Syphilis remains a growing and resurging infectious disease in China. However, exploring the influence of environmental factors on the spatiotemporal distribution of syphilis remains under explore. This study aims to analyze the spatiotemporal distribution characteristics of syphilis in Ningxia, Northwest China, and its potential environmental influencing factors. Based on the standardized incidence ratio of syphilis for 22 administrative areas in Ningxia from 2004 to 2017, spatiotemporal autocorrelation and scan analyses were employed to analyze the spatial and temporal distribution characteristics of syphilis incidence, while a fixed-effect spatial panel regression model identified the potential factors affecting syphilis incidence. Syphilis incidence increased from 3.78/100,000 in 2004 to 54.69/100,000 in 2017 with significant spatial clustering in 2007 and 2009–2013. The “high–high” and “low–low” clusters were mainly distributed in northern and southern Ningxia, respectively. The spatial error panel model demonstrated that the syphilis incidence may be positively correlated with the per capita GDP and tertiary industry GDP and negatively correlated with the number of health facilities and healthcare personnel. Sex ratio and meteorological factors were not significantly associated with syphilis incidence. These results show that the syphilis incidence in Ningxia is still increasing and has significant spatial distribution differences and clustering. Socio-economic and health-resource factors could affect the incidence; therefore, strengthening syphilis surveillance of migrants in the economically developed region and allocating health resources to economically underdeveloped areas may effectively help prevent and control syphilis outbreaks in high-risk cluster areas of Ningxia. Treponema pallidum (TP) infection. It principally spreads through sexual contact, vertical transmission, and blood transmission [Syphilis is a chronic infectious disease, commonly caused in humans by smission ,2. Earlysmission ,4. Accorsmission ,6. As onsmission . Thus, sAbout 80% of epidemiological data have spatial attributes ,10,11,12Identifying key areas of syphilis incidence based on spatiotemporal distribution studies, and combining evidence of potential meteorological or socio-economic drivers to adjust syphilis prevention strategies and allocate health resources is of great significance for effective syphilis prevention and control. Current spatial econometric methods are widely used in public health and health policy evaluation ,20,21,22Ningxia Hui Autonomous Region (referred as “Ningxia”), located in northwest China, is an economically underdeveloped region, bordering the Gansu and Shaanxi provinces. According to a report by the Ningxia Center for Disease Control and Prevention, syphilis remains a growing and resurging infectious disease. Existing evidence showed that socio-economic and health-resource factors may affect the spatial distribution of syphilis ; however(i)Yinchuan city: including Xingqing, Xixia, Jinfeng, Yongning, Helan, and Lingwu;(ii)Shizuishan city: including Dawukou, Huinong, and Pingluo;(iii)Wuzhong city: including Litong, Hongsibu, Qingtongxia, Yanchi, and Tongxin;(iv)Guyuan city: including Yuanzhou, Xiji, Longde, Jingyuan, and Pengyang;(v)Zhongwei city: including Shapotou, Zhongning, and Haiyuan.In this study, 22 administrative areas across five cities in Ningxia, China were selected as the study area. The specific research areas were as follows:Data on the syphilis incidence in the Ningxia Hui Autonomous Region from 2004 to 2017 were obtained from the National Notifiable Infectious Disease Reporting Information System (as shown in http://www.ngcc.cn/ngcc/ (accessed on 22 January 2022)).The Ningxia map base layer comes from the National Basic Geographic Information System (http://nxdata.com.cn/publish.htm?cn=G01 (accessed on 22 January 2022)), as shown in In addition, the administrative area-level meteorological factors, socio-economic, and health-resource data of 22 administrative areas in Ningxia from 2004 to 2017 were obtained from Ningxia Statistical Yearbook  of syphilis , the forijy denotes the number of reported syphilis cases in administrative area i (1 ≤ i ≤ 22) in year j (2004 ≤ j ≤ 2017) and ijE denotes the expected number of reported cases in the administrative area i in year j, which can be obtained by multiplying the population of the administrative area by the reported incidence of syphilis in the whole district in year j.Here, To visualize the spatiotemporal variations of the incidence of syphilis in Ningxia from 2004 to 2017, the three-dimensional spatial trend surface of the average incidence of syphilis in different areas was analyzed to reveal the spatial distribution characteristics of the clusters . Each diMoran’s I and the local Moran’s I are used as indicators of spatial autocorrelation analysis. The range of Moran’s I is from −1 to 1; I > 0 indicates positive spatial correlation. The closer the value is to 1, the higher the spatial aggregation is. I < 0 indicates negative spatial correlation; I = 0 indicates that there is no spatial aggregation, that is, random distribution [Moran’s I mainly includes four clusters: high–high cluster (high–high), low–low cluster (low–low), high–low cluster (high–low), and low–high cluster (low–high) [The global ribution ,27. Locaow–high) ,29.LLR). The size and position of the risk area circles are drawn according