Filters are widely used for the modulation, typically attenuation, of amplitudes of different frequencies within neurophysiological signals. Filters, however, also induce changes in the phases of different frequencies whose amplitude is unmodulated. These phase shifts cause time lags in the filtered signals, leading to a disruption of the timing information between different frequencies within the same signal and between different signals. The emerging time lags can be either constant in the case of linear phase (LP) filters or vary as a function of the frequency in the more common case of non-LP (NLP) filters. Since filters are used ubiquitously online in the early stages of data acquisition, the vast majority of neurophysiological signals thus suffer from distortion of the timing information even prior to their sampling. This distortion is often exacerbated by further multiple offline filtering stages of the sampled signal. The distortion of timing information may cause misinterpretation of the results and lead to erroneous conclusions. Here we present a variety of typical examples of filter-induced phase distortions and discuss the evaluation and restoration of the timing information underlying the original signal. Filters are a common tool used in the processing of neuronal signals. In addition to their effect on the amplitude of different frequencies, filters also have a significant impact on their phases, which results in the distortion of the underlying timing information. This distortion, which arises by the online filters used in most neurophysiological systems and is exacerbated by further offline filtering, may cause severe misinterpretation of the results and lead to false conclusions. This manuscript presents different cases in which the timing information is disrupted and discusses the evaluation and correction of the underlying phase shifts.Filters are one of the most commonly used signal processing tools in neuroscience. Different types of filters are used in multiple applications ranging from online to offline, from analog to digital and from hardware to software in their implementation. These filters are applied to neurophysiological signals on different temporal and spatial scales as well as supplementary signals such as sensory stimuli or motor activity. The typical perceived role of these filters is to attenuate certain frequencies or frequency bands from the original signal. As a result, most neuroscientists focus on the magnitude of the modulation of the different frequencies; e.g., a certain high pass filter may reduce the magnitude of oscillations below 1 Hz within the original signal by 20 dB. Filters, however, do not only change the magnitude of the oscillations but also their phase, resulting in a temporal displacement. Some filters, termed linear phase (LP) filters, cause a fixed change in the temporal shift of all the frequencies. However, most filters, termed non-LP (NLP) filters, cause a differential time shift as a function of frequency . A full The raw neurophysiological signal contains, in many cases, high energy in the low frequencies which may lead to saturations during subsequent sampling. This issue is addressed in most systems by online, hardware based, high-pass filters which attenuate these very low frequencies. The cutoff value of this filter varies dramatically and typically depends on the oscillations of interest to the researcher: a study of 0.5-Hz oscillations, for example in epilepsy , might uA significant disruption of the internal order and temporal relationship within the same signal occurs when the signal is comprised of different frequencies, specifically when some of the prominent frequencies are close to the cutoff frequency of the filter resulting in a significant phase shift, while the others are distant resulting in a minor phase change. A typical example of this scenario is an extracellularly recorded signal containing both high frequency spikes and low frequency local field potentials LFPs; . ExtraceA similar disruption of the temporal relationship between two signals can occur in studies examining the interaction between an external event and the neuronal activity. The neuronal signal is aligned to an external event and averaged around it, thus enabling researchers to explore questions dealing with the magnitude and timing of responses of the targeted neuronal systems to external events, such as sensory stimuli. However, while the timing of the external event is fixed, the timing of the recorded signal is altered because of the phase shift, resulting in a disrupted temporal relationship between the two B. The reThe temporal disruption of different oscillations within the same signal may also occur in cases in which the oscillatory frequencies are close to each other. One typical example can take place after the extraction via filtering of narrow oscillation bands such as the θ (4–10 Hz) and β (10–30 Hz) bands . In thesThe effects of filter-based phase shifts are compounded when multiple signals from different sources are compared. A common practice in neuroscience is to compare oscillations in the neurophysiological signal with those arising from another source such as changes in the sensory input or motor output . TypicalThe distortion of timing information varies across filters, depending on their specific properties. Among the properties affecting the phase response of the filter are the filter type, order, and passband frequencies. As different types of filters  differ in their amplitude responses, they also vary in their effect on phases, even for equivalent bandpass frequencies A. Using The filter design affects the directionality of the induced phase shift such that high-pass filters produce a positive phase shift resulting in the lead of the output in relation to the input, whereas low-pass filters produce negative phase shifts resulting in delayed output, and bandpass filters induce a combination of both positive and negative phase shifts ; Fig. 5AThe extent of the filter-based phase shifts and the temporal lags derived from them can be evaluated by the filter’s phase response. LP filters cause a constant time delay in all frequencies while maintaining the temporal structure of the signal. The more common NLP filters lead to differential time shifts across frequencies causing both a change in the timing of individual components within the signal and a distortion of their temporal composition. Zero-phase (ZP) filters, in which the phase shifts of all frequencies are zero, preserve the temporal properties of the signal. ZP filters, however, are not applicable in online applications. Given the exact properties of the filters applied online, the original timing of the signal can be restored, mimicking the function of a ZP filter. In an offline correction process, a filter, similar in its properties to the online filter, is applied on the reversed signal, leading to a shift of the phases back to zero, restoring the timing of the distorted signal ; Fig. 5BFilter-induced phase shifts can potentially impact the majority of electrophysiological signals, starting as early as in the initial stages of data acquisition. Multiple research fields in neuroscience deal with oscillatory signals, including epilepsy , ParkinsWhile multiple studies deal with the issue of filter induced changes of waveforms and amplitudes within electrophysiological signals , this ma


Interest in the Internet of Things (IoT) is rapidly increasing, as the number of connected devices is exponentially growing. One of the application scenarios envisaged for IoT technologies involves indoor localization and context awareness. In this paper, we focus on a localization approach that relies on a particular type of communication technology, namely Ultra Wide Band (UWB). UWB technology is an attractive choice for indoor localization, owing to its high accuracy. Since localization algorithms typically rely on estimated inter-node distances, the goal of this paper is to evaluate the improvement brought by a simple (linear) statistical model of the distance error. On the basis of an extensive experimental measurement campaign, we propose a general analytical framework, based on a Least Square (LS) method, to derive a novel statistical model for the range estimation error between a pair of UWB nodes. The proposed statistical model is then applied to improve the performance of a few illustrative localization algorithms in various realistic scenarios. The obtained experimental results show that the use of the proposed statistical model improves the accuracy of the considered localization algorithms with a reduction of the localization error up to 66%. Nowadays, the number of interconnected devices is highly increasing and it is expected that in the near future it will continue its exponential growth. For this reason, Internet of Things (IoT) is a very up-to-date research topic, which involves various application scenarios, with the aim of developing smart environments . One of UWB technology is very attractive for indoor communications. The large bandwidth and the high time resolution of UWB signals can theoretically reduce the impact of phenomena, which typically interfere with wireless communications in indoor environments  . As a maIn the late 1980s, UWB signals were first used for military applications. The interest in UWB communications grew after the Federal Communications Commission (FCC) in the USA allowed the unlicensed use of UWB devices in February 2002 and after the definition, in 2007, of the IEEE 802.15.4a standard, which provides physical layer specifications for short-range