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OBJECTIVES/GOALS: To determine if decellularized costal cartilage (DCC), which could theoretically be obtained “off the shelf,” would provide similar results to autologous cartilage grafts previously studied in this lab, thereby widening the application of our novel nipple engineering approach to all patients undergoing nipple reconstruction. METHODS/STUDY POPULATION: PLA scaffolds (diameter: 1.0 cm, height: 1.0 cm) were printed using a PRUSA 3D printer and sterilized. Lamb costal cartilage was minced (1 mm3) or zested (<0.2 mm3) and then decellularized. The quality of decellularization was assessed using DNA quantification and histological analysis. DCC was then packed into PLA scaffolds and implanted subcutaneously into immunocompetent Sprague Dawley rats using a CV flap technique. The constructs were explanted and evaluated up to 6 months after implantation. RESULTS/ANTICIPATED RESULTS: All nipple reconstructions showed well-preserved diameter and projection due to persistence of the external scaffolds at 1, 3, and 6 months. Mass and volume of engineered tissue was well-preserved over all timepoints. Compared to implantation values, engineered zested nipples demonstrated a 12% mass increase and a 22% volume increase at 6 months. Minced nipples illustrated a similar mass and volume gain with a 21% increase in mass and a 13% increase in volume at 6 months secondary to infiltration of fibrovascular tissue and growth through scaffold wall pores, respectively. Histologic analysis demonstrated a mild inflammatory infiltrate 1 month after implantation which was replaced by fibrovascular tissue by 3 months that remained stable through 6 months. The processed DCC structure remained unchanged over time. DISCUSSION/SIGNIFICANCE: Using acellular ovine xenograft within bioabsorbable scaffolds, we have engineered neonipples that maintain their volume for at least 6 months. DCC architecture is well-preserved with minimal evidence of immune-mediated degradation. By using DCC, this novel approach to nipple engineering may be applied to any patient requiring reconstruction.
The extent of the reduction of maize (Zea mays L.) kernel moisture content through drying is closely related to field temperature (or accumulated temperature; AT) following maturation. In 2017 and 2018, we selected eight maize hybrids that are widely planted in Northeastern China to construct kernel drying prediction models for each hybrid based on kernel drying dynamics. In the traditional harvest scenario using the optimal sowing date (OSD), maize kernels underwent drying from 4th September to 5th October, with variation coefficients of 1.0–1.9. However, with a latest sowing date (LSD), drying occurred from 14th September to 31st October, with variation coefficients of 1.3–3.0. In the changed harvest scenario, the drying time of maize sown on the OSD condition was from 12th September to 9th November with variation coefficients of 1.3–3.0, while maize sown on the LSD had drying dates of 26th September to 28th October with variation coefficients of 1.5–3.6. In the future harvest scenario, the Fengken 139 (FK139) and Jingnongke 728 (JNK728) hybrids finished drying on 20th October and 8th November, respectively, when sown on the OSD and had variation coefficients of 2.7–2.8. Therefore, the maize kernel drying time was gradually delayed and was associated with an increased demand for AT ⩾ 0°C late in the growing season. Furthermore, we observed variation among different growing seasons likely due to differences in weather patterns, and that sowing dates impact variations in drying times to a greater extent than harvest scenarios.
Depressive symptoms are highly prevalent among partnered dementia caregivers, but the mechanisms are unclear. This study examined the mediating role of loneliness in the association between dementia and other types of care on subsequent depressive symptoms.
Prospective data from partnered caregivers were drawn from the English Longitudinal Study of Aging. The sample consisted of 4,672 partnered adults aged 50–70 living in England and Wales, followed up between 2006–2007 and 2014–2015. Caregiving was assessed across waves 3 (2006–2007), 4 (2008–2009), and 5 (2010–2011), loneliness at wave 6 (2012–2013), and subsequent depressive symptoms at wave 7 (2014–15). Multivariable logistic regression models were used to assess the association between caregiving for dementia and depressive symptoms compared to caregiving for other illnesses (e.g., diabetes, coronary heart disease (CHD), cancer, and stroke). Binary mediation analysis was used to estimate the indirect effects of caregiving on depressive symptoms via loneliness.
