This motivated several scholars to search for various alternatives for cement and one of such alternatives is called sulfur-based concrete. This concrete composite contributes to reduce the amount of cement required to make conventional concrete. Sulfur can be used as a partial-alternate binder to Ordinary Portland Cement (OPC) to produce sulfur-based concrete, which is a composite matrix of construction materials collected mostly from aggregates and sulfur. Sulfur modified concrete outperforms conventional concrete in terms of rapid gain of early strength, low shrinkage, low thermal conductivity, high durability resistance and excellent adhesion. On the basis of mentioned superior characteristics of sulfur-based concrete, it can be applied as a leading construction material for underground utility systems, dams and offshore structures. Therefore, this study reviews the sources, emissions from construction enterprises and compositions of sulfur; describes the production techniques and properties of sulfur; and highlights related literature to generate comprehensive insights into the potential applications of sulfur-based concrete in the construction industry today.The incessant demand for concrete is predicted to increase due to the fast construction developments worldwide. This demand requires a huge volume of cement production that could cause an ecological issue such as increasing the rates of CO Sulfur is a by-product of large-tonnage waste from oil and gas production facilities. The forecast for the global production of sulfur  ) makes in: where n represents number of atoms) which allows millions of sulfur allotropes (intramolecular) to exist . It should be noted that if Sn molecules have 6–12 sulfur atoms, they exist in the form of rings (very stable) while molecules with less than six or greater than twelve sulfur atoms can either exist in the form of ring or chain (unstable).Sulfur has a large number of different allotropic modifications due to the high ability of its atoms to combine with each other to form ring or chain molecules. Allotropes of sulfur can be classified into two types of intramolecular allotrope  and intermolecular allotrope  . Sulfur 8 molecules. Liquid sulfur above 159 °C is a solution of linear chains, without regular arrangement between them, formed by opening S8 rings and polymerizing them [Allotropes differ in physical properties and are quite similar in most chemical properties . They caing them .Further, several studies focused on sulfur-based concrete, initially in North America since the 1970s ,19,20,21Sulfur can be obtained from both natural and man-made sources; although, much of the sulfur obtained worldwide from both sources is very difficult to quantify. For instance, sulfur obtained from mining and byproducts of environments  can be reasonably quantified. However, sulfur obtained from industries and electric power plants are very difficult to define. Additionally, sulfur emissions obtained through natural sources are difficult to quantify because of the variability of sources, emissions and compounds involved .The natural sources of sulfur production are very complex and difficult to quantify. Sulfur is available in various minerals in the crust of earth, which makes it one of the very few elements to be present in earth’s crust in elemental state. It is also available in coal, oil and natural gas in the form of various compounds and quantities. Additionally, sulfur is an essential part of all living creatures, including plants and animals ,29. MineAlthough, the quantity of sulfur emitted into atmosphere and sulfur cycle due to human activities is very easy to quantify as compared to natural sources , the maj2S separation. The separation of H2S is necessary due to its toxicity and corrosive nature. The natural gas constituting H2S is called sour gas which is made to pass from a solvent (like amines) [2S dissolves and the required percentage of natural gas remains insoluble. Then, the solvent is heated causing H2S to be removed from the solution [2S is then converted into sulfur by processes like Claus [The recovery of sulfur from natural gas starts with H amines) ,38 in whsolution ,38. Afteke Claus . This me2S. Until the environmental regulations of the 1970s, H2S was used as refining fuel which was obtained during the refining process. This process was limited as burned H2S releases sulfur dioxide into atmosphere. In general, The H2S produced in oil/petroleum refinery can be further processed to produce elemental sulfur [Crude oil generally constitutes carbon (84%), hydrogen (14%), sulfur (1–3%) and nitrogen/oxygen/metals/salt (<1%) . The petl sulfur .2S, CO2 and H2 [2S is under special attention as on the one hand, it plays a role in oil partial desulphurization and on the other hand, due to its toxicity, there is some difficulty to handle and transport it [One of the problems of oil sand reserves development is a rise of sulfur and nitrogen deposition in that region . Mainly 2 and H2 ,42. Sand2 and H2 ,44. Gene2 and H2 . The imp2 is transformed into H2SO4 and liquid sulfur. In the US (1990), approximately 11% of sulfur was produced through H2SO4 obtained from smelting nonferrous metals [2 emissions. In order to obtain useful sulfur or to dispose it, the desulfurization process can be applied which uses compounds like CaO, NaCO3, MgO to get SO2 while it produces elemental sulfur, CaSO4.2H2O, liquid sulfur and H2SO4 [2 and other harmful emissions. Throughout the process, the gas given off is converted to sulfuric acid, which can be used as a by-product [Combined sulfur can be obtained through nonferrous metal smelting. Smelter gases having SOs metals . Sulfur nd H2SO4 . Figure nd H2SO4 . Thereafnd H2SO4 . This pr-product .2S [2 [Natural reserves of sulfur (including sulfur ores of sedimentary and magmatic genesis) amount to more than 5 billion tons. Of these, explored deposits of native sulfur have a capacity of about 1.2 billion tons. The mining industry of sulfur is divided into two sectors: specialized and attendant. The specialized part is mainly aimed at the extraction of sulfur from the deposits of this raw material . The specialized sulfur native ores are in Iraq (about 335 million tons) , the Uni2S ,60 and s2S [2 .2S which can be converted into sulfur by several processes worldwide. One of such methods is known is Claus (named after its inventor Carl Friedrich Claus) [As every source of sulfur  produces Hh Claus) ,62. The h Claus) ,64. The 2S and the oxygen (O2) available in the air are reacted to form SO2H2S and SO2 reacts with each other to produce 3/2 S2. This reaction is high reversible exothermic reaction which lessens equilibrium transformation up to 75%. Effluent gas produced in reaction furnace is transferred to waste heat boiler (WHB) to reobtain heat and form steam (high-pressure). The S2 present in effluent gas changes to hexasulfur (S6) and octasulfur (S8)The above reaction produces a lot of heat while HWHB having effluent gas is transferred to a condenser for condensing sulfur. Condensed effluent gas is heated and transferred to 2–3 catalytic reactors. Each catalytic reaction stage produces sulfur due to cooling converted effluent gas in condenser.Dr. Herman Frasch in 1984 invented a process to recover sulfur by melting it underground and then pumping it upward to the surface . Frasch Frasch pump is inserted in the ground containing sulfur deposits.Hot water (165 °C) is introduced into mineral strata containing sulfur.Hot water melts sulfur which is pumped to the surface by pressured air.Huge, porous and rich sulfur deposits.Impermeable covering rock above the deposit.Reliable and sufficient water supply.Cost effective source of fuel required to heat large water quantities needed to melt the sulfur deposit and to provide enough power required for proper functioning of energy-consuming machineries of the process.Although about 90% of man-made sources of sulfur were recovered from Frasch mining, especially in sulfur rich countries like the US, Iraq and Mexico, this mining method requires the following conditions :Huge, poGeological conditions should be satisfied which mean that the deposits should be either bedded evaporite and salt domes having permeable sulfur (packed in impermeable formations) .Although this process is extensively being used for the recovery of sulfur; however, it is not applicable to small and shallow sulfur deposits.8 [Sulfur has several melting/freezing points that are commonly dependent upon solid allotrope under consideration (melted) which is shown in 8 . Hence, 8 ,69,70.The viscosity of sulfur depends to a large extent on the temperature. For instance, at 160 °C the viscosity of sulfur decreases by up to 7–8 centipoise, after which viscosity of sulfur increases significantly (approximately 930 poise) at 190 °C and then plummets again. The increase/decrease in viscosity also depends on the concentration/intensity and total length of sulfur chains in the liquid. In view of this, decrement in viscosity (at 160 °C) can be attributed to increase in concentration/intensity and total length of sulfur chains while the decrement in viscosity (after 190 °C) can be justified by the decrease in total length of sulfur chains.6 million atoms which this new polymerization shape reduces the density of sulfur [Like viscosity, density of sulfur also depends on the temperature. The density of sulfur increases with decrease in temperature as shown in f sulfur . Howeverf sulfur . Sulfur f sulfur . The denDifferent allotropes and melts of sulfur have different colors  as shownLike density and viscosity, thermal properties of sulfur also suffer from discontinuity due to polymerization at Lambda Temperature . There iSulfur’s strength depends on its thermal history and purity. Two researchers  comprehensively studied the compressive and tensile strength of sulfur in 1965 . It is rSulfur has been utilized in several industries  and due to the increasing environmental concern of cement production and the depletion material resources for cement ingredients, sulfur has become a valuable binding material as shown in To enhance acid and salt resistance and reduce moisture absorption.To maintain (enhance) mechanical properties of sulfur-based concrete as per conventional concrete, maintain workability and minimize drying shrinkage after hardening.Sulfur-based concrete uses sulfur as a binder in its molten state , which r2 in this country alone in 2015 amounted to 18.6 million tons and the contribution