Swimming in fecally contaminated recreational water may lead to gastrointestinal illness. A recreational water-associated outbreak of norovirus (NoV) infections affecting at least 100 people in The Netherlands occurred in August 2012. Questionnaire responses from patients indicated swimming in recreational lake Zeumeren as the most likely cause of illness. Most patients visited the lake during the weekend of 18–19 August, during which the weather was exceptionally warm (maximum temperatures 32–33 °C), and visitor numbers elevated. Patients, mostly children, became ill with gastroenteritis 1–6 days (median 2 days) after exposure. Four stool samples from patients were NoV GI positive. Subsurface sandy soil from one of the beaches where most patients swam was NoV GI positive; the water sample was negative. The epidemiological curve and the timeline of investigation based on reported symptoms demonstrate the difficulty in discovering the source in recreational water outbreaks. A NoV outbreak in a recreational lake that is not subjected to external fecal contamination sources shows the need for active communication about human shedding of viruses during and after diarrheal episodes and the advice to refrain from swimming, even a few weeks after the symptoms have resolved. The virarticles ,3. Symptarticles ,4, but tn = 25) of the outbreaks [n = 14). In a recently published study of bathing water related outbreaks in Finland that all occurred in 2014, epidemiological and microbiological data showed that NoV was the main causative agent [NoV have been genetically classified into five genogroups (G) . GI and utbreaks . The majve agent .This paper describes the occurrence and investigation of a recreational water associated outbreak of NoV infections affecting at least 100 people in The Netherlands in August 2012.www.knmi.nl). Because of the warm weather, several thousands of people swam at Zeumeren during the weekend. Most patients became ill one to one-and-a-half day after exposure to the lake water, and had swum at two of the ten possible beaches surrounding the lake . All patients, who were mainly children, had visited the lake during the previous weekend of 18 and 19 August. During that weekend, the weather in The Netherlands was exceptionally warm with maximum temperatures of 32–33 °C   [Lake Zeumeren is located in a rural area (community Barneveld) in the center of The Netherlands. It is a 32-hectare isolated fresh water lake with stagnant water, with groundwater and rainwater as sources. The maximum water depth is 17 m and it has a sandy soil. Lake Zeumeren is an official bathing site, where the water quality is monitored for fecal indicator parameters (EU BWD)  with a fn = 36). The patients were asked to answer the questions and to forward the questionnaire to anyone they knew who had swum at the same site during the same period and had become ill with the same symptoms. This approach was chosen in an attempt to rapidly identify the source of the outbreak. Since there was no aim at performing a full case-control study, no matching controls were sought. By allowing questionnaires to be forwarded, no records were (or could be) kept of the number of questionnaires distributed. Apart from demographic questions about age and gender, questionnaires included information requests about having visited lake Zeumeren (date between 15 August and 24 August 2012), having entered the water (including specification of beaches visited), having swum (including duration of swimming), health conditions , using the on-site toilets, and having bought and consumed food and beverages on-site. Analysis of questionnaire responses was done by using SPSS .The province of Gelderland and the Public Health Service VGGM sent questionnaires by email on 24 August 2012 to all patients with whom they had primary contact and for whom they had kept records  and Yersinia, and NoV at the medical microbiological laboratory of the Rijnstate Hospital in Arnhem, The Netherlands, by using routine PCR. Later, the four samples were sent to the National Institute for Public Health and the Environment (RIVM) for further testing. At RIVM, the samples were analyzed for the presence of NoV by using a real-time RT-PCR assay, with primers, probes and PCR conditions as previously described [Five patients were asked to send in stool samples; samples from four patients were received and analyzed for the bacterial enteropathogens escribed .E. coli and intestinal enterococci, by using the most probable number methods specified in the EU BWD [In order to narrow down the outbreak and to identify the source, several leads were followed. In response to the reported cases of gastroenteritis, water samples were taken from lake Zeumeren at the two official beaches  on 20 Aue EU BWD . Although lake Zeumeren does not have a history of problems with cyanobacteria, the presence of a faint greenish colouring of the water led to visual inspection for the presence of cyanobacteria and sampling of the water at beach 4  for deteCampylobacter jejuni infection that was treated with antibiotics. Although the woman did not meet the case definition, it was decided to follow this lead because of the known nuisance caused by gulls at lake Zeumeren that take over the beaches after the bathers have left. Water samples were taken at the two official beaches on 23 August and analyzed for the presence of Campylobacter spp. by using a membrane filtration method with incubation on Karmali Agar at 42 ± 0.5 °C for 48 ± 2 h . On Wednesday, 22 August, a woman reported to the province of Gelderland having fallen ill after swimming in lake Zeumeren during the weekend prior to the outbreak weekend (11–12 August). She attended a physician and had blood, urine and feces examined, which revealed a When the four analyzed stool samples appeared to be NoV positive, RIVM was contacted on 30 August and asked to take environmental samples for NoV analysis at lake Zeumeren. Sampling was done on 3 September 2012. Water and subsurface sandy soil samples were only taken from the beaches where most of the patients had stayed or swum during the weekend of 18 and 19 August as was pointed out by the questionnaire results. One water sample was taken at sampling point A, and one subsurface sandy soil sample was taken at each of the sampling points A–C .The water sample (600 L) was taken by using an on-site filtration adsorption-elution procedure for concentration of the sample ,21. The Subsurface sandy soil samples of approximately 50 g were taken by using a tubular soil sampler. Subsequently, 10 mL 0.05 M glycine buffer pH 9.0 was added to 5.0 g of each sandy soil sample and mixed at 500 rpm for 35 min at 4°C, after which it was allowed to settle for 10 min (in house method RIVM). RNA extraction was done according to Rutjes et al. , by addiA real time reverse transcriptase PCR (RT-PCR) assay as described by Verhaelen et al.  was perfn = 25) were female. The age of the respondents ranged between 0 and 59 years of age, with more than half being children of 0–12 years of age , while the others were adults of 18–59 years of age . All respondents visited lake Zeumeren between 15 and 19 August, but the majority were at the site on 18 August  and/or 19 August . In total, 27 cases were exposed on more than one day during the specified period. All cases went into the water for swimming and became ill afterwards, with health complaints starting 1–6 days (average and median 2 days) after exposure to the bathing water and beaches at Lake Zeumeren and lasting for 0.5–6 days (average and median 2 days). Reported health conditions were : diarrhea , vomiting , fatigue , and fever . None of the cases reported skin conditions, and eight cases reported other complaints than those indicated above, of which seven were related to gastro-intestinal discomfort. One case reported a headache.Public Health Service VGGM received 45 filled-in questionnaires that met the case definition. Of the respondents, 56% (n = 31) and/or beach 2 . Most cases  were in the water for 30 min to over an hour.Forty-four of the cases indicated at which beach they had swum , showing that most cases swam at beach 1  of the cases used the permanent on-site toilets, the others did not. Buying and consuming on-site sold food and beverages were not very common: 87% (n = 39) did not buy or consume food and 98% (n = 44) did not buy or consume beverages.Fifty-eight percent , and 275 overlapping with the typing region of ORF2. Genotype assignment by phylogenetic analysis was supported by 100% and 99% bootstrap analysis, for ORF1 and ORF2, respectively. Typing from RT-PCR products is reliable if the fragment has >100 nucleotides overlapping with both of the typing regions of ORF1 and ORF2.E. coli at the official beaches of 16 most probable number (mpn)/100 mL at beach 1–2 and 6 mpn/100 mL at beach 3. Compared to previous and later routine samplings during the same bathing season, slightly elevated levels of intestinal enterococci at both beaches, 230 mpn/100 mL and 160 mpn/100 mL, respectively, were observed.Water samples taken on 20 August 2012 showed levels of Microcystis spp. at beach 4; intracellular microcystin levels were very low (<2 µg/L).Examination of the samples taken for cyanobacteria analyses by microscopy demonstrated the presence of Campylobacter spp. were present in the water samples taken at the official beaches (one sample per beach) on 23 August. Numbers appeared to be low, but could not be exactly determined due to overgrowth of the culture medium. Further identification to the species level was not done.NoV GI was detected in the subsurface sandy soil sample taken at sampling point A (beach 1). The other subsurface sandy soil samples and the water sample were NoV negative. Sequencing of the RT-PCR product from the subsurface sandy soil sample was impossible because the method for typing of RT-PCR products is less sensitive than the detection method, and the amount of RNA in the subsurface sandy soil sample appeared to be too low.Campylobacter infection in combination with the presence of a large seagull population resulted in choosing, what later appeared to be, the wrong direction. Following several leads and having various patient and environmental samples examined takes time, and in this case, led to the examination of water and subsurface sandy soil samples only over two weeks after the outbreak presumably started, thus diminishing the chances of detecting the etiological agent. Due to of the time gap between the onset of the outbreak and the environmental sampling, subsurface sandy soil sampling was performed in addition to the normal procedure of water sampling because sedimentation of virus particles during the delay period could have resulted in the presence of virus particles in the subsurface sandy soil [Following the reporting of many cases of gastroenteritis that seemed related to exposure to a recreational lake in The Netherlands during an exceptionally warm weekend in August 2012, several leads were investigated in order to discover the etiological agent and the source of the outbreak. Although the epidemiological investigation implicated the recreational lake as the most likely location of contracting illness, the different directions in which the investigation went, based on reported symptoms, demonstrate the difficulty in narrowing down the possible cause of recreational water related outbreaks. The results of the examination of patient material can ease the search for the etiological agent and the source; however, in this case, the reporting of a patient with a ndy soil . In thisndy soil . The detndy soil ,24, possndy soil . In a sundy soil , thus deThe epidemiological investigation showed that most of the patients were children. It has been demonstrated that, while swimming, compared to adults, children spend more time in the water and ingest a larger volume of water, thus increasing their exposure ,27 and rThe detection of the same NoV genogroup in subsurface sandy soil and in patients two weeks after the onset of the outbreak shows that NoV may be present in the environment for prolonged time through accumulation in sediment , and mayAn outbreak of gastrointestinal illness among over 100 visitors of a recreational lake in The Netherlands during an exceptionally warm weekend was caused by NoV. The results of the epidemiological investigation, combined with the detection of NoV GI in the stool samples of outbreak related patients and in the subsurface sandy soil of the beach where most patients swam, suggest that exposure to the recreational lake resulted in the outbreak. Although the primary contamination source has not been discovered, the most likely cause of contamination of the water is an infected human, because the lake is an isolated water body that is not subject to external sources of fecal contamination. An outbreak like this warrants active communication about human shedding of viruses during and after diarrheal episodes and the advice to refrain from swimming. The epidemiological curve and the timeline of investigation based on reported symptoms demonstrate the difficulty in discovering the source in recreational water outbreaks.