to the result file of ArcGIS version exported from the spatiotemporal scan analysis .In order to further identify the spatiotemporal clustering characteristics of high-risk of syphilis in Ningxia and determine the location and relative risk of the clusters, the spatial scan analysis performed by SaTScan was employed ,31. The (1)p < 0.05, then the mixed OLS regression model should be rejected and the spatial panel regression model should be used.Lagrange multiplier test (LM test): It is used for the selection of mixed ordinary least squares (OLS) regression model and spatial regression model. If (2)p < 0.05), it cannot be degraded to SLM or SEM model, and SDM model should be used.Robustness test: Likelihood ratio test (LR test) and Wald test are used to test whether the preset SDM model can degenerate into SLM or SEM model. When the result is significant ((3)(i)p < 0.05, H0 is rejected and fixed effects should be selected.Selection of random/fixed effects: The Hausman test (HAUSMAN test) is used. The coefficients obtained from this test are generated under random effects. If (ii)p < 0.05), the two-way effect will be used.Selection of individual/time/two-way effect: The individual and time effects are compared with the two-way effect. If the test results are both significant (Model effect selection:(4)Based on the above test processes, a reasonable spatial regression model is established.Spatial panel data models were employed to identify the potential meteorological influencing factors of syphilis. Spatial regression models included: Spatial Lag Model (SLM/SAR), Spatial Error Model (SEM), and Spatial Durbin Model (SDM). Lagrange multiplier test (LM test) and Hausman test (HAUSMAN test) were required to determine which spatial regression model would be most appropriate ,22,34. Ai (1 ≤ i ≤ 22) at year t; i at year t, The spatial error model with spatial and temporal fixed effects could be specified as follows:p < 0.05 was regarded as statistically significant.Statistical description and spatial regression models were generated by Stata 14.0, three-dimensional spatial trend surface analysis was completed by ArcGIS10.6, spatiotemporal scan analysis was performed by SaTScan 9.4.1 , and spatial autocorrelation analysis was performed by GeoDa 1.10  and ArcGIS10.6, with the number of Monte Carlo randomized repeated simulations set as M = 999. The significance level of A total of 28,621 syphilis cases were reported in Ningxia from 2004 to 2017. Spatiotemporal analysis of syphilis SMR in Ningxia from 2004 to 2017, as shown in The results of spatial three-dimensional trend map revealed that the distribution of syphilis SMR in the 22 administrative areas in Ningxia was higher in the northern regions than in the southern regions in the north-south direction, and the distribution in the eastern regions was higher than the western region in the east-west direction. The results of trend surface analysis indicated that syphilis was a more serious problem in the eastern and northern regions of Ningxia b.LLR = 3972.88, p < 0.001). The second cluster occurred in south Ningxia during 2015–2017, covering Yuanzhou and Pengyang, with an area radius of 35.63 km, and the risk of syphilis in this cluster was 2.57 times higher than that found in the other areas .As shown in Moran’s I index was used to analyze the spatial autocorrelation of syphilis incidence in 22 administrative areas of Ningxia from 2004 to 2017. As illustrated in Moran’s I > 0, p < 0.05). The spatial cluster of syphilis in Ningxia was the highest in 2012 (Moran’s I = 0.5439) and lowest in 2007 (Moran’s I = 0.2369).The Moran’s I was used. We drew the scatter diagram of Moran’s I and LIAS aggregation diagram. The results are shown in To further explore the spatiotemporal clusters of syphilis in Ningxia, the local Syphilis in Ningxia showed a significant spatial discrepancy. In order to further explore the potential factors associated with the spatiotemporal distribution differences, we established the spatial regression model to identify the factors influencing meteorological, socio-economic, and health-resource factors. χ2 = 24.25; p = 0.0117). Thus, the fixed-effect spatial error model was more suitable to adopted.It follows from the LM test, that the serial autocorrelation and spatial error effect should be considered . Accordip < 0.05). Therefore, it is more reasonable to choose the spatiotemporal bidirectional fixed effect model to investigate the potential influencing factors.The fixed-effect spatial error model was constructed to consider the time fixed effect, individual fixed effect, and bidirectional fixed effect  and tertiary industry GDP  in Ningxia, indicating that higher GDP per capita and tertiary industry GDP adversely affect the incidence of syphilis. Moreover, the SMR of syphilis in Ningxia was negatively correlated with the number of healthcare facilities  and the number of healthcare personnel , which implied that the adequate medical resources was conducive to the prevention and control of syphilis. Moreover, the coefficient of spatial autoregression was λ = 0.355 (p < 0.001), which demonstrated that the aforementioned influencing factors, were also affected by the neighborhood levels.In order to effectively strengthen syphilis prevention and control, the 59th World Health Assembly adopted the Prevention and Control of Sexually Transmitted Infections: Draft Global Strategy  in 2006,Spatial autocorrelation methods were