of the cement industry (the third largest source of sulfur dioxide) was 1.47 million tons of SO2 (about 7–8%) [2 is mixed with calcium carbonate from raw materials and forms calcium sulfate (gypsum) [The use of vertical grinding units and the passage of waste gases through the mill for heat recovery and to reduce the sulfur content in the gas. In a mill, a gas containing SO(gypsum) .Selection of low sulfur fuel  and the 3 [The use of wet or dry scrubbers. Dry gas cleaning is more expensive, so this method is used less frequently than wet gas cleaning and is usually used when sulfur dioxide emissions can exceed 1500 mg/m3 .Emissions of sulfur dioxide in the production of lime are usually lower than in the production of cement, due to the lower sulfur content in raw materials. The followings are recommended ways to reduce emissions of sulfur dioxide:Selection of low volatile quarry materials .Introduction of hydrated lime or bicarbonate into the waste gas stream before the filters  and injeSulfur dioxide emissions during the production of cement are primarily related to the content of volatile or active sulfur in the raw materials and, to a lesser extent, the quality of the fuel used for energy ,97. In put 7–8%) ,50. To rMoreover, the use of sulfur, which is a waste of enterprises, for the production of building materials is efficient due to waste disposal and contribution to environmental protection. Taking into account the emission into the atmosphere of large quantities of anthropogenic sulfur (170–180 million tons per year) in the composition of flue gases, we are talking about hundreds of millions of tons of “waste” sulfur raw materials . In brieGracia et al.  in 2002 The conversion of sulfur into the reaction forms as a result of thermal decomposition at temperatures above 140 °C;Chemical interaction of sulfur with the additive.Many researchers ,108,109 The amendment of sulfur can be carried out by polymerization with a cyclic hydrocarbon in compliance with McBee ,116, by −3 Pa⋅s for the temperature range of 120–155 °C . This allows for the adjustment of the rheology of sulfur materials during heat treatment [Liquid sulfur has a dynamic viscosity in the range of (6.5–11) × 10reatment . The maxreatment . The plareatment , cast seThe strength and content of its components, the intensity of physicochemical interactions occurring at the interface, the technology of preparation, molding and so forth, affect the strength of sulfur-based concrete . The str2, Al2O3 and CaO.This analysis is used to identify the mineralogical composition which could possibly form during the hardening period ,25. The Numerous studies ,117 haveThe deformative properties of sulfur-based concrete are taken into account when determining crack resistance and structural rigidity. Deformative characteristics of sulfur-based concrete are given in lim.Since creep is associated primarily with defects in the crystal structure and the presence of extraneous (amorphous) phases, the presence of organic plasticizers in sulfur binder makes a negative contribution to this process ,110. ComHardened sulfur-based concrete is practically not subject to shrinkage. After 120 days, the signs of the indicators were insignificant and comparable in magnitude to the deformations from temperature fluctuations, that is, proportional to the coefficient of linear thermal expansion ,125. TheIn terms of the composition of the components, sulfur-based concrete consists of 70%–90% mineral fillers (aggregates) and 10–30% sulfur binder ,12. The 2/kg.Since the typical formation of sulfur-based concrete is the process of impregnation of fillers with liquid plasticized sulfur with its subsequent crystallization during cooling, it is natural to expect an analogy in the behavior of sulfur binder during heating and cooling ,77. In gMuch research has been done to increase the effectiveness of sulfur in concrete production and it has been proven that this waste has useful value for various applications ,127. In The development of effective cementless construction materials is relevant for the modern construction industries nowadays. Sulfur is deemed as a cementitious material that can be used as a partial-alternate binder to OPC. Based on previous studies, it has been found that to incorporate sulfur in concrete, sulfur modification is a prerequisite. Moreover, the workability has a significant impact on the structure of sulfur-based concrete that is highly dependent on the concentration of sulfur, the melt viscosity, fillers characteristic, type of aggregates and type and concentration of modifying additives. The characteristics of compressive strength, deformative, bending and tension for various compositions of sulfur-based concrete were extensively discussed. The persistence of sulfur-based concrete in various aggressive environments proved that it is more effective than OPC concrete to counter detrimental effects of severe environments. However, it was reported that sulfur-based concrete was applied as leading construction materials for entire underground utility systems, dams and offshore structures. To this end, this study presented a review on the sources, emissions from construction enterprises and compositions of sulfur; described the production techniques and properties of sulfur; and reviewed related literature to generate comprehensive insights into the potential applications of sulfur in the construction industry. So far, based on this wide-ranging review, the following remarks have been made:Extensive increase in the use of sulfur production has opened its usability in construction industries worldwide.The use of sulfur, as a waste material of enterprises, for the production of construction materials is efficient due to waste disposals and contributions to environmental protection.Sulfur has several melting/freezing points that depend upon the solid allotropes under consideration (melted), temperature and pressure of the mixture.Different modifiers might be applied to improve different engineering and microstructural properties of sulfur-based concrete.Sulfur-based concrete achieves its ultimate strength in few hours (3–6 h) without any specific requirements of temperature and moisture, in particular, at room temperature.The optimal sulfur content in the material is commonly determined based on the theoretical and experimental values of the porosity of compacted mixtures of fillers.Sulfur-based concrete is more resistant to strong acid effects compared to OPC-based concrete.Incorporation of sulfur in concrete supports sustainability by reducing sulfur emissions through different industries (by capturing) as well as decreasing cement production.


Is an acceptance and commitment therapy–based group intervention, delivered using videoconferencing, effective in reducing posttraumatic stress symptoms in parents of very ill children?This randomized clinical trial found that videoconference-based acceptance and commitment therapy (compared with a waiting list) was effective in reducing posttraumatic stress symptoms in parents of very ill children.This study supports the use of acceptance and commitment therapy as an approach to reduce posttraumatic stress symptoms in parents of very ill children, following an acute or unexpected illness or diagnosis, and finds that a videoconferencing platform can be used effectively to access hard-to-reach populations. This randomized clinical trial evaluates the efficacy of an acceptance and commitment therapy–based group intervention, delivered using videoconferencing, in reducing posttraumatic stress symptoms in parents of children with life-threatening illness. A substantial proportion of parents whose child is diagnosed with a life-threatening illness experience high levels of distress that can lead to long-term mental health difficulties. This can affect the child’s recovery.To evaluate the efficacy of an acceptance and commitment therapy–based group intervention, delivered using videoconferencing, in reducing posttraumatic stress symptoms (PTSS) in these parents.This study was a randomized clinical trial of an intervention for parents with elevated acute stress symptoms. It was a single-site study conducted in a tertiary pediatric hospital in Australia. Parents of children aged 0 to 18 years admitted for a life-threatening illness or injury to the oncology, cardiology, or pediatric intensive care departments were eligible. Participants were screened for eligibility within the first month after diagnosis or admission and then were randomized to the intervention group or the waiting list control group 4 to 10 months after diagnosis or admission. Recruitment commenced January 2014, and final postintervention follow-up was completed in February 2018. Data analysis was performed from July to September 2018.Treatment was a psychological acceptance and commitment therapy–based group therapy program called Take a Breath, which consisted of a 6-session parent-mediated psychological intervention delivered via online videoconferences over the course of 8 weeks. Waiting list control participants received treatment as usual and were offered the intervention 3 months after randomization.The primary outcome was PTSS, as measured by the Posttraumatic Stress Disorder Checklist–Version 5 . The PTSS was measured both before and immediately after the intervention. Changes in psychological skills taught within the intervention were also evaluated, including acceptance, mindfulness, values-based living, and psychological flexibility.d = 1.10; 95% CI, 0.61-1.59; P = .03). The mean Posttraumatic Stress Disorder Checklist–Version 5 scores decreased from 31.7  to 26.2  in the waiting list control group and from 23.3  to 17.8  in the intervention group.Of 1232 parents who were assessed for eligibility, 313 were randomized; 161 were allocated to the waiting list control group, and 152 were allocated to the intervention group. Of those allocated, 44 parents in the waiting list group and 37 in the intervention group completed the postintervention questionnaire and were analyzed . Sixty-five participants (80.2%) were women, 48 participants (59.3%) were married, and 40 participants (49.4%) lived in rural or regional areas, or in a different state. In addition, 24 parents (29.6%) were in the cardiology illness group, 32 parents (39.5%) were in the oncology group, and 25 parents (30.9%) were in the pediatric intensive care unit group. The intervention group demonstrated significantly greater improvements in PTSS