low data-rate UWB-based communications ; gaming range-free approaches do not require the availability of range measurements between nodes. These techniques can be further divided into local techniques, such as the centroid algorithm [One of the most promising aspects of UWB radios is their potential for high-precision localization, making them attractive for Wireless Sensor Network (WSN) scenarios. More precisely, positioning techniques for WSNs can be divided into two classes: range-free and range-based . As indilgorithm  or the Algorithm , and hoplgorithm .range-based approaches rely on the estimation of a signal parameter, such as the ToF or the Received Signal Strength (RSS) [At the opposite, th (RSS) . The useth (RSS) . Given tIn this paper, on the basis of an extensive experimental campaign with PulsON 410 Ranging and Communications Modules (P410 RCMs) produced by Time Domain.Ref , we deriThe paper is organized as follows. In In order to derive an analytical model for the range estimation error, an extensive experimental campaign of range measurements between two pairs of UWB sensors is carried out. The UWB sensors used to collect our results are the P410, which are equipped with RCM firmware and software  to enable ranging purposes. One of the used boards is shown in request messages from the host to the RCM with their associated confirm messages. In addition, info messages are sent to the host every time a UWB packet is received from other RCMs. Each RCM can communicate, on the UWB channel, to all the RCMs in the considered environment and each communication is associated with a message ID.Such sensors are single-board UWB radio components that can be integrated into users’ electronic devices to obtain high precision range measurement. The Radio Frequency (RF) transmission of the RCMs is centered at limeters . A typicWe consider inter-sensor distances from 1 m to 10 m, as this is realistic for many indoor scenarios. The (true) distances between the sensors have been measured using a laser. The range estimates are taken at 1 m step: more precisely, for every considered distance, Let us denote as In r and We are now set to derive a statistical model for the range estimation error, in terms of its average value. In general, one can write:In order to characterize statistically the range estimation error in Label , we analto Label ) are shoFrom the results in a and b are found by applying LS estimation. More precisely, the coefficients a and b in  approximation, based on the collected data of the range estimation errorν¯k≃ν¯k,,8), the r  position of the remaining one. We denote as Anchor Nodes (ANs) the three nodes with known positions and we denote their coordinates asFinally, we denote as Target Node (TN) the node whose position needs to be estimated and we indicate its coordinates as In order to gather experimental results, we connect the RCM, which corresponds to the TN to a host. Proper Matlab libraries have been used for the communication between the TN and its host. First, the TN collects the range estimates from the three ANs by directly interrogating, one after another, the IDs corresponding to each of the three ANs—the TN is assumed to know the IDs of the ANs. Once the TN receives the range estimates from all the ANs, recalling that the coordinates of the ANs are known, it can compute its position by means of proper localization algorithms. In the following, two relevant localization algorithms will be considered. We remark that we do not aim at introducing new localization algorithms. Rather, our goal is to investigate the impact of the statistical characterization of the range estimation error derived in In order to statistically characterize the accuracy of the position estimates, for each localization problem, we consider 1000 location estimations (denoted as iterations). In the following, we denote: The two considered localization algorithms are described in In this subsection, a simple localization algorithm, denoted as Circumference Intersection (CI), is presented. A similar approach is introduced in . In ordeHence, the TN coordinates Since the values of the true distances e system  should bThe equations in  refer toi (as in ) with raIn order to find the TN position estimates in the ified by  bf[rwithout taking into account the statistical model of the range estimation error; and, as with the use of the proposed statistical model, i.e.,  distances wn. From  and 27){ri}i=13 We first consider the CI algorithm. In From More precisely, the solid line is relative to the position estimates obtained without the statistical model for the distance estimates, while the dashed line is relative to the position estimates obtained applying the corrections in . From FiIn rrection , insteadThe true TN position (red star) is compared with the position estimates obtained over 1000 iterations with (green circles) or without (magenta pluses) the correction . From FiWe now consider the scenario shown in From  and 29)29), it fAs for the previous (“good”) scenario, we localize the TN by applying the CI and the TSML algorithms.In In From In Finally, Once more, the results in lgorithm , the proThe proposed “range error reduction” approach is based on two phases: (i) in the first  phase, a range estimation error model is derived, on the basis of experimental measurements; (ii) in a second phase, the derived model is used in practical localization algorithms, by simply correcting the estimated pairwise distances before using them in the localization algorithms. The outcome of the first phase depends on the used nodes , but the approach is general.In Moreover, we define the difference between these two values as lgorithm . Comparirding to , is morerding to ) distancIn this paper, we have first carried out, using Time Domain RCMs, an extensive experimental campaign of range measurements for various pairwise distances (between 1 m and 10 m). The average range estimation error has been statistically analyzed and the obtained results show that it is well approximated as a linear function of the true distance between the considered pair of nodes. Then, the derived statistical model has been applied to two different localization algorithms  in two realistic localization scenarios (with different nodes’ topology) in a different indoor environment. More precisely, the proposed model is used to correct the estimated pairwise distances before feeding the localization algorithms. We remark that the proposed model is valid in LoS scenarios, but the same ideas could be generalized to take into account NLoS scenarios, in which the statistical model would depend on the specific geometry of the environment and on the material of obstacles between the considered nodes. Our results show that the use of the proposed model allows for improving the performance of the considered localization algorithms. In particular, the more the improvement is pronounced, the less favorable is the nodes’ geometry. This makes the proposed approach very attractive in scenarios where the geometry of the localization problem may vary significantly, e.g., in industrial scenarios where a node  may move among fixed (anchor) nodes.


Insufficient attention towards caregivers has resulted in the emergence of psychological and health complaints. Affliction tethers more towards spouses as compared to parents and females as compared to males. The role of sibling care givers was found to be no different from parents or spouses. Marital relationships were found to suffer the most, with the caregiver leaving the traumatic brain injury (TBI) patient in his time of need. The Brief Symptom Inventory (BSI) and family assessment device (FAD) predicted a correlation between patient variables and caregiver discontent. The Blacks/Hispanics proved to cope better with stress and their caregiver roles as compared to Whites. Time elapsed since the injury was found to relieve distress, while the surprising severity of the injury has no recorded impact. Social support or rather a lack of it has been seen to have an impact on family homeostasis, which can further be deteriorated by substance abuse by the patient. The therapeutic intervention found to be most advantageous was the D'Zurilla and Nezu social problem-solving model. Current evidence suggests that emphasis should be given on proper education and encouragement of caregivers before discharge of TBI patients from hospital to reduce the incidence of stressors. Additionally, counseling sessions should be led by professionally led support groups for dealing with psychological symptoms and peer-led group to eliminate social insecurities of caregivers. Traumatic Brain Injury (TBI) is a non-degenerative, acquired insult to the brain secondary to any applied external mechanical force . In the Issues faced by singular caregiver relatives and family unitsA systematic review exploring issues centered on predicaments faced by caregivers suggests that the psychological problems predominately found in caregivers include; pressure, burden, anxiety and clinical depression. Spouses were found to be more prone to be overburdened by these psychological crises as compared to biological parents, as parents are more motivated to overtake a ‘caring and providing role'. Predominant concerns of the caregivers were complaints of less personal time. Gender of the caregiver was found to have an association with the emotions felt to vent out stress; females documented psychological depression and anxiety, while on the contrary males experienced exhaustion and agitation . Sixty-tDepression in adult sibling caregiversSiblings of the patients with