The reliable prediction of Cu(II) hyperfine coupling constants remains a challenge for quantum chemistry. Until recently only density functional theory (DFT) could target this property for systems of realistic size. However, wave function based methods become increasingly applicable. In the present work, we define a large set of Cu(II) complexes with experimentally known hyperfine coupling constants and use it to investigate the performance of modern quantum chemical methods for the prediction of this challenging spectroscopic parameter. DFT methods are evaluated against orbital‐optimized second‐order Møller‐Plesset (OO‐MP2) theory and coupled cluster calculations including singles and doubles excitations, driven by the domain‐based local pair natural orbital approach (DLPNO‐CCSD). Special attention is paid to the definition of a basis set that converges adequately toward the basis set limit for the given property for all methods considered in this study, and a specifically optimized basis set is proposed for this purpose. The results suggest that wave function based methods can supplant but do not outcompete DFT for the calculation of Cu(II) hyperfine coupling constants. Mainstream hybrid functionals such as B3PW91 remain on average the best choice. Modern correlated wave function methods (DLPNO‐CCSD and OO‐MP2) contend against density functional theory for the prediction of Cu(II) hyperfine coupling constants in a test set of realistic copper complexes. It is based on the primitives of the original 1994 Ahlrichs [8s5p3d] VTZ basis sets functions, addition of three tight and closely spaced s primitives obtained from the innermost exponent by successive multiplications with a factor of 2.5, and finally the addition of two p and one f polarization functions. The aug‐cc‐pVTZ‐J basis set of Hedegård et al.s, one p, and one d functions. Its fully decontracted version, denoted aug‐cc‐pVTZ‐Junc, corresponds to a [25s18p10d3f2g] set with a total of 168 primitive functions ; this is the largest and most flexible basis set of the present study, and is therefore used as the reference for all others.Two types of basis sets proposed as appropriate for the calculation of core properties include CP(PPP), originally engineered for the calculation of Mössbauer parameters,3)4]2+, obtained with the PBE0 functional. It is worth noting that all results discussed below have been confirmed for two other complexes ([Cu(dtc)2] and [Cu(acac)2]) using two additional functionals (TPSSh and B3PW91) and are reported in the Supporting Information . Several points become immediately apparent from Table s functions of the basis set. The aug‐cc‐pVTZ‐J (or Junc) and CP(PPP) basis sets are in close agreement with respect to AFC which is due to an important core‐shell spin polarization contribution of negative sign , a deficiency likely inherited from the parent Ahlrichs VTZ basis set.Table 2] and [Cu(acac)2] complexes when using the PBE0, B3PW91 and TPSSh functionals, as reported in the Supporting Information.The above results advocate the use of the purpose‐made aug‐cc‐pVTZ‐J basis set for the calculation of Cu HFCs, since it produces results indistinguishable from its fully decontracted version. Similar conclusions can be drawn from the results obtained with the and ΔA representing the anisotropic difference (33‐A11A). The APDs are evaluated in the following manner:To assess the performance of the basis sets, the absolute percent deviations (APD) are evaluated with respect to experimental results for three relevant parameters: 3)4]2+[Cu4]2+ using the DKH2 Hamiltonian and appropriate corresponding basis sets. Here again aug‐cc‐pVTZ‐Junc serves as the reference. DKH‐adapted versions of the standard cc‐type basis sets similarly fail for the AFC term, but the DKH‐adapted versions and p shells. CP(PPP) can be considered adequate for the AFC term but it shows the same type of deviation as seen in the non‐relativistic calculations for both ASD and ASO components. Importantly, the contracted aug‐cc‐pVTZ‐J version deviates from the reference for the crucial Fermi contact term showing that it suffers from the contraction of s functions, whereas the ASD and ASO terms are practically the same as the reference values.An additional point concerns the robustness of the basis set with respect to scalar relativistic effects, which result in spatial contraction of 3)4]2+, employing the PBE0 and B3PW91 functionals (Tables S22–S23). Applying the finite nucleus model has a very limited effect on the computed HFCs. Regardless of the functional used, the DK version of the cc basis sets still underperform and the aug‐cc‐pVTZ‐J keeps deviating from the ‐Junc analogue while predicted HFCs with both CP(PPP) and DKH‐def2‐TZVP are close to those obtained with the reference. Overall, the finite nucleus model has a very limited effect on the calculated HFCs and we recover the main trends obtained without using it.The finite nucleus model available with the ORCA program package was applied with the DKH2 Hamiltonian for 2+ confirmed the expectation that aug‐cc‐pVTZ‐J and ‐Junc recover massively more correlation energy than the CP(PPP), in line with the absence of appropriate correlation functions in the latter. All the above observations taken together would seem to suggest that the reference ‐Junc basis set would be the safest choice, however this would be computationally cumbersome. Moreover, it is clear from Tables s is unnecessary. This led us to investigate modifications of the ‐J basis sets that bring the results as close as possible to the reference while constraining the computational cost. The decontraction of s functions assures converged AFC values both in non‐relativistic and scalar relativistic calculations. However, close inspection of the Cu 1s orbital revealed that the three innermost s primitives remain practically unused and have near‐zero coefficients. The only condition under which we saw these functions making a noticeable, yet not significant, difference in HFC results was in DKH2 calculations that made use of the finite nucleus model, an approach that will not be further explored here. For the present purposes we therefore define a modified version of aug‐cc‐pVTZ‐J with decontracted s functions and removal of the three innermost s primitives  as a computationally optimal basis set for the calculation of Cu HFCs that is applicable to all methods considered in the present study.A further consideration in the context of the present study is how appropriate a basis set is for use with correlated wave function methods. Simple tests with MP2 and CCSD calculations on [CuNH4]2+ conf2.3In this section we compare the performances of density functional methods to predict reliable and accurate Cu hyperfine coupling constants. For that purpose, we exclusively employ our modified basis set, aug‐cc‐pVTZ‐Jmod, and conduct calculations on the complete set of copper complexes. Diverse density functionals are considered such as: GGA (PBE), hybrid  and range‐separated hybrid (CAM‐B3LYP); meta‐GGA  and hybrid meta‐GGA ; and double hybrid (B2PLYP). As shown in the previous section, no scalar relativity corrections need to be included in the calculations as they were proven to make no difference on average. On a more technical note, we observed that hybrid functionals are sensitive to the method used for calculating the spin‐orbit contribution. When the second flag of the SOC operator was set to compute the Coulomb term with the RI approximation, the calculated HFCs deviated remarkably from the experimental values. Setting this parameter to compute the Coulomb term exactly leads to good agreement between calculated and experimental results. When this flag was set to default (this study), the Coulomb term was computed semi‐numerically and the obtained hyperfine values are practically indistinguishable from those obtained by exact computation of the Coulomb term.3)4]2+. This is not the case for both GGA (PBE), meta‐GGA  and range‐separated (CAM‐B3LYP) functionals which deviate from experiment. While PBE and TPSS indeed provide low isoA term due to the underestimation of the core‐shell spin polarization contributions, the case of CAM‐B3LYP is quite different as it suffers from an incorrect description of the spin‐orbit contribution with underestimation from both pseudo‐contact and second‐order dipolar terms. The Minnesota functionals (M06 and M062X) do not reproduce the experimental values at all and behave quite erratically as no trend can be extracted from the predicted individual contributions. These observations are in line with previous studies[isoA 4]2+. For this parameter, the meta‐GGA functionals are also competitive with an average of 8 % deviation. As previously mentioned, the other functionals are of poor quality for the prediction of 33A. Interestingly, similar trends are observed for the average value of the HFC, isoA, where deviations do increase to about 15 % for the  group of functionals. Finally, the anisotropic parameter, ΔA, is also in good agreement with experiment with an average of 11 % deviation when looking at the hybrid functionals. The performances of the hybrid meta‐GGA, TPSSh, remain correct for both isotropic, isoA, and anisotropic, ΔA, parameters. The worst performing functionals are M06 and M062X while the GGA and meta‐GGA functionals underperform compared to their hybrid counterpart.At this first glance, hybrid functionals reproduce very well the magnitude of the largest hyperfine components, For a complete evaluation of the performances of each functional, the calculations were subsequently performed for the complete set of 20 complexes (Tables S27–S45) and the mean of each absolute percent deviation (MAPD) reported in Table From these mean absolute percent deviations, we can evaluate the ability of a given functional to predict reliable and accurate hyperfine coupling constants. Using our aug‐cc‐pVTZ‐Jmod basis sets, we obtain the following trend: B3PW91<TPSSh<B3LYP<PBE0<TPSS<PBE<CAM‐B3LYP<SCAN<M062X<M06, with B3PW91 having the lowest deviation from experiment and M06 the largest. Table 3)4]2+, Table To finalize the comparison of DFT methods, we included the double hybrid functional B2PLYP to our study and computed the HFCs for the complete set of complexes. This functional was first evaluated using the mean absolute percent deviations