This phase-field model considers spatial variations in permeability and material properties within a single unified mathematical framework derived from an energy perspective, thereby allowing us to study effects of thrombus microstructure and properties on its deformation and possible release of emboli under different hemodynamic conditions. Moreover, we combine this proposed thrombus model with a particle-based model which simulates the initiation of the thrombus. The volume fraction of a thrombus obtained from the particle simulation is mapped to an input variable in the proposed phase-field thrombus model. The present work is thus the first computational study to integrate the initiation of a thrombus through platelet aggregation with its subsequent viscoelastic responses to various shear flows. This framework can be informed by clinical data and potentially be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions.Mechanical interactions between flowing and coagulated blood (thrombus) are crucial in dictating the deformation and remodeling of a thrombus after its formation in hemostasis. We propose a fully-Eulerian, three-dimensional, phase-field model of thrombus that is calibrated with existing  Thromboembolism is associated with detachment of small thrombus pieces from the bulk in the blood vessel. These detached pieces, also known as emboli, travel through the blood flow and may block other vessels downstream, e.g., they may plug the deep veins of the leg, groin or arm, leading to venous thromboembolism (VTE). VTE is a significant cause of morbidity and mortality and it affects more than 900,000 people in the United States and result in approximately 100,000 deaths every year. Mechanical interaction between flowing blood and a thrombus is crucial in determining the deformation of the thrombus and the possibility of releasing emboli. In this study, we develop a phase-field model that is capable of describing the structural properties of a thrombus and its biomechanical properties under different blood flow conditions. Moreover, we combine this thrombus model with a particle-based model which simulates the initiation of the thrombus. This combined framework is the first computational study to simulate the development of a thrombus from platelet aggregation to its subsequent viscoelastic responses to various shear flows. Informed by clinical data, this framework can be used to predict the risk of diverse thromboembolic events under physiological and pathological conditions. Under physiological conditions, blood clots form at sites of vascular injury to prevent blood loss, but they eventually resolve as the vascular wall heals , 2. The Hemodynamics is essential in the process of thrombus growth –18: for quantitative information for thrombus deformation and embolization from in vivo studies dv/Vtotal. The velocity field and the phase-field contour for the case of VF = 0.66 are plotted in To mimic this experiment, we place a thrombus in the center of a straight cuboid channel filling the channel, as shown in 6Ψf3)]−1 , also kne depends on the local volume fraction of a thrombus, which is equivalent to the phase-field variable ϕ in this study. There are few rheometry experiments that used oscillatory shear deformations to measure the viscoelastic properties of thrombus as a function of fibrin concentration, although they did not cover a wide range of fibrin concentration. In /G′  Ψfcm, where Ψf is the volume fraction of fibrin and Ψp is the volume fraction contribution of platelets [f can be computed by an empirical relation Ψf = cFbg/[ρFbg(0.015 log(cFbg) + 0.13)], where cFbg (mg/mL) is the concentration of fibrinogen and ρFbg = 1.4 g/mL is the density of a single fibrinogen molecule  instead of the four components of Eq 1 in Supporting information.The total free energy for the blood-thrombus system can thus be written by adding the cohesive and elastic energies, respectively, asequation  , ρ(ϕ), η(ϕ), κ(ϕ) are the velocity, pressure, mass density, dynamic viscosity and permeability, respectively, with the phase-field variable ϕ ∈ . Furthermore, γ is a constant interfacial mobility of the phase-field, τ is a relaxation parameter, and g1(ϕ) is the derivative of the double well potential ϕ2(ϕ − 1)2/2h2. F and ϕ. The free energy potential μ1 for the blood-thrombus system is expressed by Etotal with respect to ϕ.The governing equations for the 3D phase-field model are summarized as followset al. Reviewer's Responses to QuestionsComments to the Authors:Please note here if the review is uploaded as an attachment.Reviewer #1: AttachedReviewer #2: The authors present a framework to integrate the Force Coupling Method (as a means to model platelet transport in fluid) and a Phase-field modeling technique (as a means to model a thrombus as a poro-elastic structure) to investigate thrombus formation and deformation. To calibrate parameters within their phase-field model, they compare to data from in vitro experiments of clot permeability and rheology. The goal is to use this framework in the future to help determine risk of thrombotic events like embolization in patient-specific geometries. The framework presented is an extension from their recent paper and adds phase field models developed by a different group. The ideas in this paper are very interesting and suited for the journal, but there are many details missing related to the platelet aggregation portion of the model and so that section of the paper is difficult to fully and fairly review. Further, the calibrations for permeability and rheology were based on studies with fibrin rich clots instead of platelet rich clots, which leaves doubt about the relevance for cell-rich clots. See detailed comments below.Major comments:1. It is unclear to the reviewer how the platelets (modeled by FCM) are adhering and aggregating, and how their “growth” is considered dynamically in time and in the fluid. In section 2.1 (platelet transport and aggregation) there is no description of how platelets aggregate or adhere to the wall. At what point do they begin to “grow”? How is the spatial distribution of the new larger platelets determined from the distribution of the smaller platelets, especially near the wall? Are the larger platelets stationary? Finally, during the growth stage, how do the authors update the fluid equations surrounding the platelets? Due to lack of details provided on the thrombus formation process makes difficult to fully assess and properly review the study.2. The usefulness of going from FCM to a PF model is the heterogeneity of the clot – then the effects of heterogeneity on the mechanics of embolization can be studied; the structure of the thrombus that initially forms is clearly extremely important. Without describing how the platelets are aggregating and which ones have actually aggregated, it is not clear that the phase field model is a correct representation of the clot itself, but rather just a mass of platelets that are flowing through the fluid, in a non-aggregated state. It is possible that this is distinguished somehow but it is not made clear to the reviewer.3. It is unclear to the reviewer where fibrinogen fits into this model. In the methods section, the concentration of fibrinogen is mentioned, and then again in the rheological study section it is used, but there is no evolution equation for fibrinogen for it to exist or interact in the thrombus or at the wall for adhesion.4. The function g1(phi) represents a double well potential when phi is in  with minima at +/-1; what is the rationale for choosing phi in  in this model?5. The calibration of the permeability of the thrombi were based on experiments with fibrin clots and the empirical formula of Davies is based on fibrous material. The referenced paper  included studies on platelet rich clots where the permeabilities were fit well with a different empirical formula (Ethier). This suggests that the permeabilities of the thrombi modeled in the current study could be significantly underestimated. The authors should instead fit to the platelet-rich clot data or justify their choice for using the fibrin clots instead of platelet-rich ones.6. Similarly, the calibrations for the shear modulus are based on rheology experiments performed with fibrin gels while the clots in this study are assumed to be primarily platelets. The section describing how the volume fraction is calculated based on fibrinogen concentration is very confusing. It is not clear what the parameters are in equation 5 or how they relate to the ‘VF’. The final sentence in that section relates the relaxation time to a fibrinogen concentration but there is no fibrinogen in the model. This section should be rewritten more carefully and explicitly state what the outcome is.7. What is the bases for having the AA completely filled with platelets as the initial placement? It seems that one of the benefits of modeling the initial thrombus formation using FCM is that it will lead to more interesting and physiologically relevant thrombus formations. To keep inline with the journal criteria for significant biological insight, it would enhance this study to show a simulation with clots that have grown in the AA that initially was empty.8. The claim is that the timescale of the phase-field modeling covers hours of time , but this claim is not justified by the simulations provided in this paper. Can the authors comment on this?Minor comments:1. The sensitivity of the surface tension parameter was tested for fixed values of h (and other parameters). The sensitivity was said to be negligible, but it was not clear what tests were used to come to that conclusion. Is the parameter sensitive as h changes? I don’t believe h was ever specified either.2. In the clot deformation in 2D/3D section, how thick was the z-direction and were the results sensitive to that? As for the two densities and viscosities, are those for inside and outside the thrombus and which is where?3. “calibration” would be a better description than “validation” for the permeability model, as it is truly calibration of a model representation.4. Units. In most of the results sections, the units were left off of the parameters. It would be helpful to at least see units on the permeability5. In the Modeling thrombin formation with FCM section, the term deposition sites is used, but in the figure, initiation sites is used. Also the reference to figure 11b on the last line of the first paragraph should reference 11c6. What is the upstream distribution of platelets during the dynamic simulation?