Peer to Peer (P2P) accommodation has effected a disruptive change in cities and traditional tourist destinations, with considerable growth in the number of customers and hosts offering services worldwide. This growth is not without the problems that arise from service quality failures. Previous research has largely concentrated on positive consumer responses to P2P accommodation, while failures in service have been neglected. Research regarding the impacts of failures on health and safety issues is particularly scarce, especially after the pandemic. Therefore, this research is exploratory in nature and drew on the real experiences of 91 guests worldwide since the beginning the pandemic until 2022. It analyses failures in public health and safety regarding P2P accommodation, classifying them and expanding the categories in order to design recovery strategies to mitigate the negative impacts. The findings provide novel insights that help understand failures in P2P accommodation from a guest’s perspective. Moreover, this research suggests recommendations to platforms and hosts that will help improve the levels of service quality and trustfulness for this type of accommodation. Airbnb is considered a successful business; this is demonstrated by the number of results yielded when one types “Airbnb” into Google: more than 228,000,000. A search performed using Google Scholar yields 41,200 documents when ‘Airbnb’ is entered, and a search on “P2P short rentals” yields more than 23,000 results. Thus, a great amount of literature regarding Airbnb has been developed, mainly by guests and hosts, regarding the availability of Airbnb units and their impacts on destinations, regulations, their impacts on the tourism sector, and on Airbnb the company  by fleas or bedbugs as soon as we lay on top of the bed.”“My sister got a zip lock bag and put the live bedbug in it.”“Finally, the fifth type of dirt was associated with pests:It was disgusting and a health hazard.”“It was definitely not COVID compliant.”“This is also a severe sanitation problem and it may pose a public health problem, as some guests asserted:In addition, these conditions provoked very negative emotion descriptors, such as “terrible”, “nightmare”, or “horrible experience”.Regarding the COVID-19 disinfection protocols promised by Airbnb, guests reported that they were not followed in these accommodations.Several authors asserted that the location of the accommodation, the amenities state and building itself are a relevant part of the guest satisfaction . Thus, aThe garden area was untidy, with the grass not cut and loose tiles on the path.”“There are broken or dirty items , and all three bedrooms did not have AC. There were two ancient AC units in the living room and dining room.”“We could see the door lock on the security gate wasn’t installed and there was a gap.”“The floor was chipped and cracked and the window screen was broken.”“In cases of lack of maintenance, guests reported serious deterioration in home infrastructure in general, with aged amenities and broken, unfixed items. This situation can produce accidents such as cuts or falls, among other things:The stained mattress was still in place, and there was a broken dishwasher and cupboards.”“Broken or dirty items (linens with blood stains and a foam mattress).”“We had a broken toilet seat.”“I checked the bed, and noticed the middle legs were broken.”“A stack of bricks [were put] on one corner of one of the beds to replace a broken leg.”“Moreover, broken amenities constituted a severe cause of dissatisfaction for guests that could contribute to health problems or accidents. For example, a broken leg on a bed could cause insomnia, or a broken chair could cause someone to fall. Thus, some of the guests’ comments were:Nonworking TV.”“The washer and dryer didn’t work.”“The washer was not working.”“The air conditioning on the first floor was not working.”“Finally, nonworking amenities could cause frustration for guests because one of the main motivations for choosing a P2P accommodation is the inclusion of amenities not available at a hotel . Some exDifferent types of nonworking amenities had different levels of severity and impact. Broken items such as a cooker or a TV can be a motivation for anger because guest expectations are not met, while other nonworking items can pose a risk of infection and become a health threat. As mentioned, safety and security concerns were also divided in two categories: (1) Safety and security inside and (2) outside of the P2P accommodation. As we were listening to him, another man who did not identify himself and was dressed in track pants and t-shirt came out of nowhere in a very aggressive way and started demanding that I, a female, leave our room and go with him to the front gate of the property to show him the code we had tried to use that wasn’t working.”“The maintenance worker put his hand on this man’s shoulder to hold him back and calm him down because he was acting so aggressive and uncontrollable.”“Host was over aggressive.”“The safety and security inside the P2P accommodation seems to be related to some threats from outside. The first emergent category was the host. Hosts can be a hazard for the guest when their behaviour or attitude is not appropriate. In fact, guests reported hosts’ aggressive and other negative attitudes that can lead to a nervous and stressful situation inside and outside the accommodation:I find it disappointing that Airbnb would be okay for a host to have an active recording camera in the living room, violating one’s privacy, and the fact that they find it okay with a host having a listing that nasty.”“Unauthorised people are just letting themselves onto the property, opening the backyard gate and walking in, totally ignoring me, but, once confronted, they run away. I’ve rented this property for a month and what privacy do I get? These trespassers are jeopardising the well-being of my beloved pooch from escaping. They are trespassing on private property and leaving the backyard fence open while doing so.”“I always put my zipper on my backpack or suitcase in a certain position. It had moved. He didn’t take anything, because I took all my valuables with me in a second backpack. But that’s a huge violation. The only lock that worked on the bedroom door was a keypad lock that he said didn’t work, but I didn’t know if he could put in a battery from the outside and try to get in. When I came in the doorknob was loose and I couldn’t turn it to get back into my room. I kept turning until it tightened and I was able to get in. Because of the lock, I had to put a table against the door and sleep in my clothes, all packed in case I had to leave in a moment’s notice.”“The most frequently pointed out actions regarding safety were violations of privacy, such as registering the guest’s baggage, entering the guest’s room or house when the guest is outside, and recording guests in their rooms:He lied. There were multiple codes to enter the elevator and the unit that didn’t work all the time either. There were also signs posted at the elevators stating that they do not allow Airbnb.’‘The Airbnb Plus property is located in a building that does not allow short-term rentals. We had to constantly lie to the concierge and every time we parked our car in the garage.’‘I am at a loss how people can be like this and rip people off and lie so blatantly.’‘Regarding inside P2P accommodations, another three subdimensions arise that pose health hazards, such as allergic reactions provoked by dust or insects bites. A second type of health hazard is injuries by cuts from broken mirrors. As mentioned, these threats are linked to sanitation issues. The third subcategory was illicit acts regarding P2P accommodation, including more guests than allowed, subleasing a property, or asking a guest to lie.It is possible to assert that inside the P2P accommodation, guests could have safety and security risks of different types, as previous research has suggested.We did not want to endanger their lives by going to our Airbnb with active threats of violence in the area we would have to cross through.”“The neighborhood is trashy, unkept, and very noisy with neighbors consistently slamming doors, babies crying, chickens crowing at all hours of the day, as well as other things.”“When we arrived we were shocked and disturbed. The apartment was in an unsafe-looking neighborhood in what looked like Section 8 housing.”“We noticed a homeless person screaming and doing her business in public.”“[The host] just left out that the home is surrounded by homeless people, tents, trash, and the walk might be one of a lifetime.”“There are also safety and security hazards outside P2P accommodations; specifically, two dimensions emerged: (1) safety and security hazards in the neighborhood and (2) animals. In relation to the neighborhood, multiple hazards were reported, such as drugs, robbers, or violence, which caused fear and insecurity as well as insalubrity in the surroundings. This analysis shows the other face that  revealedWe found [our dog] three days later torn apart by a coyote.”“A crazy drunk neighbor with a dog who bit my child and who killed a hen in front of our eyes.”“Problems with the host and his large dog.”“They had dogs that barked and might bite.”“While spending time at the pool the first day at the property, a huge rodent (rat) ran right by me.”“In regard to animals, guests especially warned about exposure to a dangerous animal, such as dogs or rats:Thus, after the full analysis, it is possible to assert that some P2P accommodations have considerable room for improvement in public health and safety issues after the pandemic. Airbnb should gather the complaints, investigate the acts reported, and try to resolve the problems. Previous research  has poinTo summarise, dirt, a lack of maintenance, and broken and nonworking amenities in P2P accommodations have been identified as major threats to public health. Severe and continuous failures were noted in different P2P accommodations by different guests and countries. Those findings warn about the necessity to establish some standards for this type of accommodation. In addition, recovery actions and procedures for the most recurrent failures should be defined and developed by Airbnb and adopted by hosts to resolve some problems immediately. These findings confirm and reinforce previous research ,13,14,22In the case of safety, inside hazards due to the host and problems at the accommodations are not acceptable. Hosts with repeatedly proven violations and who have been accused of undesirable or abusive behaviours should be expelled from the platform as a signal of compromise among all stakeholders—hosts, guests, local communities, and cities, among others. Moreover, hosts should be mindful of the necessity to show professional behaviour to both guests and platforms. Outside safety issues at P2P accommodations can be more difficult to correct, but they can be mitigated. Airbnb should monitor the location and surroundings of P2P accommodations and, if necessary, put a warning on the listing. In conclusion, these findings can help foster an understanding of the new necessities of guests after the pandemic and can help establish recovery strategies to avoid becoming a threat to public health and safety and to continue being a successful business model that is profitable for all stakeholders involved, including the tourism destinations themselves.Based on the rsults, this study reaches several important conclusions that are relevant to business management, tourism destinations, urban planners, and academics. All of the negative findings about public heath and safety imply very negative emotions on the part of guests, such as being stressed, upset, angry, and having nerves or irritation , as wellThis research extends the previous dimensions of research on public health and safety threats in P2P accommodations after the pandemic and provides novel insights to help us understand failures in those services from a guest’s perspective, although corrections of these issues have not been sufficiently studied yet. Such factors should be included in successive research to deepen understanding of the topic.To protect public health and safety, more control of P2P accommodations should be exerted both by the local governments where they are located and by their own platforms. We propose some solutions.First, a more trustful host rating system on the platform seems to be an urgent necessity. Many guests report severe discrepancies between the of accommodation information published on a platform and the actual situation. A frequent complaint is that “the host is providing misleading information on the post”. Another complaint is that guests are provided the actual location of the accommodations only after the reservation has been made. Both situations could put guests into trouble regarding health and safety threats by withholding realistic, testable information.Second, some hosts had very undesirable attitudes and/or behaviours. This is intolerable, not only for Airbnb, but also for cities. Such hosts give a bad reputation not only to the platform but also to the city and its touristic position. This situation reinforces the idea that soft regulation and some minimally proven standards should be imposed on each accommodation when it joins the platform. Moreover, P2P accommodations should maintain these standards beyond the platform rating system, in particular because the Airbnb rating system could be under question due to several guests’ assertions that Airbnb had deleted their negative opinion and evaluation or never made it visible. As a consequence of this practice, most hosts obtain a high rating on the platform.Finally, our findings provide relevant information for tourism destinations. A tourist destination’s brand could be damaged by an increase of failures by P2P accommodations. Thus, they cannot look the other way or close their eyes while they continue to offer services that can endanger public health. Specific requirements and controls should be required both for accommodations as well as their associated platform, particularly because a lack of control could be derived from problems, as  or 6] r r6] repoThis study has some limitations, such as the generalisability of the results, which are derived from the nature of the methodology used. Therefore, in the near future, more information should be gathered to compare health and safety threats before and after the pandemic, as well as their evolution, including the new services offered by Airbnb as the local concierge partners, to help hosts be more efficient and trustworthy.