for the Fermi contact term and the three components of the spin dipolar contribution with respect to the ones obtained using the B3PW91 functional and the aug‐cc‐pVTZ‐Jmod basis set. In the specific case of 2+, the HFCs obtained with B2PLYP using the SOC contributions from B3PW91 are well above an acceptable error range over the complete set of complexes (Table S47). Table 33A, isoA and ΔA making B2PLYP an unfit DFT method to predict Cu hyperfine coupling constants.While it seems promising for the case of [Cu(NH2.4nZ) series of basis sets. However, neither the standard basis sets identified in the benchmark DFT calculations as potential candidates for the calculation of copper hyperfine coupling constants, nor our final choice defined above (aug‐cc‐pVTZ‐Jmod) have dedicated auxiliary basis sets. It is noted that for the aug‐cc‐pVTZ‐J basis set it appears that the standard aug‐cc‐pVTZ/C is sufficient, both in non‐relativistic and DKH2 scalar relativistic calculations. In comparison, the aug‐cc‐pwCVTZ/C and the larger aug‐cc‐pVQZ/C auxiliary basis perform less well, demonstrating the low tolerances involved in adapting a correlation fitting basis set to a specific size and type of main basis. It is also noted that the def2/C basis sets are inadequate when either the aug‐cc‐pVTZ‐J or the smaller CP(PPP) were used as main basis sets for Cu. Modifications of standard basis sets to make them more appropriate for aug‐cc‐pVTZ‐Jmod did not show a systematic trend, therefore we opted instead for the automatic generation procedure encoded in ORCA,Most of the correlated wave function calculations required an auxiliary basis set for the resolution of the identity approximations that are used either optionally or by default, as for example in the OO methods and in DLPNO‐CCSD. Standard main basis sets often have custom‐made auxiliary bases for correlation fitting, denoted as /C. This is the case for the def2 family and the correlation consistent  hyperfine coupling constants.In this work we evaluated the performance of density functional theory and modern wave function based methods for the prediction of Cu hyperfine coupling constants using a large set of 20 complexes with experimentally known structures and resolved hyperfine coupling tensors. We defined a computationally optimal basis set for Cu, the aug‐cc‐pVTZ‐Jmod basis set, a modified version of aug‐cc‐pVTZ‐J with decontracted The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


Resilience contributes to the recovery of disaster victims. The resilience of Tibetan adolescents after the Yushu earthquake has not been properly studied. This study aimed to examine the current resilience and associated factors in Tibetan adolescent survivors in the hardest-hit area 5 years after the Yushu earthquake. This cross-sectional survey was conducted in the area hit the hardest by the Yushu earthquake. Data were collected from 4681 respondents in October and November 2015. Measurements included the participant characteristics, traumatic earthquake experience, the Connor-Davidson resilience scale (CD-RISC), and the social support appraisals (SS-A) scale. The individual datasets were randomized as 80% for the training set and 20% for the validation set. The mean resilience score of the Tibetan adolescent survivors was 55.0±12.3. Thirteen variables were entered into the regression equation. The three dimensions of social support  were positively associated with resilience , among which support from others than family/friends was the strongest . Academic performance, activeness of participation in school activities, harmonious relationship with teachers/classmates, health over the last year, and regular physical exercise were positively associated with resilience . Being female and being extremely worried about their own lives were negatively associated with resilience (both P<0.05). In conclusion, among Tibetan adolescent survivors to the Yushu earthquake of 2010, support from others than family/friends was the strongest positive factor associated with resilience, while being female and extreme worry about their own lives were negative factors. These results expand our knowledge regarding resilience in Tibetan adolescent disaster survivors. China is an earthquake-prone country. From 2004 to 2018, 191 earthquakes occurred in China, of which 37 were above magnitude 6.0. Together they were responsible for 73,176 deaths and 486,231 injured . ResilieThe factors influencing resilience are usually divided into risk and protective factors . Those fIt is known that child, and adolescent survivors are a psychological stress-susceptible population to external adverse events. Xiao et al. ,34 showeThe Yushu earthquake area is situated in the relatively remote and undeveloped plateau mountainous area in western China, where the Tibetan culture is predominant. Five years after the earthquake, the current state of resilience among Tibetan adolescent survivors, given their unique geographical, cultural, social, and economic environment, is unknown, and the factors that have affected their resilience are still unidentified. Therefore, the aim of the present study was to examine the current resilience status and identify the associated factors of resilience in Tibetan adolescent survivors in the hardest-hit area 5 years after the Yushu earthquake. The results might provide useful insights for the post-disaster management and counseling of adolescents. Eventually, such data could allow better tailoring of the counseling to each individual.This was a cross-sectional study. The participants were recruited from four secondary schools (grades 7–12) in Gyegu town in October and November 2015. Gyegu town was almost completely destroyed by the earthquake. All participants met the following inclusion criteria: 1) Tibetan; 2) personally experienced the 2010 Yushu earthquake; 3) secondary school student of 12–18 years of age; and 4) willing, along with his/her guardians, to sign the written consent form for voluntary participation. Individuals with cognitive impairment or problems with hearing, verbal, and/or written communication were excluded. Ethical approval was provided by the Human Subjects Ethics Sub-committee of Sichuan University.In theory, adolescence is the transitional period between childhood and adulthood, usually between the ages of 12 and 22. In China, much of the research on Chinese adolescents has focused on the traditional middle school years, which are 12 to 18 years old, according to China's legal school age. Anyone over 18 is considered an adult. The main social place of Chinese middle school students is school, and their main social role is to study, and they have little contact with society. Those characteristics change dramatically after middle school since they begin working or go to university, which is considered in China as adult age. Therefore, the age of adolescents in this study is defined as middle school students aged 12–18 years; this definition is also used in other studies from China –40.The survey was conducted approximately five years after the disaster. Four parts were included: demographic and injury-related data, traumatic earthquake experience, Connor-Davidson resilience scale (CD-RISC), and Social support appraisals (SS-A) scale. The questionnaire was administered in Chinese, as Chinese is the language of instruction in schools in the Yushu area. Prior to the survey, we gained the permission and assistance of the local education management departments, as well as of the principals and class teachers of the schools. The participants were asked to complete a self-administered questionnaire in their classroom with the assistance of the researchers, who were two doctoral students and a psychology professional. All three researchers had received training for data collection . Researchers collected the questionnaires after checking each one for completeness. If a questionnaire was incomplete because of negligence, it was returned to the participant to be completed.Prior to the investigation, we explained the study purpose to the participants, assured them of the confidentiality of their personal data and the contents of the questionnaire, and obtained the consent of the participants and legal guardians. In the course of the investigation, the right of withdrawal was fully respected, and attention was given to the protection of the privacy of the participants during the entire research process. In each school, there were teachers and psychological professionals responsible for dealing with the psychological discomfort that the study may have caused. Non-research team members were not permitted to access the original data. In place of each participant’s name, a code was used for data entry and analysis.Data included age, sex, single-child status, left-behind child , parental education level, relationship with family members, family financial conditions, living conditions, activeness of participation in school activities, academic performance (according to the results of the school’s last academic year), academic stress, relationship with classmates, relationship with teachers, health over the last year, whether they undertook regular physical exercise , whether they had experienced stressful events , and whether they had received psychological counseling.Each participant’s experience of the traumatic earthquake was assessed using twelve items: whether they were buried in the earthquake; whether they were injured/disabled in the earthquake; whether they had family members/classmates/teachers who died in the earthquake; whether they experienced severe property loss; whether they witnessed someone else being buried/injured or dying; whether they were extremely worried about their own lives; whether they were extremely worried about the health of family and friends; and whether they felt guilty because someone else was killed or injured in the earthquake.The CD-RISC was used to assess the level of individual resilience. The scale was developed by Connor and Davidson  and has Social support was evaluated using the SS-A scale developed by Vaux et al.  and reviStatistical analysis was performed using R software version 3.5.1 and SPSS 19 . The level of significance was set at 0.05 (two-tailed) for all statistical inferences.Participant characteristics and traumatic