**********Have all data underlying the figures and results presented in the manuscript been provided?PLOS Computational Biologydata availability policy, and numerical data that underlies graphs or summary statistics should be provided in spreadsheet form as supporting information.Large-scale datasets should be made available via a public repository as described in the Reviewer #1: YesReviewer #2: Yes**********what does this mean?). If published, this will include your full peer review and any attached files.PLOS authors have the option to publish the peer review history of their article  and recent descriptions (e.g. Jackson 07 or Kim 19). White clot is composed of vWF and platelet. Fibrin is in red clots that may form on top of white clots after the occlusion causes stagnation of the blood.Question 10: It was understood that the phase-field parameter ϕ is defined in terms of volume fractions. However, the authors use ϕ = 1 to denote blood flow and ϕ = 0 for thrombus. This is not consistent with the custom that the authors use for ϕ_f to denote the volume fraction of fibrin (solid), etc. I suggest defining ϕ = 0 as blood flow and thrombi as ϕ = 1 in the phase field model.Question 12: the authors validate the permeability calculation using existing fibrin gel data. Fibrin gel is not a thrombus. It is OK to validate the model this way given the limited experimental data. However, the author should not oversell it by calling it "validation of the permeability of the thrombus". This is only a validation of the permeability calculation using fibrin gel data.Question 13: It is understood that eventually an equilibrium configuration of the clot forms. However, this equilibrium is dynamic, meaning there is thrombi formation and rupture (or platelet adhering and detaching). This answer still does not address the fact the platelet aggregation may keep forming even during so-called "reconfiguration" process when emboli occurs. I suggest the authors state that a simplification/assumption is that they neglect the further formation of thrombi during the phase-field simulation.Reviewer #2: The authors have answered all the reviewer questions and handled the concerns.**********Have all data underlying the figures and results presented in the manuscript been provided?PLOS Computational Biologydata availability policy, and numerical data that underlies graphs or summary statistics should be provided in spreadsheet form as supporting information.Large-scale datasets should be made available via a public repository as described in the Reviewer #1: YesReviewer #2: None**********what does this mean?). 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Bio-aggregate composites such as hemp-lime offer a more sustainable alternative to traditional walling infill material. Hemp-lime, whether in situ or prefabricated, is generally either cast or sprayed, which results in a directionally dependent, typically layered, physical structure. This paper considers the impact of compaction and layering on the directional thermal conductivity, compressive strength and internal structure of the material through use of a novel image analysis method. The results presented indicate that production variables have a significant, and crucially, directionally dependent impact on the thermal and mechanical properties of cast hemp-lime. Hemp-lime is a bio-aggregate composite material produced by combining the chopped woody core of the hemp plant (shiv), a lime-based binder and water. The resulting mixture can be cast or sprayed into place and cures to form a rigid but highly voided structure. The large proportion of bio-sourced material means that hemp-lime is a net absorber of carbon dioxide that is essentially sustainable to produce –3. The mThe most common method used to manufacture hemp-lime is to mix the components into a wet mix that is cast within formwork or block moulds. The process of casting is usually conducted in layers that are individually placed by tamping. The depth of layers, the degree of compaction and the direction of compaction with respect to the direction of thermal and mechanical loading are all variables within this process. The distribution of density within cast material is known to be dependent on depth within a single layer and globally a function of compaction , 9; it iThe effect of compaction of hemp-lime on the mechanical and thermal properties has been studied previously. Nguyen et al. , 9 foundThe density distribution through specimens of sprayed hemp-lime has been assessed previously and found to vary with depth . In addiThe aggregate used for hemp-lime comes from the stem of the plant and is therefore generally of an elongated form. The application of any compaction has been shown to produce a preferential orientation of the particles towards stratified planes perpendicular to the compacting force  that is This paper considers how the variables of layer size and compaction affect the directional compressive behaviour and thermal conductivity of hemp-lime. Results are presented from uniaxial heat flow test and uniaxial compressive test for five permutations of cast material in two orientations . Additional information about the internal structure, obtained using a recently developed method of image analysis, is also presented.A single mixture of hemp-lime was used to investigate the influence of the internal structure on its properties, with the method of specimen casting the primary variable. The hemp shiv used was produced in France and the bulk properties and particle size distribution are reported in Table Mixing of the constituent materials was carried out in a revolving pan mixer. The binder and water were first combined to form a uniform slurry prior to the addition of the hemp shiv. Subsequent mixing was then conducted until a uniform mixture was achieved, paused occasionally to break up any clumps forming by hand. Pre-determined quantities of mixture were weighed out into oiled moulds and tamped to height successively to build up each specimen in the required number of layers. The specimens were left uncovered and transferred to a conditioning room at 20 °C and 70% relative humidity with the moulds being removed after six days.Specimens were produced using a range of three layer sizes: 25, 50 and 150 mm; and three compaction levels: 30, 45 and 60% volumetric decrease from the uncompact state. Two sets, one to be tested parallel to compaction and one to be tested perpendicular to compaction, were produced for each variant of layer size and compaction level; the full range of permutations considered is detailed in Table The methods and specimen ages from casting were chosen based on combination of the British Standards for compressive strength testing of concrete and insulation products , 25, as Thermal conductivity measurements were conducted on the 50 mm × 400 mm × 400 mm specimens following oven drying for 48 h at 105°. Mass and dimensions were recorded for all specimens to determine density and for use in calculation of thermal conductivity. The thermal conductivity tests were undertaken using a Fox 600 heat flow meter with a temperature gradient of 10 to 30 °C. Prior to testing the specimens were wrapped with a single layer of clear shrink wrap food packing material in order to both protect the instrument and prevent moisture loss from the specimens during testing.Assessment of each internal specimen structure was conducted using an original method developed by the authors . In brieAnalysis of the images was carried out using ImageJ primarily using the measure and partial analysis tools. Prior to analysis the images were smoothed using a median filter to remove noise and then a threshold analysis was undertaken to identify a single constituent and binaries the image. Following this the binary image was further cleaned by use of an opening algorithm to help segregate touching particles and finally a partial analysis was conducted to identify and measure the discreet binary objects (shiv particles) within each image. The orientation of each particle within the image plane was assessed by means of an ellipse fitting process, as described in  and the The 28 day average density of the different variations of material is given in Table The average stress–strain graphs for three specimens tested parallel variant 3) and perpendicular (variant 8), with the median layer size and compaction, are shown in Fig.  and perpAs insulation materials typically have much lower stiffness compared to structural materials, the compressive resistance of insulation materials, such as rigid foam, is commonly defined as the stress attained at a given strain level . A similAn alternative parameter is proposed in this study to compare hemp-lime material performance in both loading orientations. The composite rupture stress has been defined in this study thus: the stress at the strain where the tangent Young’s Modulus of the material, taken from a moving sample of twenty consecutive data points, falls to 25% of its peak value. While the selection of the proportion is in itself arbitrary, the threshold strain value is determined by the material’s behaviour. The proposed approach accounts for both the initial low stiffness (settling) and the different apparent stiffness of the hemp-lime in each direction, while being insensitive to post yielding behaviour.The effect of compaction and layer size on compressive rupture stress in both the parallel and perpendicular directions is shown in Fig. The compressive rupture stress of hemp-lime is generally independent of casting layer thickness within the range of 150to 25 mm, in both the parallel and perpendicular directions with respect to casting [Fig. The thermal conductivity results for the hemp-lime materials considered are presented in Fig. The results for the frequency analysis of particle orientation are presented in Fig. Neither compaction nor layer thickness affect the particle distribution in the parallel direction, which remained consistent in all cases Fig. . The shaIn the perpendicular direction there is again consistency in the distributions across compaction and layer thickness indicating a minimal impact. Variant 7, the lowest compaction level, appears to have the flattest graph and thus lowest degree of orientation. A relationship between compaction and degree of orientation is, however, not observed as the most compact (variant 9), is observed to have a flatter graph than the median compaction (variant 8). From Fig. It is evident from the results presented in Fig. Increasing compaction was found to produce higher compressive rupture stress and thermal conductivity in both orientations, and can be generally attributed to a reduction in the proportion of