TBI have been an understudied group while it is automatically assumed that they will overtake roles of responsibilities following the patient’s TBI episode. A study attempted to investigate the correlates of depression in 170 adult siblings by using Pearlin’s stress process model. The tools employed were: amount of care provided scale (ACPS) by the non-injured sibling, a 19-item cognitive-behavioral impairment scale (CBIS) of the TBI patient, subjective caregiving demand scale (SCBS) and caregiving demands scale (CDS) as perceived by the non injured sibling, family deprivation scale (FDS), future concern scales (FCS), the gain scale to measure the perceived growth of the non-injured person as a human being, frequency of family coping behaviors, the social provision scale (SPS) to measure perceived support from the society, and the center for epidemiologic studies depression (CES-D) scale to measure depression in the healthy siblings with a score of above 16 denoting clinical depression. Results demonstrated 66 of the adult siblings to have a CES-D score of higher than 16 denoting clinical depression. Depression was aggravated by the following factors; being female, a previous bout of depression, fewer responsibilities as a caregiver, and nonexistent family and social support. Higher levels of cognitive impairment of the TBI patient had no effect on depression. Similarly, lower perceived social support also aggravated depression. These findings demonstrated that the results for adult siblings were the same as those already described for other family relatives [Effects of traumatic brain injury on relationshipsA cohort study attempted to measure the changes occurring in close intimate relationships after an episode of TBI. Hundred and thirty-one subjects were recruited who in order to be eligible had to have a traumatic brain injury, be at least 21 years old at the time of the study, been with their partner for at least one year before TBI, and returned back to live with their partner after TBI. Further information was acquired pertaining to the severity of injury by neuropsychological assessment, the length of relationship before the TBI crises, current relationship status with the partner, and if the relationship had changed in any way. The results obtained from this showed that about 48.86% of TBI had lost their intimate partners through divorce or separation, and 6.10% of the still married respondents reported the marriage to have lost its charm. Chi-square test was conducted to find the relationship between marital stability and mature age of above 35 years old. The result (χ2=0.19 p> 0.05) denoted no relationship between the two factors. The traditional assumption that females are more likely to remain as the partner was found to be statistically insignificant ( χ2=0.02), with 45.36% of males leaving their injured partners while on the other hand, 47.1% of females partners left. The assumption that the existence of children under the age of 15 years could contribute to marital harmony and was also found to be statistically insignificant by the Chi-square-test (χ2=0). The factors contributing to relationship breakdown was where the severity of the injury, the likeliness of divorce or separation is inversely proportional to the length of relationship, and the time period of five-six years from the TBI episode to be the time when divorce or separation occurred [Effects of race/ethnicity and income of caregiverA longitudinal study was conducted to compare emotional stress, perceived burden, and coping methods between Blacks and White caregivers. Hundred and Ninty five caregivers were enrolled out of which 75% were Whites. Socio-demographic factors measuring income, education, relationship with the patient, and Glasgow coma scale to measure the severity of injury were used. Other tools utilized were: BSI, standardized ways of the coping questionnaire (WOCQ) to identify whether the respondent used the problem-focused or emotional-focused way to cope with distress, and the modified care appraisal scale (MCAS) to assess perception of caregiving by the respondents. Results showed Blacks/Hispanics to be on the lower end of education  and income . Race/ethnicity was found not to have any effect on levels of distress. The Blacks/Hispanics were more prone to assume a responsible caregiving role, and a more traditional mindset was found to be associated with higher levels of distress . Figure Effect of perceived social support on caregiversIn addition to reporting statistically similar outcomes for aforementioned factors . Ergh, et al. demonstrated that social support was the strongest variable responsible for predicting family operation and demonstrated a direct linear relationship. Caregivers who received no social support were shown to have higher levels of psychological discontent while, on the other hand, while those receiving adequate support had reduced levels of stress. Alcohol and substance abuse which is a major risk factor for TBI patients is a habit that can persist even after resolution of TBI and has a congruent effect in patients with TBI and can further deteriorate their functioning and recovery, which leads to increased levels of burden on the primary and secondary caregivers . A prospAlleviation of stress in caregivers after specific elapsed time pointsA prospective cohort study was conducted to measure levels of psychological symptoms on caregivers of individuals with TBI after specific elapsed time-points i.e. pre-discharge, post-discharge, and three months post-discharge. Around 29 caregivers completed the caregiver strain index and depression, anxiety, and stress scales at the above-mentioned points in time. Significant levels of alleviated caregiver discontent were observed at one-month post-discharge as compared to levels at pre-discharge, and an even further reduction was observed after three months of suffering the traumatic brain episode suggesting that time elapsed injury has an inverse relation with caregiver’s perceived burden .Effects of different interventions on caregiversIn contrast to the preceding studies which measured levels of stress in caregivers and factors which have a relationship with levels of stress, a recently published randomized controlled trial (RCT) evaluated an intervention in the form of a therapeutic approach known as problem-solving training program which was hypothesized to lower depression, bodily complaints and overall stressors. The caregivers were randomized into problem-solving training group  or an education-only control group . Individual with TBI in the intervention group were 26 males and seven females, whereas 24 males and 10 females were recruited for the control group. The intervention caregiver group was provided with the D'Zurilla and Nezu social problem-solving model, whereas the control group only received written educational matter. Analyses configured by the hierarchical linear models demonstrated that caregivers who received the problem-solving interventions account to a significant reductions in levels of depression, physical health, and overall social and mental comfort . SufficiIn the light of the above evidence, we recommend division of labor among all the family members. Although the primary caregiver, who ideally should be the most responsible and entrusted member of the family, other members should also overtake secondary roles of care giving. This secondary role should include allotting a few hours of their daily routine time to focus on the patient with TBI and completion of certain tasks of that patient. These measures would make sure that the primary caregiver has some time left for themselves, which they can spend on collecting their thoughts, coping and self-care. It is not an easy task to devote a substantial amount of one’s life span in the never-ending care of another individual, hence the caregiver deserves the utmost respect and the highest quality of care deemed necessary Figure .The key conclusions by the authors in this review are factors which are affecting the varied levels of stress in caregivers. There is a definitive existence of psychological problems in overburdened caregivers, with spouses as compared to parents and females as compared to males being more on the receiving side of burden. Time since injury had a considerable impact on the family homeostasis, whereas the severity of the injury was found to have no significant impact. These findings were established to be consistent with adult non-injured siblings who had assumed the role of burden and responsibilities. Marital stability was found to suffer the most by partners separating as a result of the stress resulting from TBI, in the scenario of which females were just as to be blamed for showing less empathy as the male partners. Racial prejudice was resolved by findings being in favor of Blacks/Hispanics assuming the roles of better caregivers as compared to Whites. The amount of social support provided to the patient reflected the functioning of the family. Substance abuse in TBI individuals led to the higher caregiver stress. The strongest stress allaying factor was proved to be a therapeutic intervention in the form of problem-solving training. Recommendations include proper caregiver education before discharging the TBI patients from the hospital, which would reduce the possibilities of psychological symptoms appearing in the caregivers in the future. Stress reduction was also found to be responsive to the type of intervention given according to the specific challenges faced by the caregiver and would help them deal better with their new-found role.