earthquake experiences were expressed as numbers (%). CD-RISC scores and SS-A scores were expressed as means and standard deviations. Pearson’s correlations were calculated to evaluate the potential relationships between the CD-RISC and SS-A subscales.in = 0.05, αout = 0.10) was used to build a prediction model for resilience by incorporating the features selected in the LASSO regression model. Finally, the linear regression model was validated in the validation data set.The data were randomly divided into two parts, 80% as the training set and 20% as the verification set. First, using data from the participants included in the training set, the least absolute shrinkage and selection operator (LASSO) method was used to select the optimal associated features among the potential factors of resilience in Tibetan adolescent survivors. Features with non-zero coefficients in the LASSO regression model were selected . Second,A total of 5508 participants met the inclusion criteria, and 565 individuals from the four participating schools declined to participate. A total of 4943 questionnaires were administered, and 4681 (94.7%) valid questionnaires were collected. The mean age of the participants was 15.7±1.8 years, and 2466 (52.7%) were female. Among the participants, 6.9% were burried, 14.6% were injured, 0.9% were disabled, 17.4% had family members who died, 33.9% had classmates or teachers who died, 42.9% experienced severe property loss, 36.9% witnessed someone else being buried, 62.9% witnessed someone being injured, 44.7% witnessed someone dying, 64.2% were extremely worried about their own life, 84.8% were extremely worried about the health of their family and friends, and 80.0% felt guilty because someone else was killed or injured. The participant characteristics and traumatic earthquake experience are shown in Tables The mean CD-RISC score was 55.0±12.3 . Tables Of the participant characteristics, earthquake traumatic experience, and social support, 33 features were reduced to 21 potential factors on the basis of the training set  with non2 was 0.2731 (p<0.001).Resilience contributes to the recovery of disaster victims. The resilience of Tibetan adolescents after the Yushu earthquake of 2010 has not been properly studied. This cross-sectional survey aimed to examine the current resilience and associated factors in Tibetan adolescent survivors in the hardest-hit area 5 years after the Yushu earthquake. The results suggest that among Tibetan adolescent survivors to the Yushu earthquake of 2010, support from others than family/friends was the strongest positive factor associated with resilience while being female and extreme worry about their own lives were negative factors. These results expand our knowledge regarding resilience in Tibetan adolescent survivors.Tibetans enjoy good economic policies, so many adults work in their hometowns, and there are few left-behind children. Tibetans also did not implement the one-child policy, so there are fewer only children. Because the Yushu Tibetan area is located in a remote mountainous area, the education received by the older generations was mainly family education and temple education. In this paper, many of the respondents are the first generation of students in their families. Therefore, most of their parents' education background is primary school or below. In the univariable analysis, the scores of mental resilience of parents with college or above degrees were higher than those of parents with other educational levels, but the educational levels of parents did not enter the final regression equation.In the present study, the CD-RISC score (55.0) of Tibetan adolescent survivors was lower than that (69.6) found in a study by Yu et al. , who useBeing female was found to be a negative factor for resilience in the present study, as supported by Yu et al.  and StraGood health and performing regular physical exercise were found to be positive factors associated with resilience in our study, as supported by previous studies ,54. ReguThe positive relationship between academic performance and resilience found in this study is consistent with findings from de la Fuente et al. . To a ceThe item ‘activeness of participation in school activities’ was also an important factor for resilience. Of course, social life and school systems between China and the Western countries are very different. The main social place of Chinese middle school students is school, second only to home, their main social role is to study, and they have little contact with society beyond their fellow students, the teachers, and the school staff. Therefore, it might be considered that Chinese adolescents participating in school activities is like engaging in normal activities in a Western context. Returning to normal activities is seen as a way of being resilient . In addiIn the present study, all the measured dimensions of social support were positively associated with resilience, consistent with previous studies ,68. If pWe found that different earthquake traumatic experiences had different effects on resilience. Notably, ‘feeling guilty about someone else being killed or injured’ and ‘extreme worry about the health of family and friends’ were both positive factors of resilience for Tibetan adolescent survivors, while ‘extreme worry about their own lives’ was a negative factor. The three items were subjective responses to the earthquake and provided a reminder that the subjective responses of individuals to disasters are closely related to mental health, as supported by previous studies ,71. It iThis study has several limitations. First, the target population of this study included all the Tibetan secondary school students in Gyegu town who experienced the 2010 Yushu earthquake. Unfortunately, about 1200 potential participants were not included in this study because of the refusal of the principal of one junior high school. Although the general information of students in this school is not obviously different from that of other schools, according to the educational administration department, it might still lead to a bias. Second, the limitation of the cross-sectional study design makes it impossible to determine the causal relationship between variables, as well as the evolution of resilience in time. In addition, no data from before the earthquake are available. Third, the nature of quantitative research makes it difficult to understand how those factors influence the development of Tibetan adolescent survivors’ resilience. Further qualitative research is necessary to explore this. Fourth, due to the specific characteristics of the Chinese culture, social system, and schools, the international generalizability of the conclusions is currently limited. Similar studies should be carried out in various countries. This would provide interesting results about the similarities and differences among different countries/cultures. Fifth, because of the logistics, legal, and ethical complexity of studies dealing with the psychological/psychiatric health of children, the present study did not examine the effect of counseling or psychiatric assessment after the trauma. This is planned for another study. Finally, the Tibetan Buddhist religious was not included in the study because religion is not talked about in school, but the questionnaire was complete and the spiritual item was included. Despite these limitations, this study revealed the associated independent factors of Tibetan adolescent survivors’ resilience. As support from others than family/friends was found to be the most significant associated factor of the participants, and school-level items  were also found to be the associated independent factors, school-based, teacher-mediated intervention programs might be suitable and feasible to improve adolescents' resilience after a natural disaster. The results provide an empirical basis for the selection of the target population for intervention. Future studies should attempt to design, implement, and evaluate training programs for people with relatively low resilience. This study also showed that different disaster experiences had different effects on resilience, and subjective responses of individuals to disasters were independent influencing factors, especially "extreme worry about their own lives". In the process of post-disaster psychological aid, both the screening of negative psychological problems and the selection of psychological intervention populations should consider the subjective components of the earthquake trauma experience, especially those with extreme worry about their own lives should be paid more attention.Some of the included students were about 7 years of age when the earthquake struck, and they might have a different perception than those who were already adolescents at that time. During the study, we could observe that after the early fear and sadness, these children showed more gratitude, treasure in life, and hope for the future. They are generally more grateful for others' help, and they also want to help others in the future. They cherish their homes and families now. Although the earthquake brought great trauma to Yushu, it also brought in a new life. The construction assistance from all over the country not only made the whole city look brand-new but also increased communication with the outside world. Now Yushu is no longer a remote and backward town in western China, but a famous tourist city in China. The improvement of living conditions and economic conditions increased the hope and expectation for the future in those children.In conclusion, the findings provide insight into the context-specific factors associated with the levels of resilience among Tibetan adolescent survivors. The results suggest that their resilience needs to be improved despite the fact that many years have passed since the earthquake. This empirical knowledge base can be used to design post-disaster interventions and deploy much-needed resources and services to boost Tibetan adolescent survivors’ resilience. More support should be directed particularly toward females and individuals who experienced the trauma of the earthquake and reported ‘being extremely worried about their own lives’.S1 Checklist(DOCX)Click here for additional data file.S2 Checklist(DOCX)Click here for additional data file.


