrotron Radiation Research Center (NSRRC), Taiwan. The particle distribution, morphology, and crystal structure are studied by a transmission electron microscope operated at 200 keV (Philips Technai G2 FEI-TEM) . The ultraviolet–visible (UV–Vis) spectra were recorded using a Jasco V-670 spectrophotometer . The photoluminescence properties were investigated using a Jasco FP-8500 spectrofluorometer . The X-ray absorption near-edge fine structure (XANES) measurements at the Ce 2 nanoparticles and CeO2/polymer composites with different amounts of CeO2 nanoparticles. The XRD pattern of CeO2 nanoparticles indicates peaks at 2θ about 28.5°, 33.1°, 47.4°, 56.3°, 59.1°, 69.3°, 76.7° and 79.1° which corresponds to the lattice plane of (111), (200), (220), (311), (222), (400), (331) and (420) of CeO2 with space group2/polymer composites contains all peaks from both components which indicates that the efficient blend of two components.2 nanoparticles and CeO2/polymer composites. As can be seen from 2 nanoparticles highly aggregated together due to the small size and Van der Waal’s forces. The size of the cluster is as large as the micron scale. According to selected area electron diffraction (SAED) analysis , the degree of dispersion in the polymer is suppressed. The size of the CeO2 cluster was then increased again  is a unique method that provides electronic structural information on the orbital symmetry and spin state of the materials and was thus utilized to determine the C hybridization as well as the Ce charge statecaused by the composite formation.The decrease in the CeOmoieties . Due to K-edge XANES of the composites are shown in 2, the polymer peak intensity decreased significantly, indicating that more electrons transfer into the polymer. As for the peak located at 290.4 eV (peak B), which correspond to carbon atoms in polymer attached to hydrogen, nitrogen or other species, shows a clear increase. This suggests that the interfacial C–O–Ce bonding is formed for the CeO2/polymer composites.The C 2 was investigated using XANES of the Ce-L edge. The normalized XANES spectra of Ce L3 edge of composites containing different ceria nanoparticle concentration are shown in 1(5d6s)4 state). Therefore, the Ce3+ concentration in the CeO2 matrix (Ce3+/(Ce3+ + Ce4+)) can be then expressed as the ratioC is the deconvoluted peak C intensity and IT is the intensity sum of peaks A, B and C [3+ concentration (the ratio of the concentration of Ce3+/(Ce3+ + Ce4+)) was about 10% in the raw CeO2 nanoparticles. For the composite, whereas the weight ratio between CeO2 and polymer is 0.2 and 0.4, the Ce3+ concentration decreases to 7.5% and 7%, respectively. The decrease in the Ce3+ concentration confirms that electrons transfer from CeO2 into the polymer.The variation in the Ce charge state in ceria between the composites and pure CeO B and C . AccordiK edge and Ce L edge demonstrated the charge transfer between CeO2 nanoparticles and the polymer, which results in the increase in electrons in the C=O of polymer and the decrease of hybridization between Ce and O in CeO2 nanoparticles. This implies that more Ce3+ was induced at the particle surface. It is worth noting that among composites with different amounts of CeO2 nanoparticles, the decrease in the Ce3+ concentration is almost the same. This suggests that the interaction occurs only at the CeO2 nanoparticle surface.The above XANES analysis of the C p valence band (VB) of O2− to the 4f conduction band (CB) of Ce4+ in CeO2. For the polymer, a broad absorption band was observed possibly due to the π-π* transition and the intramolecular charge transfer between spirobifluorenes and naphthalene bisimides [2 nanoparticles the polymer absorption is enhanced and the absorption edge shifts to the longer wavelength. This broad absorption and longer absorption edge can be attributed to the charge transfer from the ceria nanoparticles into naphthalene bisimide moieties of the polymer as demonstrated by XAS analysis in the previous section.The original characteristics of both components would be affected by the change in the electronic structure as mentioned above. The UV–Vis spectra of the ceria, polymer and composites are shown in isimides . It shoua is a constant and n is the index characterizing the nature of electronic transition causing optical absorption. n can take on values of 3, 2, 3/2, or 1/2, corresponding to indirect prohibited, indirect permitted, directly prohibited, and directly permitted transitions, respectively. A