compared with the waiting list group (Cohen The findings of this study support the use of acceptance and commitment therapy to reduce PTSS in parents of very ill children, regardless of diagnosis. These findings also suggest that a brief, group format using a videoconferencing platform can be used effectively to access hard-to-reach populations, particularly fathers and caregivers living in nonmetropolitan areas.ACTRN12611000090910Australian New Zealand Clinical Trials Registry Identifier:  Importantly, these clinically significant distress reactions in parents have been found across many illnesses, including children who have experienced trauma,12 those admitted to pediatric or neonatal intensive care units,15 and those newly diagnosed with type 1 diabetes.Parents of children diagnosed with a life-threatening illness or injury are faced with significant psychosocial demands that may challenge their own psychological well-being. Although most parents adapt with time, a proportion suffer from psychiatric conditions, including posttraumatic stress disorder, as a direct result of their child’s illness.3 This is consistent with the Pediatric Medical Traumatic Stress Model,17 which provides a useful framework in which to understand important associated factors and the development and trajectory of psychological disorders in parents associated with child medical trauma, as well as identifying the optimal time for treatment.Interventions targeting these early distress reactions in parents are critical, because these initial reactions have been found to be associated with long-term outcomes.19 that have attempted to develop and test interventions have demonstrated limited success, with some evidence supporting problem-solving and family therapy approaches in parents of children with cancer.Despite the emotional vulnerability of this population, evidence-based, preventive mental health interventions are lacking. The few studies21 to evaluate the effectiveness of Take a Breath, a brief group intervention for parents of children with a range of life-threatening illnesses and injuries. It is based on acceptance and commitment therapy (ACT)22 and comprises key elements of acceptance, mindfulness, values clarification, and goal setting. Given that intrusive thoughts, avoidance, and high levels of emotional arousal are among the most common distressing symptoms in parents of children with a serious illness or injury,24 the group-based ACT model was selected because it provides peer support and modeling of coping strategies and helps normalize the challenges faced by parents. The ACT-based intervention is delivered using videoconferencing to maximize accessibility for a highly stressed and geographically dispersed population.Our study builds on promising pilot resultsThis study aimed to determine the efficacy of the ACT-based program in reducing posttraumatic stress symptoms (PTSS) in parents. It was hypothesized that the program would result in a significant reduction in PTSS in the intervention group compared with a control group assigned to a waiting list for the intervention. The study also investigated whether the ACT-based program resulted in improvements in the psychological skills addressed in the intervention, such as mindfulness, values-based living, and psychological flexibility. Secondary outcomes explored whether there were improvements in other aspects of parental well-being, specifically, the parent’s experience of their child’s illness and family functioning. We hypothesized that the intervention group would show significantly better functioning within these areas compared with the waiting list group.47 Written informed consent was obtained from eligible parents. This study follows the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline. The full protocol is available in 25Ethics approval for this randomized clinical trial was granted by the Royal Children’s Hospital Human Research Ethics Committee. All procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Declaration of Helsinki of 1975, as revised in 2008.Eligible participants were randomized to either an intervention or a waiting list control group. Parents completed questionnaires at 3 time points: within 4 weeks of their child’s diagnosis or admission , 2 weeks before intervention commencement, or approximately 4 to 6 months after the diagnosis or admission , and immediately after intervention completion .26; and (4) parents who were sufficiently fluent in English to complete questionnaires and participate in the program. Parents were excluded if they presented with a pre-existing psychiatric disorder, they had experienced another trauma  in the 2 months before the child’s diagnosis, they were no longer the primary caregiver at the time of the intervention, or their child was deemed eligible for palliative care  or had died.Participants were parents of children with a recently diagnosed life-threatening illness or injury admitted to the oncology or cardiology departments or the pediatric intensive care unit (PICU) at the Royal Children’s Hospital, Melbourne, Australia. Admissions into these departments were chosen because of the sudden onset of the child’s illness and the significant threat posed to the child’s life and future functioning. Participants were recruited from consecutive first admissions to these departments from January 2014 to February 2016. Eligible participants were (1) the primary caregiver (aged ≥18 years) of a child aged 0 to 18 years; (2) parents of a child with a first-time presentation for a new cancer diagnosis, cardiac surgery within the first month of life, or admitted to the PICU for more than 48 hours; (3) parents reporting elevated levels of acute stress symptoms as measured by the Acute Stress Disorder Scale (ASDS)26 and collection of demographic information at T1. At 4 months after admission, eligible parents were contacted by telephone and invited to take part in the trial. The intervention was not undertaken in the early stages of admission to allow for natural recovery of parents’ initial acute stress reactions. The timing of the ACT-based intervention is consistent with the Kazak Pediatric Medical Traumatic Stress Model.4 In some families, both parents were eligible; however, randomization occurred at the family level. Thus, parents from the same family were always in the same condition. Partners of eligible parents who did not meet eligibility criteria were also invited to participate because they were seen as a key source of support for enacting changes27 and may have also benefited from the program. Data from parents who were invited but not eligible were not included in analyses.The child’s medical team was consulted to determine study eligibility. Parents were approached on the hospital wards (or by telephone if the child had been discharged) by the research team to discuss participation and to screen for eligibility. Screening included completion of the ASDSParents were asked to consent to trial participation and were enrolled at T2 before randomization. The Murdoch Children’s Research Institute’s Clinical Epidemiology and Biostatistics Unit, independently of the research team, generated the randomization list with a computerized randomization plan generator using the method of randomly permuted blocks. Three randomly allocated lists were created, 1 for each hospital department . A researcher independent of participant recruitment and intervention delivery managed the lists and allocated parents to intervention or the waiting list using sequentially numbered, sealed envelopes. This process ensured that parents and the research team were blind to participant allocation at assessment. Once the intervention was completed, both the intervention and waiting list groups completed their surveys at T3.25 It consists of five 90-minute consecutive weekly sessions, with a sixth and final session held 3 weeks after the fifth session. Parents participated from their homes using the Google Hangouts videoconferencing application (Alphabet) on a study-provided iPad .The program is a 6-session, parent-mediated, psychological intervention based on ACT.Each ACT session was delivered by 2 trained mental health clinicians. Session content and structure are reported in eTable1 in A total of 4 facilitators received training in ACT and in the delivery of the intervention from a senior ACT clinician, who is a specialist in trauma-focused psychotherapy. Each session was audio recorded and reviewed fortnightly during team supervision sessions. Fidelity of program delivery was recorded and assessed using session monitoring checklists completed by both facilitators after each session. An audio recording of 1 session from each group was randomly selected and reviewed for fidelity by an independent clinician, using a fidelity monitoring checklist.The ASDS and a demographic information questionnaire were completed at T1 only. All other measures were completed at T2 and T3 by parents in both groups. Each measure has been evaluated as a valid and reliable measure in these clinical populations.26 measures acute stress reactions within 4 weeks after a traumatic event and is highly predictive of the development of longer-term PTSS and mental health problems.28 The ASDS measures symptoms of dissociation, re-experiencing, avoidance, and arousal and can be scored using a total score cutoff 26 or in terms of symptom clusters. A score of 9 or higher on the dissociative cluster, as well as a score of 28 or higher on the combined re-experiencing, avoidance, and arousal cluster scores, indicates the presence of clinically significant levels of acute stress disorder symptoms26. Both scoring methods were used in this study to determine eligibility, with parents required to be eligible on at least 1 scoring method to be invited to participate. Internal consistency (Cronbach α) was 0.80 for the ASDS total score, 0.71 for dissociation, 0.32 for re-experiencing, 0.75 for avoidance, and 0.64 for arousal.The ASDS29 It contains 20 items that assessed 20 criteria for posttraumatic stress disorder in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition).30 Parents were asked to complete the measure in relation to their child’s diagnosis. The total score  was used, with higher scores indicating greater PTSS. The PCL-5 has been found to be a valid and reliable measure across many populations.31 Internal consistency for the total score in the current study was α = .93. Secondary outcomes measured included