Care for a partner with dementia was associated with higher odds of depressive symptoms at follow-up compared to those not caring for a partner at all (odds ratio [OR] = 2.6, 95% confidence intervals [CI]: 1.4, 5.1). This association was partially mediated by loneliness (34%). Care for a partner with other conditions was also associated with higher odds of depressive symptoms compared to non-caregiving partners (OR = 1.7, 95% CI: 1.2, 2.5), but there was no evidence of an indirect pathway via loneliness.
Loneliness represents an important contributor to the relationship between dementia caregiving and subsequent depressive symptoms; therefore, interventions to reduce loneliness among partnered dementia caregivers should be considered.
In this paper the configurations of shock wave–boundary layer interactions (SWBLI) are studied theoretically and experimentally in Mach number 2 and 2.5 flows on test models with various wedge angles ranging from $9^\circ$ to $21^\circ$. The proposed theoretical method couples the free interaction theory (FIT) with the minimum entropy production (MEP) principle to predict the appearance of separation shock, resulting in convex, straight and concave separation shock waves according to different solution combinations, which agree well with current experiments. Additionally, several influences on SWBLI are studied experimentally, in which the parameters related to theoretical solutions are found mostly determining the flow configuration, and SWBLI is much more sensitive to incident shock strength than incoming flow properties. Separation could be suppressed by incident shock when the MEP solution is smaller than the FIT, while it could be intensified when the MEP solution is larger than FIT; by contrast, the effects of separation position and model mounting height could be very weak.
Previously the GABA(A) receptor beta-2 subunit gene GABRB2 was found to be associated with schizophrenia (SCZ). for SNPs and haplotypes in GRBRB2, the associations with bipolar disorder (BPD), the functional consequences on GABRB2 expression and their relationship to demographic and clinical characteristics in BPD and SCZ remain to be elucidated.
Case-control analysis was performed for association study of GABRB2 with BPD, and its mRNA expression in postmortem BPD brains was examined using quantitative real-time PCR. Quantitative trait analysis was subsequently employed to assess the covariate effects of demographic and clinical characteristics on genotypic correlation of GABRB2 expression in SCZ and BPD.
Significant association of GABRB2 with BPD and reduction in GABRB2 mRNA expression in BPD brains were observed in the present study. Duration of illness (DOI) was found to be a significant covariate for the correlation of the disease-associated SNPs rs1816071, rs1816072 and rs187269 with GABRB2 expression in both SCZ and BPD. for individuals with homozygous major genotypes of these SNPs, while GABRB2 expression increased with age in the controls, it decreased with DOI and age in SCZ, and with DOI in BPD. with age of onset as covariate, these three SNPs were significantly correlated with antipsychotic dosage in SCZ.
These results have thus revealed correlations of GABRB2 SNPs and expression not only with the occurrence of SCZ and BPD, but also with the clinical characteristics of patients, therefore providing support for a shared etiological role played by the gene in both diseases.
GABRB2, the gene for β2 subunit of the gamma-aminobutyric acid type A (GABAA) receptor, is known to display two splicing isoforms in the brain, namely β2L containing Exon 10 and β2S devoid of Exon 10. Previously, the expressions of these isoforms were correlated with both schizophrenia and various sequence polymorphisms of the gene. in the present study, a series of deletions made on Intron 9 of a minigene construct affected the expression of Exon 10, and generated additional splicing variations suggesting the existence of additional splicing variants of β2subunit. A search among brain cDNAs uncovered the two novel short forms: β2S1which is devoid of Exons 10 and 11 and bears an extended Exon 9, and β2S2 which is devoid of Exon 10 and bears a shortened Exon 11.Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics, 30 bipolar disorder and 31 controls of US population, showed that the level of β2S2 was significantly decreased in bipolar disorder, and marginally decreased in schizophrenia, while β2S1 was marginally increased in both of these psychotic disorders. Significant genotypic effects of rs1816071, rs1816072 and rs187269 on β2S2 level were observed in male schizophrenic and bipolar patients. These findings pointed to the neighborhood of Exon 10 as an alternate-splicing hot-spot, and underlined the relevance of β2 subunit isoforms to the etiology of psychotic disorders.
Quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) are commonly used in cost-effectiveness analysis (CEA) to measure health benefits. We sought to quantify and explain differences between QALY- and DALY-based cost-effectiveness ratios, and explore whether using one versus the other would materially affect conclusions about an intervention's cost-effectiveness.