air voids in the composite, Table To ascertain to what extent variation in density might explain the seemingly directionally dependent influence of compaction, the dry density can be plotted against compressive rupture stress, Fig. The layer sizes used in the casting process were not observed to influence either the thermal conductivity or the rupture stress of the material within the range of 25 to 150 mm. It had been thought that the layer size would influence the local distribution of material during casting with smaller layers leading to a more homogenous material. This in turn could reduce possible stress concentrations or thermal bridges through the material thus influencing behaviour. The results indicate that this is not the case for the range of layer sizes considered here, however, the results of others who have plotted density with depth of larger specimens indicate that it may still have bearing at larger layer sizes .A common way to model the thermal conductivity and compressive strength of hemp-lime is as a linear function of dry density , as thisρ is the dry density of the composite, θ is the direction of thermal or mechanical loading with respect to the direction of casting compaction and n is a constant that can be derived by fitting to experimental data. The four linear functions fitted to the data in Fig. To provide a form for the orientation function a comparison can be made to timber, where the compressive strength is modelled with respect to grain direction by the Hankinsons distribution . As thisentclass1pt{minimaThis paper considers the influence of the casting process on the thermal and mechanical properties of hemp-lime and applies a newly developed method of image analysis to investigate the role of the internal structure in the manifestation of these properties.A clear anisotropy in the material’s structure is observed through the image analysis for all variations considered in this study. This is attributed to the compaction produced in casting causing the elongated particles of hemp to tend towards perpendicular strata. The influence of this on the physical properties of thermal conductivity and compressive behaviour is shown to be profound and so necessitates that further study into bio-aggregate composites accounts for it.The thickness of the layering used to cast the material was found to have no clear impact on the internal structure or the mechanical properties for the range of layer sizes considered. An initial assumption that a larger layer size would create a less homogenous material was shown not to be the case within the range of this study, however, it is considered likely that this may not apply to larger layer sizes. From a commercial standpoint it can be stated that there is no benefit to using layer sizes smaller than 150 mm during the manufacture of hemp-lime.The degree of compaction used in casting was found to influence both the internal structure and in turn the physical properties of the composite. Increasing compaction was found to decrease the proportion of air voids in the material and thus increase both the compressive rupture stress and the dry thermal conductivity; in both cases this was found to be more pronounced in the perpendicular direction. It is considered possible that this is due to a higher level of orientation being produced at higher compaction however this was not confirmed by the image analysis possibly due to a limitation of the method.The finding that compaction does not have a global impact on the properties of hemp-lime, but rather a directionally dependent one, is of high significance in the modelling of properties and development of the material. A new form of directionally weighted linear model for thermal conductivity and compressive strength is suggested based on a previously established model for timber, although further work is required to ascertain if the Hankinsons form of the weighting equation is more generally applicable.


Tversky and Kahneman introduced the term framing for the finding that people give different answers to the same question depending on the way it is posed. One form of framing involves presenting the same outcome as either a gain or a loss. An experiment on starlings by Marsh and Kacelnik suggests that this form of framing occurs in non-humans. We argue that the experimental result demonstrates framing in the general sense of context dependence but does not provide compelling evidence of framing in terms of gains and losses. A version of scalar utility theory which is extended to include the possibility of memory errors accounts for the data and suggests future lines of research. It is well established that the way in which a problem is worded influences the answer that people give, see Kahneman and Tversky , TverskySturnus vulgaris) that they consider to provide an example of this form of framing , so that the coefficient of variation is constant. This scalar property of the theory is based on Ernst Heinrich Weber’s concept of a “just noticeable difference”. Approaches based on the scalar property have been used in the study of spatial and temporal behaviour  being judged preferable to the variable alternative using the cumulative distribution, as a weighted sum:We represent an option with outcome Kacelnik . The seta being judged preferable to some other fixed option with outcome b:a or b is confused with the standard option and with probability a is preferred over outcome b is 1/2, independent of the values of a and b.To reflect such a confusion mathematically, we extend SUT by a memory parameter, mentclass2pt{minimmentclass2pt{minimmentclass2pt{minimmentclass2pt{minimf) and one variable option (outcomes a or b) and a standard trial (outcome s), Eq. Next, we generalise the expression for the probability of preference with one option being variable Eq. . For a cFigure v|θ) Eq.  for a raKacelnik  , i.e. \For mentclass2pt{minimKacelnik ). Note tAs can be seen from Fig.  e Abreu . It is, entclass1pt{minima e Abreu ; Bateson e Abreu  and esti e Abreu ]. The fientclass1pt{minimaAlthough it is difficult to give a rigorous definition of framing, the central idea is that it involves presenting essentially the same problem in different ways. This is relatively easy to do in experiments on humans; language allows different descriptions of the same problem. Work on non-humans has to find other ways of framing, e.g. Bhatti et al. ; KrupenyWe conclude that the experimental findings on starlings by Marsh and Kacelnik can be explained with a version of SUT which is extended to include the possibility of memory errors. To our mind, this is a more consistent explanation than the concept of framing in terms of gains and losses offers. Our approach makes quantitative predictions that can be checked by estimating


In Egypt, many girls are still married before the age of 18, which is a fundamental violation of the girls’ human rights. Early marriage is associated with an alarmingly elevated risk of all types of intimate partner violence that have various negative consequences. The purpose of this study was to identify the predictors of exposure to spousal violence among the early married girls in rural Upper Egypt.A household survey was carried out and covered 23 villages in Assiut and Sohag governorates reaching to a sample of 729 married girls before the age of 20. Listing and enumeration of 4 districts was done to identify the study participants. Data was collected by personal interviews using a structured questionnaire. Bivariate and stepwise regression analyses were performed to identify the predictors of exposure to spousal violence.β = − 1.07, OR 0.34) and sexual  violence. The perceived attitude of husbands and mothers-in-law about considering wife beating “a husband's right” was found to be a risk factor of exposure to physical and sexual violence. Longer duration till the first pregnancy was also associated with more exposure to sexual violence .It was found that 15.2% of the study participants were exposed to physical violence while 17.8% were exposed to sexual violence and 7.3% were exposed to both types. Girls married before the age of 18 were more exposed to spousal violence. Stepwise regression analysis found that girls’ acceptance to get married was a protective factor against exposure to physical (Married adolescent girls (MAGs) are highly exposed to physical and sexual violence. This is mainly due to ignoring girls’ preference to postpone their marriage, cultural concepts of accepting violence against women, and low sexual satisfaction. This study shows that most determinants of spousal violence were related to culture issues. Identifying these determinants is required to combat such a crucial public health problem that has serious consequences on adolescent health. In Egypt, despite the legislation of the Child Law of 2008 which sets the minimum age of marriage at 18 years for females and males, many girls are still married before the age of 18, which is a fundamental violation of the girls’ human rights [The 2014 Survey of Young People in Egypt (SYPE) revealed that 1.7% of married female youth aged 25–29 in 2014 had been married before age 15, 4.2% before age 16, and 21.1% before age 18 which is the legal age of marriage in Egypt. Moreover, child marriage remains to be common in some parts of the country; 33.3% of married female youth aged 25–29 residing in rural Upper Egypt were married before age 18, compared to just below 10% of those in the Urban Governorates and urban Lower Egypt [Early marriage has been associated with withdrawal from school and low opportunity for employment and social mobility , 4. HencFurthermore, evidence suggests that early marriage is associated with an elevated risk of intimate partner violence –8. The 2Spousal violence is a major public health concern, since it is documented to be associated with poor health outcomes including injuries, sexual/reproductive health problems, anxiety, and depression .While rural Upper Egypt has the highest levels of spousal violence , little Data was collected using a household survey of married adolescent girls (MAGs) in Assiut and Sohag governorates, which are among the poorest and most conservative governorates in Egypt , 14. TheMarried adolescent girls (under 20 years) who had been married for at least 3 months at the time of data collection were invited to participate in the study. Enumeration of all households in the selected communities and listing married inhabitants of these households were conducted by a trained team to identify the households with at least one MAG. The team was escorted by community outreach workers to facilitate