depression, anxiety, and stress 33; the parents’ adjustment and experience of the illness 34; and the family’s ability to manage caring for a child with a chronic condition .35The primary outcome was PTSS in parents as measured by the Posttraumatic Stress Disorder Checklist–Version 5 (PCL-5).37 various aspects of day-to-day mindfulness (Five Facet Mindfulness Questionnaire–Short Form),39 values-based living and the degree to which people live by their values ,40 and the level of psychological flexibility in parents .42Changes in the psychological skills taught within the intervention were also evaluated. These included acceptance (Acceptance and Action Questionnaire–II),Information was collected regarding parent age, sex, marital and employment status, level of education, and country of birth, as well as their child’s age and sex. Medical diagnosis, date of diagnosis, and treating department were extracted from hospital medical records.P < .05 and power of 0.80, 72 participants were required per group. Allowing for an estimated 35% lost to follow-up, it was projected that a total of 210 participants was needed to be randomized across the 2 groups.To detect a difference of 7.5  in the primary outcome measure (PCL-5), between the 2 treatment groups, with a significance level of 2-sided 2 test.Demographic, illness group , and ASDS screener characteristics were compared between groups. For parent-level data (for couples that were both eligible), categorical variables were compared using generalized estimating equation models to account for within-couple correlation (with the exception of parent sex and illness group). A generalized estimating equation with a Gaussian distribution was used to compare group means of the ASDS screener. For child-level characteristics, child ages at diagnosis and at each subsequent time point were compared using negative binomial regression models because of positive skew. Time between measurements using linear regression models and illness group distributions were compared using a χd values were calculated between groups for T3 scores (adjusted for T2 scores) and were interpreted as small (<0.2), medium (0.2 to <0.5), large (0.5 to 0.8), and very large (>0.8).43 These analyses were all stratified by illness group.Generalized estimating equation models also compared mean outcome measures between groups at T3, adjusting for scores at T2 (included as a model covariate). Again, models accounted for within-couple correlations. Effect size Cohen P < .05. To not unduly penalize the data, multiple comparison adjustment was not applied. Data analysis was performed from July to September 2018.All analyses were performed using Stata statistical software version 15.1 (StataCorp). Two-sided statistical significance was set at The recruitment flow of participants can be seen in the Reasons for nonenrollment included parents being unable to be contacted (65 parents [20.8%]), declining participation for various reasons, including time constraints (124 parents [39.6%]), and child death or unstable health since screening (8 parents [2.6%]). Results from between-group analyses are presented in Preliminary analyses also explored the differences between participants who consented and participated, and those who consented but did not participate across these same sociodemographic factors (eTable 2 in P = .03), PECI unresolved sorrow and anger , PECI uncertainty , and PECI negative appraisal . Preintervention functioning at T2 was therefore controlled for in subsequent analyses as a model covariate. Concerning the investigation of the differences between the intervention and waiting list groups from T2 to T3, significant differences were found on the primary outcome measure (PCL-5), after accounting for preinjury functioning at T2, with greater improvements in the PTSS after the intervention. For the intervention group, mean PTSS scores decreased from 23.3  at T2 to 17.8  at T3. For the waiting list group, mean PTSS scores decreased from 31.7  at T2 to 26.2  at T3 waiting list , for a mean reduction of 5.5 points for both groups. Significantly greater improvements were also found at T3 for the experience and impact of the illness on parents , with greater improvements found in the emotional resources , uncertainty , and the overall negative appraisal subscales . No additional group differences were identified in the other mental health , family functioning , and other parent experience measures .Fidelity of program delivery was rated at 98% across all sessions. There was a total of 26 groups, with group sizes ranging from 3 to 8 parents. d = 0.80; 95% CI, 0.33-1.27; P = .02), as well as greater improvements in mindfulness, specifically in nonjudging of inner experience (Five Facet Mindfulness Questionnaire–Short Form) , living according to values  , and committed action  . There were no other significant improvements in the other functional outcomes from T2 to T3.Functional outcomes are displayed in 5The Take a Breath program is an ACT-based group intervention designed to prevent and reduce parents’ PTSS after the diagnosis of a serious illness in their child. Delivery via online videoconferencing sought to increase accessibility. To our knowledge, this randomized clinical trial provides the first evidence internationally to support the use of this type of approach for parents of children with diverse illnesses. Before the intervention, parents randomly allocated to the intervention condition were significantly less distressed across a range of measures than parents allocated to the waiting list control group. On our primary outcome measure, parents in both the intervention and control conditions had a mean reduction on their PTSS score of 5.5 points between T2 and T3. This represented a significantly larger relative reduction for intervention parents when their lower initial distress was taken into account. On the secondary outcome measures, parents in the intervention group showed significantly greater improvements than parents in the control group on 3 aspects of their subjective experience of the illness: improved emotional resources to manage the illness, reduced perceptions of uncertainty, and reduced negative appraisal associated with their child’s illness. Inspection of the measures of psychological skills addressed by the intervention suggests that these improvements may be associated with greater acceptance, mindfulness , values-based living, and committed action in parenting flexibility. Together, these results suggest that participation in the intervention improved parents’ capacity to better manage the demands of caring for a sick child and potentially ameliorated the negative impact of parental PTSS on the child.44 or problem-solving therapy.24 Although we found significantly greater improvements in PTSS for parents receiving the 6-session intervention, there was no difference between groups for our secondary mental health measures of anxiety, depression, and stress. It is possible that a longer intervention is required to successfully address these additional mental health concerns; however, the program was not designed to address these symptoms. Past intervention studies in this field have all focused on the parents of children with cancer.41 The ACT-based intervention was beneficial regardless of the child’s illness or injury, providing support for intervention approaches that target parents across the wider hospital system. The findings also support the use of videoconferencing as a promising approach to enhance accessibility, which is a key barrier to the provision of evidence-based treatments for this population.45 Approximately half of our participants lived in rural or regional Victoria, Australia, or in another state. Use of the videoconferencing platform provided access to these parents who would not have been able to attend a traditional face-to-face service. Engaging parents within a tertiary hospital setting has been recognized as particularly challenging.46 Our approach also demonstrates the feasibility of using videoconferencing for a group program to provide opportunity for peer support and the normalization of experiences.The application of an ACT-based intervention is highly novel in this population, with past studies using traditional cognitive behavioral therapy46 Other limitations that may have biased the findings include that the study only used self-reported measures and that, at the time of postintervention assessment at T3, the participants were no longer blinded as to group allocation. Additionally, multiple comparison adjustments were not applied to secondary and functional outcomes, potentially inflating the type I error rate. Furthermore, significant baseline differences in mental health symptoms between the intervention and waiting list groups indicate that randomization did not successfully allocate equivalent groups to treatment groups. It is unclear why this occurred; hence, replication of differential postintervention improvements using a sample with equivalent groups at baseline is required to substantiate the important findings reported here.Implementation of this trial presented many challenges, and our study has some limitations. Recruiting parents when their child was seriously ill was difficult, and it took 2 years to recruit the sample despite working within a large tertiary hospital. As a result, our modest sample size meant that we were only able to detect large differences between the intervention and control groups. In addition, attrition rate of parents initially screened and enrolled but then lost to follow-up before commencement of the program was 64%. Primary reasons for attrition at this stage were time constraints or feeling that intervention was not needed. Fathers and parents whose primary language was not English were overrepresented in the study dropouts. This finding is not uncommon in intervention studies and further highlights the need to ensure that recruitment and intervention materials reflect diversity and are engaging to all.The findings of this randomized clinical trial support the use of an ACT approach to reduce PTSS in parents of children who are seriously ill, across various illness groups, indicating that Take a Breath has potential for wide use within the pediatric hospital system. The findings also suggest that a videoconferencing format can be used in a clinically effective way to access geographically dispersed populations and engage their participation in a group program.