used to analyze the spatiotemporal distribution characteristics of syphilis incidence in Ningxia from 2004 to 2017. There were clusters of syphilis incidence in Ningxia in 2007, 2009, 2010, 2011, 2012, and 2013. The “high–high” cluster areas were mainly in northern Ningxia , surrounding Yinchuan, the provincial capital of Ningxia. The “low–low” clusters were mainly located in southern Ningxia, with a tendency of distribution towards the central regions. This result was consistent with the findings of the spatiotemporal scan analysis, which confirmed that two spatial-temporal clusters were detected in Ningxia, the first cluster was identified during 2011–2017 in north of Ningxia (area radius of 149.84 km) and the second cluster was identified in south Ningxia during 2015–2017 (area radius of 35.63 km) with 2.94- and 2.57-times higher risk of syphilis than that found in other areas, respectively. The results of the three-dimensional trend surface analysis demonstrated that syphilis was more prevalent in the eastern and northern regions of Ningxia. It may be related to the continuous socio-economic development and change in people’s ideology in recent years; the gradual opening up of attitudes toward sexual behavior and presence of risky sexual behaviors results in a significant increase in the chance of infection contraction, which may explain the rapid increase in the number of syphilis cases . TherefoRegarding the factors influencing the spatiotemporal distribution of syphilis incidence, this study included meteorological, socio-economic, and health-resource indicators into the spatial error model for exploratory analysis. After adjusting for the effects of spatial autocorrelation, the results showed that the incidence of syphilis in Ningxia may be related to the tertiary industry GDP, per capita GDP, and the number of healthcare personnel. The incidence of syphilis in Ningxia may be positively correlated with the tertiary industry GDP and per capita GDP, while negatively correlated with the number of healthcare facilities and healthcare personnel. However, sex ratio and meteorological factors were not significantly associated with syphilis incidence in Ningxia.−7 and 4.38 × 10−6 units of syphilis SMR, respectively. The socio-economic factors may play an important role in aggravating the high-risk spatial clustering of syphilis at the neighborhood level. With the rapid development of tertiary industry and the acceleration of urbanization, an increasing migrant population may be partially responsible for the high-risk regions located in the economically developed areas of north Ningxia. The research of related scholars [Increasing 1 unit of tertiary industry GDP and GDP per capita may lead to an increase of 3.19 × 10scholars ,42 showsscholars  found thscholars ,44,45. TOur results provided an insight into the relationship between allocation of health resources and incidence of syphilis in Ningxia. The incidence of syphilis was negatively correlated with the number of healthcare personnel. This may be related to the imbalance in the construction of medical institutions, recruitment of healthcare personnel, and the inadequate capacity for diagnosis and treatment of sexually transmitted diseases in medical institutions in each administrative area. It is suggested that rational allocation of medical resources can reduce the incidence of syphilis to a certain extent. Consistent with previous studies ,39,46,47The current study has some limitations. First, this study did not provide a detailed sub-population analysis of the different stages of syphilis characteristics due to limited data; thus, we could not provide more precise recommendations for different sub-populations. Second, the data on influencing factors was limited by the data of covariates, such as education, urbanization rate, and population migration and it is recommended that more extensive and detailed research variables be selected for in-depth analysis in subsequent studies. Third, considering the serious health impact of syphilis on adults and its vertical transmission from mother to child, more attention should be paid to strengthening maternal surveillance efforts to minimize congenital syphilis; thus, further studies should address the spatial heterogeneity of congenital syphilis. Finally, this study was an ecological study examining the association between the incidence of syphilis and its influencing socio-economic and health-resource factors, the potential ecological fallacy is inevitable.In summary, the results of this study provide empirical evidence for the heterogenous spatiotemporal distribution of syphilis in Ningxia and its influencing socio-economic and health-resource factors. The incidence of syphilis in Ningxia has increased in recent years and there were significantly spatial clusters. Two spatial-temporal clusters were detected, with 2.94- and 2.57-times higher risk of syphilis than that found in other areas. We found that the socio-economic and health-resource factors could affect the incidence of syphilis to different degrees and in different directions. However, sex ratio and meteorological factors were not significantly associated with syphilis across Ningxia. Understanding the spatial heterogeneity of syphilis incidence and associated influencing factors plays an important role in implementing precise and effective public health intervention strategies for the control and prevention of syphilis.