their entry into the houses and alleviate the tension of the locals. The heads of the households were approached by the members of the enumeration and listing team asking them to list all married women in the household together with their ages and duration of marriage and data was validated using the identity cards of the listed married women. The listing process yielded only 730 MAGs, who were all included in the study rather than applying random selection. The interviews were conducted at a quiet area at the MAG’s house or a place of her choice  and lasted for about 1 h. Field training of data collectors involved pilot testing of the instrument among 20 MAGs in two villages that were not selected for the study.All the study participants were interviewed using a structured questionnaire divided into sections covering all the variables that we hypothesized to be associated with exposure to spousal violence. The first section of the questionnaire detailed the socio-demographic characteristics. The second section assessed the practices related to asking the girls’ opinion before marriage, pre-marital counseling, marital sexual relation, pregnancy, and delivery. The third section explored the social support to the MAGs by their husbands and mothers-in-law including her social mobility and participation in decision-making as well as the attitudes of husbands and mothers-in-law about violence as reported by the MAGs. The fourth section discussed the exposure of MAGs to physical and sexual violence in the year preceding data collection.Data were analyzed using SPSS Statistics for Windows . Descriptive analysis was performed for the participants’ socio-demographic data. Frequencies of exposure to physical and sexual violence were calculated.The MAGs were considered to be exposed to physical violence if responded “Yes” to any of the following: being slapped or having something thrown at you that could hurt you; being pushed or shoved; being hit with a fist or something else that could hurt; being kicked, dragged, or beaten up; being choked or burnt on purpose; and/or being threatened with, or actually, having a gun, knife, or other weapon used on you. While the MAGs were considered to be exposed to sexual violence if responded by “Yes” to any of the following: practicing sex against will, having a sexual relation when the husband was drunk or drugged, and being forced to do sexual acts that she was not comfortable with.Decision-making index was created by using 10 questions expressing the girls’ participation in taking different decisions. The response was given a score of “1” if the girl participated in the decision and “0” if she did not. Social mobility index was also created by using variables expressing the free mobility of the MAGs; 12 questions were used including the ability of the MAG to go to different places unescorted such as the doctor, family house, friend’s house, and market. The score “1” expressed the ability to go to the place and “0” as inability to go. Cronbach’s alpha for both scales was calculated as 0.7 and 0.6 respectively.In the previous indices, an additive score was computed by summing the scores and the mean score percent was calculated as score/optimal score × 100.Reported sexual satisfaction was assessed using a single question which asks about the overall sexual satisfaction and was graded along a Likert scale ranging from 1 to 5, where the score “1” denoted the least sexual satisfaction and the score “5” denoted the highest satisfaction.T test and chi-square test were used to identify the significant factors associated with exposure to physical and sexual violence. All significant variables on bivariate analysis were considered for inclusion in the backward regression analysis. P value < 0.05 was considered as significant.Table The norm for the studied MAGs in the early years of their marriage is to live in an extended family (the husband’s family): 84% and 91.6% in Assiut and Sohag respectively.Table Table Table In Egypt, 30% of ever-married women aged 15–49 reported having been ever subjected to at least one episode of physical, sexual, and/or emotional violence inflicted by their current or most recent spouse; however, sexual violence was only reported by 4% of the participants [Despite the fact that all married women from all age groups are at risk of spousal violence, married adolescent girls are at much higher risk of exposure to violence and its consequences . In EgypEarly marriage is still common in Upper Egypt, and most (89.7) of the participants in this study got married under the age of 18. Since the legal age of marriage in Egypt is 18 years, girls who married before completing their 18th birthday were in discordance with the law and are more liable to be exposed to spousal violence. According to our study, 15.2% of the study participants were exposed to physical violence while 17.8% were exposed to sexual violence in the last year (prior to the year of data collection). This percentage would have been definitely higher if we asked about exposure throughout the marital life.Our study showed that spousal violence was associated with various cultural factors. In many cultures, it is acceptable for men to control their wives’ behavior and those women who refuse may be punished. Studies found that violence is frequently viewed as the husband’s right to discipline his wife . MoreoveTaking the girls’ acceptance about the timing of getting married and the person she will marry not only is a human right, but also significantly affects her exposure to physical and sexual violence. Multivariable logistic regression analysis in our study showed that girls’ acceptance of the marriage timing was a significant protective factor against exposure to physical and sexual violence. This was consistent with a study conducted in Turkey to identify factors associated with domestic violence. The study found that the prevalence of domestic violence was significantly lower among women whose marriage was by mutual agreement . This isIt is common in rural Upper Egypt for married couples to live in extended families specially married adolescent girls, 88.2% of our study sample lived in extended families. The extended family can significantly affect the marital relationship of a couple, especially in the early years of their marriage, and can play a positive as well as a negative role. Bivariate and multivariable logistic regression analyses in our study showed that exposure of MAGs to physical and sexual violence was significantly associated with living with the husband alone while living with other family members was a significant protective factor against exposure to physical and sexual violence. Consistent with our study, a qualitative study done in Pakistan and the UK indicated that the husband’s family can have a positive effect by minimizing conflict through offering the couple personal time and helping the wife to adjust to her new family and the wife’s family could contribute by helping their daughter to adjust to her new extended family .Moreover, a study done in Jordan to identify the role of the extended family on women’s risk of intimate partner violence using mixed-methods study found that residence with the respondent’s in-laws act as a protective factor against conflict and intimate partner violence between a husband and wife . HoweverSexual satisfaction is an integral part of marital life that affects the couple’s relationship . Our stuThe norm of Egyptian society is not postponing pregnancy of the first child especially in rural communities. Failure to conceive directly after marriage affects the psychological state of the husband, which leads to violence. Violence against women experiencing delayed pregnancy is an important health problem with serious consequences for their physical and mental health . Our stuConsistent with our study, a systematic review on the relationship between infertility, sub-fertility, and intimate partner violence found that infertility (inability to become pregnant)/sub-fertility (inability to maintain a pregnancy) are associated with violence in low- and middle-income countries . MoreoveThis large survey investigated an important and relatively unspoken issue but has some limitations; If husbands and mothers-in-law were interviewed, more insight on the problem would have been given, but this was very difficult in such conservative societies. Many families denied the presence of MAGs during the listing process since the legal age of marriage in Egypt is 18 years and families of MAGs who were below 18 years might face legal penalties if the case was reported to the authorities. To overcome this challenge, the enumeration and listing team members were escorted by outreach workers from the local communities to establish rapport with the families and enable the team to clarify that the collected data will be used for scientific purpose, will never be shared with the authorities, and that the filled questionnaires will have no identifiers, will not be linked to the developed lists, and the results will be presented in an aggregate form. Moreover, the data collectors were provided with identification cards affiliated to Assiut University and copies of the Central Agency for Public Mobilization and Statistics (CAPMAS) approval of the study to assure them that they were only research-participants.Girls married before the age of 18 are exposed to spousal physical and sexual violence. Taking the girls’ opinion at the time of marriage and obtaining their acceptance are protective against exposure to physical and sexual violence. Moreover, cultural beliefs that consider spousal violence acceptable defiantly increase the risk of girls being exposed to violence.In rural communities, young girls that lived with their husbands alone were more exposed to violence, which could be attributed to their inability to be totally independent. This study clearly illustrates the need for enforcement of laws as well as raising the community awareness to delay the age of marriage and respect “the girl’s will” to delay her marriage until she is more autonomous, able to participate in decision-making, and more capable of bearing other marital responsibilities. In addition, mass media campaigns and public educational sessions directed towards the elimination of gender discrimination should be widely used in order to change the cultural concepts that consider wife beating a “husband right.” Incorporation of sexual counseling within the MCH services and making it available for couples is required to improve sexual satisfaction, conflict resolution skills, and other life skills.