TiO2) nanostructures with different anodization processes. We produced a total of 100 samples, and we assessed changes in TiO2 nanostructures’ thicknesses by performing anodization. We successfully grew TiO2 films with different thicknesses by one-step anodization in ethylene glycol containing NH4F and H2O at applied voltage differences ranging from 10 V to 100 V at various anodization durations. We found that the thicknesses of TiO2 nanostructures are dependent on anodization voltages under time differences. Therefore, we tested the feasibility of applying machine learning algorithms to predict the deformation of TiO2. As the characteristics of TiO2 changed based on the different experimental conditions, we classified its surface pore structure into two categories and four groups. For the classification based on granularity, we assessed layer creation, roughness, pore creation, and pore height. We applied eight machine learning techniques to predict classification for binary and multiclass classification. For binary classification, random forest and gradient boosting algorithm had relatively high performance. However, all eight algorithms had scores higher than 0.93, which signifies high prediction on estimating the presence of pore. In contrast, decision tree and three ensemble methods had a relatively higher performance for multiclass classification, with an accuracy rate greater than 0.79. The weakest algorithm used was k-nearest neighbors for both binary and multiclass classifications. We believe that these results show that we can apply machine learning techniques to predict surface quality improvement, leading to smart manufacturing technology to better control color appearance, super-hydrophobicity, super-hydrophilicity or batter efficiency.This study aims to demonstrate the feasibility of applying eight machine learning algorithms to predict the classification of the surface characteristics of titanium oxide ( TiO2) nanotube arrays obtained by Ti anodization have overwhelmingly attracted scientific and technological interests because of their functional properties. Among its various applications, TiO2 plays a pivotal role because of its chemical stability, nontoxicity, and biocompatibility [TiO2 is used in solar cells production [TiO2 is also considered a synthetic bone graft substitute [TiO2 nanotubes/nanoporous arrays are the most frequently fabricated nanostructures. Therefore, various methods such as template-assisted sol-gel synthesis, play a crucial role in the fabrication of Ti nanostructures [Ti. Anodization is a simple electrochemical process performed to produce thick nanoporous/tubular metal oxide and subsequently precious such as Al, Ti, and Mg [Ti in electrolytes containing fluoride ions is the most common method used to create self-organized nanotube arrays [TiO2 is associated with different parameters, which affect the surface morphology and quality of the structure [TiO2 nanostructures. Based on the systematic control over the two parameters, we obtained 100 samples and categorized surface characteristics from the surface image. We investigated whether we could apply machine learning algorithms to predict an anodic formation of TiO2 structure. We clearly aimed to predict surface characteristics that were classified into two or four groups based on pore structures. Besides the common parameters assessed in TiO2 structures such as surface thickness, these oxide structures are considered significant because they are superhydrophilic, superhydrophbic, and have excellent color appearance on a Ti surface. We believe that if we are able to determine certain parameters of the pore structures without conducting labor-intensive experiments, the time and cost of conducting several experiments can be sufficiently utilized. In this study, a total of 100 samples were produced, and this sample size is relatively small when assessing the feasibility of machine learning algorithms compared to other domains. However, if we can determine the feasibility of predicting surface characteristics, we will be able to harness the appropriate predictive model that should be used to estimate generated surface characteristics, allowing us to focus more on higher granularity of experimental conditions to generate the desired surface characteristics.Nowadays, ordered titanium dioxide  supervised learning, where input and output variables are given and the model is determined from the labeled input dataset; (2) unsupervised learning where a self-organized learning method determines unknown patterns in a dataset without pre-existing labels; and (3) reinforcement learning, where an intelligent agent is defined and interacts with its environment by performing actions and learning from errors or rewards, termed as a trial-and-error approach for learning .TiO2 structures, such as pore structure and thickness, by performing different anodization processes.Classification is a type of supervised learning technique that categorizes data from prior information. The algorithm is used to predict a discrete value that is assigned to a particular class or group. Imagine a set of photographs of animals where each photo is labeled as a cat, rabbit or other animals. When a new image is assigned, the algorithm has to classify it into one of these labeled categories. Each testing instance is matched with a category, which we call labeled data and is used for training. Classification is performed in two phases, and the labeled dataset is divided into training and test dataset. First, a classification algorithm updates its model with the training dataset, and the analytical model extracted is validated against a labeled test dataset to calculate the model performance and accuracy. Compared to different applications such medical imaging detection or quality control in manufacturing, materials science has recently applied these machine learning techniques considering the difficulties they faced in collecting a large sample of data. However, the prerequisite for machine learning is the existence of prior data. To obtain thousands of input data with traditional experimentation methods, a significant amount of cost, time, and effort is required in materials science. Therefore, current research in materials science primarily aims to discover and design new materials by using public datasets on material properties . In our Ti sheets by sonicating in a solution of acetone, ethanol, and deionized (DI) water for 30 min. Subsequently, we applied two different polishing methods. Electrochemical polishing was performed in a mixture containing acetic acid, sulfuric acid and hydrofluoric acid (60:15:25 in volume) at a constant current density of 140 mA/cm and a temperature of 20 °C for 1 min. Chemical polishing was performed by dipping Ti samples into a stirred mixture of hydrofluoric acid and nitric acid (1:3 in volume) for 10 s. Subsequently, the samples were rinsed with water and ethanol and dried in the air. A combined pretreatment method was conducted by electrochemical polishing followed by chemical polishing. The polished Ti samples were prepared via one-step anodization in an electrolyte of ethylene glycol containing 0.25 wt% NH4F and 2 wt% DI water at 0 °C. The process was performed at 10 V intervals from 10 V to 100 V in a two-electrode cell, with polished Ti samples as anodes and platinum as a cathode. The duration of anodization was at 1 min intervals from 1 min to 10 min. Structural and morphological characterizations were executed using a field emission scanning electron microscope (FE-SEM). The structural features and thickness of anodized samples were examined directly from FE-SEM images by Image J software.We degreased the Class 0: oxide layer creationClass 1: oxide layer creation with roughnessClass 2: oxide layer creation with pore creationClass 3: oxide layer creation with uniform pore generationThe data were categorized based on the characteristics of surface morphology. We introduced the methodology for the multiclass and binary class categorization on the obtained data. Initially, the surface was labeled into four groups based on the images obtained from FE-SEM images. The second author designed the coding scheme based on the formation of an additional layer, roughness with the hexagonal pattern and pore formation. Each aspect is built upon another, for example, a pore would be created after a layer was formed. Both authors used the scheme and independently coded the same 100 images. The inter-rater reliability was found to be good with kappa = 0.94. The two raters slightly modified the coding scheme after validation. The four classes are described below  , naïve Bgorithms . A machiTo calculate the performance of the machine learning models, we used K-fold cross-validation because it is suitable for a dataset with limited sizes . Cross-vTP = true positive, TN = true negatives, FP = false positives, and FN = false negatives.)For binary classification, we used area under the receiver operating characteristic (ROC) curve (AUC) . We willPrecision and recall are additional ways to assess the results by breaking down the accuracy formula. Precision quantifies the number of classes predicted positive that actually belong to the positive class. Precision is a good performance measure to apply when the costs of false positive are high.Recall quantifies how many of the actual positives our model captures through classifying it as positive (true positive). It is a good performance measure when there is a high cost associated with false negative.F1 score balances both precision and recall in one number. It is the weighted average of precision and recall. Therefore, this score concerns both false positive and false negative into account. F1 score is usually more useful than accuracy, especially when you have an uneven class distribution.ROC curves shows the trade-off between the true positive rate  and false positive rate for the extracted model using different probability thresholds. If we lower the classification threshold, the model classifies more items as positive, thus increasing both false positives and true positives. AUC stands for “area under the ROC curve.” The AUC measures the entire two-dimensional area below the ROC curve from  to , which means that AUC provides an indication of how good or bad our classifier is performing across all possible classification thresholds. Therefore, AUC ranges in value from 0 to 1. If the classifier is perfect, then the AUC score is 1.0. If the predictions are 100% wrong, then the AUC is 0. The advantage of applying the AUC measure is that it is invariant of data imbalance . For theWe used the AUC value as the performance measure. A high AUC value greater than 0.8 denotes a reasonably good prediction rate , while ac is the class label.When the number of classes is high, it becomes more complicated to