Together for Healthy and Successful Schools Initiative (THSS).The benefits of youth engagement are well documented. In this paper, we examine youth engagement in America's Promise Alliance's Every School Healthy initiative, a part of the Robert Wood Johnson Foundation's Six community acceleration sites were selected through a competitive grant‐making process. Sites were required to describe youth engagement strategies. A case study design was employed to examine how sites conceptualize youth engagement as well as youth engagement strategies employed across 6 sites. Data sources included observations, team member debriefs, and document review.youth engagement and youth voice are conceptualized in educational settings, and readiness for youth engagement. Sites actively solicited and implemented youth engagement resources and strategies.There was variation in how By failing to engage young people, well‐intentioned adults miss important opportunities. Youth engagement presents an exciting opportunity for school leaders, policymakers, and program planners to gain a deeper understanding of the factors that influence individual and community health and wellbeing and, in turn, helps them to develop responsive policies and programs. Youth participation has been characterized in the literature as the process through which young people engage with and influence the organizations, institutions, and systems that impact their lives.Every School Healthy (ESH) initiative. ESH, by design, was intended to center young people employing the Whole School Whole Community Whole Child model (WSCC)In this paper, we explore the process of infusing youth participation in school‐community partnerships to accelerate school and community action to advance health through an illustrative case study of the America's Promise Alliance, A brief background on youth participation and voice is provided followed by an overview of the ESH initiative. The case study methodology employed is outlined and the results are presented and then discussed in the context of the extant literature. We conclude by discussing the limitations as well as the youth participation implications for school health.Youth participation in schools has been defined as a partnership or collaboration between students and diverse adult stakeholders in the school setting.youth voice in the ESH initiative in addition to community stakeholder engagement. Youth participation has been referred in the education literature as student or youth voice. Like youth participation and engagement, it is not consistently defined in practice. For example, it is not merely the collection of youth priorities or opinions by adults. More so, it refers to meaningful engagement in decision‐making and goal‐setting that leads to changes in school programs and policies that reflect youth priorities.Given the benefits of the youth participation and its alignment with the mission and values of America's Promise Alliance (APA), the organization sought to infuse In 2017, with funding from the Robert Wood Johnson Foundation, APA launched ESH. ESH is a multi‐year, multisector initiative that was designed to catalyze a national movement advancing school health. The initiative included 3 primary objectives and was grounded in the notion that all schools can be healthy schools. The first objective was focused on local action to advance health equity. The team recognized solutions to pronounced inequities in both health and education demand investment in local knowledge and decision‐making. As such, 6 unique school‐community partnerships from across the country were selected through a competitive application process. The second objective was to promote bidirectional capacity building and cross‐site learning, whereby practitioners from local sites as well as youth and partners, researchers, and school leaders were learning from one another—both informing and adopting best practices. The learning laboratory, as it was developed, was then extended across sites to form a multisite learning community. Finally, broad dissemination was employed to further contextualize and amplify learnings. Real‐time sharing occurred with APA partners across the nation through webinar and local dialogues as well as, traditional earned media, listservs, and social media. At the center of this initiative were young people, students. As part of the application, process sites were asked to describe their plans for ensuring youth voice in their efforts. The level of youth engagement at each site was assessed. Using instrumental case study design, we describe the ranking process, and explore how youth engagement was conceptualized across sites. Youth engagement strategies and perceived technical assistance needs related to youth engagement are also examined. What emerged was a story about the promises and challenges associated with youth engagement as well as the need to explore organizational readiness for youth engagement.Instrumental case study design was employed to qualitatively examine how ESH sites conceptualize youth engagement as well as youth engagement strategies employed across 6 sites.The overall goal of observations was to explore youth engagement strategies as well as conceptualization of youth engagement and perceived technical assistance needs. Observations were planned and conducted by the youth engagement specialist at in‐person site visits, in addition, conference calls and remote meetings were observed. Comprehensive notes were taken during and at the culmination of each observation. Observation notes were typed and then analyzed thematically.Similar to the observations, document review was designed to explore how sites conceptualized youth engagement as well as strategies and technical assistant requests. Project documents included: ESH program descriptions developed by APA, applications and applicant narratives, evaluation reports, and learning agenda reports and grant reports from sites as well as materials released via websites, newsletters, and social media.Finally, themes were captured from debriefs with APA staff over the course of the project. In addition, debriefs with sites about their youth engagement technical assistance needs were conducted. The data collection and analysis, were continuous and emergent themes were shared with APA staff over the course of the initiative. Similarly, site‐specific themes were shared with sites after meetings and observations.Two types of data analysis were employed, holistic analysis of the whole case and embedded analysis of specific parts of the case.Each document was read multiple times to search for meaningful patterns,How youth engagement was assessed across the site application process is presented accompanied by youth engagement levels. We then highlight the approach to technical assistance strategies used by APA and its core partner organizations as well as youth engagement activities employed across the selected sites. The section concludes with an overview of the challenges of youth engagement as described by sites.Six acceleration sites were selected from a total of 138 eligible applications from 20 states. Figure …the campaign [initiative] will meet communities where they are when it comes to youth engagement. Some communities are ready for and have a need for infusing youth voice into their discussions, others want and need to have youth at their decision‐making table, and still others want to engage youth in pursuing inquiries that are needed for making decisions. [APA document]Youth engagement was scored separately from the overall application and did not impact the overall scoring. According to project documents, opportunities for youth involvement at both the national and local levels were intentionally built in. The goal was to work with sites to build their capacity for youth engagement throughout the process:Catalyze shifts in school, district, and broader community practices and policies that incorporate more youth voice in decision‐making processes and support youth as agents of change for healthy environments… [APA document]Increased knowledge, attitudes, and beliefs of direct stakeholders  of the factors that contribute to a healthy school environment and the key levers for systems‐level change. [APA document]The hope was that focusing on meaningful youth engagement would:According to project notes, the level of youth engagement was ranked for each application using content analysis and scoring. The content was coded based on the nature of the activities using the levels described in Table The review process involved scanning application content to determine the presence of youth engagement activities described in the criteria outlined in Table Of the 138 sites, 16 finalists were selected. Youth engagement scores varied among the 16 sites. The mean score was 1.6. Half of the 16 (50%), scored 1, 37.5% scored 2, and 12.5% scored 3. The APA team and core partners met to narrow the 16 applications to 6. All applicants were discussed and finalists were selected using a consensus decision‐making process with the group, that involved dot polling followed by group discussion. The process continued until the pool was narrowed to 6.How will youth be engaged in the decision‐making process?Will [youth] teams only provide feedback or will they be encouraged to lead the way?How will you ensure those [youth] most impacted will be at the [decision‐making] table? [review documents]The 6 finalists participated in telephone interviews with APA staff. Sites were asked a number of clarification questions associated with their youth engagement plans in an effort to further hone their level. For example, one site was asked:Interview responses were reviewed and coded using the process previously described. Scores were then adjusted. The 6 selected sites participated in telephone meetings with technical assistance (TA) providers including the youth engagement specialist.There are many terms that get used interchangeably when referring to how young people are involved with a program—eg, Youth Engagement, Youth Participation, Youth Voice, Youth Leadership, Youth Empowerment. [project report]Technical assistance (TA) began with an introduction to youth engagement. Hart's ladderPlanning notes indicate that after the initial training individualized plans were developed based on level goals and TA activities outlined in Table Some acceleration sites have strong programming in other areas . In this instance the youth engagement consultant [specialist] offers them support to modify the existing materials and curriculum so that it is appropriate for young people and the goals associated therewith. [internal initiative report]…provided a 2‐day youth assessment training to young people from 2 high schools as well as a train‐the‐trainer workshop for site staff to provide these trainings in the future. [external initiative report]…[TA materials] not only served as a resource but also provided a template for the “State of Child Report” that the … site was working on, wherein the young people talk about the biggest issues that impact young people in the city and the changes needed to solve those issues. [external initiative report]…[TA] provided them with strategies, concepts, and framework that they had not thought through before. For example, one of the sites mentioned that they had not thought about how youth who are more vulnerable backgrounds  take more risk when they engage and make their voices heard as compared to youth who are less vulnerable. This led some sites to more careful planning in the first year [external initiative report]Another project director mentioned that the idea that the site could involve youth equipping them with basic research skills and data collection methodology so they can analyze and interpret their own data was new to the project director. [external initiative report]Level one sites, the goal was to provide a steady flow of information and to begin to explore strategies to plan.…Interviewees said that engaging youth as leaders has the potential to bring new insights to the health and well‐being of young people, provide a broader understanding of young people's wellness, and increase their skills, confidence, and agency. Most importantly, engaging them made sure “that interventions and programs in school settings are actually addressing the needs of young people as they state them” (site project director). [external initiative report]Overall, data indicate sites benefited from youth engagement frameworks and examples as well as brainstorming trouble shooting and direct training.Youth‐led Councils have been formed in 2 high schools and one middle school… All 3 student wellness councils have been trained in health equity and have chosen their top health issues to focus on next school year… [site report]All 6 acceleration sites have implemented or are in the process of implementing youth leadership collectives.Youth groups are referred to as action groups, ambassadors, councils, and advisors. The structure and function of youth leadership collectives vary across sites. Activities, for example, range from service and peer education to research and policy advocacy. Youth engagement activities are shown in Table Youth engagement was not without its challenges. Sites described a number of impediments to establishing partnerships with young people and engaging them in meaningful ways. These challenges varied but in most cases were structural. Namely, community‐level factors such as transportation and organizational factors related to interagency collaboration, resource scale‐up, and staffing issues. Individual factors related to behavior, capacity, and life circumstances were also noted. Table youth‐initiated activities and programs, there were instances when youth engagement was characterized as tokenism or assigned and informed.Consistent with the literature, we found there is a great deal of variation in how youth voice and youth engagement are conceptualized.structure, systems, strategy, skill, staffing, style, and shared values.There are multiple elements that comprise an organization. For example, McKinley lays out 7 organizational elements: Overall, sites found Hart's Ladder to be a framework by which to understand engagement and provided clear goals to target. Some sites used the graphic of the Ladder with youth to reflect on where they were with respect to programming. Exploring the rungs of the ladder together, youth and adults evaluated their engagement and were able to collaboratively generate partnership goals as well as strategies for arriving at their desired destination. Similarly, sites benefited from resources and TA activities aimed at examining how adultism operates within systems. Authentic youth engagement calls for adults ready to tackle ideology, systems and structures that proliferate adultism and impede engagement. At the end of the day, this work takes both time and intentionality. Organization readiness assessments may facilitate efforts to engage youth authentically.This work is not without limitation. We present an analysis of observational data and program documents coded by a single reviewer, which may have introduced bias. To compensate for this limitation study, findings have been reviewed by and discussed with APA staff to explore the extent to which finding reflect their lived experience. In addition, the triangulation of multiple data sources has helped to ensure validation.As we strive to implement WSCC strategies for improving outcomes,Consistent with the literature, we found efforts to create healthy environments for students that fail to meaningfully engage them to run the risk of employing adult‐centric approaches.In the context of COVID‐19, we, adults, need to be particularly mindful of what it means to authentically engage young people. The goal of any social system is to maintain equilibrium. Youth engagement is complicated because it challenges norms within social systems, including schools. Today, systems are in crisis and having to adapt to a new landscape. As such, we run the risk of setbacks if we do not continue to both think and act intentionally about how we collaborate, partner, and engage with youth.This research was determined not to be human subjects research by the Boston University Charles River Campus Institutional Review Board.Linda Sprague Martinez is a research consultant for Americas Promise Alliance and the Community Clinic, Inc. She was previously a research consultant for RAND and Human Impact Partners.