Saccharomyces cerevisiae. In addition to the well-known specific responses to starvation for an essential nutrient, like nitrogen or phosphate, the presence of fermentable sugar or a respirative carbon source leads to predominance of fermentation or respiration, respectively. Fermenting and respiring cells also show strong differences in other properties, like storage carbohydrate levels, general stress tolerance and cellular growth rate. However, the main glucose repression pathway, which controls the switch between respiration and fermentation, is not involved in control of these properties. They are controlled by the protein kinase A (PKA) pathway. Addition of glucose to respiring yeast cells triggers cAMP synthesis, activation of PKA and rapid modification of its targets, like storage carbohydrate levels, general stress tolerance and growth rate. However, starvation of fermenting cells in a glucose medium for any essential macro- or micro-nutrient counteracts this effect, leading to downregulation of PKA and its targets concomitant with growth arrest and entrance into G0. Re-addition of the lacking nutrient triggers rapid activation of the PKA pathway, without involvement of cAMP as second messenger. Investigation of the sensing mechanism has revealed that the specific high-affinity nutrient transporter(s) induced during starvation function as transporter-receptors or transceptors for rapid activation of PKA upon re-addition of the missing substrate. In this way, transceptors have been identified for amino acids, ammonium, phosphate, sulfate, iron, and zinc. We propose a hypothesis for regulation of PKA activity by nutrient transceptors to serve as a conceptual framework for future experimentation. Many properties of transceptors appear to be similar to those of classical receptors and nutrient transceptors may constitute intermediate forms in the development of receptors from nutrient transporters during evolution. The nutrient-sensing transceptor system in yeast for activation of the PKA pathway has served as a paradigm for similar studies on candidate nutrient transceptors in other eukaryotes and we succinctly discuss the many examples of transceptors that have already been documented in other yeast species, filamentous fungi, plants, and animals, including the examples in human cells.The nutrient composition of the medium has dramatic effects on many cellular properties in the yeast  Saccharomyces cerevisiae growing in a complete nutrient medium with a fermentable carbon source display a range of phenotypes indicating that the activity of PKA is high, while the opposite is true for cells growing on a non-fermentable carbon source or for stationary phase cells  cells in which the cAMP-PKA pathway had first been activated by glucose, as evidenced by transient activation of trehalase, and to which a nitrogen source was added to support growth initiation by the cells. Interestingly, addition of the nitrogen source caused an immediate reactivation of trehalase, without any change in the cAMP level . This in0 . As a reBy using temperature-sensitive mutants in cAMP synthesis at permissive and restrictive temperature it was confirmed that nitrogen-, phosphate-, and sulfate-induced activation of trehalase do not use cAMP as second messenger, although maintenance of a basal level of cAMP is required for full activation . BecauseS. cerevisiae will be discussed in the next section. An overview of the different nutrient transceptors identified in S. cerevisiae and their role in activation of PKA in concert with the cAMP-PKA pathway is shown in Figure 1.Recently, the concept of non-cAMP mediated activation of PKA through the FGM pathway has been expanded from the macro-nutrients, nitrogen, phosphate, and sulfate, to the micro-nutrients iron and zinc . In eachProving an additional nutrient sensing property of a transporter is not straightforward and requires several levels of evidence (1) excluding the involvement of intracellular sensing and thus also of other transporters that can take up the relevant substrate, (2) identification of non-transported competitive or non-competitive inhibitors with agonist signaling function, (3) transport-deficient versions of the transceptor that have retained the signaling function, for instance by mutating the residues involved in proton-coupling required for symport of the substrate , and (4)GAP1 is strongly enhanced and the protein is present in high quantity at the plasma membrane  analysis showed that transport and signaling use the same substrate binding site in Gap1  which did not trigger signaling and showed that other transported amino acids do not trigger signaling in concentrations below their Km , a G-protein that plays an essential role in the initiation of protein synthesis and cell growth . The clo unclear .As previously explained, re-addition of the nutrient for which the cells have been starved triggers transceptor endocytosis and degradation in the vacuole. Hence, transceptor signaling to PKA has to be transient. In spite of this, the cells maintain a high PKA phenotype throughout exponential fermentable growth, conditions under which all starvation-induced transceptors remain repressed. This may suggest that fermentable sugar like glucose continuously activates PKA through the cAMP pathway during fermentative growth and that starvation-induced downregulation of PKA is caused in a cAMP-independent way by the transceptors. One straightforward and plausible hypothesis could be that the free catalytic subunits of PKA bind to the transceptor(s) and remain in this way sequestrated from their targets as long as the cells remain starved for at least one essential nutrient. This would result in the typical downregulation of the whole range of PKA targets, which is observed in all stationary-phase cells. In this case, the many different transceptors would only need a common intracellular binding site for the catalytic subunits of PKA, which would be exposed when the substrate of the transceptor is absent. When the substrate is added and transported by the transceptor, the latter changes its conformation and releases the catalytic subunits of PKA, triggering the typical sudden burst in PKA activity. This hypothesis can explain in a straightforward manner why so many different nutrients can trigger the same downregulation and re-activation of PKA through their own specific transceptor using basically the same mechanism. The glucose requirement of nutrient transceptor signaling can then be explained by the requirement of maintaining an adequate cAMP level and thus also an adequate amount of free catalytic subunits of PKA. Moreover, the presence of glucose also causes inactivation of the kelch-repeat proteins Krh1,2, which strengthen the binding of the catalytic and regulatory subunits. Their inactivation thus increases the amount of free catalytic subunits even in the presence of a constant cAMP level . In the In virtually all eukaryotic cell types, transporters and receptors are found in the plasma membrane. It seems plausible that nutrient transporters originated first in evolution since for any unicellular organism nutrient import is essential for survival and proliferation. Sensing and signaling by receptor proteins appears as a more sophisticated property generated later in evolution. It is unclear how receptors originated in evolution, but the close similarity between neurotransmitters and nutrients has led many years ago already to the suggestion that receptors might originate from nutrient transporters . The latFigure 2). This could provide an evolutionary advantage to a microorganism in allowing it to adapt its metabolism, gene expression machinery and/or other cellular properties more rapidly, i.e., before the nutrient has been able to affect these properties through its metabolism, i.e., by increasing energy levels, reducing power or availability of precursors. Nutrient transporters undergo multiple conformational changes during the transport cycle. Hence, it is not difficult to envisage that a specific conformation triggered by transport of the substrate would allow the transporter to interact with an intracellular protein, whereas the transporter in its basic conformation would not be able to do so. The yeast high-affinity transporters that are strongly induced during deprivation of their substrate, Gap1, Mep2, Pho84, Sul1,2, Ftr1, and Zrt1, and that all signal to the PKA pathway, are prominent examples of such transporters that gained an additional signaling function to rapidly affect a pleiotropic range of cellular properties upon detection of their nutrient substrate. It appears likely that loss of the transport function in such transporter-receptors has led to the transporter-like proteins with a pure nutrient sensing function . These proteins have retained the capacity to bind the nutrient substrate, possibly allow it to enter to some extent the transportation channel, and as a result switch the transporter conformation into the signaling conformation. Further transport of the nutrient toward release into the cytosol would have become defunct. The yeast Snf3, Rgt2, and Ssy1 proteins are prominent examples of such nutrient sensors. The demonstration that the mammalian SGLT3 non-transporting glucose transceptor can be converted into an actively transporting carrier by a single amino acid change in the glucose-binding domain provides strong support that the transition from transporting transceptor to non-transporting receptor would be a simple evolutionary step .We may consider all transporter-related proteins with a nutrient signaling function as transporter-receptors or transceptors. Hence, there are transporting and non-transporting transceptors. The distinction between the two categories may not be sharp. It is quite likely that eukaryotic transceptors with a primary signaling function may be discovered that have retained residual transport activity. Actually, such a protein has been discovered already in activity . Intermeactivity . Conversactivity . These dThe similarity of transporting transceptors and classical receptors in undergoing substrate/ligand-induced internalization also extends to the non-transporting transceptors. The low-affinity glucose sensor Rgt2 remains stable only in high-glucose grown cells, and the high-affinity glucose sensor Snf3 is stable only in cells grown in media with a low glucose level. Both proteins undergo ubiquitination-induced internalization and degradation in the vacuole under adverse conditions. In addition, constitutively active, signaling forms of the glucose sensors do not undergo endocytosis, whereas signaling defective sensors are constitutively targeted for degradation, suggesting that the stability of the glucose sensors may be associated with their ability to sense glucose .Subsequent to the discovery of transporting and non-transporting nutrient transceptors in yeast, many