Clostridioides difficile infection (CDI) at a single site from 2018 through 2020. Overall, 78 patients had nonrecurrent infections. Among inpatient antibiotics, intravenous meropenem had the highest CDI rate . Among outpatient antibiotics, metronidazole had the highest rate .We examined risk associated with antibiotics used for  Clostridioides difficile infection (CDI) is a diarrheal disease commonly associated with antibiotics. CDI caseloads have decreased through antibiotic stewardship, infection prevention, and more specific testing recommendations. However, CDI continues to be an avoidable source of morbidity and mortality. CDI risk shifts to antibiotics that are used. The objectives of this pilot project were to identify the antibiotics associated with CDI in our institution and to estimate the risk of these antibiotics by the amount of antibiotic consumed or prescribed.As antibiotic stewardship programs (ASPs) seek to avoid high-risk antibiotics ,C. diff toxin polymerase chain reaction assay, followed by positive glutamate dehydrogenase enzyme-linked immunosorbent assay (EIA) and toxin EIAs based on the recommended multistep testing algorithm.This retrospective cohort included patients diagnosed with CDI at the Richard L. Roudebush Veterans’ Administration Medical Center from July 2018 to December 2020. CDI cases were identified based on a positive  Chart review confirmed CDI diagnosis, excluded recurrent infections, and collected demographics, antibiotic exposure, CDI disease severity , body mass index (BMI), and, over the 30 days prior to diagnosis, proton pump inhibitor (PPI) use, receipt of cancer chemotherapy, and abdominal surgery.All nonrecurrent CDIs were included. We did not combine antibiotics of the same class, nor did we analyze antibiotic combinations or multiple antibiotic exposures. Antibiotics associated with only 1 CDI case were excluded. Inpatient antibiotic days of therapy (DOT) and outpatient number of pills dispensed were used to quantify antibiotic consumption for rate calculations. Oral and liquid preparations rarely used or those with specific niche uses  were excluded.We defined an antibiotic exposure as an antibiotic given or prescribed for ≥3 calendar days within 30 days prior to CDI diagnosis. On average, 32 CDI diagnoses were made in the institution annually. Given a 2.5-year study period, we anticipated a sample size of 80 CDI patients and 63 antibiotic-associated cases. This study was approved by Indiana University Institutional Review Board.Descriptive analysis was stratified by CDI severity for antibiotic exposure. Means, frequencies, and rates were calculated using Microsoft 365 Excel software . The estimated prevalence of antibiotic use was 76.8% in the 30 days prior to CDI.In total, 91 CDI cases were diagnosed; 78 were nonrecurrent infections. Of these 78 CDI patients, 75 (96.15%) were male, and the mean patient age was 68.83 years  (Table Antibiotics were commonly prescribed in the preinfection period (72 antibiotics exposures): 37 (47.44%) of 78 cases had an antibiotic of ≥3 days duration in the 30 days before CDI Table . The mosThe highest rate of postantibiotic CDI occurred with inpatient meropenem  and outpatient metronidazole (0.071 CDI per 1 KPD).In this pilot study, we were able to quantify the CDI risk of antibiotics used in our facility by dividing the number of CDI cases associated with each antibiotic by a measure of antibiotic consumption (DOT for inpatient and number of pills dispensed for outpatient medications). The denominator data were readily available from our pharmacy and through our ASP. These calculations provided an institution-specific risk profile that reflected our antibiotic use pattern and guided our stewardship efforts. Although the risk estimates may not be generalizable to other institutions, the approach provides a simple way to describe institution-specific antibiotic CDI risk. Future studies should validate this approach to measuring CDI risk of antibiotics and should evaluate whether changes in ASP recommendations can shift CDI risk and/or decrease CDI events.Overall, PTZ was the most common IV antibiotic given prior to CDI (n = 9 cases). We will leverage this finding to encourage more rational PTZ use, especially when anaerobic or antipseudomonal coverage is not indicated. Ceftriaxone (CTX) was associated with 5 CDIs. CTX is one of the most common antibiotics used in the hospital, and the CDI rate with this antibiotic was relatively low (0.72 CDI per 1 KDOT). In diseases for which ampicillin-sulbactam is an alternative to CTX , favoring the former may increase CDIs; ampicillin-sulbactam had a higher CDI rate (1.58 CDI per 1 KDOT). We have limited the use of meropenem to those at risk for extended-spectrum β-lacatmase–producing Enterobacterales, and we are considering opportunities to further reduce inappropriate use. Cefepime had a lower CDI risk than PTZ. Although some data suggest that PTZ is protective of CDI, our findings suggest that cefepime may be preferentially recommended over PTZ in infections when either is appropriate.Meropenem was associated with 2 CDI cases but had the highest CDI rate among the IV antibiotics for inpatients (3.56 CDI per 1 KDOT). Although the CDI rate is likely affected by low consumption and use in high-risk  patients, our finding was consistent with the prevailing literature.In common diseases like inpatient urinary tract infections, we may recommend de-escalation to oral regimens like AMC or cefuroxime. Cefuroxime had higher CDI risk (3.17 CDI per 1 KDOT) than AMC (1.16 CDI per 1 KDOT). However, it is doubtful that AMC was safer, given that it was associated with 5 outpatient CDI cases. We were unable to combine inpatient and outpatient AMC data because the measures differ. Also, we were unable to determine whether all dispensed antibiotics were consumed. Finally, being an inpatient increases CDI risk. were also identified as high risk in our study. Some narrow-spectrum and lower-risk antibiotics were also associated with CDI in our study , perhaps due to high utilization or their use in combination with higher-risk antibiotics. We did not assess the effects of multiple antibiotic exposures on CDI risk.High-risk antibiotics  consistent with our results. Only 10.26% of cases had chemotherapy prior to CDI, consistent with studies in which no specific chemotherapy has been shown to be an independent risk factor for CDI. PPIs were commonly used prior to CDI, similar to prior studies.Most CDI cases were not severe. Increased age has been associated with increased severity,Our study had several limitations. We considered every antibiotic exposure as an independent exposure, and we did not analyze the effects of combined antibiotics or multiple antibiotics given prior to CDI. We also limited our chart review to our institution’s records; thus, antibiotics prescribed and CDI diagnosed elsewhere were not included. The single-center nature of the study limited generalizability and did not supplant the established antibiotic risk based on larger studies. Although we examined the association between antibiotics and the development of CDI, causality cannot be inferred. The relatively small sample size limited comparisons of CDI risk across antibiotics. We intend to conduct a future study when we have additional years of data and can examine how modified antimicrobial policies may have changed CDI risk for individual antibiotics.In this single-institution evaluation, simple calculations using readily available data to stratify CDI risk to help guide antibiotic stewardship policies to reduce CDI.