Microcirculation refers to the smallest blood vessels within the body. During inflammation, changes can occur within these vessels which can further disease processes. Blood vessels in the gut are particularly vulnerable. Videomicroscopy devices are important for examining these changes. In animal experiments, intravital microscopy is the gold standard for evaluation. This technique allows for the visualization of these vessels within living animals. The changes that occur vary depending on the length of time the inflammation has been occurring for. Examples of these changes include changes in blood flow, vessel density and immune cell activation. This review discusses these changes in the context of various inflammatory conditions including infections of the intestine and pancreas, and non-infectious conditions of the bowel.Because of its unique microvascular anatomy, the intestine is particularly vulnerable to microcirculatory disturbances. During inflammation, pathological changes in blood flow, vessel integrity and capillary density result in impaired tissue oxygenation. In severe cases, these changes can progress to multiorgan failure and possibly death. Microcirculation may be evaluated in superficial tissues in patients using video microscopy devices, but these techniques do not allow the assessment of intestinal microcirculation. The gold standard for the experimental evaluation of intestinal microcirculation is intravital microscopy, a technique that allows for the in vivo examination of many pathophysiological processes including leukocyte-endothelial interactions and capillary blood flow. This review provides an overview of changes in the intestinal microcirculation in various acute and chronic inflammatory conditions. Acute conditions discussed include local infections, severe acute pancreatitis, necrotizing enterocolitis and sepsis. Inflammatory bowel disease and irritable bowel syndrome are included as examples of chronic conditions of the intestine. Microcirculation refers to the circulation of blood through microvessels with a diameter of less than 100 μm, which include arterioles, capillaries and venules. Larger vessels from the macrocirculation, including arteries and veins, supply blood to the microcirculation. The microcirculation has many roles within the body, as reviewed in detail by Guven et al. [The gastrointestinal (GI) tract is supplied by three major arteries, with the superior and inferior mesenteric arteries supplying the small and large intestine. A large number of anastomoses are present to facilitate continuous flow through the intestine. Intramural blood flow is not uniform, with the mucosal layer receiving 70–80% of the blood supply depending on food intake . Not allIn a state of homeostasis, macro and microcirculation are coupled to each other . Inflammation, either local or systemic, may result in microcirculatory disturbances and ultimately in the uncoupling of these circulatory systems. Because of the uncoupling of macro and microcirculation, therapies aimed at restoring microcirculatory parameters may not be effective at a microcirculatory level . Acute i® software to the semiautomated AVA3® technique noted that while the parameters are statistically related, further development is needed before the implementation of the fully automated software [Two key parameters are established for assessing the microcirculation. Capillary density and blood flow can be assessed directly using a variety of microscopy techniques. Assessment of the microcirculation in patients is limited to areas with superficial vasculature such as sublingual mucosal tissue. Accurate assessment of the microcirculation of internal organs, such as the intestine, remains challenging. Changes in the sublingual microcirculation are known to parallel those of the intestine, but this data may not always be representative of the intestinal microcirculation . Rectal software .The intestinal microcirculation can also be impacted by other factors which are not as easily addressed using imaging techniques. The gut is home to a rich, diverse microbiome which can vary during states of disease. Changes in bacterial populations have the potential to impact the immune response and affect the microcirculation. Amedei and Morbidelli reviewed the effects of various circulating metabolites produced by gut microbiota on endothelial cell function . One stuVarious imaging techniques are used to assess the microcirculation experimentally. Intravital microscopy (IVM) is an experimental technique that allows for the visualization of biological processes in vivo. The term encompasses various types of microscopy which can be used for in vivo visualization. IVM typically images tissue architecture and functions by fluorescently labeling components of interest. Various methodologies used in IVM are reviewed by Weigert et al. . IVM canHelicobacter pylori and rotavirus, as well as severe acute pancreatitis (SAP), necrotizing enterocolitis (NEC) and sepsis. Inflammatory bowel disease and irritable bowel syndrome are discussed as chronic inflammatory pathologies. The major changes found in each of these conditions are summarized in This review identifies some of the changes within the intestinal microcirculation during both acute and chronic inflammation. Acute pathologies addressed include various acute infections, such as infection with H. pylori is a common gastrointestinal pathogen, frequently infecting both the stomach and duodenum. As observed mainly by IVM, H. pylori infection can impact the microcirculation via changes in blood flow, leukocyte activity and the endothelial cells. Yoshida et al. demonstrated a significant increase in leukocyte adhesion in rat mesenteric venules after superfusion with H. pylori [H. pylori infection in mice resulted in a 30% reduction in mucosal blood flow as evaluated by laser Doppler [H. pylori infection was associated with a decrease in mucosal blood flow in patients who had undergone endoscopic mucosal resection [H. pylori infection discussed here are related to acute infection, it should be noted that this infection often becomes chronic, resulting in the formation of ulcers. Infection of the GI tract with an enteric pathogen can result in acute inflammation. Altered microcirculation is a common feature of infection by various pathogens, including bacteria, viruses and parasites ,70,71. E. pylori . An addi. pylori . H. pylo Doppler . Clinicaesection . While tInfection with rotavirus, a double-stranded RNA virus, serves as an additional example of microcirculatory changes during acute infection. Rotavirus is a common cause of gastroenteritis among children, resulting in vomiting and diarrhea. This infection can impact both the small and large intestine. Intestinal microvascular endothelial cells are able to recognize double-stranded RNA via Toll-like receptor 3, leading to production of proinflammatory interleukin-12 . InfectiSevere Acute Pancreatitis (SAP) is a serious illness featuring sudden inflammation of the pancreas, often secondary to gallstones or alcohol abuse. SAP has a mortality rate of approximately 40% and often progresses to sepsis and multiorgan failure . The GI Necrotizing Enterocolitis (NEC) is an inflammatory condition that primarily affects the intestine of preterm infants. The intestinal microcirculation of infants is particularly vulnerable to disease due to the variety of age-dependent changes that occur during the postnatal period . The defSepsis is a complex syndrome, defined as life-threatening organ dysfunction caused by the dysregulated host response to infection . With ovA systemic inflammatory response occurs early in sepsis. The innate immune system initiates a vigorous immune response, including the release of proinflammatory cytokines and the recruitment of leukocytes to the affected area. This immune response is dysregulated and can lead to tissue damage, edema and ultimately organ failure . PatientThe accurate identification of organ dysfunction is a current priority in sepsis research . Sepsis Hemodynamic resuscitation, a standard therapy for septic patients, is associated with reduced mortality . Obonyo Other microcirculation-targeted therapies for sepsis have reached the clinical trial stage, with limited success. Inhaled nitric oxide was unable to correct microcirculatory parameters in septic patients despite macrocirculatory stabilization as assessed by sidestream darkfield videomicroscopy of the sublingual microcirculation . AdminisInflammatory Bowel Disease (IBD) is an umbrella term that describes inflammatory disorders affecting the GI tract. There are two major types: Crohn’s disease (CD) and ulcerative colitis (UC), which are distinguished primarily by the portion of the GI tract affected. While CD may impact any part of the GI tract, UC is typically restricted to the large intestine. In addition, CD is a transmural disease, affecting all layers of the gut, while UC is restricted to the mucosal layer. It is important to consider these specifications when considering the impact of these conditions on the intestinal microcirculation. Despite these differences, both diseases feature symptoms including abdominal pain, diarrhea, fatigue and weight loss. One recent global meta-analysis suggests that the prevalence of IBD exceeds 0.3% of the population in Westernized countries . IBD is Different patterns of vascular perfusion have been linked to different stages of IBD progression. Historically these changes were hypothesized to be secondary to histological changes. Animal models, which allow the investigation of very early changes during the disease course, have been essential to this research. In experimental UC induced by either trinitrobenzensulfonic acid or mitomycin-C, perfusion is increased in the early stages of disease and then reduced in chronic phases . These fChronic inflammation, characteristic of IBD, results in important changes within the intestinal microvasculature which may impact perfusion. Chronic inflammation and hypoxia within the GI tract upregulate various growth factors and other cytokines involved in angiogenesis. Vascular endothelial factor A (VEGF-A) has been linked to both inflammation and angiogenesis in samples from patients with IBD . IncreasBecause IBD patients experience chronic inflammation, there is involvement of the adaptive immune system. Lymphocyte homing is of particular relevance. Patients with IBD express high levels of chemokine ligand 20 (CCL20), which facilitates lymphocyte homing to chemokine receptor 6 in intestinal tissues ,36. IncrOnce patients enter remission, it is unclear what happens within the microcirculation. One macroscopic study indicated patients primarily experience a return to normal blood flow, with differences in flow possibly predicting treatment outcomes . A studyIrritable bowel syndrome (IBS) is a functional disorder of the GI tract which has a prevalence of approximately 12% in North America . IBS is Visceral hypersensitivity, as a result of autonomic dysfunction, has been suggested as a possible mechanism for IBS . FingertChronic, low level inflammation may play a role in IBS pathogenesis . ExperimMicrocirculatory dysfunction resulting from inflammatory illnesses is a serious clinical concern associated with negative outcomes including tissue damage and organ dysfunction. Despite the variety of clinical conditions discussed here, inflammatory conditions impacting the intestinal microcirculation have many common characteristics regardless of whether the inflammation is acute or chronic in nature . Microci