examples of nutrient transceptors have been found or suggested in other eukaryotes. As in yeast, most of these transceptors have been discovered in connection with regulatory responses to deprivation or to resupplementation of the substrate of the transceptor. Hence, these transceptors generally function in specific processes controlled by the substrate of the transceptor and often related more or less directly to the metabolism and/or the uptake of the substrate. For several of these transceptors there is evidence for control of multiple downstream processes and in some cases it has been shown that separate signaling events are involved. There are no clear examples yet in other eukaryotes of transceptors for different nutrients that control the same signaling pathway, as in the case of the yeast transceptors that trigger activation of the PKA pathway. In general, disconnection between uptake activity of a transporter and/or metabolism of its nutrient substrate and one or more regulatory responses triggered by the nutrient has led to awareness that the transporter might act as a sensor. Convincing experimental demonstration generally requires further detailed genetic modification of the transporter to separate transport and sensing more clearly to show that it truly functions as a transceptor.S. cerevisiae, the Mep family members Ump2 in Ustilago maydis , was shown to control growth via a mechanism that does not require bulk transport of amino acids into the cell  by direct interaction with proline-rich tyrosine kinase-2 (PYK2) . Loss ofExpression of a transport deficient mutant form of the human CNT1 nucleoside transporter in pancreatic cancer cells affected multiple processes in a similar way as expression of the wild type CNT1 transporter, which led to the suggestion that it may function as a transceptor .D-aspartate and small molecule inhibitors, that elicited the same response as glutamate  by nutrient transceptors, in particular the signaling proteins that directly interact with the nutrient transceptors, the identification of other examples of the same cellular process affected by multiple transceptors for different nutrients, the identification of similar signaling domains and downstream signaling pathways in transceptors from multiple distantly related species and elucidation of the connection between substrate binding, transport and signaling in a transceptor.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


Although bodies of evidence on copayment effects on access to care and quality of care in general have not been conclusive, allowing copayment in the case of emergency medical conditions might pose a high risk of delayed treatment leading to avoidable disability or death.Using mixed-methods approach to draw evidence from multiple sources , we are were able to shed light on the existence of copayment and its related factors in the Thai healthcare system despite the presence of universal health coverage since 2001.The copayment poses a barrier of access to emergency care delivered by private hospitals despite the policy proclaiming free access and payment. The copayment differentially affects beneficiaries of the major 3 public-health insurance schemes hence inducing inequity of access.We have identified 6 drivers of the copayment i.e., 1) perceived under payment, 2) unclear operational definitions of emergency conditions or 3) lack of criteria to justify inter-hospital transfer after the first 72 h of admission, 4) limited understanding by the service users of the policy-directed benefits, 5) weak regulatory mechanism as indicated by lack of information systems to trace private provider’s practices, and 6) ineffective arrangements for inter-hospital transfer. With demand-side perspectives, we addressed the reasons for bypassing gatekeepers or assigned local hospitals. These are the perception of inferior quality of care and age-related tendency to use emergency department, which indicate a deficit in the current healthcare systems under universal health coverage. Finally, we have discussed strategies to address these potential drivers of copayment and needs for further studies.The online version of this article (doi:10.1186/s12913-016-1847-y) contains supplementary material, which is available to authorized users. Many health authorities advocate for universal health coverage (UHC) regardless of economic status of a country citing potential benefits such as financial protection from catastrophic illnesses, increased access to healthcare, and reduction in out-of-pocket payments (OOP) , 2. For In 2001, a new major public-health financing program  was introduced in Thailand providing coverage of healthcare extending to 75 % of the population. This major step advanced the national health insurance reforms towards full universal coverage on top of the previous public-health insurance schemes . Over a decade of the full universal coverage in Thailand, evidence has shown increased financial risk protection and increased service utilization . TogetheIn addition, users’ perception of quality of care can influence choices of providers hence resulting in OOP when bypassing the assigned local providers for provider of choice. Using multiple logistic regression model to analyse in-patient survey data, Cheng et al. revealed a strong association between perceived quality of care  and choices of providers .In April 2012, the Thai government undertook a nation-wide unified Emergency Medical Services (EMS) policy initiative in mobilizing private hospitals in addition to those participating in 2 major public health financing programs (SSS and UCS) to fill the perceived gap of access to EMS for all health insurance beneficiaries. The perceived gap of access was highlighted by the Prime Minister out of a concern of inequitable access due to different amount and mechanisms of payment among the three major schemes . In otheTo guide the policy implementation, a two-phase independent evaluation was undertaken employing a mixed methods approach (to be presented in detail below) to shed light on the progression, obstacles and alternatives for policy adjustment. The first phase covered the first six months of the policy implementation from which findings and respective feedback to policymakers and stakeholders guided the second phase. An important finding from the first phase deals with patient outcomes. Using an administrative dataset of 22,900 records for the unified purchasing model, Paibul et al. reported a discrepancy in fatal and non-fatal outcomes at discharge from inpatient care among the beneficiaries of different schemes . In compThe copayment seems likely given the fact that there is no legal provision to support the policy expectation of no extra payment. In addition, the haste in policy implementation (less than 2 weeks in preparation phase) may preclude consultation with private providers about payment rates. Comparing the single payment rate for inpatient care to private providers of 10,500 baht per relative weight (RW) of diagnosis-related-group (DRG) under this policy to that of 15,000 baht per RW under an earlier program of the UCS, it could readily be argued that perceived under payment among the private providers could be a crucial issue. Following the implementation, we sought to document the prevalence of copayment under the new policy and to identify the main drivers of copayments and to evaluate the implications of copayments for access.These are the key policy questions to be explored in this report. Answering these questions may be useful in the further development of laws, processes and institutional responsibilities that define private sector participation in the provision of essential health services under UHC. Notwithstanding careful searching of the main bibliographic databases covering health services no reports on the effects of copayment on utilization of EMS and factors related to the copayment in low and middle-income countries were identified.Over the last 3 decades, EMS systems in Thailand have gradually evolved in response to the emergency health needs. The EMS systems include pre-hospital ambulance services, medical emergency dispatch centers, ED services and inpatient definitive care organized mainly by public providers in rural and urban settings and to a certain extent by private providers in major cities.Since 2001, UCS, SSS and CSMBS have mainly financed hospital emergency services including ED and inpatient definitive care. The payment methods and payment rates differ among the 3 schemes with some overlapping as follows.Under the UCS, all the contracted hospitals, both public and private, are paid for EMS provided to a non-registered UCS member by fee for service (FFS) with a ceiling of 700 Baht for ED visits and DRG with global budget for inpatient care. FFS with ceiling was adopted to pay private hospitals outside the contract for both ED and inpatient care. Under the SSS, public hospitals are paid according to the billing for ED visits and the first 72 h of admission. For private non-registered hospitals, both under and outside the contract, the patients have to pay upfront and reimburse from the central fund by FFS with ceiling for both ED visits and the first 72 h of admission. After 72 h of admission, the registered hospital is fully responsible for the costs of service provided.Under CSMBS payment methods, all public hospitals are reimbursed on a fee schedule for ED visits and on the DRG basis for inpatient care plus boarding and medical supply based on a predefined list. Prior to the policy initiative, the reimbursement for inpatient care to private hospitals was capped at 4,000 Baht (133 United States Dollar (USD)) per admission. There was no payment for ED service to private hospitals. Notably, a CSMBS beneficiary is not required to register to any hospitals, as opposed to those of SSS and UCS. Should there be a need for inter-hospital transfer after initial admission to a hospital for an emergency condition they are more likely to face difficulty in seeking another hospital for the transfer.Without an exclusive dataset for ED services, an unofficial estimate of total ED visits to public hospital was reported to be 13 million annually . Based oThe unified EMS policy aims to close the gap of access to EMS under the three health insurance schemes. The policy interventions include mobilizing private hospitals outside the previous contracts; unification of payment methods and payment rates for purchase of EMS from these private hospitals; public policy communication to inform the beneficiaries on the right of access without copayment; and monitoring of the progress for ongoing adjustment. The National Health Security Office (NHSO), in charge of UCS, is assigned to be the responsible agency in executing this policy. The unified purchasing model is characterized as single payment methods and single payment rates for ED visits and hospitalization