measure the performance. The combinations of true and false classifications for each class increases. Therefore, micro- and macro-averages are calculated for precision and recalls . HoweverIn multi-class classification, the count of all false instances is as below (Equation ), therefA macro-average computes the metric independently for each class and then calculates the average by treating all classes equally. On the other hand, a micro-average computes the average aggregating the contributions of all classes. If there is class imbalance, macro average will have lower values. However, it actually indicates the overall accuracy for all classes, that is, predicting each class is equally important; therefore, we also report the macro-average values.Ti oxide layers are fabricated by a one-step anodization process. In the present study, it is evident that the dimension of the nanostructure, such as thickness, strongly depends on the anodization conditions used. The key factors are the anodization time and voltage. After some preliminary experiments, considering duration and voltage, the formation of the nanostructure is possible in a mixture of ethylene golycol/DI water/NH4F in a duration ranging from 10 V to 100 V and a duration ranging from 10 min to 100 min. The association between the voltage and time on the thickness of the TiO2 films formed on polished Ti samples was observed by FE-SEM. TiO2 produced by anodization at different voltages and times. TiO2 structures have significant TiO2 nanotube and display more uniform films. As can be seen, with increasing anodization time and applied voltage, the rate of oxide growth increases and the TiO2 films become thicker. As anodization of Ti procedure is performed, metal ions (Ti4+) migrate from metal to the oxide/metal interface and dissolve into the solution. At the same time, the oxygen-containing ions (O2−) are generated at the oxide/electrolyte interface by the field-enhanced dissolution of H2O or OH− under the influence of the electric strength (reactions of 8 and 9) [Nanoporous anodic 8 and 9) .(8)Ti→TTiO2 in ethylene glycol-based electrolyte is nearly 100%. We can expect that the thickness of the grown oxide is proportional to the electric charge exchanged from electrolyte during anodization process. In other words, the anodizing potential difference by changing current density, anodizing time, and applied voltage determines the thickness of TiO2. Ti anodization in ethylene glycol-based electrolyte. As can be expected, significantly thicker oxide films are created at higher anodizing duration and applied voltage. At relatively higher voltages (greater than 50 V), however, it can be observed that the growth of thickness decreases at specific anodization times. It was considered that the decreasing electrolyte viscosity on the rate of oxide growth in the diffusion during anodization performed in ethylene glycol-based electrolyte. The steady-state oxide growth is a dynamic equilibrium between the rate of oxide growth and the rate of oxide etching at the oxide bottoms. During the oxide growth , pH at the oxide bottoms decreases due to reaction 10 [It is clear that the thickness of the grown oxide is closely related to the operating condition during anodization. The effective current efficiency of the formation of ction 10 .(10)Ti+H2O and NH4F (reaction 11) [In contrast, decreasing pH at the oxide bottoms encourages the etching of oxide at the oxide film in the ethylene glycol-based electrolyte containing tion 11) .(11)TiOTi4+) that appear in the electrolyte as a result of the increasing rate of the oxide growth at higher voltage and time. The hydrolysis consequence in the deposition of the hydrous Ti oxide on the TiO2 surface. Consequently, the thickness is reduced by the deposition. Therefore, the rate of deposition not only the hydrolysis is greater than the rate of chemical etching of the TiO2 layer.Moreover, it can be attributed to the effect of enhanced hydrolysis of metal ions (Next, we visualized the thickness by experimental settings and separated them by the labels we used for classification to understand the thickness difference among each classification group. Although AUC is our core measure, we report accuracy, precision, and recall measures together. As shown in There are several implications that we can achieve from the visualization see . First, Prediction scores for binary classification in this study show that our model is capable of predicting the presence of pores using the experimental levels of time and voltages. Researchers can predict whether pores will exist with the experimental settings. With the multiclass classification the evaluation scores were relatively lower. However, even with unbalanced and small sample size to predict four levels, over 0.7 for macro recall and precision shows the potential to move forward with the approach. Higher micro scores can be also interpreted; that is, certain levels have higher prediction scores. To obtain a reliable classification model even for small data sets, Beleites et al. recommended at least 75 to 100 samples per class to achieve a reasonable precision .Overall, we can see that ensemble methods are superior for the binary classification problem. RF and GBT had a score of 1 for AUC. Ensemble methods are learning models based on the intuition that combining the opinions of multiple learners lead to better performance. RF uses a fully grown decision trees that have low bias, which are prone to overfitting. The idea is to resample the data multiple times and train a new classifier each time independently. In contrast, GBT adds a classifier each time, so that the next classifier is trained to improve the previous one. Both cases have shown good performance because they combine multiple individual models and show superior prediction power . For mulTiO2 nanostructures can be created in an ethylene glycol-based electrolyte by one-step anodization performed over various anodization voltages at anodization time ranging from 1 min to 10 min. Anodization time and applied voltage have a great impact on the nanostructures of TiO2 and regularity of pore arrangement. With increasing applied voltage, the growth of oxide thickness increases. In addition, it was found that the oxide thickness changes its thickness in time with increasing tendency and decreasing tendency at specific anodization time and voltage. The highest values of oxide thickness and the regularity of the pore arrangement are observed at 100 V and 10 min as well. These consequences are described in terms of the blocking effect on the TiO2 surface caused by developed hydrolysis. On the above-obtained results, the ability to control the growth of TiO2 is an important factor towards a targeted development of Ti nanostructure because it is expected that a variety of nano-geometry industry exists.The present work demonstrates that the well-aligned formation of Therefore, we also applied machine learning to test the feasibility of predicting the surface aspects by the experimental settings, voltage and duration. We have observed that predicting the binary classification had higher accuracy than predicting the multiclass classification. However, the size of the dataset is relatively small than usual machine learning experiments. This is an innate limitation when applying machine learning techniques to experimental data for material science. We believe we have demonstrated classification capability to predict certain aspects from experimental results, which can help identify less useful experimental settings and properly use the cost and time to focus on specific experiments to achieve accurate results.


G0 and 15G0 and their corresponding Fourier transforms (FTs). The FT analysis of the conductance histograms exhibits a clear preference for thinning along the [100] direction. Using well-established models, both atom-by-atom steps and ranges of stability, presumably caused by electronic shell effects, can be discriminated. Although the directional motion of atoms during EM leads to specific properties such as the instabilities mentioned, similarities to mechanically opened contacts with respect to cross-sectional stability were found.Even though there have been many experimental attempts and theoretical approaches to understand the process of electromigration (EM), it has not been quantitatively understood for ultrathin structures and at grain boundaries. Nevertheless, we showed recently that it can be used reliably for the formation of single atomic point contacts after careful pre-structuring of the initial Ag nanostructures. The process of formation of nanocontacts by EM down to a single-atom point contact was investigated for ultrathin (5 nm) Ag structures at 100 K by measuring the conductance as a function of the time during EM. In this paper, we compare the process of thinning by EM of structures with constrictions below the average grain size of Ag layers (15 nm) with that of structures with much larger initial constrictions of around 150 nm having multiple grains at the centre constriction prior to the formation of a point contact. Even though clear morphological differences exist between both types of structures, quantized conductance plateaus showing the formation of single point contacts have been observed for both. Here we put emphasis on the thinning process by EM, just before a point contact is formed. To understand this thinning process, the semi-classical regime before the contact reaches the quantum regime was analyzed in detail. For this purpose, we used experimental conductance histograms in the range between 2 The transition from a three-dimensional (3D) conductor to single atomic chains or atomic point contacts is an intriguing process, which has been addressed many times over the years. Its many aspects ranging from bulk solid-state physics to the stability of various types of clusters, and their attachment to the environment to one-dimensional 1D) properties of atomic chains and contacts have been treated in many different studies D propert. Howevere2/h , [100] and [111], respectively  direction, is absent in these structures. This result contrasts with a MCBJ experiment using Au nanowires -oriented grain boundaries occurs. This dominance of the peak at 1 in both types of structures not only gives evidence that the atomic point contact thinning occurs at the [100]-oriented interface, but also demonstrates the prominence of electronic shell effects  direction once only a single grain is the starting point of EM. Assuming that the [100] thinning direction is the energetically most favorable one, the [111] direction is only observed when the reduction of conductance from multiple grains to a single grain involves directional changes of the current so that the less likely [111] direction still appears. This is exactly what is seen in On