Bimetallic surfaces can exhibit an improved catalytic activity through tailoring the concentration and/or the arrangement of the two metallic components. However, in order to be catalytically active, the active bimetallic surface structure has to be stable under operating conditions. Typically, structural changes in metals occur via vacancy diffusion. Based on the first‐principles determination of formation energies and diffusion barriers we have performed kinetic Monte‐Carlo (kMC) simulations to analyse the (meta‐)stability of PtRu/Ru(0001), AgPd/Pd(111), PtAu/Au(111) and InCu/Cu(100) surface alloys. In a first step, here we consider single‐atom alloys together with one vacancy per simulation cell. We will present results of the time evolution of these structures and analyse them in terms of the interaction between the constituents of the bimetallic surface. Vacancies matter: metal atoms can typically only change places in metals through vacancy‐assisted diffusion. Here we address the diffusion in single‐atom surface alloys by performing kinetic Monte Carlo simulations based on density functional theory calculations. We illustrate how the separation and recombination with a surface vacancy determine the trajectory of the foreign atom in such a surface alloy. It is well‐known that the activity and selectivity of bimetallic catalysts is often superior to the one of elemental metals due to the additional degrees of freedom through the variation of the concentration and/or the arrangement of the two metallic components.3, 4 FHowever, the catalytically most active bimetallic structure will be worthless if it is not stable under operating conditions16, 17In spite of the technical importance of the thermal stability of bimetallic catalysts, it is fair to say that there are only few theoretical studies addressing this issue.In metals, structural rearrangements typically occur through substitutional changes involving the presence of vacancies.30, 31However, to model structural changes of bimetallic surfaces requires to perform simulations on macroscopic time scales and mesoscopic length scales. Here the method of choice are kinetic Monte Carlo (kMC) simulationsIn a first step to address the (meta)‐stability of structures in bimetallic systems, we focus here on the vacancy assisted diffusion on single‐atom alloys. These alloys have recently been discussed as efficient catalysts offering the advantage that the active precious metal can be diluted at the atomic limit.First‐principles electronic structure calculations have been performed using the periodic DFT code Vienna ab initio simulation package (VASP).The metal surface alloys are modelled by periodic slabs consisting of five atomic layers and 6×6 unit cells for Cu(001) and Ru(0001) and 5×5 in the case of Pd(111) and Au(111). The top three layers of the slabs are fully relaxed, while the lowermost two layers are fixed at their bulk positions. A vacuum of 15 Å separates the slabs to avoid any interaction between the periodic images. The wave functions were expanded up to a cutoff energy of 400eV and a [3×3×1] k‐point grid for all surfaces and alloys.48×48unit cells. The rates entering the kMC simulation were derived from the DFT calculations using transition state theory (TST).The first‐principles based kinetic Monte Carlo simulations32, 4122.1In this work we consider surfaces that consist of one vacancy and one foreign atom per unit cell leading to a single‐atom surface alloy. In order to assess the stability of the studied structures in the single‐atom surface alloys, we first determined formation energies using DFT.EsurfVis the total energy of the metal or alloy surface with the vacancy per unit cell and EbulkMis the bulk cohesive energy of the metal M that has been occupying the vacancy site before the formation of the vacancy, and surfE is the energy of the surface without the vacancy. This means that we assume that the metal atom whose extraction has lead to the vacancy is inserted into a metal bulk reservoir which for example could also be realized by attachment to a corresponding kink site of the metal.where The alloy formation energya is extracted from the surface whose energy is given by surfE and is replaced by a foreign metal atom Mb leading to the formation of the single‐atom surface alloy whose energy is given by alloyE. Both metal atoms Ma and Mb are assumed to be exchanged with the corresponding bulk metal reservoir.reflects the process that a metal atom MBoth the vacancy surface and the alloy formation energy of the considered systems based on a Ru0001), Pd(111) and Au(111) substrate, respectively, are listed in Table , Pd(111)exp(-Hf/kBT)as measure of the vacancy concentration, at room temperature even for Au(111) with the lowest vacancy formation energy a vacancy concentration of below 10−10 results.According to Table To form a single‐atom surface alloy with a foreign atom that has a lower cohesive energy than the host is energetically favorable, even if the foreign atom is larger, as the examples Pt@Ru(0001) and Ag@Pd(111) confirm. Note that the lattice mismatch between Ru(0001) and Pt(111) is about 2.5 % and almost 5 % for Ag(111) and Pd(111), so naturally, Pt and Ag exert a strain of their neighbouring atoms. Still, the electronic interaction corresponding to the ligand effect obviously over‐compensates the strain introduced through the geometric effect because of the different atom sizes. In contrast, the replacement of a surface atom by a foreign atom with a higher cohesive energy is energetically unfavorable, as the result for Pt@Au(111) shows which has been obtained before.52, 53Finally, we address the question whether the formation of a vacancy‐foreign metal atom pair adjacent to each other is more favorable than having both separated from each other. This can be derived by comparing the formation energies of V@… with those of V@M@…We find the same trends as for the alloy formation energies. For Pt@Ru(0001) and Ag@Pd(111), it is energetically more favorable to have the vacancy and the foreign atom adjacent to each other because then one bond with the less strongly interacting foreign atom is broken whereas it is the other way around for Pt@Au(111). Hence thermodynamically it not preferred that in PtAu/Au(111) a Pt atom and a vacancy form a pair.In Figure For both systems, in these cases the ligand effect becomes even stronger. In PtRu/Ru(0001), at a second nearest neighbour distance a vacancy is formed with only Ru−Ru bonds being broken, one of which is even stronger as one Ru atom is located adjacent to the foreign Pt atom which does not interact so strongly with the Ru atom. Conversely, in PtAu/Au(111) at a second nearest neighbour distance, the vacancy formation is only associated with the breaking of weak Au−Au bonds, one of which is even weaker as one of the Au atoms is more strongly bound to the adjacent Pt atom. This also means that for PtAu/Au(111), the second nearest neighbour site is the energetically most preferred site. So although the vacancy does not prefer to be located adjacent to the foreign atom, it is still energetically favorable to stay close to the foreign atom.Finally we like to note that the incorporation of a vacancy in subsurface layers and further into the bulk is energetically less favorable than a surface vacancyon the surface is possible. Hence the vacancy acts as a “mixer”. In a pure single‐metal surface, vacancy diffusion can be regarded as a random walk with every possible vacancy diffusion step being equally probable. However, the presence of a foreign atom breaks this symmetry, as illustrated for a (111) surface in Figure ortho, meta and para positions relative to the location of the foreign atom. For some of the events, initial and final positions are also inequivalent so that the barriers for the forward and backward jumps become different. The corresponding diffusion barriers are all collected in Table ortho, meta and para diffusion are plotted in Figure Changes in the configuration of a surface alloy can only occur via vacancy diffusion as long as no diffusion It is important to recall that the primary influence on mobility is the number and strength of broken bonds and the size of the atom which is moved.meta and para diffusion is hindered by smaller barriers than the ortho diffusion. Apparently both the ligand and the strain effect make the transition state even more unfavorable than the initial state. Both the diffusion from the meta and the para position exhibit lower barriers for the backward diffusion which simply reflects the fact that in these systems the vacancy adjacent to the foreign atom is more favorable than the vacancy at a second‐nearest neighbour distance to the foreign atom  and AgPd/Pd(111) that  and AgPdortho diffusion is preferred compared to meta and para diffusion, and in the latter two cases the backward diffusion becomes more hindered than the forward diffusion. Still, as in the PtRu/Ru(0001) and AgPd/Pd(111) systems these results can only be understood under the assumption that the ligand effect overcompensates the geometric effect.Again, the PtAu/Au(111) surface shows an opposite behavior because here the foreign atom is smaller, but more strongly interacting than the host metal atoms. Therefore now 2.2ν0 entering this expression that can be interpreted as an attempt frequency is often approximated to be 10131sin order to avoid the considerable numerical effort to derive vibrational frequency. Furthermore, whereas activation energies enter the transition rates jk exponentially, the frequencies only enter linearly so that they have a minor influence on the rates. Still, we have derived the prefactors from vibrational frequency calculations within harmonic approximation according toThe main goal of this study is to address the (meta‐)stability of bimetallic surface structures. In the previous section, we have studied the energetics of single‐atom surface alloys together with a vacancy using periodic density functional theory calculations. Now we will consider the question whether the considered structures are stationary based on kinetic Monte Carlo simulations. The transition rates entering the kMC formalism will be obtained using Arrhenius expressions derived from the DFT calculations based on transition state theory.