graph plotted between (αhυ)1/n as ordinate and hυ as abscissa. The extrapolation of the linear part of the graph to (αhυ)1/n = 0 (Tauc’s plot) gives the optical band gap. Accordingly, the optical band gap is 2.97, 2.02 and 1.70 eV for CeO2 nanoparticles, polymer, and composite in which the ratio between CeO2 to polymer is 0.4, respectively. The change in the composite band gap indicates the intramolecular charge transfer between spirobifluorenes and naphatalene naphthalene bisimides that leads to a change in the band structure.The optical band gap can be determined using Tauc’s model using the UV–Vis absorption spectra. Tauc’s model is given by:2 nanoparticles can be observed. A broad emission band from 550 nm to 750 nm with a maximum emission peak (631 nm) was observed for the polymer. The excitons were created by photoexcitation in which the holes and electrons are located in the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of the polymer, respectively. The electron and hole recombination is responsible for this emission peak. After the composite formation, the fluorescence quenching, as well as red shifting of the emission maximum, is observed. The fluorescence quenching may indicate the intramolecular charge transfer that takes place between the two species as has been confirmed by XANES. The emission peak of the composites shifted from 631 nm to 643 nm. This redshift suggests that there is a change in the polymer electronic structure as well as the chemical environment, which was demonstrated by UV–Vis spectra and XANES of the C-K edge of the polymer. This shift may arise due to the reduction in bandgap and the variation in the interface between the CeO2 nanoparticles and the polymer.Photoluminescence (PL) is a remarkable method to probe certain structural aspects and provide information at short and medium-range, where the degree of local order such as structurally inequitable sites can be distinguished by their different types of electronic transitions and are linked to specific structural arrangements. The structural and electronic order or disorder effects and the nature of bonding in a conjugated polymer have a key impact on the optical property. s) of the CeO2 is 0.008 emu/g , pristine polymer and pure ceria NPs measured at room temperature were shown together in inset in , which i2 NPs, the value of Ms was 0.2 emu/g. It is lower than that of pure polymer. According to the magnetic behavior of pristine polymer and ceria NPs, the decrease in magnetization could be attributed to the lesser content in the polymer. However, it is worth mentioning that the Ms of composite is higher than the linear combination of both components, demonstrating the magnetism of both components changed by interface interactions. For ceria NPs, it has been demonstrated that within a wide range of defect concentrations, the value of Ms is proportional to the Ce3+ concentration at the surface. As shown in the previous section, the Ce3+ concentration is less after the composite formation. Based on the above results, the decrease in CeO2 ferromagnetic contribution is predicted. In other words, the polymer magnetic response became stronger in the composite. Both polymer conjugation and delocalization was affected by the electron transfer. Similar results were reported by B. Yang et al. They observed that the saturation ferromagnetism of polymer P3HT mixed with phenyl-C61-butryic acid methyl ester (PCBM) was about 0.65 emu/g and suggested that the ferromagnetism origin is associated with P3HT crystallization and the charge transfer between P3HT and PCBM [In the polymer composite with 40 wt% CeOand PCBM . Accordi2 NPs was successfully produced using an ex situ preparation method. This method has an advantage over the in-situ method as it is free from the unnecessary solid remaining in the hybrid and it is simple and used for large-scale production. TEM and XAS analysis results showed that the nanoparticles are well dispersed in the polymer matrix with charge transfer that occurred between the two components. The difference in band structure resulted in a broader absorption peak than the individual components UV–Vis spectra. Photoluminescence revealed the fluorescence quenching and red shifting of the composite peak compared to that of the pristine polymer. The difference in electron hybridization and localization also affected the magnetic response of both components. The magnetization of the pristine polymer was found to be enhanced.Polymer composite with CeO