We identified CEAs using both QALYs and DALYs from the Tufts Medical Center CEA Registry and Global Health CEA Registry, with a supplemental search to ensure comprehensive literature coverage. We calculated absolute and relative differences between the QALY- and DALY-based ratios, and compared ratios to common benchmarks (e.g., 1× gross domestic product per capita). We converted reported costs into US dollars.
Among eleven published CEAs reporting both QALYs and DALYs, seven focused on pharmaceuticals and infectious disease, and five were conducted in high-income countries. Four studies concluded that the intervention was “dominant” (cost-saving). Among the QALY- and DALY-based ratios reported from the remaining seven studies, absolute differences ranged from approximately $2 to $15,000 per unit of benefit, and relative differences from 6–120 percent, but most differences were modest in comparison with the ratio value itself. The values assigned to utility and disability weights explained most observed differences. In comparison with cost-effectiveness thresholds, conclusions were consistent regardless of the ratio type in ten of eleven cases.
Our results suggest that although QALY- and DALY-based ratios for the same intervention can differ, differences tend to be modest and do not materially affect comparisons to common cost-effectiveness thresholds.
A growing number of frail older adults are treated in the emergency department (ED) and discharged home. There is an unmet need to identify older adults that are predisposed to functional decline and repeat ED visits so as to target them with proactive interventions.
A prospective cohort study was conducted in patients 75 years or older who were being discharged from the ED. The objective was to test the value of frailty screening tests, namely 5-meter gait speed and handgrip strength, to predict repeat ED visits at 1 and 6 months and functional decline at 1 month using multivariable logistic regression.
After excluding 7 patients lost to follow-up, 150 patients were available for analysis. The mean age was 81.1 ± 4.9 years with 51% females, 13% arriving by ambulance, and 67% having at least two comorbid conditions. At ED discharge, 41% of patients were found to have slow gait speed, whereas 23% had weak handgrip strength. After adjustment, only slow gait speed was independently associated with functional decline at 1 month (odds ratio [OR] 1.39 per 0.1 meters/second decrement, 95% confidence interval [CI], 1.12 to 1.72) and repeat ED visits at 6 months (OR 1.20 per 0.1 meters/second decrement, 95% CI, 1.01 to 1.42).
Gait speed can be feasibly measured at the time of ED discharge to identify frail older adults at risk for early functional decline and subsequent return to the ED. Conversely, grip strength was not found to be associated with functional decline or ED visits.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
The elastoplastic behavior of a Functionally Graded Material (FGM) simply supported beam consisting of elastic material A and elastoplastic material B under uniformly distributed load is investigated. A power function is used to describe the volume fractions of the constituent materials, and the average stress of the FGM beam is obtained by using the averaging method. This method can avoid the assumption of the varying properties of the whole material, and can consider the different Possion’s ratios of the different constituent materials. What’s more, only the elastoplastic material B in the FGM beam will yield, and the yield function is determined by the stress of material B only, rather than the average stress of the whole material. The method used in this work is more closer to the real material than the method by assuming the variation of the whole properties of FGM. The theoretical results show a good agreement with the finite element results, which indicates that the method provided in this work is valid. With this method, the variation of the elastic and plastic areas, the stress distribution on the cross section, variation of the curvature and neutral layer, and the residual stress distribution of the FGM beam are discussed through numerical results. This work can provide a new way for the design and in-depth investigation of FGM material.
Polarimetric studies of pulsars at low radio frequencies provide important observational insights into the pulsar emission mechanism and beam models, and probe the properties of the magneto-ionic interstellar medium (ISM). Aperture arrays are the main form of next-generation low-frequency telescopes, including the Murchison Widefield Array (MWA). These require a distinctly different approach to data processing (e.g. calibration and beamforming) compared to traditional dish antennas. As the second paper of this series, we present a verification of the MWA’s pulsar polarimetry capability, using two bright southern pulsars, PSRs J0742–2822 and J1752–2806. Our observations simultaneously cover multiple frequencies (76–313 MHz) and were taken at multiple zenith angles (ZA) during a single night for each pulsar. We show that the MWA can be reliably calibrated for ZA ≲45° and frequencies ≲270 MHz. We present the polarimetric profiles for PSRs J0742–2822 and J1752–2806 at frequencies lower than 300 MHz for the first time, along with an analysis of the linear polarisation degree and pulse profile evolution with frequency. For PSR J0742–2822, the measured degree of linear polarisation shows a rapid decrease at low frequencies, in contrast with the generally expected trend, which can be attributed to depolarisation effects from small-scale, turbulent, magneto-ionic ISM components. This effect has not been widely explored for pulsars in general and will be further investigated in future work.