Chloride penetration resistance is one of the most important performance measures for the evaluation of the durability of concrete under a chloride environment. Due to differences in theory and experimental conditions, the durability index (chloride diffusion coefficient) obtained from laboratory accelerated migration tests cannot reflect the real process of chloride ingress into concrete in the natural environment. The difference in test methods must be considered and the transfer parameter  Chlorine ion transmission in concrete and induced steel corrosion are the main causes leading to the damage of coastal reinforced concrete structures. The durability and lifetime of the concrete structures in chloride environments depend on the anti-chloride ion permeability of concrete; therefore, the diffusion coefficient of chloride ions is one of the most important indicators in measuring the capability of concrete resisting chloride erosion. According to the test principles and test conditions, two types of diffusion for chloride in concrete can be categorized. One is the natural diffusion coefficient, which reflects the long-term transmission of chloride into concrete and can be directly used for durability design and service life prediction for marine concrete structures. Extensive research has been carried out on the natural diffusion coefficients ,2,3,4,5.The second is the chloride diffusion coefficient obtained from the accelerated test, including the electrical non-steady-state migration coefficients, the apparent diffusion coefficient of the salt ponding test, and a variety of steady and non-steady-state chloride migration coefficients proposed by Wang and Xu . Those dIn summary, existing comparative studies of diffusion coefficients focused on differences between a variety of coefficients obtained from laboratory tests with standard methods, and, generally, the steady-state diffusion coefficients were specified as the input parameter to the durability life prediction of concrete, lacking in consideration for the disparity between laboratory rapid test results and the long-term performance of concrete in the natural environment. Due to the difference in temperature and humidity, salinity, chloride ion adsorption, and the saturation state of concrete, the chloride diffusion (or migration) coefficients obtained by laboratory tests can hardly reflect the chloride ingress process of concrete in natural marine situations. Wang and Fu  deemed tIn 2002, we started to place concrete test specimens at the Exposure Test Station in Zhanjiang in southern China. The natural chlorine diffusion coefficients at different exposure durations were measured, and the relationship between the natural chloride diffusion coefficient and the exposure duration in the actual marine environments was established. We also compared the natural chloride diffusion coefficients of specific exposure duration with the apparent diffusion coefficients, which were obtained by applying an external electric field to drive the chloride ions in the concretes of the same compositions. By analyzing the diffusion coefficients from different test methods, we obtained direct conversion factors to rapidly characterize the long-term performance of concrete durability by the accelerated electromigration method.The tested binder materials include Portland cement (P·II.42.5), fly ash (FAII), and ground blast furnace slag . Due to the long interval between the two tests, two different binders were used. The concrete aggregates include crushed granite with 5~25 mm continuous gradation and river sand grains with a fineness modulus of 2.60. FDN-5 high-efficiency water-reducing agent, with its main components being the condensation polymer of β-naphthalene sulfonic acid and formaldehyde, is used to reduce water by > 20%.Concrete specimens were cut into cubes of 100mm to investigate the chloride ingress of each mix proportion over a specified period. Concrete was designed using Portland cement, fly ash, and GGBS, mostly with water-to-binder ratios (W/B) of 0.35 . CylindrThe specimens used were concrete rods with a diameter of 100 mm and a height of 50 mm. The concrete specimens were placed on the plastic support in the catholyte reservoir, which was filled with about 12 L of 10% NaCl solution. The sleeve was filled above the specimen with 300 mL anolyte solution (0.3 M NaOH). The test device is shown in Cubic concrete specimens (100 mm × 100 mm × 100 mm) were first removed from molds one day after being cast and were then cured in fresh water at 20 °C for 28 days. As shown in The concrete was broken into particles smaller than 4.75 mm, and the particles with diameters between 2.36 mm and 4.75 mm were screened for the mercury injection test. The PASCAL140 and 240 automatic mercury injectors manufactured by Thermoelectric Finnegan Italy were used.Due to the continued hydration of the binder, concrete permeability decreases over time. From the 10-year exposure test results in South China, the relationship between time and the chloride diffusion coefficients of concrete in the actual marine environment can be obtained, as shown in tD is the chloride diffusion coefficient at time t, refD is the chloride diffusion coefficient at time reft, and m is the age factor of the chloride diffusion coefficient.Takewaka and Mastumoto  proposedm of the diffusion coefficient can be derived for concrete with different cementitious materials, and the water-to-binder ratio is 0.35 in South China coastal areas of the marine environment  of concrete at 28 days and 56 days, which corresponds to long-term resistance to chloride permeability for concrete in marine environments in South China.According to the curvilinear relationship in RD) was measured through an RCM experiment after curing in standard conditions for 28 days and 56 days. All the diffusion coefficients obtained from exposure and RCM are shown in With the development of testing technologies, the non-steady-state electro-migration method (RCM method) becomes the main method to measure the chloride ion resistance of the concrete in China. The Hong Kong–Zhuhai–Macau Bridge and many other large projects applied this method as the standard method for the quality control of concrete durability ,27. To cAccording to De and RD have a similar value for concrete without an active admixture at the same age, meaning that the results of the non-steady-state electric acceleration test based on the Nernst–Planck equation can reflect the short-term durability indicators and long-term performance when not considering the influence of an active admixture.The coefficients De is smaller than RD. Since the accelerated tests hardly reflect the secondary hydration effect on durability improvement, the diffusion coefficients RD of 56 days are closer to the natural diffusion coefficients compared to the 28-day test results.Due to the secondary hydration of the active admixture of fly ash and GGBS, the concrete structure tends to be denser over time, and the concrete durability improves. Therefore, the natural diffusion coefficient The pore structure characteristics of concrete are the most important factor affecting the chloride ion transport in concrete. appD(t) is the effectual diffusion coefficient at time t used for life prediction, RD(reft) is the apparent diffusion coefficient at time reft measured by the RCM test, kt is the transfer parameter, ke is the environmental variable, t is the time when the diffusion coefficient becomes stable , and m is the age factor.The effective chloride diffusion coefficients used to predict the service life of reinforced and non-cracked concrete structures exposed to chloride is an indicator of the long-term durability of concrete. The steady diffusion coefficients after long-term decrescence can be calculated by using the following equation based on Equation (1):t0) is plotted together with the exposure test results, and a regression line (dotted line in m in Equation (2) is obtained through regression analysis, where the transfer parameter kt is 1. The disadvantage of this approach is the introduction of an accelerated index for the electric field to describe the long-term migration of chloride ions, resulting in a deviation from the attenuation theory. In this paper, natural diffusion coefficients at t0 are calculated according to exposure regression curves firstly , without considering the external influencing factors such as tide, temperature and so on . In somem can be shown in kt can be obtained by a coefficients analysis between natural diffusion and rapid tests, according to Therefore, the age factor RD and De at the age of 28 days and 56 days are shown in kt is approximately 0.9. After using activated admixtures, the value is related to the age, type, and dosage of the admixture. For fly ash concrete, kt is in the range of 0.25 to 0.31 (28 d) or 0.32 to 0.43 (56 d). For GGBS concrete, kt is in the range of 0.26 to 0.48 (28 d) or 0.30 to 0.35 (56 d).The relationships between RD of the same age greater than the De. In addition, the RCM method is based on electric acceleration, and the selection of the initial current of the applied electric field is affected by the pore structure. Referring to De derived from the long-term natural diffusion coefficient fully reflects the adsorption effect of FA and GGBS on chloride ions. Therefore, the kt of FA concrete or GGBS concrete is much smaller than that of Portland cement, and, according to the comparison of pore structure parameters and the analysis of the chloride ion adsorption effect, the values of the FA concrete and GGBS concrete are very close.The chloride diffusion coefficient is concentration-dependent, while the RCM method uses a 10% chloride concentration solution, which is much higher than the chloride concentration in natural seawater , resulting in a kt might be only adequate for coefficient conversion and durability design for similar environmental conditions in the South China coastal area. For other environmental conditions, such as cold areas, the transfer parameter kt should be reanalyzed by considering the influence of temperature differences and frozen thaw and be amended by the test results in areas exposed to cold.The discussion above is based on the comparison of RCM results with the exposure diffusion coefficients in the South China coastal environment; therefore, the value of (1)m of the chloride diffusion coefficient is calculated based on the 10 years of data from marine exposure tests in South China.The age factor (2)With the extension of age, the pore diameter distribution of the concrete shifts to the direction of small size. Moreover, using FA or GGBS refines the pore diameter of concrete. At 12-years-old, the gel hole of concrete with FA or GGBS is more than 50% of the total pores.(3)Chloride diffusion coefficients measured by the electric field accelerated method (RCM) are significantly greater than the natural diffusion coefficients at the same age, being calculated from the long-term exposure test results in South China. Since short-time accelerated test results do not reflect the effect of secondary hydration caused by active admixtures on concrete pore structure and chloride ion adsorption improvement, there is a difference between the two diffusion coefficients, which are more obvious for concrete using FA and GGBS.(4)kt is related to the engineering environment conditions, test method, test age, and binder system. When the concrete structures are situated in a high-temperature and high-humidity environment, which is similar to South China, the transfer parameter kt can take the values of 0.9 for Portland cement concrete, 0.25~0.31 (28 d), and 0.32~0.43 (56 d) for FA concrete, and 0.26~0.48 (28 d) and 0.30~0.35 (56 d) for GGBS concrete.The durability rapid test results should be converted to an effective chloride diffusion coefficient in the service lifetime prediction of reinforced concrete structures. The transfer parameter