ωi0) and at the TS (ωiTS). In order to keep the computational effort in a manageable range in the finite difference scheme to derive the vibrational frequencies, the unit cell size was reduced to 4×4. Furthermore, the structures of the ground state and TS taken from the NEB calculations have been fixed and finite differences were only taken with respect to the particular atom of interest. The calculated prefactors ν0 are collected in Table 131swhich hence would have been a reasonable approximation in this case.These vibrational frequencies have to be determined both at the ground state  is done.The factor s298) for the diffusion of an isolated vacancy at 298K in Ru(0001), Pd(111) and Au(111)  to move about 100nm at room temperature. Note that the age of the universe is about 5×1017 seconds which means that it takes the vacancy about 1100of the age of the universe to move this rather small distance. This illustrates how immobile vacancies are in metal surfaces at room temperature.Using Eq. 4, we derived the self‐diffusion coefficient Ds298 for the D directly from the jump rates according to Eq. 4, it is also possible to evaluate D from the mean‐square displacement using Eq. 5. We have run 100 different kMC trajectories, and for each trajectory we have taken 100 different initial points equally spaced in time. This means that the mean‐square displacement has been derived by sampling of 10,000 trajectories. As an example, the results for a vacancy in Ru(0001) are plotted in the inset of Figure Instead of deriving the self‐diffusion constant 48×48unit cell of the kMC simulations which means that we assume a constant vacancy concentration of 0.04 % and a 1 : 1 ratio between foreign atom and vacancy. In Figure 1.5×1014s, the vacancy hardly moves away from the initial position. This is due to the attraction between the vacancy and the Pt atom so that the vacancy basically always returns to the Pt atom leading to almost no net displacement. After 1.5×1014 s, the vacancy then separates from the Pt atom and does not return back. Hence a random walk of the single surface vacancy starts, as described above, exhibiting a linear dependence of the square displacement on time.We now turn to the diffusion of one vacancy and one foreign atom within the 6 kMC steps for PtRu/Ru(0001) at 1350K and for AgPd(111) at 800 K. Due to the different absolute values of the jump rates in these two systems and at two temperatures ,−6 s in Figure Still, in Figure ortho, meta, and para processes (see Table Regarding the PtRu/Ru(0001) simulation, it is also interesting to note that many of the Pt migration events corresponds just to jumps back and forth. This is due to the fact that the barrier for the movement of the foreign atom is considerably smaller than the barriers for the Thus the diffusion of the foreign atom is coupled to the diffusion of the vacancy. In such a situation, the diffusion coefficient can be deriveda corresponds to the lattice parameter, kx is the jump rate proportional to exp(-Eb/kBT), ΔHfvacthe enthalpy of forming a vacancy in the clean surface, Ebindingvac-xthe binding energy of the vacancy and the foreign atom estimated by the energy difference of having a vacancy as nearest neighbour and second nearest neighbour, and fx is a foreign atom correlation factor.[Here, 2> and time t, we enlarge the sampling time Δ t to a time range in which the foreign atom is moving. In this way, the period of time in which the vacancy is separated from the foreign atom so that it can not move can be bypassed. These periods are the flat regions in the plot of the distance as a function of time in Figure t for the different considered systems, the time‐axes in Figure Since the diffusion of foreign atoms is dependent on the return probability of the tracer in addition to the temperature and energy barriers, deriving the diffusion coefficient via the kMC simulation is more complicated than for the vacancy diffusion. In order to reproduce the linear relation between the mean square displacement <Rortho, meta, and para processes. Such correlations are obviously not fully reflected in Eq. 6. At high temperatures when the relative difference between the different rates become less pronounced, these correlations matter less so that Eq. 6 better captures the coupled diffusion of the foreign atom and the vacancy.Here we now find significant deviations between the diffusion coefficients derived from the mean‐square displacement and those obtained using Eq. 6, in particular at low temperatures. As Figure exp-ΔHfvacsurf/kBTin Eq. 6 as being related to the probability to create a vacancy adjacent to the foreign atom. However, in the systems considered in this study, the vacancy does not need to be created but is already present on the surface, as is also the foreign atom. Hence it should rather give the probability that an existing vacancy is adjacent to the foreign atom which is obviously underestimated by the exponential expression given above.In order to understand the differences between the diffusion coefficients derived from Eq. 6 and from the mean‐square displacement  along the kMC trajectories, we have plotted their logarithm as a function of the inverse temperature in Figure The slope of the kMC results in Figure Pt=0to the diffusion coefficient from the mean‐square displacement of Pt in Au(111) which in fact agrees with the result derived from Eq. 6. Indeed, the time Δ t between to vacancy diffusion events for the vacancy is in the range of 10-14-10-12 s, whereas a successful Pt diffusion event can take 1014 s which makes it practically impossible to observe such an event in the kMC simulations.Due to the immobility of Pt in Au(111) found in the kMC simulations, as discussed above, we can only assign D2.3In addition to the three transition metal alloys, the square InCu/Cu(001) surface alloy was investigated, motivated by a scanning tunneling microscopy study of Frenken et al.27, 28enclose diffusion barrier relative to the opposite diffusion barrier, which is consistent with the difference between ortho and para processes in the case of PtRu/Ru(0001), and AgPd/Pd(111) surface alloy, which results when a larger foreign atom is embedded in a metal host with smaller atom size.Due to the square symmetry of the Cu(001) surface, the number of possible diffusion processes for the In atom and the vacancy being adjacent is reduced in comparison to a hexagonal surface. These possible processes are illustrated in Figure ·10-4which is significantly larger than the concentration of about 10−9 present in the experiment at room temperature.Using the calculated barriers transformed to migration rate via transition‐state theory, we performed kMC simulations with one vacancy and one In atom present on Cu(001) in a periodic setup with an 47×47 unit cell. Note that this corresponds to a vacancy concentration of about 44 and 105, corresponding to 1.38·10-5 s and 1.27·10-4 s time resolution, respectively. This means that not necessarily all positions of the In atom along the trajectory are recorded, as can well happen in a STM experiment. The time evolution of the steps along the trajectory is colour‐coded from blue to red. For example, the colour‐coding in Figure Due to the fact that the barrier for In atom jumps in the presence of the vacancy is so low, most of the kMC steps are associated with the flipping of the vacancy and the In atom. A true migration of the In atom can only occur through a combination of Cu jumps from the enclose and the opposite sites with a subsequent recombination of the In atom with the vacancy. In order to see whether our setup is able to reproduce the multi‐lattice‐spacing jumps observed in the experiment, in Figure 6 steps or 1.38·10-3 s the In atoms can propagate about 10−15 Å. Note that after about 4·10-4 s, the In atom becomes immobile because the vacancy has been separated from the In atom. When we coarse‐grain the resolution by a factor of 10 , PtRu/Ru(0001), AgPd/(Pd111) and InCu/Cu(001) single‐atom surface alloys. The energies barriers entering the kMC simulations via