Questionnaires regarding hormonal factors were distributed from the index date. Data regarding CVE were obtained from the Swedish National Health Register and Cause of Death Register. Associations between CVE and hormonal factors were analyzed using Cox proportional hazard regression. Of the postmenopausal women, 64 women had a CVE after RA onset. The time period from menopause to RA onset was significantly longer for CVE cases with higher proportion of postmenopausal women. In Cox proportional hazard regression models, years from last childbirth and multiparity were associated with higher CVE risk. Adjustments for traditional risk factors did not affect the results except for hypertension. RA onset after menopause and a longer duration from menopause until onset increased the CVE risk. Multiparity was associated with higher CVE risk whilst oral contraceptives decreased the risk. These results can contribute to identification of high-risk patients for CVE beyond traditional risk factors.Hormonal and reproductive factors affect the risk for cardiovascular events (CVE) in the general population. Although the risk of CVE is increased in rheumatoid arthritis (RA), the knowledge about the impact of hormonal factors for CVE in RA is sparse. Female postmenopausal patients ≤80 years with early RA were consecutively included in this observational study ( Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD), which contributes to the largest proportion of excess mortality compared with the general population, particularly ischemic heart disease, not fully accounted for by traditional risk factors ,2,3. OthFurthermore, there is a difference in traditional risk factors, in general, between men and women, where results increasingly suggest that several reproductive factors associate with later-life CVD ,10.In relation to the development of RA, hormonal factors have been analyzed in a number of studies ,12,13. TOther hormones, such as androgens, progesterone or prolactin, also exert effects on the immune system. The postmenopausal stage, an early age at menopause, the post-partum period, and the use of anti-estrogen agents are associated with RA onset. All these phenomena have in common an acute decline in ovarian function and/or in estrogen bioavailability .Several hormonal and reproductive factors in women of the general population have been shown to associate with the risk of developing later-life CVD, although findings are diverse and inconsistent ,21,22,23In the light of studies concerning hormonal and/or reproductive factors for both CVD per se and for RA, we have analyzed the associations between hormonal and reproductive factors, and RA disease-related factors for the risk of developing CVE in women with early RA. We have, as one of the first studies focused on factors previously analyzed for women of the general population, to explore the impact of these factors in women with RA for affection with CVE.Patients from the northern region of Sweden  with early RA (symptoms ≤12 months) fulfilling the 1987 American Rheumatism Association (ARA) classification criteria for RA  were conData regarding Disease Activity Score (DAS28)  includinn = 3) menopause. Reproductive lifespan was calculated as the time period in years between menarche and menopause. Information regarding smoking habits and body mass index (BMI kg2/m) was also asked for. The patients were classified either as being a non-smoker or ever-smoker (past or current).Self-administered questionnaires concerning hormonal and reproductive factors, such as age at menopause and menarche, number of childbirths, abortion or miscarriage, duration of breastfeeding, hormonal birth control, and hormonal replacement therapy (HRT) were continuously sent out to female patients ≤80 years between two to five years after inclusion into the early arthritis cohort. In total, 1239 patients with early RA were eligible for the study but 40 were excluded as they had deceased after index date before receiving the questionnaire, six had developed dementia, another eight were not possible to identify due to wrong addresses, incorrect personal identification numbers or emigration and five did not want to participate. Of the remaining 1185 patients diagnosed with early RA, 928 (78.6%) patients completed the questionnaires and were included in the study . FurtherData regarding cardiovascular events (CVE) was obtained from the Swedish National Health Register and Cause of Death Register and were defined as hospital admissions or death as the underlying cause, e.g., ischemic stroke , transient ischemic attack (ICD-10 code G45.9), amaurosis fugax (ICD-10 code G45.3), acute myocardial infarction , unstable angina (ICD-10 code I20.0) or angina with presence of intervention  . ComplemThe Regional Ethics Committee at the University Hospital in Umeå  approved the study. The participants gave their written informed consent and it was performed according to the Declaration of Helsinki.Enzyme-linked immunosorbent assay (ELISA) was used to detect ACPA (anti-CCP2 antibodies) and performed according to the manufacturer’s instructions . The RF were analyzed using ELISA  and erythrocyte sedimentation rate  according to Westergren method were analyzed at each hospital. Genotyping of HLA-DRB1 was performed as previously described . HLA shaRadiographs of hands, wrists, and feet were assessed at index date and after 24 months and graded according to the Larsen score method  by two et-test or the Mann–Whitney U test were used when appropriate. Cox proportional hazard regression analyses were used to take time into account for calculating hazard ratio (HR) and 95% confidence intervals (CI) of hormonal factors for CVE as dependent variable. Area under the curve (AUC) was calculated for cumulated values of DAS28 and ESR over the period of 24 months according to the trapezoid model  [24. Since there were missing values in almost all covariates under consideration, we performed a sensitivity analysis using multiple imputation (MI) where missing covariate values were imputed using the other available covariates as well a crude estimate of cumulative baseline hazard as explanatory variables, as suggested by White and Royston [p-values ≤ 0.05 were considered statistically significant. SPSS software  was used for the statistical analyses.For analyses of categorical data, the chi-square test was used. For comparison of independent continuous variables between two groups, the Student’s ctively) . No sign Royston . We perfOf the 803 postmenopausal female patients with early RA