the other hand, a noticeable difference between  and 3 in  and 3 in Interestingly, another difference in the peak structure between 1.5G0 lead us to the conclusion that only a single contact existed in most cases. A large range of unstable configurations between 14G0 and 5G0 may be characteristic for the EM process at a temperature where only limited thermal diffusion is possible, since such a range of instability was not found in experiments with other techniques. At this point, due to the limited available data set involving only Ag contacts, it remains unclear how general this phenomenon is. It may, however, be related to the observed instability of other thinning directions for Ag.The EM process in ultrathin nanocrystalline Ag structures on Si(100) was investigated for structures that had a narrowest constriction of 100 to 150 nm. These were compared with those further structured down using FIB to 15 nm, i.e., below the size of a single grain. Although the mesoscopic evolution of structures with filament formation for the large structures was very different from that of the structures that were initially only 15 nm wide, the similarity of conductance histograms below 15Although the thinning mechanism of EM seems to be quite different from that of mechanical stretching, we conclude from our FT analysis that the underlying atomistic processes seem to be quite comparable. Similar conclusions are drawn in . This siThis study thus complements existing data from MCBJ measurements of Ag and HRTEM investigations on Ag point contacts and provides a concrete information on the mechanism of thinning in ultrathin Ag films.Low-doped Si(100) substrates (1000 Ω·cm at 300 K), which are good insulators at temperatures around 100 K, were used. Structuring was carried out by a three-step process. As a first step, we patterned the contact pads by photolithography. Secondly, electron beam lithography was employed in order to obtain nanostructures of bow-tie shape that were 100 to 200 nm wide at the smallest constriction. After HF dip, in order to get a hydrogen-terminated surface, 1 nm of Ti served as wetting layer before we evaporated 5 nm of Ag onto the substrate at room temperature. Thirdly, these bow-tie structures were further patterned by using a FIB in order to reduce the centre width below the size of a single grain. By writing elliptical structures into the Ag nanostructures, we were able to reduce the centre width of the nanostructures to below 20 nm. The detailed steps of the sample fabrication were reported in a previous publication ,28.−10 mbar). This facilitated cooling of the structures down to 100 K without any spurious condensation. Furthermore, the UHV environment was important for the Ag structures as they are quite susceptible to sulfur contamination under ambient conditions. UHV also provided an ultra-clean environment for point contact measurements. Two out of the four available tips were used for the EM measurements. The tips were pre-cooled by making electrical  contact with the contact pads produced by photolithography.All measurements were performed within a four-tip SEM/STM UHV chamber , which Conductance traces were obtained during EM thinning, which demonstrated step-like conductance plateaus. Details of point contact characterisation can also be found in our earlier publication . Conduct


Tumor necrosis factor (TNF) superfamily ligands show diverse biological functions, such as the induction of apoptotic cell death or cell survival and proliferation, making them excellent therapeutic targets for cancer and autoimmunity. We review the latest literature on TNF receptor superfamily signaling with a focus on structure-function. Using combinatorics, we argue that receptors that cluster on the cell surface and are activated by membrane-bound ligands need to arrange in a highly ordered manner, as the probability of random ligand and receptor arrangements matching up for receptor activation is very low. A growing body of evidence indicates that antiparallel receptor dimers that sequester the ligand binding site cluster on the cell surface, forming a hexagonal lattice. Upon ligand binding, this arrangement puts the activated receptors at the right distance to accommodate the downstream signaling partners. The data also suggest that the same geometry is utilized regardless of receptor type. The unified model provides important clues about TNF receptor signaling and should aid the design of better therapies for cancer and various immune mediated diseases. The TNF-related apoptosis-inducing ligand TRAIL/Apo2L)  is a memL  is a mTRAIL and other TNFSF ligands are type II membrane proteins that share the classic TNF homology domain (THD) and form noncovalent trimers ,10. TrimExperimental data support receptor oligomerization of TRAIL and other TNFRSF receptors on the cell surface but there have been conflicting models proposed over the years ,6,13,14.We can simplify the translation problem by subtracting patterns from the 17 trillion total that only occupy one half of the 10 × 10 matrix. Every such pattern in one half of the matrix can be translated onto a matching pattern in the other half. This can be calculated as C = 50!/(40! × 10!) ~10 billion, a small rounding error compared to the 17 trillion total. There are other patterns that are counted more than twice, but their numbers are even smaller and can be neglected. The ~17 trillion combinations have to be divided by 4 to take into account the four 90 degree rotations that transform one pattern into another. After taking rotational and translational symmetry into account, we end up with more than 4 trillion unique patterns or unique ways the receptor trimers can be arranged. Ligand-free TNFRSF receptors have been shown to form two different dimers ,19. One 230) from each monomer. The loss of Zn ion can lead to instability and loss of activity of human recombinant TRAIL (hrTRAIL) [Among the TNFSF, TRAIL signaling biology is one of the most complex. In addition to binding to its two death receptors, TRAIL receptor 1  and TRAIL receptor 2 (TRAIL-R2/DR5), it also binds to three decoy receptors, TRAIL-R3  and TRAIL-R4  and soluble receptor osteoprotegerin (OPG) that can sequester TRAIL and therefore also functions as a decoy receptor ,24,25,26hrTRAIL) ,28. SevehrTRAIL) .TRAIL-R1/R2, similar to Fas induce apoptosis via formation of the death inducing signaling complex (DISC) that, in addition to the death domain (DD) of TRAIL contains Fas associated death domain (FADD) and the cysteine protease, Caspase-8. The Fas-DD-FADD complex structure provided insight into how these intracellular DISC components may form a hexagonal lattice after Fas ligand binding and Fas receptor activation . Shen etIn summary, the experimental data on both the cell surface receptors and in the cytosol on DISC assembly are consistent with the hexagonal lattice model with a separation of ~100 Å or more between receptor trimers proposed earlier ,14,30,312 to effectively block TNF binding [Historically, it has been challenging to design powerful antagonists against TNFRSF members. TNF receptor 2 (TNFR2) is a master switch of cell survival and proliferation  and, as  binding . In addi binding ,38. In a binding . The ant binding . As we dHVEM (TNFRSF14) functions as a molecular switch modulating B and T lymphocyte activation , dendritcis complex on the cell surface and not the model that was put forward in the original study [cis configuration BTLA does not interfere with LIGHT or LT-α binding, instead it serves to facilitate HVEM oligomerization on the cell surface and to inhibit the ligand independent activation of HVEM. In contrast to BTLA, the CD160-HVEM structure shows a 1:1 complex and it has a lower affinity for HVEM than BTLA [cis may function to limit HVEM oligomerization on the cell surface in the above model. This shines potentially new light onto BTLA, CD160 function. Rather than being true ligands, they serve as regulatory proteins modulating HVEM oligomerization and control receptor activation. In addition to cis interactions, both BTLA and CD160 can also interact in trans adding to the complexity of HVEM regulation [BTLA is an immune-globulin superfamily (IgSF) glycoprotein with two immunoreceptor tyrosine-based inhibitory motifs . BTLA isal study . CD160 aal study ,49. On than BTLA . There ahan BTLA ,52,53. IIt is important to note here that the viral protein HCMV UL141 that blocks TRAIL-R2 surface expression interacts with TRAIL-R2 via its Ig-like domain. This highlights a potentially more extensive relationship between the Ig and TNF superfamilies then previously appreciated. As is shown in We have argued that the probability of random receptor arrangement on the cell surface matching up with randomly arranged membrane bound ligands is extremely low. Membrane bound ligands are more efficient at receptor activation because they allow the simultaneous activation of multiple receptors. However, for that to happen, the receptors and their corresponding ligands need to be arranged on the cell surface in a highly ordered manner with matching geometry. This should apply to not only members of the TNF receptor superfamily but to every clustered receptor activated by membrane bound ligands. We discussed how TRAIL-R1/R2 and other TNFRSF members cluster on the cell surface forming highly ordered hexagonal lattices. The available experimental data supports a receptor quiescent state of a hexagonal lattice made up of trimers of antiparallel dimers. For receptors like HVEM that are unable to dimerize on their own, co-regulatory proteins may aid receptor oligomerization on the cell surface and modulate receptor function. It remains to be seen if this more broadly applies to other TNFRSF receptors. The same process can also be exploited by viral proteins to modulate immune function. The antiparallel arrangement not only prevents accidental receptor activation but places the receptors with the right geometry for the downstream signaling partners to assemble. There may be exceptions but the same geometry seems to apply to both the death receptor family and for the TRAF-interacting TNFRSF members. Having the same scaffolding geometry can allow the switching between apoptosis and NFκB activation for the same receptor such as TNFR1 depending on the downstream binding partners.Many questions still remain about the mechanism of TNFRSF signaling, but the presented model provides important insights into TNFRSF biology and for the design of better targeted therapies at the molecular level for cancer and other immune mediated diseases. Antibodies that lock in the antiparallel dimer provide an effective strategy for creating antagonist therapeutics against TNFRSF receptors. On the other hand, effective agonism may include both ligand and antibody-based approaches that utilize the hexagonal model of activation.