The activities of IgG1-AM (6-52) and IgG4-AM (6-52) were higher than those of IgG1-AM and IgG4-AM. Sufficient concentrations of IgG1-AM (6-52) and IgG4-AM (6-52) were observed in blood 14 days after a single subcutaneous administration. Furthermore, after IgG1-AM (6-52) or IgG4-AM (6-52) administration, tissue transfer to the kidney and small intestine was observed. Treatment with IgG4-AM (6-52) inhibited blood pressure increase in spontaneously hypertensive rats. Fc-AM produced from mammalian cells can be easily prepared and might be an effective novel therapeutic agent.Adrenomedullin (AM) is a hypotensive peptide hormone that exerts anti-inflammatory effects and is involved in wound healing and embryogenesis. However, treatment requires continuous administration as the half-life of native AM is short in blood. To resolve this, we developed four human IgG1 and IgG4 Fc-fusion proteins containing full-length hAM or hAM residues 6-52 using mammalian cells. The Fc-AM produced were amidated and in the active form. All Fc-AMs stimulated cAMP production in HEK-293 cells stably expressing the AM1 receptor. Fc-AM (6-52) induced higher cAMP levels for the receptor than Fc-AM. After the administration of IgG1-AM (6-52) or IgG4-AM (6-52) to rats, tissue transfer to the kidney and small intestine was observed. In addition, treatment with IgG4-AM (6-52) inhibited blood pressure increase in spontaneously hypertensive rats. (4) Conclusions: Fc-AM produced from mammalian cells can be easily prepared and might be an effective novel therapeutic agent.(1) Background: Human adrenomedullin (hAM) is a hypotensive peptide hormone that exerts powerful anti-inflammatory effects. AM also had therapeutic effects in various animal experimental models of disease. However, treatment required continuous administration as the half-life of native AM is short in blood. To resolve this, we developed four human IgG1 and IgG4 Fc-fusion proteins containing full-length hAM or hAM residues 6-52. (2) Methods: We used mammalian cells to produce recombinant Fc-AM derivatives and tested the pharmacokinetics and biological activity of Fc-AM. (3) Results: We developed four Fc-fusion AMs (Fc-AM), which are long-acting AM derivatives in mammalian cells. Fc-AM had a prolonged half-life in blood and retained its ability to bind to the AM Human adrenomedullin (hAM) was originally isolated from a human pheochromocytoma by monitoring cyclic adenosine monophosphate (cAMP) in rat platelets . AM consIn previous studies, we showed that AM was rapidly digested by thrombin in serum . The maiTo improve the pharmacokinetic properties, we developed polyethylene glycol (PEG) -conjugated AM (PEG-AM)  and humaA non-neutralizing anti-AM antibody, adrecizumab, binds to the N-terminal region of endogenous AM in blood and causes a long-lasting increase in its levels . TherefoEscherichia coli [E. coli are not amidated. Therefore, AM produced in E. coli requires refolding and amidation, as well as purification at each step. IgG Fc-fusion proteins produced in mammalian cells have the advantage that refolding or amidation are not required [On the basis of these studies, we previously produced Fc-fusion AM by genetic recombination using hia coli . Howeverhia coli . Furtherrequired . In the Genes encoding recombinant proteins were designed using GENETYX Ver.13 . Genes encoding the IgG1 or IgG4 Fc region and AM or AM (6-52) were connected with a sequence encoding a (GGGGS)3 linker. The amino terminus of AM or AM (6-52) were attached to the Fc region as the carboxy end of AM is essential for biological activity. The structures of AM-IgG4 and AM-IgG1 were previously described in the Supplementary Data . The cloStellar Competent cells  were transformed with the ligation mixtures and single bacterial colonies were obtained after overnight growth on LB- based agar medium with Zeocin .6 cells/mL) were transformed with 1.0 mg of these plasmids and expression was induced using an enhancer kit (NeoFectionEN-1) . After free floating culturing for 5 days, supernatants were collected and the recombinant proteins were purified from the medium by protein A affinity chromatography . The purification was performed according to the manufacturer’s manual: 30 mL of supernatant was filtered through a 0.22 μm filter. The obtained eluate was applied to 1 mL of HiTrap Protein A HP and washed with 10 mL of Binding Buffer  and eluted with elution buffer . The eluate was immediately neutralized with neutralizing buffer .The recombinant plasmids, pFUSEN-IgG1 Fc-AM, pFUSEN-IgG1 Fc-AM (6-52), pFUSE-IgG4 Fc-AM, and pFUSE-IgG4 Fc-AM (6-52) were confirmed by PCR and DNA sequencing. The plasmids used in this study are transient expression vectors. The 1L of Expi293F cells based on human embryonic kidney (HEK293) cells  as previously published .1 receptor), which were prepared as previously described [2 incubator maintained at 37 °C. After culturing for 3 days, cells at 90% confluency were subjected to experiments in which intracellular cAMP accumulation was stimulated using Fc-AMs. The culture media were replaced with Hanks’ Balanced Salt Solution containing 0.2% bovine serum albumin, 0.035% NaHCO3, and 0.5 mM isobutylmethylxanthine, and then cells were incubated with Fc-AMs for 15 min at 37 °C. The reactions were terminated by the addition of 0.1 M HCl. Finally, cAMP levels in supernatants were measured using an enzyme immunoassay kit  followed by the protocol of Item No. 581002.To measure cAMP accumulation induced by recombinant AM-Fc-fusion proteins in vitro, we used HEK-293 cells stably expressing the AM type I receptor (AMescribed . HEK-293n = 2/group). Peripheral blood samples were drawn via the tail vein and placed into Kantan-tubes , containing heparin sodium, and then centrifuged at 2000× g for 3 min at room temperature. The plasma samples were then placed into tubes containing 21 μg aprotinin and 0.3 mg Na2-EDTA. Blood was collected before injection (day 0), and then 1, 2, 4, 6, 8, 10, 12, and 14 days after administration. Tissues were collected 7 and 14 days after administration, carefully resected after decapitation, and stored at −80 °C until use. The PK parameters  were calculated with WinNonlin at the BoZo Research Center Inc. . For the control measurement using AM, 50 nmol/kg native AM was administered subcutaneously (n = 3) and blood was collected before injection (0 min), and then 15, 30, 60 and 120 min after administration.All male 7-week-old Wistar rats were purchased from Charles River Laboratories Japan  and housed under a 12 h light/12 h dark cycle and specific pathogen-free conditions with a normal diet. We used 8 rats in this study. The study was performed in accordance with the Animal Welfare Act and with approval from the University of Miyazaki Institutional Animal Care and Use Committee (2019-533-2). To determine plasma IgG1-AM (6-52) and IgG4-AM (6-52) concentrations, 30 nmol/kg Fc-AMs were administered subcutaneously to rats  [Tissue samples obtained after the administration of Fc-AMs were homogenized in PBS containing Protease Inhibitor Cocktail  using a Polytron mixer and immediately centrifuged at 20,000× AM (mAM)  uses an AM (mAM)  uses an n = 5). The high-salt diet was given to rats until the final day of the experiment. Blood pressures of rats were measured using the tail-cuff method , at the indicated time points  according to the manufacturer’s instructions. The study was performed in accordance with the Animal Welfare Act and with the approval of the University of Miyazaki Institutional Animal Care and Use Committee (2019-527-2).Male 8-week-old spontaneously hypertensive rats (SHRs) were purchased from Charles River Laboratories  and housed under a 12 h light/12 h dark cycle and specific pathogen-free conditions. IgG4 AM (6-52) (50 nmol/kg) or saline (control) was injected subcutaneously on the same day as the start of the administration of a high-salt diet (8% NaCl) . Multiple comparisons were evaluated by one-way  and two-way  ANOVA followed by Tukey’s multiple comparison test. Figure 4c,d were analyzed by the Mann–Whitney Each recombinant Fc-AM was purified from 1 L of supernatant as described in the Methods. The amount of tAM recovered per liter was 10.8 mg for IgG1-AM, 116.4 mg for IgG1-AM (6-52), 24.4 mg for IgG4-AM, and 12.0 mg for IgG4-AM (6-52), respectively, and 10.2, 108.1, 28.1, and 13.2 mg mAM, respectively, was recovered per liter. As the concentrations of tAM and mAM were similar, it was considered that all Fc-AMs were amidated. The molecular weights of recombinant proteins were estimated at approximately 66,500 Da by SDS-PAGE, corresponding to the dimeric forms of Fc-AM. These sequences were identical to the known amino acid sequences of human IgG1 and IgG4 as previously reported [1 receptor. As shown in −8 M were 3, 3, 12 and 29%, respectively, taking the maximum activity of native AM as 100%. Similarly, at 10−7 M, the relative activities were 25, 28, 57 and 77%, respectively , IgG4-AM, and IgG4-AM (6-52) to stimulate the intracellular accumulation of cAMP in HEK-293 cells stably expressing the AMectively . Derivatectively . IgG1 anWe compared IgG1-AM (6-52) and IgG4-AM (6-52) concentrations in the peripheral blood of rats after subcutaneous injection. After the administration of IgG1-AM (6-52), mAM concentrations in the blood after 0, 1, 2, 4, 6, 8, 10, 12, and 14 days were 31.2, 5757.4, 2865.0, 1145.6, 530.1, 281.1, 141.0, 81.5, and 34.0 pM, respectively a. SimilaWe further clarified the blood mAM and tAM concentrations after subcutaneous administration of AM b. The T1We compared IgG1-AM (6-52) and IgG4-AM (6-52) concentrations in the tissues of rats after subcutaneous injection. n = 5) (n = 5) (DBPs at the same timepoints after treatment with IgG4-AM (6-52) were 12.8 ± 7.1, 26.5 ± 7.3, 29.8 ± 7.0, and 37.7 ± 7.3 mmHg, respectively b. DBPs in = 5) c. The tA (n = 5) d.E. coli [E. coli requires refolding and amidation, whereas Fc-AMs produced in mammalian cells do not require refolding or amidation. Indeed, Fc-AMs could be measured by mAM assay, which recognizes the amidated form, indicating that Fc-AM produced in mammalian cells were amidated.We developed Fc-AMs, which are long-acting AM derivatives. We previously produced Fc-fusion AM proteins by genetic recombination in E. coli . HoweverFc-AMs, generated in a mammalian cell production system can therefore easily be produced in large amounts with few purification steps. This system reduces their manufacturing costs, so it may be possible to provide them to many patients. The recombinant fusion of IgG Fc fragments and peptides, enzymes or cytokines has been recognized as a new therapeutic strategy . Indeed,E. coli in a previous study [The biological effects of AM are mediated by the calcitonin receptor-like receptor (CLR), which can function as an AM type 1 or 2 receptor when co-expressed with receptor activity-modifying protein-2 (RAMP2) and -3 (RAMP3) . The Fc-us study . InteresFrom the results of cAMP production , a pharmAs expected, Fc-AMs were less active in the cAMP assay compared with AM. We produced various analogs of PEG-AM whose N-terminus was attached to various sizes of PEG ,24. We fWhen comparing