included in the study, a total of 103 patients had one or more CVE. Of them, 39 had their first event before they were diagnosed with or had their first symptoms of RA, mean (SD) 3.5 (5.2) years before RA onset and were thus excluded from further analysis. The other 64 patients had their first CVE after RA diagnosis. In the subsequent analyses, we have focused on comparing patients without CVE with those who had their first CVE after RA onset, since we wanted to focus on events in relation to RA. The total time at risk for first CVE after menopause was 7433 person-years and the incidence rate of first CVE was 7.76/1000 person-years.24 was significantly higher in the cases affected with a CVE, although there were no differences in treatments with corticosteroids and DMARDs. We did not find significant relationships between age at onset and CVD risk factors, e.g., ever-smoking, or diabetes or DAS-AUC24 except for presence of hypertension that was related to age at onset. Regarding treatment, there were no differences between the groups  time from onset of RA to CVE was 7.4 (4.8) years and the postmenopausal time period was long until CVE was observed, mean time 17.4 years (10.1) .In patients who had a CVE, the time in years from menopause until RA onset was significantly longer  and the s = 0.27, p < 0.001), years from menopause to RA onset , years from last childbirth , and DAS-AUC24 . In multiple variable analyses, the covariates being significant in simple variable analysis except for age at onset were included; the number of children calculated as continuous variable or stratified into 3 groups, and years from last childbirth remained significantly associated with having a CVE . Smoking, BMI, and use of oral contraceptives did not have a significant association with CVE. Furthermore, the significances for hypertension and diabetes were lost in multiple variable analysis. Analyses after multiple imputations presented in p = 0.053 and HR = 1.033, 95%CI 0.987, 1.08, p = 0.161, respectively). Further, no significant results were observed in the simple variable analyses of age at menopause, early menopause (≤45 years), reproductive life span, breastfeeding, HRT, progestagen, miscarriage or abortion, ESR-AUC24, HLA-SE, anti-CCP antibodies or RF.In simple Cox proportional hazard regression models focusing on CVE after RA onset, higher risk of CVE was associated with age at debut, Larsen score at 24 months, number of children, number of children stratified into 3 groups, menopause (ref. before or after RA onset), years from menopause until RA onset, years from last childbirth to RA onset, and lower age at first childbirth besides having diabetes and hypertension . In the ng a CVE a. SignifIn this inception cohort of women with recent onset RA, we have evaluated hormonal and reproductive factors, and the reproductive lifespan in relation to development of CVE. Both RA and CVE are related to hormonal factors, and we have, in addition to Pfeifer et al., as one of the first studies analyzed the impact of these factors for CVE in RA .p < 0.05) who had reached menopause. These findings suggest that it is not a long duration of disease burden in RA that account for the increased risk for CVE. Instead, the timing of disease development in relation to hormonal status appears to contribute most to the increased risk. This might be due to a certain vulnerability including aging blood vessels when getting RA after menopause when the hormonal protection of endogenous estrogen exposure is diminished. As reported elsewhere, the incidence of CVD is much lower in premenopausal than postmenopausal women in the general population [According to our findings, the convincing majority of cases with later CVE had their RA disease onset after menopause. In nine cases with CVE, RA onset predated menopause, although the mean (SD) age at onset for the nine cases was 54 (4.3) years, suggesting a very late menopause. Patients with CVE after RA onset were significantly older compared with those without a CVE , of those diagnosed with early RA and younger than 80 years of age, within the catchment area of northern Sweden. Another strength is that we have chosen a rather strict definition for CVEs and have not included all types of cardio- and cerebrovascular diseases. This strict definition decreases the risk of including patients with other causes for cardio- and cerebrovascular diseases. In contrary to some other studies, patients with other cardio-and cerebrovascular diseases such as congestive heart failure and cerebral hemorrhage were not included, although these conditions might also have been affected by hormonal and reproductive factors and the RA disease. Moreover, in our analyses, we have performed adjustments for traditional risk factors. We could confirm that the RA patients with CVE had higher frequencies of being a smoker, hypertension and/or diabetes mellitus compared with those without an event, although these factors were not significant in multiple variable analyses.Although this study included a fairly large number of patients, stratification into subgroups resulted in a limited number of cases. Another limitation could be the difficulties in accurately recalling past hormonal events. Even though the agreement has been shown to be high between medical records and interview data regarding the duration and use of oral contraceptives, women might have difficulties in accurately recalling what specific types of preparations they have used ,50. FurtThe aim of this study was to evaluate the contribution of hormonal and reproductive factors for the development of CVE in patients with early RA. Some of the factors seem to act similarly for the two diseases with increasing or decreasing the risk, where previous studies have described contradictory effects ,20. Numb24 was higher in cases with a CVE, although that was lost when time was taken into account. It is evident that the hormonal and reproductive factors act both similarly and differently in RA versus the general population, which makes it difficult to conclude about the interactive effects of these factors in RA and CVE per se. Understanding the role of female hormonal factors is of key importance for the identification of women at high risk for CVE so that preventive strategies can be initiated. These findings help to identify factors that can cause increased mortality and morbidity in women with RA besides disease-related factors and traditional risk factors for CVD.In summary, this is one of the first studies exploring the impact of hormonal and reproductive factors for CVE in women affected with RA. Female RA patients with CVE had a late RA disease onset, in most cases, after menopause. A higher number of childbirths increased the risk for CVE, as well as years from last childbirth, irrespective of traditional risk factors. Several other hormonal and reproductive factors showed a trend for increased risk of CVE, such as early menopause, pregnancy at an early age, and reproductive life span, although not significantly. Larger studies are needed to evaluate this further. The DAS28-AUC