to the outside contracted private hospitals. For ED visits, the payment is based on the fee schedule of the existing CSMBS protocol plus extra items beyond the fee schedule, but does not exceed 1,000 Baht. For hospitalization, DRG is a case-based payment at 10,500 Baht (approximately 350 USD) per adjusted RW which is used to reimburse the private hospitals. The private hospitals receive extra payments for high cost medications and medical instruments . Financial audit of every claim is mandatory prior to the reimbursement. This includes checking severity classification, DRG related data, health insurance entitlement, patient identification (ID) code, hospital ID code, and date/time of hospital visit and discharge. NHSO also acts as the Clearing House to process reimbursement claim, patient complaints, and to coordinate, in collaboration with Ministry of Public Health (MOPH), inter-hospital transfer of patients. An administrative dataset was exclusively set up to facilitate the financial claim processes using online transactions.As part of the policy implementation, the government made use of mass media and out-door media for public communication campaign to raise awareness of free access to all public and private hospitals nation-wide in case of a need for EMS despite the fact that supply-side interventions are limited to 255 outside contracted private hospitals . In addition to the unified payment mechanism, the MOPH held several official meetings with representatives of the private hospitals to press them to participate citing the mandate stipulated in The Sanatorium Act B.E. 2541. The law requires private hospitals to provide emergency care for any patients until the emergency condition has been stabilized without mentioning any hospital payments and definitions of the conditions. The combined supply-side and demand-side interventions of the programs mentioned are expected to work together in promoting better access to emergency services. It is noteworthy that the majority of the outside contracted private hospitals previously chose to focus on the high-end well-paid market of healthcare. Setting the payment rate without adequate participation of these private hospitals hence posted a challenge in their compliance to the service provision. The lack of any regulatory capacity to compel the private hospitals not to charge copayments above the EMS payments posted another challenge of copayment.In practice, the program involved a large body of representatives mainly from the outside contracted private hospitals, 3 departmental units of the MOPH, and the 3 schemes. In every high-level decision-making forum, the Prime Minister chaired the meetings herself indicating a strong policy commitment. Monthly reports of the progress in policy implementation in terms of outputs and public responses (directly from the complaint channel and indirectly from mass media) were key inputs to the forums. Multiple stakeholders with multiple perspectives were brought into the policy arena along with the ambitious purpose of achieving more unified healthcare financing mechanism (after a decade of stagnation on this policy track)  and acceThis study was approved by the Institutional Ethical Review Board of the Faculty of Medicine, Ramathibodi Hospital.Given the complicated financial arrangements and complexity of the policy implementation, we chose to use a mix-methods approach to fill the knowledge gaps. In principle, a mixed methods has been considered suitable for research questions fitting any of the following characteristics: exploring the meaning of a construct or phenomenon from more than one perspective; explanation of anomalous findings or getting behind the mechanism of action of an effect; theory development followed by testing/extension; measure development using grounded concepts; or augmenting evaluation studies with better understanding of intervention implementation –20.In our case, the posted research questions seem to be, largely, in keeping with these characteristics. First, the complexity of the policy initiative precludes any single perspective to dominate making sense of the meanings of the policy phenomenon. Second, to understand the constraints and drivers regarding access to EMS and the underlying functions and mechanisms requires qualitative findings from in-depth interviews with multiple stakeholders and quantitative findings from the user complaint channel or more systematic user survey. The following describes details of the methods in the data acquisition.It is notable that the two-phase evaluation was carried out with substantial participation from key actors from the inception  to drafting of the final reports. The key actors comprised the 3 schemes, MOPH as regulator, the Clearing House, and the Private Hospital Association. This participatory approach enabled the authors to get access to relevant policy documents and the administrative (electronic claim) dataset. Nonetheless, despite the involvement of the Private Hospital Association, the authors did not have access to any financial data from the targeted private hospitals. In addition, we could not access to the minutes of all the meetings chaired by the Prime Minister.In order to explore potential explanatory factors of copayment, we employed in-depth interviews with key actors: regulators, private hospital directors, the Clearing House administrators and the administrators of the health insurance schemes Table . EmerginSelected private hospitals were purposively chosen aiming at hospitals with billing at the 3rd quartile 6,525 USD) or over and those under the 2nd quartile  or below. This selection criterion enabled us to contrast factors, which might explain relevant hospital behaviors . Distribution of selected private hospitals and their locations is shown in Table 5 USD or To ascertain the prevalence of copayment, independent of those from the official complaint dataset, a telephone survey was  during April 2012 to December 2013. Ninety one percent of the records dealt with inpatient care. The EMCO dataset contains 50 variables including those extracted for the present study: amount of claims, amount of reimbursement, claim approval status, adjusted relative weight AdjRW), and service delivery data , date/time at discharge, and outcomes at discharge.We reviewed documents to supplement and triangulate findings from the user survey and in-depth interviews. We searched documents purposively using Google Scholar and Google Search and PubMed based on the following keywords: EMS, regulation, definition, private hospital, payment methods, access, ED, outpatient, inpatient, annual report of regulatory agencies. We contact key actors mentioned above for relevant documents not accessible via internet. From the Clearing House, we try to identify 3 major types of documents i.e., a report of user complaints, a summary report on progress of the program and telephone survey reports. Finally, we employ snowball search strategy to obtain further documents to better understand emerging issues from review of previous documents and in-depth interview.We performed statistical analyses using IBM SPSS Statistics version 18.0 . Profile of patients in the 3 groups of health insurance schemes and monthly access to inpatient care were compared using percentage for categorical data and mean for continuous data Table . CMI, caDigital electronic records of the in-depth interviews conducted during the first three months of the program were transcribed verbatim. The key interview questions included opinions on the policy, operational definitions, mechanism and process of policy implementation, regulatory function and mechanism, provision of care and claim process, and feedback on payment system. We performed thematic content analysis to capture emerging themes. Subthemes and details are organized under the emerging themes. Relationships between themes and subthemes are identified. These were carried out in parallel by the first three authors. The authors discussed the findings to achieve consensus on the conclusions. Similarly, we applied the processes to documentary reviews. Table Analysis of the EMCO dataset reveals 43,588 patient claim visits to 225 private hospitals  during the first 21 months of the program (April 2012 - December 2013). The majority of claims (91 %) were for inpatient care. Table The majority of patients reportedly visited with urgent conditions  shown in Table Hospitals participating in the program varied in size from 10 to 500 beds with a median of 150 beds (top quartile 230 beds and bottom quartile 100 beds). Over the period, claims from small hospitals  . AccordiN = 128) for the first month of the program found the prevalence (%) of copayment varied from 80 % for CSMBS beneficiaries to 50 % for UCS and 30 % for SSS beneficiaries. The prevalence of copayment requirements reflects the fact that private hospitals perceived the reimbursement rate set by the Clearing House as under compensation to the cost of services.With the perceived under payment, hospitals might opt for copayment in addition to the upward adjustment of charges or withdrawal. Based on the paid-charge ratios, it could be inferred that the hospitals might request for a substantial copayment from roughly 40 to 80 % of the total charge. This notion is supported by evidence from the consumer surveys. As part of the feedback to the policy implementation, the Clearing House ran a series of telephone surveys in 3 consecutive periods , which showed the prevalence of copayment varied from 53 to 95 % as shown in Table N = 1,257 records). We found different prices per adjRW for the services among 3 categories of hospitals: security-market registered hospitals, general private hospitals, and not-for-profit private hospitals. On average security-market registered hospitals are bigger than the others . The median price varied as follows: 47,246 Baht, 38,565 Baht and 35,727 Baht, respectively . Further analysis taking account expected differences in fixed and operating cost between hospitals in Bangkok and regional provinces, we found no difference in price among security-market registered hospitals operating in Bangkok or regional provinces. To the contrary, the differences were demonstrated for the other two categories i.e., higher price for hospitals operating in Bangkok and lower price for hospitals in regional provinces. These findings vividly indicate different pricing policies among different categories of the hospitals. It should be noted that security-market registered hospitals charged the highest price despite the fact that they are in a better position to access loans at the lowest interest rates compared to the others. Finally, in the same report, our team conducted a head-to-head comparison of itemized prices  on 80 selected patients of the private hospitals to those prices of a tertiary care public hospital to shed light on rational of the pricing. We