the activities of AM and Fc-AM, the maximal activities at high concentrations were equivalent. Therefore, we think that a higher concentration of Fc-AM might exert the same effect as AM. As AM has a high affinity for the AM receptor, it causes rapid hypertensive effects when it is administered as a bolus. However, Fc-AM is expected to have no rapid antihypertensive effects and therefore be a safe drug, as in the case of PEG-AM .Sufficient concentrations of IgG1-AM 6-52) and IgG4-AM (6-52) were observed in blood 14 days after a single subcutaneous administration. The pharmacokinetics of IgG1-AM (6-52) and IgG4-AM (6-52) were similar a. We hav-52 and I1 receptor is expressed by a variety of tissues, including the kidneys and small intestines [In the pharmacokinetic study, the plasma concentrations of Fc-AMs were high, even after 2 weeks; therefore, we investigated their transferability to tissues. As shown in testines . Howevertestines . AlthougWe further investigated the pharmacokinetics of AM after the subcutaneous injection of 50 nmol/kg of AM. The peak mAM concentration was 12.5 pM for AM. This value is much lower compared to those of IgG1 S-AM (6-52) and IgG4 S-AM (6-52). In addition, the plasma half-life of IgG1 S-AM (6-52) and IgG4 S-AM (6-52) was much longer and the Tmax was much later than that of AM a,b. ThusInterestingly, in In SHR, IgG4-AM 6-52) suppressed increased blood pressure, especially the SBP. However, there were no significant differences in DBP measurements between the IgG4-AM (6-52) and control groups. Thus, IgG4-AM (6-52) can partially inhibit the increase in SBP increase in SHRs. These effects may be related to the functions of native AM, including vasodilation and suppressive effects on aldosterone and vasopressin secretion . In addi suppress1, and AM2 receptors) [1 receptor but not the CGRP or AM2 receptors. We think that Fc-AM may activate the CGRP and AM2 receptors. The effect of Fc-AM on CGRP or AM2 receptors should be examined in the future. Another limitation was that the sample size was small in the PK experiments, although the data are clear. We could not increase the sample size, as the amount of AM-Fc-fusion protein was limited. Fc-fusion proteins are easily produced in large amounts by industrial methods; however, the preparation of Fc-fusion proteins is difficult and limited in the laboratory. Therefore, the PK experiments of Fc-AM derivatives in this study were preliminary.Although Fc-AM is a promising therapeutic drug for various diseases including cardiovascular and inflammatory diseases, there were some limitations in this study. AM can activate three distinct receptors  . HoweverFc-AM produced from mammalian cells was easily produced and might be a candidate novel therapeutic agent.


Introduction: Distraction osteogenesis (DO) has become an important technology for the correction of various congenital and acquired skeletal ridge deformities. It is widely used in oral and maxillofacial surgery, orthopedics, and other disciplines. From 1980 to 2021, the cutting-edge research of DO has been continuously promoted, and the interaction between disciplines has also been deepening. However, the analysis on the global trend and status of DO is relatively rare. Therefore, the aim of our study was to summarize the global trends and current status of DO through bibliometrics.Materials and methods: Web of Science (WOS) core collection database and Medline were used to search DO-related literatures published during 1980–2021. The collected data are imported into Microsoft Excel, Microsoft Word, VOSviewer software for analysis and drawing figure/table.Results: A total of 7,721 publications were included in this study. The United States is the main contributing country to DO . Harvard University was the main contributing institution to DO. Journal of Craniofacial Surgery is the main contributing journal of DO related articles. Buchman, SR is the main contributing author to DO related articles. DO related publications can be summarized into 7 clusters: 1) “mechanism study”, 2) “limb bone distraction study”, 3) “alveolar bone distraction study”, 4) “temporomandibular joint ankylosis study”, 5) “maxillofacial surgery study”, 6) “skull distraction study” and 7) “mandible distraction study”. Mandible distraction study has been a hot topic in recent years. In addition, the “management”, “osteogenesis” and “reconstruction” of DO have been the research hotspots from 1980 to 2021.Conclusion: From 1980 to 2021, the total number of DO articles has increased rapidly and maintained a steady trend. The United States is the predominant country in the field. Surgery, dental, and oral surgery and orthopaedics are hot fields of DO research. The study of mandible distraction has been paid more and more attention and will become a hotspot in the future. Our study is beneficial for scientists to specify the research hotspot and development direction of DO. Distraction osteogenesis (DO) was first used by Codivilla (1905) to lengthen the femur axially . The priFrom 1980 to 2021, more and more publications have reported the clinical application of DO in orthopaedics, oral and maxillofacial surgery and neurosurgery around the world . HoweverAll publications were sourced from Web of Science (WOS) Core Collection database  and Medline .All publications were searched in WOS on October 2022. The search terms were TS = (“distraction osteogenesis” OR “bone lengthening”) and document types: (Article OR Review). We selected publications with publication dates ranging from 1 January 1980 to 31 December 2021.The full records  were extracted from the retrieved literature by two independent authors (QL and YZ). The disagreements were resolved by discussions to prevent potential bias. The obtained publication information was exported in TXT format, and then imported into Microsoft Excel 2019 and VOSviewer (v.1.6.18) for analysis.Microsoft Excel 2019 was used to analyze literature data and draw graphs. Bibliometric indicators, including total publications, sum of times cited, average citations per item, H-index and self-citation times, were included in this study. Total publications are widely used to measure the contribution to a field. Sum of times cited and average citations per item reflects the level of attention . The H-iVOSviewer is one of the much scientific knowledge graph software, which can demonstrate the influence, cooperation and evolution of research field through bibliographic coupling analysis, co-authorship analysis, co-citation analysis and co-occurrence analysis. Bibliographic coupling analysis is a way of showing similar relationships between items by the number of references co-cited by items. Co-authorship analysis is a way to assess the intensity of collaboration between items by counting the number of co-authored publications. Co-citation analysis is a way of presenting the relevance of items based on how many times an item is cited together. Co-occurrence network visualization is created by analyzing the number of publications in which keywords appear together in the title or abstract. The aim is to identify hot research directions and topics that are essential to tracking scientific developments . In someOur study identified 7721 DO-related publications, including article 6685) and review (1036), published between 1980 and 2021. The annual publications related to DO have maintained a steady trend after rapid growth. During 1980 to 2021, the number of annual publications on DO increased fifteenfold, from 22 in 1980 to 350 in 2021 . It showAs shown in this study, from 1980 to 2021, the number of DO-related publications peaked in 2012 and then leveled off. We can predict that there will be more than 250 DO-related publications per year in the next few years. In addition, DO-related publications in the United States and China will continue to increase. From the fan chart, we can see that DO related researchers come from all over the world, especially in the United States, China, and Japan.From 1980 to 2021, about 5742 institutions around the world have studied DO. The top 10 main contributing authors to the analysis of the quality of the author’s publication are shown in Among the top 10 journals, Journal of Craniofacial Surgery rank first, which is the journal with the largest contribution to DO-related publications. In addition, Plastic and Reconstructive Surgery ranked third, ranking first in the sum of citations and H-index. The higher average citations per item indicate that a higher level of attention for its publication . HoweverDO-related publications are divided into 118 different research fields on WOS. We analyzed the top 10 research areas of DO-related publications. Surgery, dentistry oral surgery medicine, orthopaedics and radiology nuclear medicine medical imaging have been widely and deeply studied for their attention to the influencing factors, surgical methods, diagnosis and treatment of DO. Meanwhile, anatomy morphology had also been intensively investigated within the development of surgery. In the field of pediatrics, the emphasis was placed on DO bone reconstruction surgery for the treatment of skeletal dysplasia in children. DO can correct skeletal deformities such as limb and head deformities in children, so as to promote the recovery of skeletal function and morphology in patients. As shown in The overlay visualization can give items different colors depending on the average time of keyword appearance. The bluer the color, the earlier the keyword appears, the more yellow the color, the later the keyword appears . By compOur study employs bibliometric research methods to provide a comprehensive and objective picture of global trends and the current state of DO-related publications from 1980 to 2021. However, the study also has some limitations. First, the study measures the quality of publications primarily by comparing the number of citations and the average times of citations for per item. However, highly cited publications do not equate to high scientific quality. The number of citations can be influenced by some factors, such as the hot issue of research topic, fame degree of researcher, or even over-cited artificially. Secondly, there are differences in publications from different databases, and we used only the WOS core collection database and Medline for literature data search, which may have an impact on the accuracy of the study results. Finally, the influence of publication time on the total number of citations was not considered. The fact that the most recent high-quality articles are rarely cited may be overlooked. Therefore, it is also important to pay attention to the most recent publications.Our study identifies DO-related publications from 1980 to 2021 and introduces their global trends and status. In the past 42 years, the number of total publications of DO research has maintained a steady trend after rapid growth. The United States ranks first in terms of total publications, sum of times cited, the H-Index and self-citation times. Harvard University, University of California and Egyptian Knowledge Bank are the top 3 contributing institutions to DO. Journal of Craniofacial Surgery, Journal of Oral and Maxillofacial Surgery and Plastic and Reconstructive Surgery are the top 3 contributing journals to DO. Buchman SR, Mccarthy JG and Cheung LK are the top 3 contributing authors to DO. Surgery, orthopaedics and anatomy morphology are the top 3 fields of DO research. In addition, the DO research on the mandible will become the focus of scholars in the future.