LAMOST has obtained a large number of spectra for K-giant stars whose metallicities are well measured and released in DR5. Combining with the distances, radial velocities and proper motions provided by Gaia DR2, the full position and velocity information has been obtained. Using the Bayesian method we have constrained the rotational velocity of the halo and thick disk components in the local volume within 4 kpc from the Sun. The values of the rotational velocity are and for the halo and disk respectively, with the velocity of LSR assumed to be 232 km s−1. The dispersions of the rotational velocity are and for the two components. What’s more, another hot retrogradely rotating component is discovered.
A major uncertainty in the determination of the mass profile of the Milky Way using stellar kinematics in the halo is the poorly determined anisotropy parameter, , where σr is the Galactocentric radial velocity dispersion, and σθ and σφ are the tangential components of the velocity dispersion. We have used a sample of over 24,000 Galactic halo K giant and blue horizontal branch stars from the LAMOST stellar spectroscopic survey and SDSS/SEGUE, combined with proper motions from Gaia Data Release 2, to measure β(rgc) over a wide range of Galactocentric distances rgc from 5 to 80 kpc. Kinematic substructures have been carefully removed to reveal the underlying diffuse stellar halo prior to measuring β. We find that orbits are generally radial (β > 0) and β is constant out to distances of about 40 kpc, with a dependence on metallicity of the stars, such that β declines with lower metallicity. Similar behavior is seen in both the K giant and BHB samples.
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep.
Introduction: Deep vein thrombosis (DVT) can lead to significant morbidity and mortality if not diagnosed and treated promptly. Currently, few methods aside from venous duplex scanning can rule out DVT in patients presenting to the Emergency Department (ED). Current screening tools, including the use of the subjective Wells score, frequently leads to unnecessary investigations and anticoagulation. In this study, we sought to determine whether two-site compression point-of-care ultrasound (POCUS) combined with a negative age-adjusted D-dimer test can accurately rule out DVT in ED patients irrespective of the modified Wells score. Methods: This is a single-center, prospective observational study in the ED of the Jewish General Hospital in Montreal. We are recruiting a convenience sample of patients presenting to the ED with symptoms suggestive of DVT. All enrolled patients are risk-stratified using the modified Wells criteria for DVT, then undergo two-site compression POCUS, and testing for age-adjusted D-dimer. Patients with DVT unlikely according to modified Wells score, negative POCUS and negative age-adjusted D-dimer are discharged home and receive a three-month phone follow-up. Patients with DVT likely according to modified Wells score, a positive POCUS or a positive age-adjusted D-dimer, will undergo a venous duplex scan. A true negative DVT is defined as either a negative venous duplex scan or a negative follow-up phone questionnaire for patients who were sent home without a venous duplex scan. Results: Of the 42 patients recruited thus far, the mean age is 56 years old and 42.8% are male. Twelve (28.6%) patients had DVT unlikely as per modified Wells score, negative POCUS and negative age-adjusted D-dimer and were discharged home. None of these patients developed a DVT on three-month follow-up. Thirty patients (71.4%) had either a DVT likely as per modified Wells score, a positive POCUS or a positive age-adjusted D-dimer and underwent a venous duplex scan. Of those, six patients had a confirmed DVT (3 proximal & 3 distal). POCUS detected all proximal DVTs, while combined POCUS and age-adjusted D-dimer detected all proximal and distal DVTs. None of the patients with a negative POCUS and age-adjusted D-dimer were found to have a DVT. Conclusion: Two-site compression POCUS combined with a negative age-adjusted D-dimer test appears to accurately rule out DVT in ED patients without the need for follow-up duplex venous scan. Using this approach would alleviate the need to calculate the Wells score, and also reduce the need for radiology-performed duplex venous scan for many patients.