In different models of asthma, PGE2, 15d-PGJ2, and LXs reduced lung inflammation and remodeling. Furthermore, these SPMs inhibited chemotaxis and function of several inflammatory cells involved in asthma pathogenesis, such as eosinophils, and presented an antiremodeling effect in airway epithelial, smooth muscle cells and fibroblasts in vitro. In addition, PGE2, 15d-PGJ2, and LXs are all able to induce macrophage reprogramming to an alternative M2 pro-resolving phenotype in vitro and in vivo. Although PGE2 and LXA4 showed some beneficial effects in asthmatic patients, there are limitations to their clinical use, since PGE2 caused side effects, while LXA4 presented low stability. Therefore, despite the strong evidence that these AA-derived SPMs induce resolution of both inflammatory response and tissue remodeling in asthma, safer and more stable analogs must be developed for further clinical investigation of their application in asthma treatment.Asthma represents one of the leading chronic diseases worldwide and causes a high global burden of death and disability. In asthmatic patients, the exacerbation and chronification of the inflammatory response are often related to a failure in the resolution phase of inflammation. We reviewed the role of the main arachidonic acid (AA) specialized pro-resolving mediators (SPMs) in the resolution of chronic lung inflammation of asthmatics. AA is metabolized by two classes of enzymes, cyclooxygenases (COX), which produce prostaglandins (PGs) and thromboxanes, and lypoxygenases (LOX), which form leukotrienes and lipoxins (LXs). In asthma, two primary pro-resolving derived mediators from COXs are PGE Asthma is a high prevalence chronic inflammatory pulmonary disease, the respiratory symptoms of which include cough, wheezing, shortness of breath, and chest tightness which leads to elevated morbidity, mortality, and disease social and economic costs –3. PulmoThe resolution of inflammation is an active and controlled process that reduces inflammation through the elimination of danger signals, leading to the restoration of tissue homeostasis and preventing the progression towards an uncontrolled chronic inflammatory state. Thus, catabolization and antagonization of pro-inflammatory mediators, a decrease in leukocyte numbers at inflammatory sites, and tissue repair are key events in the resolution process . It is n+ cells to M2 and T regulatory phenotypes respectively, sequestration and counter-regulation of pro-inflammatory mediators, apoptosis of polymorphonuclear cells with subsequent phagocytosis by M2 macrophages, and tissue repair , peptides , proteins , and nucleotides (i.e. adenosine and inosine) –19. Theye repair –22.Among the SPMs, the lipid mediators activate many aspects of the resolution process . These e(COX), especially COX-2 isoform, play a pivotal role in the conversion of AA into different pro-inflammatory lipid mediators, including prostaglandins (PG) and thromboxanes , a metabolite of PGD2 , mPGES-2, and cytosolic PGES (cPGES), which use PGH2 as substrate. The actions of PGE2 are mediated by four distinct 7TM receptors (EP1–EP4)  time: the kinetics of PGE2 release can separate its pro-inflammatory and pro-resolving effects due to the presence of different targets  . Althougcontexts . So, wha targets , 32; ii)opposite , 33, 34;hance it .2 production by dendritic cells through reduction of COX-2 and mPGES-1 expression -induced lung eosinophilia  activation, but some of its effects are independent of this receptor , an enzyme that catalyzes PGHose mice . Furtherose mice . We prevhe lungs . The proulocytes . The inhinophils . Howeverof PPARγ . 15d-PGJagonists , 89.2 reversed structural changes related to airway remodeling, including epithelial thickening, mucus exacerbation, and EM deposition, in both OVA and HDM murine models of asthma  and 15-LOX are the main LOXs involved in the metabolization of AA , resultiby 5-LOX , and in by 5-LOX . It is depi-LXB4 . LXA4 anted ALXR . ALXR isceptor 1 . Neverthentified .4 levels in BAL fluid, sputum, and whole blood compared to moderately asthmatic individuals. This reduction in LXA4 concentrations observed in severe asthma was associated with a higher degree of airway obstruction  cells and ILC2s are important in the control and exacerbation of asthma, respectively. NK cell depletion induced a persistent allergic airway inflammation in association with reduction of the LXA the BAL . LXA4 entivation . Meanwhitivation . LXA4 intivation .In vitro, LXA4 and 15-epi-LXA4 reduced IL-8 secretion induced by serum amyloid A in a human alveolar A549 cell line (4 increased basal proliferation and wound repair of human airway epithelial cells (4 reduced mucus production (4 reduced both LTE4- and IL-13–primed ASM migration toward platelet-derived growth factor in vitro (4 inhibited connective tissue growth factor-induced human lung fibroblast proliferation in vitro (in vitro (4 reversed bleomycin-promoted fibrosis and lung damage in mice (ell line . Also, aal cells . In a mual cells  and LXB4oduction . ASM hypin vitro . Anotherin vitro . Moreovein vitro  and blocin vitro . Besides in mice . Altoget4, some clinical trials using this LX, its analogues, or LXA4 receptor agonist BML-111 were administered in asthmatic patients. The nebulization of LXA4 reduced LTC4-induced bronchoconstriction (4 (4 analog or BML-111, which is more potent and stable than LXA4 itself (4 analog and BML-111 were well tolerated and presented no side effects (Due to the possible therapeutic application of LXAtriction ; howeverction (4  make its4 itself , improve4 itself  (Table  effects .2, 15d-PGJ2, and LXs with better physical-chemical properties, allowing greater stability and superior selectivity for specific receptors. Moreover, new analogs of AA-derived SPMs could also improve efficiency and reduce the required dose of glucocorticoid, the latter often leading to adverse effects and steroid-refractoriness, despite being the best asthma treatment so far.This mini-review presents several aspects of the pro-resolving effects of COX- and LOX-derivative mediators in asthma Figure 1DI, MF, and DC contributed to the conception and design of the study, wrote the manuscript, discussed the content, and contributed to the manuscript revision. MM discussed the content and contributed to the manuscript revision. VC contributed to the conception and design of the study, wrote the manuscript, discussed the content, and contributed to the manuscript revision. All authors reviewed and/or edited the manuscript prior submission. All authors contributed to the article and approved the submitted version.This work was supported by PrInt Fiocruz-CAPES Program N° 01/2020.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This paper presents a series of compression tests performed on a variety of high performance lightweight cellular materials conventionally used in energy absorption applications. Compressive tests were performed over a range of strain rates with a universal testing machine and a single stage gas gun. Experimental results revealed a dependency of the mechanical properties on the polymeric precursor, density, infill topology and strain rates. The dynamic strength of the investigated materials was determined through a material parameter identification study via the finite element (FE) method. Numerical results matched well with the experimental results and revealed a substantial enhancement in the compressive strength of the tested material from quasi-static to dynamic loading regimes by as much as 87%. The strength of 3D printed polymers was superior with respect to the tested polymeric foams. On the other hand, polymeric foams showed higher efficiency and energy absorption ability. Cellular materials such as honeycombs and foams are increasingly exploited in engineering applications due to their excellent ability to absorb energy, low weight and relatively low cost. The main applications for soft and semi-rigid foams include insulation, packaging and cushioning, whilst rigid foams and honeycombs are also employed in structural applications, as well as the core of lightweight sandwich structures. The selection of the material is application dependant and should be based on factors such as in-service force and pressure, duration and direction of the load, design constraints, environmental conditions and cost. Hence, a thorough understanding and evaluation of the mechanical behaviour under different loading conditions is necessary in order to determine the range of applications in which certain materials would have the best response. There is extensive experimental data available in the open literature on the mechanical properties of polymeric foams. For example, different peer reviewed articles document the compressive properties of polyurethane foams ,2,3,4, eIt is generally accepted and was experimentally confirmed in ,10,13,14 strains .In the last 30 years, additive manufacturing (AM) technology has been rapidly developed and is increasingly exploited for the creation of prototypes and complex shape parts. Thermoplastic polymeric materials such as ABS, PA, PLA and TPU can be processed using such techniques . When thOne of the fields in which AM could have enormous potential is in the construction of nano and micro Unmanned Aerial Systems (UASs). Yeong et al.  reviewedThis paper presents a series of compression tests performed on a range of lightweight materials conventionally used in energy absorption applications and 3D printed cellular solids. The experimental programme consisted of quasi-static compression tests performed with three different strain rates on thirty six different types of materials. The materials that showed the highest compressive strength, sensitivity to the strain rate, absorbed energy and efficiency were tested under dynamic conditions