In order to study the load-bearing failure characteristics of a RPCCP under internal load, a field prototype test was designed, and a finite element model was established. An internal load was applied up to 2.0 MPa step by step and the force variation law of each part was obtained. During the production of the RPCCP, by wrapping prestressed steel bars around the concrete core with a cylinder, the core was subjected to an initial precompression stress. In the loading process, the protective cover cracked first, from where the concrete core gradually changed from the initial compression state to a tension state, finally cracking from the inner and outer diameter. The stresses of the cylinder and steel bars increased steadily with the internal load and did not yield. The finite element calculation results were in good agreement with the test results, and the influence characteristics of the tension control stress of the steel bar and the concrete strength on the failure of the RPCCP under internal load were discussed. The results showed that the internal load of the protective cover was independent of the tension control stress, but decreases with a decrease in concrete strength, while the load corresponding to the concrete core entering plasticity is related to the tension control stress and the concrete strength, and the relationships were basically linear. A rebar-prestressed cylinder concrete pipe (RPCCP), which follows the Chinese standards SL702-2015  and AWWARPCCP has only been in use for less than 7 years and previous studies mainly focus on PCCP. In the last century, researchers such as Ross , ZarghamCompared with PCCP, RPCCP has the following two characteristics ,22: (1) fcu,k is the standard value of the compressive strength of concrete, and ft′ is the design value for the tensile strength of concrete.The geometrical sizes and material mechanical parameters of the tested RPCCP are shown in During the test, the pipe was filled with water, and the internal water pressure was evenly applied to the inner wall of the concrete core, which mainly led to longitudinal cracks along the pipe length, while circumferential cracks did not easily appear. Therefore, this study mainly arranged the testing points in the circumferential direction of the pipe body.First, in the production process of the test RPCCP, three circumferential resistance strain gauges, R-1, R-2, and R-3, as shown in Second, seven circumferential resistance strain gauges were arranged on the outer wall of the cylinder in advance during the production of the RPCCP. Among them, two were arranged 100 mm near the ends of the spigot and the bell, respectively, and their numbers were C-1, C-2, C-3, and C-4. Then, three sections were set at 1500 mm and 3000 mm close to the pipe ends, and a resistance strain gauge was arranged on each section, namely, C-5, C-6, and C-7. The specific arrangement numbers of the measuring points are shown in Third, in order to obtain the strain of the prestressed steel bars in the bearing-load process accurately, after the concrete protective cover was poured, three measuring points were selected to cut the concrete cover outside, and the resistance strain gauges were arranged on the prestressed steel bars, numbered as S-1, S-2, and S-3, respectively. The specific arrangement numbers of the measuring points are shown in Finally, a total of five sections were set at both ends of the spigot and bell, as well as 1500 mm near the ends and 3000 mm in the middle of the pipe. Seven circumferential strain gauges, numbered P-1, P-2,…, P-7, as shown in The test was conducted at the production site of Ningxia Qinglong Pipe Industry Group Co., Ltd in Wuzhong, Ningxia Hui Autonomous Region, China. Since the ends of the RPCCP and PCCP have the same type of spigot and bell, the same equipment can be used when pressurized. Regarding the load, only the internal load was considered, and a horizontal pressure device was adopted, as shown in (1)Material nonlinearities were considered, and geometric nonlinearities were not.(2)Suppose the deformations were small.(3)The effects of shrinkage and creep of the concrete were not considered.The RPCCP structure is similar to that of a PCCP. According to the mechanical characteristics of RPCCP and the related references on PCCP finite element models ,25, on t(1)It was assumed that there was complete contact between the cylinder and the inner and outer concrete core, and the deformation coordination was satisfied without considering the slip and separation between layers.(2)Due to the effect of prestress, the outer concrete core had a good bond with the prestressed steel bars, and the slip and detachment between them were not considered. In this regard, the constraint equation was used in the finite element model to coordinate the degrees of freedom of the steel bar element and the concrete element to simulate the bond.(3)There was no treatment between the prestressed steel bars and the concrete protective cover; that is, it was assumed that when the protective cover cracked or denudated, it would not have a direct impact on the steel bars, and the bond between them was transmitted through the outer concrete core indirectly.(4)“Tie” was used to simulate the connection between the concrete protective cover and the outer concrete core.The RPCCP 3D finite element model included all the actual components of the structure. The cylinder, concrete core, prestressed steel bar, and concrete cover were modeled separately. The type of RPCCP was embedded, in which the cylinder divided the concrete core into an inner concrete core and outer concrete core. Therefore, the model consisted of an inner concrete core, a cylinder, an outer concrete core, prestressed steel bars, and a concrete protective cover from inside to outside—a structure with a total of five layers. It was very important for the reliability and correctness of the model to consider the connection between each layer reasonably. Under the action of the internal load, the failure of each layer was mainly controlled by the circumferential tensile stress, and all of them were pressurized in the radial direction. This paper dealt with the relationship between each layer according to the following measures:The concrete was simulated by solid element C3D8R, which had eight nodes, and each node had 3 degrees of freedom. The steel cylinder belonged to a thin-walled structure and was simulated by the thin shell element S4R. The prestressed steel bar was simulated using a beam element. The final finite element model is shown in (1)Constitutive model of concreteThe concrete damaged plasticity model was adopted for the constitutive model of concrete . This moσc is the compressive stress of concrete, dc is the compressive damage coefficient, the value range is 0~1, dc = 0 indicates that the concrete has no compressive damage, dc = 1 indicates complete compression failure, Ec is the elastic modulus of the concrete, εc is the compressive strain of the concrete, and The stress–strain relationship of the concrete after compression damage is shown in Equation (2), where σt is the tensile stress of the concrete, dt is the tensile damage coefficient, the value range is 0~1, dt = 0 indicates that the concrete has no tensile damage, dt = 1 indicates complete tension failure, εt is the tensile strain of the concrete, and The stress–strain relationship of the concrete after tension damage is shown in Equation (3), where (2)Constitutive model of prestressed steel barfsu is the standard value of the tensile strength, fsg is the control stress for prestressing, and the yield stress of the prestressed steel bar is 85% of its tensile strength, fsy = 0.85 fsu.The constitutive model of the prestressed steel bar adopted the following stress–strain relationship , as show(3)Constitutive model of cylinderfyy = 235 MPa, and the ideal elastic-plastic stress–strain relationship was adopted, as shown in According to the data provided by the manufacturer, the design value of the tensile yield strength of the cylinder was t is the amount of cooling that needs to be applied, fsg is the control stress for prestressing, Es is the elastic modulus of the prestressed steel bar, and αt is the linear expansion coefficient, which is taken as 0.0001 in this paper.In finite element models, there are usually four methods to simulate the prestress of steel bars: equivalent load method, initial strain method, initial stress method, and equivalent cooling method . The equIn order to make the results of the finite element model more reliable and strike a balance between accuracy and computational efficiency, an appropriate mesh density should be selected. Take the concrete model in the protective cover and the outer concrete core as an example, the circular cross section was divided into different number of meshes—50, 75, and 100—and the corresponding concrete model in the inner concrete core was divided into 100, 150, and 200 in the circular cross section. The models were named Mesh Ⅰ, Mesh Ⅱ, and Mesh Ⅲ from left to right, as shown in In the three models, a node of the concrete unit of the protective cover in the middle of the pipe body was taken as an example, and the variation curves of displacements with the internal load are shown in In the initial stage of loading, the pressure was small, the force of the whole pipe was uniform, and no visible cracks appeared in the concrete cover. When the internal pressure was loaded to 1.5 MPa, the first visible small crack, with a length of 140 mm, appeared in the protective cover near the end of the spigot, indicating that the concrete cover began to crack. The internal load 1.5 MPa was the initial cracking load.As the load increased, the second and third cracks appeared at 1.6 MPa, and the first crack expanded, with its width increasing. When the internal