found that medication prices differed from 1.15 to 399 times and 1.55 to 4.4 times for medical supply. By reviewing medical records and hospital bills, we also found seemingly unnecessary charge items on the hospital bills. For instance, the items included a screening test for prostate cancer in a patient with pneumonia, bone fixation in a patient with hypertension, and blood transfusion without proper medical indications. Results of the head-to-head comparison and the review of medical records cum hospital bills suggested inappropriate pricing of some private hospitals. After viewing these findings, reaction from representatives of the hospitals turned out quite predictable. They argued that private hospitals have to fully rely on themselves from the first to the last dollar in capital investment and daily operation, which is not the case for public hospitals. As a result, they argued comparisons are not appropriate. With regard to the findings from the review of medical records and hospital bills, they did not give any opinion.The discrepancy in the amount reimbursed and the total charge clearly demonstrates a conflict between pricing policy of the hospitals and the adopted payment policy. To support the pricing policy, the hospitals argued that they set prices to reflect full cost recovery and a surplus of under 15 % per annum Table . Based oN = 128) revealing the most common reasons for bypassing closest public or private hospitals were due to a perception of inferior quality of care. Finally, the private hospitals vindicate copayment by attributing to the lack of criteria to justify inter-hospital transfer after the first 72 h of admission while the patients demand further stay.In-depth interview provided further evidence related to the copayment level. Private hospitals cited unclear operational definitions of emergency conditions as a reason to impose copayment to deter perceived abuse of the services by patients. This perception emerges from the hospitals report of encountering patients with non-urgent conditions requesting free access to ED and inpatient care. This notion sounds logical given the large proportion (90 %) of patients accessing ED by informal means . This reOur telephone survey on the 128 patient samples revealed over 90 % of them were ignorant of the channel for making complaint to the Clearing House. During the early months of the program, analysis of complaint calls from the patients or relatives to the Clearing House identified 1,165 calls asking for clarification of eligible emergency conditions; 633 calls of eligible hospitals for access; and 409 calls of the conditions for copayment. These findings indicate inadequate public policy communication to the users.The high degree of freedom in price setting by the hospitals raises an issue of hospital regulatory mechanism. The Sanatorium Act B.E. 2541 (section 32) requires hospitals to disclose prices of medical and hospital services which hospitals have to comply with accordingly. To enforce the laws, the Health Facility Committee has been set up and chaired by the Permanent Secretary of the MOPH. Its voting members consist of the Heads of 4 departments of the MOPH, a representative of the Council of State and of the Office of Consumer Protection. In addition, the committee includes 3 health practitioners, a representative of each of the health professional councils and technical advisors which have to be representatives from the private hospitals for at least 1 person and no more than 3. The Committee has been tasked with issuing regulations, granting permission for establishing and operating a hospital, promoting quality improvement and processing appeals. Since the law has been in place for almost two decades, there have not been any information systems to keep track of the hospital behaviors. Alarmingly, informal interview found a key informant,  who maintained that he had never witnessed a single case of hospitals being seriously dealt with for misconduct. This notion is in keeping with findings from the review of the annual reports in 2006–2014 of the department overseeing the Sanatorium Act, which found no evidence pertinent to the law enforcement .Turning to the payment rate issue, in-depth interview with high-ranking officers of the Clearing House and the health insurance schemes revealed the rationale behind the DRG-based payment rate. We find the rate was being set without concrete evidence about the cost of hospital services except for a concern of future financial burden to the UCS if a higher rate than the current one would have been adopted. However, in effect, a higher rate of DRG-based payment to private hospitals has been adopted for other previous programs under the UCS for medical services for premature newborns, patients with severe head injury, cardiac catherization etcetera.Finally, in-depth interview of the administrators of the 3 schemes revealed no concrete evidence of any progress in the attempts to make changes in rules and regulations pertinent to the program requirement i.e. harmonizing the payment mechanism and payment rates to facilitate access to EMS of the hospitals. Hence, the existing payment made possible using the financial resources and personnel of the UCS assigned to take major responsibility in the program execution through the Clearing House. Major obstacles cited by the administrators of SSS and CSMBS are the concern of potential impacts of the expected amendment of rules and regulations on all other benefit packages for non-emergency conditions.Using a mixed methods, this report is able to shed light on the existence of copayment despite the public financing of access to the hospital provision of EMS during the 21 months of the program implementation. The copayment existed in parallel with inequitable access to EMS among the beneficiaries of the 3 schemes as shown in Table In similar to several countries in Organisation for Economic Co-operation and Development (OECD) with UHC, under the policy directive Thai patients in urgent conditions are allowed to directly seek hospital ED without copayment . HoweverThe declining percentage of patients with critical conditions over the 21-month period shown in Table These difficulties confronting the U.S. hospitals (mainly private) are, in turn, instructive to improvement of the provisions and enforcement of the Sanatorium Act in Thailand. First the Sanatorium Act should include provisions with more specific details requiring hospitals to provide screening, stabilizing and transfer for the patients similar to those of EMTALA. Provisions for penalty should also be clear and substantial enough like that of EMTALA. Apart from the provisions; the effectiveness of enforcing EMTALA lies on the so-called “Medicare death penalty” i.e. termination of Medicare contract to hospitals based on result of investigation of potential law violations by the Centers for Medicare and Medicaid Services (CMS) . The deaConcerning well-informed decision of the users, the findings on limited knowledge of the users indicate inadequate policy communication based mainly on mass media and out-door media. This could be addressed through regulatory measure mandating the hospitals to make formal notification of the right of access to every patient visiting ED as is the case under EMTALA. In many European countries, hospitals are required to bear the burden of proof in case of liability for malpractice and errors in providing information . This kiReview of national efforts among BRICS countries  reveals substantial contribution of private providers in healthcare provision . In factConsidering a need for strategic purchasing from powerful private sector in pursuit of UHC, the present report indicates a number of inter-related key specific issues for further studies: capacity building for healthcare financing agencies in negotiating with private providers based on rational and evidence-based price setting; and design of technically strong and high commitment of regulatory mechanism to set up effective legal framework to ensure sufficient access and fair pricing. Both these issues should be conceived along with the development of sufficient information systems to keep track of private providers in terms of service provision  and pricing. Finally, further studies should focus on assessment of implementation of the suggested legal measures to enhance providers’ sensitivity to users’ need for relevant information at the point of care. Finally, systematic assessment on the impacts of the provision of after-hour clinics by public hospitals should be conducted taking account ED as an indicator.We chose to focus on inpatient dataset hence rendering inadequate exploration of ED visits. The results of user survey could be biased due to substantial number of non-respondents or failure to make contact. We could not explore methodological details of the telephone survey of the Clearing House, which might be subject to selection bias and information bias. Without access to minutes of the executive meetings during the policy implementation, we were not able to explore interactions among policymakers and the key stakeholders. In-depth interviews were conducted during the first few months of the program, hence the findings may not be up-to-date given the dynamicity of the policy context resulting in changing faces of policymakers during the 21-month period. Finally, administration of the EMCO dataset is not sophisticated enough, hence quite substantial relevant data are missing for some variables. This deficit in data quality might affect parameter estimation.Using a mixed-methods approach to draw evidence from multiple sources, we have been able to shed light on the existence of copayment in the Thai healthcare system despite the presence of UHC since 2001. The copayment poses a barrier of access to emergency care delivered by private hospitals according to the policy proclaiming free access. The copayment differentially affects different beneficiaries of the major 3 public-health insurance schemes hence inducing inequity of access. We have identified 6 drivers of the copayment i.e., perceived under payment, unclear operational definitions of emergency conditions or lack of criteria to justify inter-hospital transfer after the first 72 h of admission, limited understanding by the service users of the policy-directed benefits, weak regulatory mechanism as indicated by lack of information systems to trace private provider’s practices, and ineffective arrangements for inter-hospital transfer. With demand-side perspectives, we addressed the reasons for bypassing gatekeepers or assigned local hospitals. These are the perception of inferior quality of care and age-related tendency to use ED, which indicate a deficit in the current healthcare systems under UHC. Finally, we have discussed strategies to address these potential drivers of copayment and needs for further studies.