similar to a Taylor impact test. Hence, the finite element (FE) method was employed in order to quantify the strength at higher strain rates. The FE methodology involved the solution of an inverse problem where the material parameters were calibrated by matching the response of the virtual specimen with the experimentally observed response.A series of commercially available lightweight materials were procured and tested. The nominal thickness of the as-received panels was 25 mm. The physical properties of the investigated materials are listed in 3D printed specimens were prepared in-house using two different 3D printers (Makerbot Replicator 2X and Ultimaker 3 Extended) via the fused filament fabrication (FFF) method. A variety of raw materials  and different infill densities (10% and 30%) and infill topologies  were investigated. The experimental testing campaign was divided into two levels of testing. Level 1 consisted of conventional quasi-static compression tests on all materials listed in −1, 0.013 s−1 and 0.133 s−1, respectively. All tests were performed at room temperature. Quasi-static compression tests on 3D printed specimens were performed with cylinders of 20 mm diameter and 25 mm long. Although not recommended by the standard, this specimen geometry was chosen in order to compare the compressive properties of the specimens under quasi-static and dynamic conditions directly. It was necessary to print the skin to ensure the stability of the specimen and replicate periodic boundaries as in real structures.Uniaxial compression tests were carried out according to ASTM D1621-16 “Standard Test Method for Compressive Properties of Rigid Cellular Plastics” . Tests aThe compressive stress was determined by dividing the load by the initial cross-sectional area of the specimen;As cellular materials experience variations in the local strain field under compression, the average compressive strain was determined optically by tracking the relative displacement of two points drawn on the compressive platens.® Video GaugeTM software. The diameter of the specimen was chosen such that the cross-sectional area of the specimen was smaller with respect to the cross-sectional area of the tip of the Taylor bar. The length of the foam specimens was chosen to be the same as the thickness of the received billets in order to avoid cuts and bonding with adhesives. The length of 3D printed specimens was chosen to be the same as the other specimens in order to have a direct comparison throughout the testing campaign. The tip of the bar was lubricated with silicone grease to minimise frictional effects. The effect of the vacuum during the tests was neglected. For such testing conditions, the compressibility of the air would be insignificant compared to the structural stiffness of the tested materials.The dynamic characterisation of selected materials was carried out by firing the specimens onto a rigid bar anvil, in the manner of a Taylor test , using aIt could be observed that the global compressive behaviour of foams depended mainly on their precursor polymer and its relative density and the mechanical properties related to the cell structure. Generally, the higher the density, the higher the collapse stress  steeply .I, L, O, R) and ranged between 2.6 MPa and 5.3 MPa when tested at the slowest cross-head displacement rate. Soft and semi-rigid foams were the most compliant with a The highest collapse strength F, G, S, T) almost completely recovered their initial shape after removing the compressive load, regardless of the applied strain rate. As their structure was more compliant, low density PE and PVDF based foams are not used for structural applications, but mainly for their electro-magnetic and thermal properties, as well as acoustic insulation [A, B, C, D, E, J, K, L plastically deformed with a partial recovery of their initial shape after removing the compressive load. Foam Types H, I, M, N, O, P, Q, R plastically deformed without any shape recovery. Instead, small crumbles were observed on the surfaces of the latter types, indicating brittle crushing.Soft foams . The efEquation ): (1)W=∫A, B, C and AC, AD were similar to those observed for the other investigated materials.By plotting ® RIST and Rohacell® IG. EPS foams had an envelope gradient 14% and 6% lower with respect to the former materials, respectively. The envelope gradient calculated for 3D printed PLA with a linear infill pattern was 0.505, i.e., the highest amongst the 3D printed materials. Nevertheless, its gradient was about 16% smaller with respect to Rohacell® RIST. The lowest ability to absorb energy was found for 3D printed CPE specimens, which were brittle and compliant. It also appears from It can be seen from A summary of the collapse stress vs. density is shown in Although PLA specimens had the highest collapse strength amongst the investigated materials, the plateau stress was unsteady and, when normalised with respect to the specimen density, similar to the normalised plateau stress of ABS specimens. Hence, the latter material was selected for dynamic compression tests.U and W progressively plastically buckled in a similar way to axially compressed tubes, whilst 30% filled specimens showed plastic deformation only near the impact face, which mushroomed. It also appeared that the 3D printed specimens with the highest core density produced the steepest reduction in velocity  showed the slowest deceleration and the highest compression strain amongst the investigated ones. The impact was almost completely elastic, and rebound velocity was about 42% compared with the initial velocity. Fluctuations in the rebound velocity could be attributed to elastic waves bouncing within the specimen itself. Amongst the tested materials, Type G was the only one able to recover its initial shape after impact. PET and PMI based foams pulverised upon impact at the impact face  mounted behind the tip of the bar, it was not possible to record any meaningful data. The momentum generated upon impact was too low to trigger the load cell, regardless of the set force threshold. Therefore, the dynamic strengths of the tested materials were calculated through a finite element (FE) study. FE can also simplify the problem as variations of specimen density, inertia effects and instantaneous acceleration are automatically computed by the solver.3; element aspect ratio between one and 1.8). The virtual specimens were set to impact a planar rigid wall with an initial velocity equal to 160 m/s. No friction was defined upon the contact between the specimen and the rigid wall.The simulations of the dynamic compression tests were carried out using the explicit LS-Dyna FE code . For eacAmong the different material models available in the FE solver, the Material Type 63 *MAT_CRUSHABLE_FOAM was selected for all the simulations of foam specimens. *MAT_CRUSHABLE_FOAM requires the user to input five parameters: density (RO), elastic modulus (E), Poisson’s ratio (PR), a load curve LCID, which defines the yield stress vs. volumetric strain, tensile stress cut-off (TSC) and a rate sensitivity damping coefficient (DAMP). Nevertheless, when an LCID was defined, it was found that the variation of E and TSC did not affect the behaviour of the virtual specimen. For all simulations, the values of PR and DAMP were set to zero and 0.1, respectively, whilst the value of RO was equal to the density of the real specimen. A piecewise stress vs. volumetric strain curve a was useanalysed b.2; element aspect ratio between one and 2.2) with a thickness of 0.3 mm and 0.6 mm were used for the core and for the outer skin, respectively. The impact conditions were the same as those used for the crash simulations of the foams. Amongst the different material cards available in LS-Dyna, an elasto-plastic constitutive material model  was chosen. *MAT_24 requires the user to define an arbitrary stress vs. strain curve via the definition of effective plastic strain values and their corresponding yield stress values. In order to calibrate the models, the Young’s modulus E and the yield strength SIGY were set as variables. The plateau stress was assumed constant at the value of The FE models of 3D printed specimens were created so as to reflect the actual geometry and topology of their real counterparts. O (Rohacell® 110RIST) is shown in As mentioned in the previous sections, an inverse approach was adopted to determine the dynamic strength of the specimens via the FE method. The material parameters were iteratively varied until a close correlation between the numerical and experimental results was found. In order to establish the predictive ability of the material model used, quasi-static compression tests were simulated using the stress vs. strain relationship sketched in The correlation between numerical and experimental results for quasi-static tests was good by using a simple elastic perfectly plastic stress vs. strain relationship with a Young’s modulus equal to 160 MPa for all the simulations and YL (Rohacell® 110RIMA) under dynamic compression. The same approach was adopted for all the other impact cases  was experimentally investigated through a series of mechanical tests. The investigated materials were subjected to different loading conditions, from quasi-static regimes to impact loading. The experimental results revealed marked differences in the compressive response of the investigated material as far as the stress and strain were concerned. All the investigated materials were strain rate sensitive and showed enhanced strength with an increase in strain rate.Amongst the thirty six tested materials, ten were selected for the dynamic characterisation under dynamic conditions. A single stage gas gun was employed to fire cylindrical specimens onto a rigid bar anvil, in the manner of a Taylor test. High speed cameras were employed to record the deformation history of the specimen. The experimental results revealed an increase of the compressive strength of the materials with increasing the test strain rate. The mechanical properties were dependant on the material density, precursor material and infill topology. It was found that 3D printed materials can have higher collapse stress with respect to polymeric foams. On the other hand, the latter would be more efficient and able to absorb higher amounts of energy compared to the former class of materials for the same density. In order to determine the strength of the materials under dynamic conditions, the FE method was used. Numerical results matched well with the experimental results and revealed a further increase of the plateau stress by as much as 87% with respect to the strength calculated at quasi-static test rates.