load reached 1.75 MPa, several cracks appeared in the pipe body, which was finally pressurized to 2.0 MPa due to the capacity of the pressurizing device and safety considerations. The bearing capacity of the RPCCP under the internal load was significantly higher than 2.0 MPa. The distribution and expansion diagram of the cracks in the protective cover of half of the pipe body is shown in (1)Wrapping processThe results of the field wrapping test are shown in (2)Strain variation law of concrete coverThe strain curves of the concrete cover under internal load are shown in The visible crack of the concrete cover was taken as the failure criteria in the test, and entering plasticity was taken as the failure criteria in the finite element model. According to the tensile constitutive model of concrete in According to the theory of uniform pressure inside the ring or cylinder in elasticity, the tensile stress on the inner surface should be the largest, and the inner surface of the concrete core should be the first to crack under tension. However, in the process of bearing internal load, the concrete cover cracked before the concrete core. During manufacturing, the concrete core was wrapped by the prestressed steel bars so that it was subjected to an initial precompression stress, and then the outermost concrete cover was poured but which was not subject to any force. Therefore, when the RPCCP began to bear an internal load, the concrete protective cover was tensioned directly, and the initial compressive stress of the concrete core would offset some of the internal load.(3)Strain variation law of cylinderAfter the cylinder was manufactured, seven strain gauges were pasted on the surface. However, because it was buried in the concrete core, which should be vibrated during pouring, some strain gauges failed. In addition, the cylinder and the concrete core rotated together during wrapping, and the strains were not measured until the internal load was applied. Finally, effective strain data were collected at measurement points C-1, C-5, and C-7. Moreover, the cylinder was initially subjected to the precompression stress caused by the prestressed steel bars, so the measured strains in the test were not the true strains. Meanwhile, in order to facilitate comparison, the results of a node in a unit of the cylinder model after wrapping were zeroed and the internal load–strain relationship curves of the test and the finite element model are shown in The prestress loss would occur inevitably after wrapping prestressed steel bars. The calculation of loss referred to the specification , which m(4)Strain variation law of steel barsA node in a unit of the steel bar model was selected, and the calculation results were also zeroed. The internal load–strain curves of the test and finite element model are shown in Similarly, the strains measured during the test were not the true strains of the steel bars, because they had an initial effective tensile stress of 337 MPa and the corresponding initial tensile strain was 1664 με. Under the internal load of 2.0 MPa, the maximum tensile strain measured was 570 με, and the total tensile strain after superposition was 2214 με, which was far less than the yield strain of 3137 με corresponding to the yield strength of 650 MPa. There was no yield failure in the steel bars and the whole pipe could withstand a greater internal load.It can be seen from (1)Effect of tension control stressfsu, where fsu is the standard value of the tensile strength of the bars. In order to study the influence of tension control stress on the bearing performance of the RPCCP, five different tension control stresses  were added, and the internal load was applied until the concrete core entered plasticity. The calculation results are shown in It can be seen from (2)Effect of concrete strengthThe concrete used in the prototype test and model has a strength grade of C50. The strength, including compressive and tensile properties, certainly has an impact on the bearing capacity of the RPCCP. On the basis of the strength of the C50 concrete and keeping other conditions unchanged, the compressive and tensile properties were multiplied by four coefficients  to carry out the model calculation, respectively. The results are shown in In this section, through the calculation of finite element models, the influence laws of the tension control stress of the steel bar and concrete strength on the protective cover and concrete core are obtained; the influence of these two factors on the yield of cylinder and steel bars were not analyzed. When they yield, the corresponding internal loads are very high, and by then the concrete has long failed and is out of service. In the actual test, the two layers were not loaded to yield, and the strength of the concrete has little influence on the internal loads corresponding to the yield of the cylinder and steel bars. The smaller the initial tension control stress is, the larger the difference between its value and the yield strength is. Because the yield strength of the steel bar is fixed, a greater internal load is required for the steel bar to yield.Pti is the calculated anti-cracking internal load of the test; As is the area of circumferential prestressed steel bars in unit length; fsr is the final effective prestress of the circumferential steel bars; An is the converted area of the concrete core, cylinder, steel bars, and mortar protective cover in unit length; α is the controlling cracking coefficient of the mortar, which is 1.06 for an embedded PCCP and 0.65 for a lined PCCP; ftk is the standard value of the tensile strength of the concrete; b is the calculated axial length of the pipe, with the value being 1000 mm; and r0 is the calculated radius of the pipe wall section.It is stipulated in the specification  that theAfter calculation and summary, the calculated anti-cracking internal load of the test, the cracking loads of the protective cover, the cracking loads of the concrete core, and the yield loads of the cylinder and the prestressed steel bars are shown in The designed working pressure of the test RPCCP is 1.0 MPa, while the calculated anti-cracking internal load of test is 1.42 MPa, which is larger than the design working pressure. The cracking loads of the concrete cover obtained by the test and the finite element model are also 0.4~0.5 MPa larger than the design working pressure, indicating that each layer of the RPCCP under the design working pressure is in the elastic stage. The larger the difference between the test and finite element results and the design working pressure, the less likely the protective cover is to crack and the larger the safety stock is in the actual operation.The results of the finite element model are smaller than those of the actual test, because entering plasticity is taken as the failure criteria in the finite element model, which does not mean that the concrete begins to crack. Cracking is usually generated after plastic accumulation to a certain process. The cracking load of the concrete core in the test RPCCP is 0.4 MPa higher than that of the protective cover. In the finite element model of the RPCCP, the internal loads corresponding to the yield of the cylinder and the steel bar are very close, indicating that the material selection and size design of the RPCCP are reasonable.(1)In the process of RPCCP production, strain gauges are pre-arranged to obtain the cracking loads of the protective cover and concrete core and the force variation characteristics of the cylinder and prestressed steel bars. Finally, the failure law of the RPCCP under internal load is revealed. During the loading process, the concrete protective cover cracks first, form where the concrete core gradually changes from the initial compression state to the tension state, and finally cracks from the inner and outer diameter. The cracking load is greater than that of the protective cover.(2)The finite element model of RPCCP under internal load is established by selecting the appropriate material constitutive relationships and a reasonable mesh density and simulating the prestress by the equivalent cooling method. The whole process of RPCCP from the application of prestress to the final failure was analyzed. The finite element results were compared with the test results to verify the rationality of the model, and the influence characteristics of the tension control stress of the steel bars and the concrete strength on the failure of the RPCCP under internal load were discussed.(3)The calculated anti-cracking internal load of the RPCCP according to the specifications is consistent with the results of the test and finite element model, which are all higher than the design working pressure, indicating that each layer of the RPCCP under the design working pressure is in the elastic stage. The larger the difference between the test and finite element results and the design working pressure, the less likely the protective cover is to crack and the larger the safety stock is in the actual operation.In this paper, the initial cracking load of the RPCCP with an inner diameter of 1400 mm under internal load was obtained by the field test and finite element simulation. Several conclusions can be obtained as follows:In this study, the failure law of the RPCCP under internal load is revealed through a field prototype test and finite element model. However, the RPCCP in actual operation must bear an external load as well as internal load, so it is necessary to carry out research on the mechanical performance of the RPCCP under external load. In addition, this study made some assumptions and simplifications when establishing the finite element model of the RPCCP. The reliability of this model in calculating the bearing performance of the RPCCP under external load needs to be further studied.