The COVID-19 pandemic has spread rapidly and heavily hit the globe, and the mutation and transmission speed of the coronavirus have accelerated so that the world is still in danger. Thus, this study aims to investigate the participants' risk perception and explore the associations of risk perception of COVID-19 with negative emotions, information value perception and other related dimensions.A cross-sectional, population-based online survey was conducted from April 4 to 15, 2020, in China. A total of 3,552 participants were included in this study. A descriptive measure of demographic information was used in this study. Multiple regression models and moderating effect analysis were used to estimate the effect of potential associations of risk perceptions.p < 0.001) on the relationship between negative emotion and perception of risk was significant.Those who showed negative emotions  and perceived video information in social media to be useful were positively correlated with risk perception, whereas individuals who perceived experts' advice to be useful, shared risk information with friends and thought that their community made adequate emergency preparation reported lower risk perception. The moderating effect of information perceived value (β = 0.020, Individual differences in risk cognition during the COVID-19 pandemic were observed in subgroups of age level. Furthermore, the role of negative emotional states, the perceived usefulness of risk information and the sense of security also contributed to improving the public's risk perception. It is crucial for authorities to focus on residents' negative emotions and to clarify misinformation in accessible and effective ways in a timely manner. The rapid spread of the virus evolved into a global public health emergency, and many countries failed to contain the outbreak so that the world faced prolonged danger. According to the weekly epidemiological report, by the end of August 8, 2022, there have been about 5.81 hundred million confirmed cases of COVID-19, including 6,410,961 deaths 9 hit the. Timely Risk perception acts as a buffer between information exposure and decision-making behavior. It is generally defined as a cognitive judgment of the likelihood of encountering hazards when received risk information is minimal , 8. In gLerner  and LernMeanwhile, previous studies have focused on many intervening factors related to risk perception, such as demographic characteristics, trust, social environment, and government –18. HoweTo assess the public's reaction to COVID-19, we used a cross-sectional online survey of citizens in China in early April 2020. Participants were recruited from the eastern, central, and western regions of China by using a directional convenient sampling method. Regarding the severity of the epidemic, two severely affected provinces with the highest number of confirmed patients and one province with the lowest number of patients based on the prevalence of COVID-19 in the early pandemic stage were selected from each region  Depression was measured by the following question: “Would you say since the beginning of the pandemic you have been feeling depressed?” (2) Would you say since the beginning of the pandemic you have been feeling helpless? (3) Would you say since the beginning of the pandemic you have been feeling loneliness? . ParticiSince the outbreak of COVID-19, I have been afraid of being infected with this disease.Since the outbreak of COVID-19, I have been afraid of dying from this disease.Since the outbreak of COVID-19, I have felt nervous after hearing news about COVID-19.I am worried about being infected with COVID-19, so I have difficulty sleeping.Since the outbreak of COVID-19, it has been difficult for me to stay at home for a long time.When someone mentions COVID-19, my heart beats faster.Risk perception was set as the outcome variable. It was evaluated with the use of a five-point Likert scale ranging from 1 (strongly disagree) to 5 , and all 6 items were summarized from 0 to 30. Higher scores indicate greater risk perception level.Finally, this study examines the common method biases test by exploratory factor analysis, and the variance explanation rate of all the first factor is 29.34% (< 40%), which means common method deviation is not serious. Next, confirmatory factor analyses were conducted. Model fitting results show that GFI < 0.9, most RMSEA > 0.08. These results verified that common methodological variance was acceptable in this study.Previous work and studies address a number of crucial determinants that are important for risk perception , 23, 24.This investigation was conducted online from April 4, 2020, to April 15, 2020. To ensure the randomness of sampling and the reliability of inferences, trained project managers were recruited to coordinate the selected provincial survey and supervise the local investigations. Consenting participants were enrolled and asked to fill out the online questionnaire, which took ~15 min to complete. After receiving the data collected online, we arranged for a dedicated reviewer to be responsible for filtering questionnaires by answering time, content quality, and data format.P < 0.05 for all the analyses.For statistical analysis, we used descriptive methods to summarize data on demographic information. Data were reported as frequencies (n) and percentages (%) for categorical variables among different groups of risk perception. Then, we calculated the means and standard deviations. Multiple regression and moderating effect analysis were used to identify associations between various factors and respondents' risk perception. Statistical analysis in this study was performed by Microsoft Excel and R 3.6.0 software packages. The alpha level was set at The study protocols were approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (#2020S107). Oral informed consent was obtained from each participant before conducting the online survey.n = 1,860) were women, and 40.68% (n = 1445) were unmarried. Older