Increasing evidence has demonstrated that the environmental conditions experienced by parents can shape offspring phenotypes. Here, we examined the effects of the photoperiod and temperature experienced by parents on the incidence of diapause in their progeny in the cabbage beetle, Colaphellus bowringi, using three experiments. The first experiment examined parental diapause incidence under different photoperiods at 25°C and the incidence of diapause in progeny from both non-diapausing and diapausing parents under the same rearing conditions. The results revealed that the incidence of diapause among progeny was exactly opposite to that of their parents, i.e., higher parental diapause incidence led to lower progeny diapause incidence, showing a negative relationship in diapause incidence between the parental generation and the progeny generation. The incidence of diapause among progeny produced by diapausing parents was higher than that in progeny produced by non-diapausing parents. The second experiment examined parental diapause incidence at different temperatures under LD 12:12 and the incidence of diapause in progeny from both non-diapausing and diapausing parents under the same rearing conditions. Similarly, the incidence of diapause in progeny was also opposite to that of their parents. However, the incidence of diapause in progeny produced by non-diapausing parents was different from that in progeny produced by diapausing parents. In the third experiment, naturally diapausing adults were maintained at a constant temperature of 9, 28°C or the mean daily summer temperature of 27.84°C under continuous darkness for 3 months of dormancy. After dormancy, the progeny of these post-diapause parents were reared under different photoperiods at 25°C. The results showed that the incidence of diapause among progeny was higher when their parents experienced high temperatures than when they experienced low temperatures. All results demonstrate that the photoperiod and temperature experienced by parents may significantly affect the diapause incidence among progeny.
The Murchison Widefield Array, and its recently developed Voltage Capture System, facilitates extending the low-frequency range of pulsar observations at high-time and -frequency resolution in the Southern Hemisphere, providing further information about pulsars and the ISM. We present the results of an initial time-resolved census of known pulsars using the Murchison Widefield Array. To significantly reduce the processing load, we incoherently sum the detected powers from the 128 Murchison Widefield Array tiles, which yields ~10% of the attainable sensitivity of the coherent sum. This preserves the large field-of-view (~450 deg2 at 185 MHz), allowing multiple pulsars to be observed simultaneously. We developed a WIde-field Pulsar Pipeline that processes the data from each observation and automatically folds every known pulsar located within the beam. We have detected 50 pulsars to date, 6 of which are millisecond pulsars. This is consistent with our expectation, given the telescope sensitivity and the sky coverage of the processed data (~17 000 deg2). For 10 pulsars, we present the lowest frequency detections published. For a subset of the pulsars, we present multi-frequency pulse profiles by combining our data with published profiles from other telescopes. Since the Murchison Widefield Array is a low-frequency precursor to the Square Kilometre Array, we use our census results to forecast that a survey using the low-frequency component of the Square Kilometre Array Phase 1 can potentially detect around 9 400 pulsars.
The Lower Devonian Posongchong Formation (Wenshan, Yunnan Province, southwestern China) consists of a series of continental deposits with an outstanding plant megafossil diversity. More than 20 years ago, this formation was interpreted as ‘Siegenian' (∼Pragian) in age based on palynology. However, such interpretation needs further evidence because of the known differences between the dispersed spore assemblages from South China and Euramerica/northwestern Gondwana. Here, we present new dispersed spore assemblages recently recovered from the Posongchong Formation. The isolated spore diversity is highly diverse, with 18 genera and 32 species. The recognised taxa include, among others, Ambitisporites avitus, Aneurospora conica, Aneurospora posongchongensis sp. nov., Aneurospora xujiachongensis, Apiculiretusispora plicata, Archaeozonotriletes chulus, Concentricosisporites agradabilis, Dibolisporites echinaceus, Emphanisporites rotatus, Gneudnaspora divellomedia, Latosporites ovalis, Retusotriletes triangulatus, Tetrahedraletes medinensis and Verrucosporites polygonalis, with Aneurospora and Retusotriletes being the most abundant forms. The known Posongchong palynoflora (previous spore data included) suggests that the Posongchong Formation assemblages can be correlated with the Pragian interval of the polygonalis–wetteldorfensis Oppel Zone (PoW). This age determination is supported by the presence of index species of PoW, such as Verrucosporites polygonalis, Dictyotriletes subgranifer and Camarozonotriletes parvus (sensu Steemans, 1989), the latter being known only from the Pragian of Belgium and Germany. Recent advances in the study of the marine faunas in the overlying sequences also indicate a Pragian age for the Posongchong Formation. This new investigation of the Posongchong palynoflora highlights differences of abundance at species level between the Gondwanan–Laurussian floras during the Early Devonian.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.