transition state theory have been derived from periodic DFT calculations. The migration of the foreign atom in the host metal can only proceed when the vacancy and the foreign atom become nearest neighbors and thus exchange places. Depending on the specific combination of foreign atom and host metal, the barriers for the exchange of the vacancy and the foreign atom range from 0.1 eV to 1.4 eV which leads to the fact that diffusion of the foreign atom is possible at room temperature or only at temperature above 1000 K. The apparent activation barrier is increased with respect to the simple exchange mechanism between vacancy and foreign atom, but only to a value in the range of the other diffusion barriers that contribute to the movement of the foreign atom. If the barrier for the exchange between vacancy and the foreign atom is signficantly larger than the vacancy diffusion barrier in the host metal, as in the system PtAu/Au(111), then the foreign atom will practically become immobile even at high temperatures as the vacancy will rather switch places with the atoms of the host metal than with the foreign atom. Finally, our kMC calculations confirmed that the apparent multi‐lattice‐spacing jumps in the system InCu/Cu(001) observed in STM experiments are a consequence of the low temporal resolution of the STM imaging.The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


Background and aimsThe Accreditation Council for Graduate Medical Education (ACGME) mandates that Internal Medicine residents shall place all the orders for their patients. The purpose of this rule is to assure comprehensive knowledge of patient information and direct involvement in decision-making. However, there is a general perception that a large proportion of orders for patients taken care of by the residents are being written by consultants or other providers. The objective of the study was to determine the proportion of routine orders placed by Internal Medicine residents in comparison to consultants/subspecialty providers for patients under the care of the Internal Medicine Residency Service (IMRS). Material and methodsAll the orders on patients admitted to the IMRS at AdventHealth Orlando from July 9, 2017, to July 15, 2017, were documented. Of these, Emergency Department (ED) orders, “STAT/ASAP/NOW orders,” “discharge by consultant” orders, and “consent for procedure” orders were excluded. The main outcome measure was the proportion of orders placed by Internal Medicine residents as compared to consultants and all other providers.ResultsA total of 6471 orders placed on 90 patients admitted to the IMRS and with at least one consultant were included in the study. Of them, 96.8% of all orders were placed by Internal Medicine residents. Only 3.1% of all orders were placed by consultants and other providers. Of them, the majority of the orders were specialty-specific orders and were appropriate. Only 1.1% of all orders were “routine” orders placed inappropriately by consultants and other providers. A total of 121 consultations were made, and there were no new consultations initiated by consultants and other providers during the study period.ConclusionThe vast majority of orders for patients taken care of by the IMRS were placed by the Internal Medicine residents themselves. Only a very small proportion of the orders were placed by consultants and other providers in this limited timeframe study. The findings are consistent with the ACGME mandate that residents write all orders for patients under their care except in special circumstances. The use of the electronic health record (EHR) has become increasingly common in US medical institutions . In teacThe Accreditation Council for Graduate Medical Education (ACGME) mandates that residents should write all routine orders for patients admitted under their care, with appropriate supervision by the attending physician . This enThe objectives of this study are: (1) to determine the percentage of routine orders placed by Internal Medicine residents for patients under their care and (2) to determine the proportion and appropriateness of orders written by consultants or other providers.This is a retrospective quality improvement project conducted in Florida Hospital Orlando  from July 9, 2017, to July 15, 2017. All 90 patients who were under the care of IMRS during this time period were enrolled in the study. A total of 6542 orders were placed on these patients. After the exclusion of departmental orders, “discharge by consultant” orders, and “consent for a procedure” orders, 6471 orders were included in the study. The study was approved by the Institutional Review Board and the Ethics Committee of the hospital.Appropriate orders (by consultants or other providers) were defined as specialty-specific orders, such as dialysis orders, anesthesia orders, pre-surgical orders, surgical orders, and post-surgical orders.Inappropriate orders  were defined as routine orders, which should have been put as a recommendation in their notes and could have been placed by residents.Of the 6471 orders included in the study, 96.8% (n=6270) of all orders were placed by the Internal Medicine residents. Only 3.1% of all orders (n=201) were placed by consultants and other providers. Of them, the total number of routine orders inappropriately placed by consultants was 37  and the total number of routine orders placed by other providers was 39 , making it a total of 76 orders (1.1%). The remaining 125 orders placed by consultants and other providers were specialty-specific, appropriately placed orders (Figure Graduate medical education develops physicians who focus on excellence in the delivery of safe, equitable, affordable, and quality care, and on the health of the populations they serve. The use of EHR and the practice of writing appropriate orders under supervision is an integral part of medical education and the delivery of safe and quality care. There have been several studies that have evaluated the usage of EHR in academic health institutions in the United States, the impact of EHR on the training of medical students/residents, and its value as an educational tool -4. HowevThe ACGME mandates that residents must write all orders for patients under their care, with appropriate supervision by the attending physician. In unusual circumstances when an attending physician or subspecialty physician writes an order on a resident's patient, the attending or subspecialty physician must communicate his or her action to the resident in a timely manner . We desiOur study demonstrates that a vast majority of the orders for patients admitted to the IMRS are placed by the Internal Medicine residents. The proportions of orders placed on the same subset of patients by consultants and other providers were very small and only 1.1% of all orders were placed inappropriately. The majority of the orders placed by consultants and other providers were appropriately placed specialty-specific orders, which were in the best interests of the patients. We also did not find new consultations placed by consultants and other providers over the study time frame. Overall, the practice of placement of orders for patients admitted to the IMRS by the Internal Medicine residents themselves is consistent with ACGME rules.This is a remarkable finding in the context of an academic program working in conjunction with a large number of private sub-specialty services in a tertiary-level community hospital with a large patient burden in need of specialized care. The findings are in contrast to the general perception that consultants place the majority of orders instead of Internal Medicine residents. This may be a reflection of the efforts by the residents to establish a direct line of communication between the services, before or as soon as the consult requests are placed. In addition, the hospital EHR software notifications directed to consultants requesting them to communicate with the primary service before orders are put in may also have contributed to the findings. Overall, these efforts may contribute to high-value care while minimizing the duplication of orders and, at the same time, help maintain mutual respect between services. Most importantly, they would strengthen a sense of ownership for the residents, which is fundamental to their training.There are some major limitations to this study. This is a single-center study conducted in orders placed over a very short time period. Besides, this study does not take into account the variability amongst different specialty services. A larger study conducted over a longer time frame, with more sub-specialty specific analysis, may be needed to further assess the extent of this perceived problem.In this study, it was demonstrated that the majority of the orders for patients taken care of by the Internal Medicine Residency Service were placed by the residents themselves despite working in conjunction with a large number of specialty services in a large tertiary-level center. The findings highlight the importance of efforts to establish prompt communication between residents and specialists, which may contribute to high-value medical care and education.