adults (>60 years) accounted for 16.60% (n = 590) of the total sample. Furthermore, 51.35% (n = 1824) had attained a junior high school degree or higher. Nearly 42.80% of the participants' annual household income was < CNY 100,000. Examination revealed significantly higher mean for risk perception scores in the elderly (>60 years), and the individual who thought their communities made adequate preparation for emergencies . Of these, 52.36% (rgencies .The greatest percentage (55.49%) of participants feared being infected; 52.51% feared death from COVID-19; and 46.03% were nervous about reports and news of COVID-19. Respondents did not have difficulty sleeping (52.59%) and had no trouble staying at home (50.53%). When the COVID-19 pandemic was mentioned, 42.15% of respondents did not have symptoms of rapid heartbeat .Multiple regression analysis showed that participants' risk perception was significantly affected by age, helplessness, depression, loneliness during the pandemic, the usefulness of expert advice, the usefulness of social media video, community's emergency preparation and information forwarding behavior. These variables accounted for 56.33% of the total variance .p < 0.001).p < 0.001), and it had a steeper slope, meaning it was even more statistically significant. This finding indicated that the relationship between negative emotion and risk perception would be stronger for those who have higher levels of information perceived value, as compared to those with the lower, but these relationships overall stay positive.An interaction plot was generated for visual illustration. This study indicated that risk perception varied at different ages. Participants who are over 60 years old reported the highest risk perception score in regard to the COVID-19 pandemic; Risk protection awareness of vulnerable and susceptible people and prior emergency experiences may have played a certain role among these participants . In addiThis study also demonstrated that adequate community emergency preparedness can provide a vital measure for the government in helping people strengthen self-protection and reduce risk perception. One possible explanation is based on the unique “community grid governance model” in China , which iAnother finding of this study was that negative emotions were positively correlated with the perceived likelihood of risks and the perceived severity of the threats. Loneliness, depression, and helplessness were chosen to reflect an individual's negative emotions  . Some elThe role of information exposure was positively associated with risk perception. Regression analyses confirmed that in the risk information dimension, participants had higher risk perception when they forwarded risk-related messages with their friends. People who are willing to share risk information usually seek out more media coverage of epidemic-related information in advance. Furthermore, their perceived stress response increases with excessive exposure to risk information –38.Our survey indicated that individuals' perceived value of authoritative information sources has a critical effect on their health risk perception. This is in line with the results of Jian Raymond's and Qingchuan Liu's studies , 39. TheIn addition, information perceived value exerts a moderating effect on the relationship between negative emotion and epidemic risk perception. At a high information perceived value, individuals with high negative emotion orientation are relatively more able to perceive the impact of risk . People This study had some limitations. First, many elderly individuals who had no access to the internet were not adequately investigated, and there was a lack of a random sample. Second, we omitted variable bias in this study, and there needs to be a more specific measure (standard questions) of the public's risk perception. Third, a cross-sectional design did not produce very precise or convincing results and made it uncertain. Last, there is a reciprocal cause-effect relationship between risk perception and emotion. It is impossible to determine the exact cause-and-effect relationship between them in this study. Further studies are needed to improve the scientific validity of these findings.Perceived risks are important for residents' acceptance of government preventive measures. However, the public's excessive dependence on social media weakens the effect of government trust on public risk perception. It is not conducive to the implementation of prevention measures and self-protective behavior. This study highlighted that individual differences in risk perception were not only related to the age factor. Emotion, perceived usefulness of the information, forwarding behavior and thought community made adequate emergency preparation important. It is crucial for authorities to strengthen the management of new media and guide the release of risk information during the epidemic. In addition, the government should pay attention to the complex negative emotions that threaten residents during the epidemic. Effective health communication and education interventions advocated by public health experts are the most accurate sources of information, which could clarify misinformation and answer public concerns in accessible ways.We conducted a nationwide online survey during the peak of the COVID-19 outbreak in China. The results were a satisfactory reflection of respondents' risk perception status during the crisis situation. This is based on two important dimensions of individual perception analysis, namely, information usefulness and negative emotions. Exploring and analyzing the above factors and their association with risk perception have implications for the adjustment of the public communication and risk prevention strategies adopted by the government.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. The patients/participants provided their written informed consent to participate in this study.CC: conceptualization, data curation, formal analysis, investigation, methodology, software, validation, and writing—original draft. ZF: investigation, project administration, and supervision. ZY: data curation, investigation, and methodology. CS: data curation, investigation, and visualization. ST: conceptualization, investigation, editing subsequent versions of the manuscript, and revising the original manuscript. LJ: support participant recruitment, support data analysis, and interpretation. XS and RW: investigation, writing—review and editing, and supervision. All authors have read and approved the manuscript.