During machining of stainless steels at low cutting -speeds, workpiece material tends to adhere to the cutting tool at the tool–chip interface, forming built-up edge (BUE). BUE has a great importance in machining processes; it can significantly modify the phenomenon in the cutting zone, directly affecting the workpiece surface integrity, cutting tool forces, and chip formation. The American Iron and Steel Institute (AISI) 304 stainless steel has a high tendency to form an unstable BUE, leading to deterioration of the surface quality. Therefore, it is necessary to understand the nature of the surface integrity induced during machining operations. Although many reports have been published on the effect of tool wear during machining of AISI 304 stainless steel on surface integrity, studies on the influence of the BUE phenomenon in the stable state of wear have not been investigated so far. The main goal of the present work is to investigate the close link between the BUE formation, surface integrity and cutting forces in the stable sate of wear for uncoated cutting tool during the cutting tests of AISI 304 stainless steel. The cutting parameters were chosen to induce BUE formation during machining. X-ray diffraction (XRD) method was used for measuring superficial residual stresses of the machined surface through the stable state of wear in the cutting and feed directions. In addition, surface roughness of the machined surface was investigated using the Alicona microscope and Scanning Electron Microscopy (SEM) was used to reveal the surface distortions created during the cutting process, combined with chip undersurface analyses. The investigated BUE formation during the stable state of wear showed that the BUE can cause a significant improvement in the surface integrity and cutting forces. Moreover, it can be used to compensate for tool wear through changing the tool geometry, leading to the protection of the cutting tool from wear. Austenitic stainless steels are widely used in chemical industries and nuclear power industries because they have a good combination of high mechanical strength and corrosion resistance. However, the residual stresses induced by machining operations can affect their ability to withstand loading conditions such as stress concentration, corrosion, cracking, and fatigue ,2. AusteA BUE consists of highly deformed material layers, which are bonded to the tool surface and can lead to change the tool geometry and the mechanics of the process . BUE is Surface integrity of a machined workpiece can be described by three main parameters: the residual stresses, the surface roughness, and the work hardening in the surface zone . The resFew studies on surface integrity induced in machining of AISI 304 stainless steel have been performed. Xavior et al.  reportedFew papers are available concerning the interaction of worn cutting tools on the residual stress state in the machines surface of stainless steels ,28. Howe3). The microstructure of the AISI 304 workpiece was characterized using a Nikon ECLIPSE IV 100 microscope  equipped with UC30 camera  lead to less provoked BUE formation, whereas lower cutting velocities (vc < 60 m/min) result in wear rates that are too low for reasonable wear tests. The cutting tests were performed under wet condition to reduce friction and heat generation during the cutting process. The cutting fluid was applied at a flow rate of 11 L/min via a nozzle positioned directly above the cutting tool and directed toward the tool tip. The cutting fluid chosen was semi-synthetic coolant-CommCool™ 8800, manufactured by the Wallover Company , at a concentration of 7%, typically used with stainless steel alloys.In this research, a round bar (120 mm diameter by 500 mm length) of an austenitic stainless steel AISI 304 was investigated during turning (finishing operation). The chemical composition and mechanical properties of the material are shown in mera see . The turThe tool flank wear was measured using a KEYENCE—VHX 5000 digital microscope , equipped with a charge coupled device (CCD) camera and image analyzer software. The tool life criterion was set to a flank wear of 0.3 mm according to the recommendation of the ISO 3685 Standard . During To evaluate the influence of BUE formation in the steady state zone on surface roughness, the surface roughness of the machined workpiece was measured across the tool feed direction by means of an Alicona Infinite Focus-with the Profile roughness module. The procedures of surface roughness measurements were performed according to EN ISO standard 25178 . Roughneavg = 1.79026 Å) and Power settings: 35 kV, 45 mA. Residual stresses were analyzed in DIFFRAC.Leptos version 7.8 , and the parameters used for analysis are summarized in c) and the direction of feed motion  as shown in Throughout the steady state region of tool wear, small pieces of the machined workpiece were cut using a water jet to evaluate any changes in machining induced residual stresses, which might be affected by BUE formation. X-ray stress data was collected using the Bruker D8 DISCOVER with DAVINCI.DESIGN diffractometer , equipped with Cobalt Sealed Tube Source λavg = .79026 Å During the machining tests, the cutting force measurements were performed with a 3D component tool holder Kistler dynamometer type 9121  with a data acquisition system. The signals of the forces from the dynamometer were transmitted to a Kistler 5010 type amplifier, and then recorded on a computer using LABVIEW version 14.0 software . The acquisition rate was 1000 data points per second, scale was 20 MU/volt and sensitivity was 3.85 mV/MU.As discussed previously, the focus of this research is to understand the effect of BUE formation on surface integrity and cutting forces. To understand this idea in more detail, a wear performance of the uncoated cemented carbide cutting tool during machining AISI 304 stainless steel associated with progressive SEM images of BUE formation is presented in The BUE increases the contact between workpiece and cutting tool and it engages the material being deformed in the same way as a punch . TherefoWe have seen similar behavior in the steady state zone, as shown in To understand more about how the BUE is formed through the steady state zone, it was necessary to measure its average height during cutting. The average height of BUE in the steady state zone was measured using the KEYENCE microscope and plotted in To investigate the chemical composition of the tool and BUE, an EDS analysis was performed and the results are shown in One of the main factors contributing to natural surface roughness is the occurrence of the BUE. In the steady state zone, the BUE is continually building up and breaking down, which may lead to the fractured particles being carried away on the surface of the chip and the workpiece surface. Thus, it would be expected that the larger the BUE, the rougher would be the surface produced. However another phenomenon is observed here: BUE is an unstable structure; during cutting, the highly strain hardened fragments of BUE was torn off, and may adhere to the workpiece and/or chips surface, leading to increase surface roughness. A number of different phenomena are occurring simultaneously within the steady state zone.1. At the beginning of the steady state zone (from point 1 to point 2), BUE is continuously growing and engaging the machined surface, leading to the production of deep grooves, lowering the quality of surface finish . Specifically, the effect of the variation of BUE height in the steady state zone on process outputs was studied. Surface roughness, residual stresses, and cutting forces were examined to evaluate the BUE formation. The following conclusions can be drawn from this research:1. BUE formation is an unstable process; it gradually increases layer by layer and when it has reached a certain size, it tears off. This causes cracks and damage on the tool surface, leading to a cutting edge break out. However, sometimes the BUE prevents sliding at the interface, protecting the tool from wear.2. BUE growth is responsible for a decrease in surface roughness of the machined surface as the BUE is an unstable structure, and, when it is broken off, some of the BUE particles detach from the surface and reduce surface finish. However, in some situations, broken BUE was removed by chips, leading to improved machined surface finish.3. Tensile residual stresses were found on the surface of the machined workpiece; these stresses were decreasing when the BUE height increased, as the machined surface was softened as a result of high cutting temperature, eventually decreasing the residual stresses. Residual stresses were measured in both feed and cutting directions and it was found that that the hoop residual stresses are larger than the axial component ones, and the maximum compressive stresses and their depth are the same because tool wear remains the same in the steady state zone.4. The peak half width reduced when the BUE height increased because of high cutting temperature, which leads to softening of the machined surface, causing a reduction in peak half width. Its value was the highest on the surface and then decreased continuously for the unaffected workpiece, whereas the thickness of the work hardening layer was found to be 250 µm.5. The cutting force varied greatly, increasing when a BUE was torn off, and decreasing as a new BUE was formed. When a BUE increased, the wedge angle was reduced, resulting in a reduction in cutting force. It was also reported that the cutting force oscillations were gradually reduced when the BUE is more stable.Finally, it is important to emphasize that the BUE formation always follows the same scenario: it forms, accumulates, and breaks off, and then a new BUE is formed again. However, its form and intensity change under same cutting conditions. This study is useful to investigate the beneficial effect of BUE on tool life and understand how the BUE affects the surface integrity and cutting forces.