The simulation of complex physics models may lead to enormous computer running times. Since the simulations are expensive it is necessary to exploit the computational budget in the best possible manner. If for a few input parameter settings an output data set has been acquired, one could be interested in taking these data as a basis for finding an extremum and possibly an input parameter set for further computer simulations to determine it—a task which belongs to the realm of global optimization. Within the Bayesian framework we utilize Gaussian processes for the creation of a surrogate model function adjusted self-consistently via hyperparameters to represent the data. Although the probability distribution of the hyperparameters may be widely spread over phase space, we make the assumption that only the use of their expectation values is sufficient. While this shortcut facilitates a quickly accessible surrogate, it is somewhat justified by the fact that we are not interested in a full representation of the model by the surrogate but to reveal its maximum. To accomplish this the surrogate is fed to a utility function whose extremum determines the new parameter set for the next data point to obtain. Moreover, we propose to alternate between two utility functions—expected improvement and maximum variance—in order to avoid the drawbacks of each. Subsequent data points are drawn from the model function until the procedure either remains in the points found or the surrogate model does not change with the iteration. The procedure is applied to mock data in one and two dimensions in order to demonstrate proof of principle of the proposed approach. The complex physics model in our case is given by the modelling of particle transport and plasma-wall interaction in the scrape-off layer of fusion plasmas, which is carried out numerically by the interplay of two extensive codes either describing the plasma solving a fluid equation or the transport of neutrals by a Monte-Carlo method. Each code part produces data sets that the other part of the code needs to process—a circumstance which leads to running times in the order of weeks. Still, after years of computer runs for multiple parameter settings, quite a large database has been gathered with over 1500 entries. With these data at one’s disposal one is tempted to employ some surrogate modelling in order to explore the data set for extrema in certain data ranges motivated by physics, or simply to give advice for which parameter setting the next computer run has to be executed in order to increase the information content of the database most effectively.A long established method in global optimization of complex multi-modal models is the construction of a response surface via fast surrogate models . The numThe paper is organized as follows. The Gaussian process method has been appreciated much in the fields of neural networks and machine learning ,4,5,6,7.n input data vectors The problem of predicting function values in a multi-dimensional space supported by given data is a regression problem for a non-trivial function of unknown shape. Given The Gaussian process method defines a distribution over functions. One can think of the analysis as taking place in a space of functions (function-space view) which is conceptually different from the familiar view of solving the regression problem of, for instance, the standard linear model (SLM)As stated above the defining quantity of the Gaussian process method is the covariance function. Its choice is decisive for the inference we want to apply. It is the place where we incorporate all the properties which we would like the (hidden) function describing our problem to have in order to influence the result. For example, the neighbourhood of two input data vectors For the covariance function itself we employ a Gaussian type exponent with the negative squared value of the distance between two vectors d 5.4 in ). HoweveMoreover, we consider the degree of information which the data contain by a term r 2.2 in ) that inm = 1 ofThe hyperparameters  regimes . A compr regimes . HoweverThe result for the respective hyperparameter from Equation  is inserGaussian priors are employed for the hyperparameters with mean and variance one but constrained to be positive,The marginal likelihood As we deal with the Gaussian process the probability functions are of Gaussian type, with the likelihood as )∝N . Thus, tEquations  and 13)13) constIn a region of interest (RoI) set by the experimentalist we alternate among two well established, but conceptually different utility functions—expected improvement and maximum variance—and search the chosen one for its maximum. Each utility function gets input from the surrogate model represented by target value Equation  and its Equation . MaximizI of the maximum For a first utility function approach ,26 whichEquation ,(14)UEIInserting Equation  into 1414 and sox = 0.25 is not at the position of the global optimum of the true model at x = 0.3. Moreover, most disappointingly, even with more and more iterations, the proposed positions to calculate a new data point are kept locked in the existing ones. An example of this behaviour may be found in Optimizing this utility to find the global optimum of the true model via its surrogate has the known drawback  that theThe other utility function we use is just the variance of the surrogate from Equation ,(16)UMVFirstly, looking for the maximum of Equation  has nothTo search the utility function  10.5 of ). We choThe task of the algorithm is to get a surrogate model to represent a complex model function costly to evaluate with respect to certain input variables. A side condition is that the surrogate should provide the best possible representation of the model at least at the most important point we are looking for, i.e., the global optimum, and is allowed to be vague otherwise. Moreover, the algorithm should benefit from a combination of alternating utility functions and a sophisticated choice of initial values for the maximum search of the utilities. The dimension of the problem is set by the number of input variables.In a real-world problem we would start with a set of data points already obtained from the complex simulations within a region of interest, which conveniently encloses the maximum we are looking for (surrogate modelling fails outside of the region supported by the data). Here, for demonstration purposes, we work with mock data drawn from a multi-dimensional Sobol sequence. Although real data may be spread less evenly over input space a Sobol sequence seems to describe best the attempts of an experimentalist to provide full coverage of parameter space. To ensure that the Gaussian process is unhampered by large scales and to that the data subjected to the numerical treatment is free of any bias, the input data is scaled to [−1:1] in all dimensions and the target data is whitened, i.e., scaling to [−1:1] and removal of a possible linear trend. Next the Gaussian process method is applied to determine a surrogate model given by Equation  and its Equation  by MCMC.Equation  and 16)〈θ〉 to beIn order to demonstrate our algorithm we examine a Rastrigin-like function  with a bThe global maximum is set at 0.3, while the variability of the function within the RoI [−1:1] is given by the factor N = 3 already the data point for x = 0 represents a local maximum which is hard to overtop for methods ignoring the uncertainty of the surrogate model . And inAn overview of how many iterations it takes to reveal the global optimum is given by In all one-dimensional cases our proposed algorithm was capable of finding it, sometimes with far fewer iterations than in the runs with applying one of the utilities. Only for amebsa, chapter 10.9 of [T = 1000 and 3000, while the number of function evaluations at each iteratively diminished temperature level had to be in between 10 and 40. However, exactly those adjustments by hand are what we want to avoid when we come to complex models with hidden extremal structures. We simply will not know when to stop the adjustments. Moreover, even worse, it takes at least a factor of ten more function calls to the complex model than our proposed algorithm needs. Though the running time with respect to the mere simulated annealing part is much less compared with our algorithm, it is this extensive calling of the complex model function which dominates the overall computing effort. Regarding our algorithm the use of a particular utility function (at least for the ones employed in this paper) is of no consequence for the running time, since the calculation of the hyperparameters with MCMC is by far the largest time-consuming part-again apart from calling the complex model function.For the sake of comparison the results of the global optimization by a simple simulated annealing approach are shown in  10.9 of ) all getEventually, we turn in Equation , it getsFinally, for the two-dimensional Branin function  the resuAll three characterizing extrema at An algorithm for global optimization was demonstrated to autonomously reveal dominant maxima. The Bayesian approach benefits from the self-adjusting skills of hyperparameters in the Gaussian process, which enables the surrogate model to adapt to fine structures on top of broader extrema of the complex model. To be instructive the procedure was characterized for two low-dimensional examples. The proposed method does not explore full hyperparameter space during the maximum search in the surrogate. As was shown by Osborne et al. , the sprIt is left to ongoing research to show the feasibility of the proposed method for identifying extrema in more than two dimensions. For instance, instead of simply taking the middle inbetween neighboring data points, one has to think of more sophisticated strategies like Voronoi diagrams in order to identify initial values for the maximum search with the boundary condition of largest distance to the acquired data (within the RoI). Moreover, in the search for the maximum within the surrogate one could profit from the gradients intrinsically at hand for Gaussian processes. Even the distribution function of the gradients is available. Furthermore, one may think of other utility functions additionally employed or modifications of the used ones from Equations  and 16)16). For