The elective control of follicular wave emergence and ovulation has had a great impact on the application of on-farm embryo transfer, especially when large groups of donors need to be superstimulated at the same time. Although estradiol and progestins have been used for many years, practitioners in countries where estradiol cannot be used have turned to alternative treatments, such as mechanical follicle ablation or the administration of GnRH for the synchronization of follicle wave emergence. In vitro embryo production also benefits from the synchronization of follicle wave emergence prior to Cumulus Oocyte Complexes (COCs) recovery. As Bos indicus cattle have high antral follicle population, large numbers of oocytes can be obtained by ovum pick-up (OPU) without superstimulation. However, synchronization of follicular wave emergence and superstimulation is necessary to obtain high numbers of COCs by OPU and blastocysts following in vitro fertilization in Bos taurus donors. Finally, embryos can now be transferred in commercial beef or dairy herds using efficacious synchronization and re-synchronization protocols that are easily implemented by farm personnel. These technologies can also be used to resolve reproductive problems such as the reduced fertility observed during summer heat stress and/or in repeat-breeder cows in commercial dairy herds.Knowledge of follicular wave dynamics obtained through the use of real-time ultrasonography and the development of the means by which follicular wave dynamics can be controlled have provided practical approaches for the  Regardless of the method of embryo production, these technologies can be implemented in commercial beef and dairy operations for genetic improvement and even to increase fertility during the summer heat stress and/or in repeat-breeder dairy cows. The objective of this manuscript is to briefly summarize the existing protocols for superstimulating donors for in vivo and in vitro embryo production and to propose alternatives by which embryo transfer technologies can be implemented more widely in commercial herds.The objective of ovarian superstimulatory treatments in cattle is to stimulate the growth of the maximum number of antral follicles that produce competent oocytes . The usur 5 days . HoweverBos taurus  embryos in the same donor  or 5 mg estradiol-17ß and 50 – 100 mg progesterone (P4) and insertion of P4-releasing device 4 days before initiating FSH treatments . This pr2α, a P4-device and GnRH to induce ovulation prior to initiating FSH treatments. Basically, a persistent follicle was induced by treatment with PGF2α at the time of progestin device insertion; following administration of GnRH 7 days later, ovulation occurred in more than 95% of the animals. Superstimulation initiated 36 hours after GnRH (with the P4-device remaining in place) resulted in a superovulatory response that did not differ from controls superstimulated on Days 8 to 12 of the estrous cycle. More recently, Attempts to synchronize follicular wave emergence for superstimulation with GnRH were initially unsuccessful; however, subsequent field data were more promising. In these cases, GnRH was administered 1.5 to 3.0 days after the insertion of an intravaginal P4-device which may have increased the probability of an LH-responsive follicle at the time of treatment with GnRH. Indeed, vs 4.9 ± 0.9) in an unselected group of donors , consistent with a numerically greater number of follicles ≥ 10 mm just prior to ovulation . Moreover, ovulations occurred more synchronously in the 7-day group (93% of ovulations occurred 12 to 36 hours post-LH as compared to 66% in the 4-day group) suggesting that the superstimulated follicles were more mature and capable of responding to an LH stimulus. Although the total number of ova/embryos, fertilized ova and transferable embryos did not differ statistically, all end-points favored the 7-day group. In addition, when data from two cows with fertilization failure were removed, the number of transferable embryos tended to be higher in the 7-day group .A more recent study evaluated the superovulatory response and embryo recovery in donors treated with either a 4-day or a 7-day FSH treatment protocol utilizing the same total dose of 400 mg FSH  administered twice daily at a constant daily dosage (vs 11.6) and embryos (6.7 vs 5.9) were numerically higher in the 7-day group.In another study . As indicated earlier, Bos indicus cattle have a higher number of follicles recruited per wave as compared to Bos taurus breeds and this has resulted in the recovery of a higher number of oocytes with OPU  Treatment with estradiol and P4 or the removal of the dominant follicle (DFR) were equally efficacious in the synchronization of follicular wave emergence for OPU; 3) Superstimulatory treatment with FSH increased the number and quality of COCs obtained by OPU in Bos taurus breeds, but not in Bos indicus breeds. In an experiment conducted in Brazil with Holstein donors ; however, COCs from FSH-treated cows yielded a higher blastocyst rate  and more transferable embryos per OPU session than the control group . It was concluded that superstimulation of Holstein donors with FSH before OPU increased the efficiency of IVP by increasing COC and embryo quality. In addition, non-lactating donors had a higher percentage of in vitro blastocyst development and produced more embryos per OPU session than lactating cows. In a later study, similar results were obtained when the four doses of FSH were replaced by a single i.m. injection of 200 mg of FSH diluted in a 0.5% hyaluronan solution  and are selected depending on the availability of the hormones in different countries. In either case, the recipient protocols include the insertion of a P4-device for 7 or 8 days  based treatments are the most commonly used protocols to synchronize follicle wave emergence and ovulation of recipients in South America  in a GnRH-based protocol (named 5-day CoSynch+CIDR) .2α treatments 14 days apart and estrus detection. Furthermore, Using a modified 5-day CoSynch+CIDR protocol , Bos indicus cows that were synchronized for FTAI or FTET at the beginning of the breeding season  in cows that were FTAI (59.4% and 59.4% for 2 FTAI and FTAI/FTET group respectively) than those that were FTET . Similarly, pregnancy rates after the second service also differed (P = 0.06) among groups: 2 FTAI (50.8%), FTAI/FTET (40.6%) FTET/FTAI (51.9%) and 2 FTET (35.0%). Finally, the cumulative pregnancy rate (first + second service) was higher in the groups that receive 2 FTAI (80.0%) than those receiving 2 FTET (55.8%); pregnancy rates in the other groups that received the combined techniques were intermediate and did not differ . The conclusion of this study was that although the use of two consecutive FTET had a lower cumulative pregnancy rate than two consecutive FTAI, the association between FTAI and FTET programs can be considered as an alternate strategy to increase number of offspring from embryo transfer.Although the numbers of embryos produced have increased over the years in several regions of the world , the maiOther approaches have been implemented in the field. In one study , an embryo transfer program was implemented in an extensive Hereford herd in Southern Argentina. In this herd, cows were synchronized with a conventional estradiol/P4-based synchronization protocol for FTET (n = 62) or were FTAI at the beginning of the breeding season (n = 300). In the FTET 49 cows (79.0%) had CL 9 days after P4-device removal and received IVD frozen/thawed embryos. The day after FTET all cows were exposed to clean up bulls for the remaining of the breeding season. Twenty cows (40.8%), were pregnant following FTET and the pregnancy rate to FTAI was 54% . However, the overall pregnancy rate at the end of the breeding season was 91.0% and did not differ among groups.2α and ECP and are inseminated on Day 32. The Resynch 14 protocol involves the use of color Doppler ultrasonography for the detection of pregnancy based on the vascularization and size of the CL on Day 22 after the first AI. The resynchronization treatment starts 14 days after FTAI with the re-insertion of a used P4-device and the administration of 100 mg P4 IM  that do not have any apparent abnormality that can be diagnosed by a veterinary examination. In a recent study, the transfer of embryos to repeat breeders resulted in increased pregnancy rates compared to AI, without differences in embryo/fetal losses between 30 and 60 days (in vivo, especially in cows with reduced antral follicle populations, because the time necessary for all growing follicles to acquire the ability to ovulate is extended. With respect to the IVP of embryos, cattle with Bos indicus influence adapt very well to this technology because they have a high antral follicle population and, consequently, more COCs are obtained by OPU than in Bos taurus breeds. In Bos taurus donors, synchronization of follicular wave emergence and the use of FSH have resulted in a greater number of COCs per OPU and the IVP of a higher percentage of blastocysts. Nowadays in vitro and in vivo production of embryos can be combined with efficient synchronization and FTET programs that are easily implemented in the field and permit the inclusion of commercial beef herds in embryo transfer programs, combined with FTAI or simply with clean-up bulls. Although the embryo transfer technology has been used in dairy herds for many years, primarily for genetic improvement in a limited number of cows the technology can now be used to resolve reproductive problems such as the reduced fertility observed during the summer months and in repeat breeder cows.The use of protocols that control follicular development and ovulation have the advantage of allowing the widespread application of assisted reproductive technologies. The treatments used to synchronize follicle wave emergence for superovulation by many practitioners around the world have proven to be practical and easy to perform by field staff. Lengthened the superstimulation protocol is also an interesting alternative to produce embryos