Access, Watch and Reserve) classification based on the impact of different antibiotics on antimicrobial resistance. For ambulatory patients, WHO recommends Access antibiotics to represent >60% of all prescriptions, and an Access to Watch (AW) index of ≥1.5. The use of Access and Watch antibiotics has not been evaluated in ambulatory patients in Latin America. The aim of this study was to describe antibiotic use among members of two health plans within a private health insurance in Bolivia.The World Health Organization (WHO) has established the AWaRe  per 1,000 member-days, and compared between two plans, one a Health Maintenance Organization (HMO)  and the other a Preferred Provider Organization (PPO) . In the HMO plan, members have a general practitioner (GP) as the primary point of care, whereas in the PPO plan, members can access specialists directly without a referral from the GP. Differences between groups were calculated using Byar test with 95% confidence intervals (CI).Access and 45% were Watch (AW index: 1.24). By patient group, 52% of pediatric and 58% of adult prescriptions were Access; diff. –6%; p< 0.001 . By health plan, 62% of HMO and 53% of PPO antibiotics were Access; diff. 9%; p< 0.001 .Antibiotic use in DDD/1,000 member-days for the study period was 8.31 in ambulatory, 10.7 in the Emergency Department, and 0.72 in the hospital. Ambulatory antibiotic use in the HMO plan was lower than the PPO plan  (Table). Of all ambulatory antibiotics, 55% were Access antibiotics was lower than the recommended by WHO; however, we found less broad-spectrum antibiotic use in the HMO plan compared to the PPO plan. These findings highlight the urgent need for antibiotic stewardship in the ambulatory setting, and the important role of GPs in appropriate antibiotic prescribing.Ambulatory antibiotic use in this cohort was high. Overall use of Sara E. Cosgrove, MD, Basilea: Member of Infection Adjudication Committee.


It was hypothesized that unmasked hexanal and hexanal masked by eugenol, a molecule with a smell resembling clove, would increase the level of trust in human–robot interaction, compared to eugenol alone or a control condition consisting of only the neutral smelling solvent propylene glycol. Contrasting previous findings in human interaction, no significant effect of unmasked or eugenol-masked hexanal on trust in robots was observed. These findings indicate that the conscious or nonconscious impact of smell on trust might not generalise to interactions with social robots. One explanation could be category- and context-dependency of smell leading to a mismatch between the natural smell of hexanal, a smell also occurring in human sweat, and the mechanical physical or mental representation of the robot.The level of interpersonal trust among people is partially determined through the sense of smell. Hexanal, a molecule which smell resembles freshly cut grass, can increase trust in people. Here, we ask the question if smell can be leveraged to facilitate human–robot interaction and test whether hexanal also increases the level of trust during collaboration with a social robot. In a preregistered double-blind, placebo-controlled study, we tested if trial-by-trial and general trust during perceptual decision making in collaboration with a social robot is affected by hexanal across two samples ( Trust is central to effective interactions and collaborations with robots , 2. The and is an established social communication channel in humans, namely smell.Trust during human–robot interaction can be defined as “the attitude that an agent will help achieve an individual’s goals in a situation characterized by uncertainty and vulnerability” , p. 54. social chemosignaling, has gained interest in recent years. The impact of our sense of smell is often being underestimated, although over the last years research has uncovered that humans have a remarkably acute and perceptive sense of smell 34], and At the start of the experiment, the participant was escorted to the lab, where the experiment was explained. After receiving this information, the participant provided written consent. At the start of the experiment, Vector was introduced as a modern and advanced robot and the participant was instructed to pet Vector and put Vector on its side to elicit an emotional reaction by Vector. The participant was then told that Vector was programmed to cooperate with them on the task. The interaction with Vector lasted a maximum of two minutes per participant. Vector was then placed on its docking station, for which the participant was told that it was connected to the computer to Vector to collaborate. Vector was positioned, next to the monitor within eyesight of the participant during the experiment. As part of the cover story, it was explained that Vector was connected to the computer and participated in the task by interacting with the computer directly. In reality, there was no interaction between the computer and robot, and the task was set up in such a way that Vector’s answers were pre-determined by the experimental task.2 (air circulation: 5 cycles/h), similar to . To test if eugenol did not affect the trust-relationship between humans and robots, the second contrast compared Hexanal and Hexanal masked by Eugenol with Eugenol . The third contrast compared Hexanal with Hexanal masked by Eugenol , to test the impact of Hexanal masking. Following , we starFor sample 2, the following model, with smell condition as a fixed effect, by-subject, by-trial, and by-round random intercepts successfully converged:To test an effect of smell on general levels of trust, a linear model was fitted with smell condition (contrast coded) as fixed effect.We also report Bayesian posterior distributions as an additional source of information about the evidence for the alternative hypothesis versus the null-hypothesis given the data.F = 0.55, p = 0.645, ηp2 = 0.01; sample 2 F  = 2.07, p = 0.107, ηp2 = 0.05. There was no effect of odour condition on arousal, sample 1 F  = 0.42, p = 0.739, ηp2 = 0.01; sample 2 F  = 0.72, p = 0.545, ηp2 = 0.02.To confirm that conditions did not differ in the amount of induced arousal or induced changes in mood, the scores on the MAS were compared using two repeated measures ANOVAs. There was no effect of the different odour conditions on mood, sample 1 r(124) = 0.14, , p = 0,14; sample 2: r(139) = 0.26, , p = 0.034,), confirming the validity of the operationalization of trust  and 1.9 (sample 2) out of 15 trials. Decisions to trust the robot were consistent through the rounds of the collaborative perceptual decision-making task , or Eugenol alone  , but not for sample 1 , trial-by-trial trust decisions were higher for Hexanal compared with the Hexanal masked by Eugenol. Bayesian analysis revealed similar results with moderate support for the null hypothesis (See online supplementary files on https://osf.io/ys8na/).Hexanal and Hexanal masked by Eugenol did not increase trust decisions on a trial-by-trial basis compared with Eugenol and the no smell condition , or Eugenol alone, . Directly contrasting Hexanal with Hexanal masked by Eugenol showed that general trust ratings were higher for Hexanal compared with the Hexanal masked by Eugenol for sample 1 , but not for sample 2 . Bayesian analysis revealed similar results with moderate support for the null hypothesis .Hexanal did not impact general levels of trust ascribed to the robot, as measured using the Reliance Intention Scale Fig. D. HexanaTogether, these results contrast with our predictions: Neither Hexanal nor Hexanal masked by Eugenol increases trial-by-trial trust decisions during collaborative perceptual decision-making or general levels of trust.n = 43 for sample 1, and n = 40 for sample 2.Finally, to check whether the conditions differed in pleasantness, familiarity and intensity, the odour ratings for each condition were compared by means of three repeated measures ANOVAs, with condition as factor and the ratings as dependent measure. Due to an error in the programming of the experiment, these values were not recorded for the first few participants. This resulted in different sample sizes for this analysis: F = 1.0, p = 0.397, ηp2 = 0.02; sample 2: F = 11.2, p < 0.001, ηp2 = 0.22. In sample 2, hexanal was rated as more pleasant than hexanal masked by eugenol condition , p = 0.019, and hexanal was rated as more pleasant than eugenol , p = 0.001. Propylene glycol was also rated as more pleasant than eugenol , p < 0.001. Critically, there was no difference between the condition pairs pertinent for the hypotheses tested in the study, i.e., hexanal and propylene glycol, and hexanal masked by eugenol and eugenol alone.There was a difference in the ratings for pleasantness in sample 2, Sample 1: F = 32.9, p < 0.001, ηp2 = 0.46; sample 2:  = 38.9, p < 0.001, ηp2 = 0.50. Bonferroni corrected pairwise comparisons suggested that the eugenol conditions were significantly more intense than the other two conditions, p’s < 0.001. Critically, the propylene glycol condition did not differ in intensity from the hexanal condition , p > 0.05, nor did the eugenol and hexanal masked by eugenol condition differ from each other , p > 0.05. While there was a difference in the ratings of familiarity in sample 1, F = 2.98, p = 0.034, ηp2 = 0.07, there was no difference in familiarity ratings for sample 2, F = 1.51, p = 0.217, ηp2 = 0.04. No pairwise comparisons were significant after Bonferroni correction for multiple testing.There was a difference in the ratings for intensity; sample 1: The aim of this study was to investigate the impact of smell on trust during human–robot collaboration. As a conceptual replication of previous work during human interaction , we testPerceiving and interacting with social robots is determined by an interplay between visual features of the robot, such as the shape and size, and knowledge factors within the human observer, such as expectations and beliefs . A similTrust can be operationalised and measured in various ways. Here, we assess trust on two levels by measuring trial-by-trial trust decisions during a collaborative perceptual decision-making task and general trust as measured by an established questionnaire. These measures have successfully been used in previous human–robot studies e.g., , 29, 32,For humans, the sense of smell drives approach and avoidance behaviour, serves as a guide to what we eat, and has a social function , 44. Humthe smell of data, an odour specifically designed to serve as a warning signal in case of data leaks by olfactory artists Leanne Wijnsma and Froukje Tan [Before dismissing the effect of hexanal on trust, or on human–robot trust, completely, several alternatives should be considered. First, a closer replication of the previous study , using aukje Tan . Anotherukje Tan , future ukje Tan , 49 coulukje Tan . Items uIn conclusion, we did not observe an effect of hexanal on trust in human–robot collaboration, which was operationalized using two different dependent measures. A category- and context-dependency could potentially underlie these results, whereby the associative learning linked to social chemosignaling mismatches with the cognitive representations of the robot. Since smell is a means to communicate a diverse array of signals, social chemosignaling offers a new vista for human–robot interaction and to enable fluent collaboration between robots and humans. The current research is a first endeavour into how the sense of smell is potentially involved in human–robot interaction and highlights the need for more research into the social functions of smell more broadly.