Q2; 0.55 , p = 0.04, Q1 vs. Q3; 0.54 , p = 0.05, Q1 vs. Q4, respectively). Potential effects of dietary flavonol intake against cancer death was observed especially in participants aged 50 or above, males, whites, former smokers, people who used to drink or drink alcohol mildly, people without hyperlipidemia, and people with hypertension. Moreover, the dietary intakes of peonidin, naringenin, and catechin were inversely associated with cancer mortality , p = 0.03; 0.98 , p = 0.05, respectively). Furthermore, a nomogram based on flavonol intake is feasible for assessing cancer mortality for each participant. Taken together, our results could improve personalized nutrition amongst cancer patients.Cancer is a leading cause of death worldwide, posing a huge burden upon society and individuals. The adequate intake of fruit and vegetables is reported to be an effective strategy for primary cancer prevention. Fruits and vegetables are rich in nutrients, such as vitamins and flavonoids, which may reduce the occurrence and progression of cancers. However, the importance of each flavonoid and the sub-classes remains controversial regarding cancer mortality. The population benefiting from increased flavonoid intake has not been determined. An estimation of cancer mortality by flavonoid intake is not established. We explored the association between the intake of flavonoids and cancer mortality amongst 14,029 participants in the National Health and Nutrition Examination Survey. During a median follow-up of 117 months, 405 cancer deaths were confirmed. Being in the second, third, and fourth quartiles of flavonol intake, the cancer mortality was inversely associated with the intake of flavonols (multivariate analysis HR (95% CI] 0.58 ,  Cancer is a disease resulting from the uncontrolled growth and division of abnormal cells in the body and is the leading cause of death and an important obstacle to extending life expectancy worldwide . It was To explore the association between dietary flavonoid intake and cancer-related mortality, we downloaded all the publicly available data in the Database of Flavonoid Values for USDA Food Codes and Flavonoid Intake Data Files from What We Eat in America (WWEIA), National Health, and Nutrition Examination Survey (NHANES) . Until 1NHANES is a program of studies designed to evaluate the health and nutritional status of adults and children in the US. NHANES is a program of the National Center for Health Statistics, which is part of the Centers for Disease Control and Prevention . The NHAAll data in our study are publicly available and without personally identifiable information. All analyses were conducted following the relevant guidelines and regulations . The surThe dietary flavonoid values in our study were obtained from the database of flavonoid values for USDA Survey Foods and Beverages (flavonoid database for short), which was established in 2003–2004 . The flaBased on the stratified and multistage probability sampling designed in the NHANES, we used the mean of the two-day intake of each flavonoid, as well as the weights “wtdr2d” constructed for participants who completed two days of dietary recall in making estimates representative of the US non-hospitalized population .The updated follow-up date was 31st December 2019. A total of 14,092 participants with an available survival status were included in our study. The time in months from the household interview to mortality was assessed as the follow-up time. A death caused by cancer was ascertained by the National Death Index and International Classification of Diseases-10 C00-C97 as a malignant neoplasm. A potential nonlinear association between total flavonol intake and cancer mortality was evaluated using restricted cubic splines. The association between flavonoid intake and cancer mortality was assessed using Cox proportional hazards analysis.2). The term “never” regarding the smoking status was defined as fewer than 100 cigarettes during life; “former” as more than 100 cigarettes during life and not at all currently smoking; and “now” as more than 100 cigarettes during life and smoking some days or every day. The classification of alcohol usage was as described in  . Being in the second, third, and fourth quartiles of flavonol intake, the cancer mortality was inversely reduced compared with that in the first quartile    . Partici = 0.02) . As 37.9 = 0.02) .We then built an easy-to-use and clinically adaptable risk nomogram for predicting the survival probability at ten years g. A highSince the bioavailability of flavonoids is low, the flavonoid intake might not accurately reflect the effect of flavonoids utilized by the body on cancer mortality. We considered using urinary flavonoid and their metabolite levels to explore the correlation with cancer mortality. Due to data access privileges, we were only able to obtain urinary levels of isoflavones and relevant metabolites in 2007–2010 during our study period. As shown in The global cancer burden is expected to increase by 47% to 28.4 million cases by 2040 in comparison with 2020 . PrimaryOur results demonstrated that the inverse association between flavonol intake and cancer mortality is coincidental with Danish results . InteresA comprehensive understanding of the mechanisms of flavonoids in cancer could help define new strategies for cancer management and prevention. The bioavailability of flavonoids is affected by dietary patterns, interaction with the food matrix, host genetics, intestinal microbiota, and the phase I and II metabolism in the liver ,45,46, win vivo [Moreover, although the flavonoids have low solubility and low bioavailability ,49, certin vivo . For exain vivo . In compin vivo ,52. HoweNotably, we found that the intakes of peonidin, naringenin, and catechin are inversely associated with cancer mortality. Peonidin, present in red wine and berries, can inhibit lung cancer metastasis . NaringeThe estimated amounts of individual flavonoids in plants and foods were reported to be influenced by nonrepresentative sampling, different cultivars, different growing, and processing conditions, and analytical bias . To geneIn addition, the effects of seasonal variation on amounts of flavonoids in plants or on total flavonoid intake may be not as significant as other factors ,57. It iConsidering that an individual’s dietary structure may change over a lifetime, we compared changes in flavonoid intake across a study population spanning ten years. We found that the flavonoid consumption remained relatively stable, although there were significant differences in the intake of some flavonoids. We employed the mean of the two-day intake of each flavonoid as well as the weights “wtdr2d” constructed for participants who completed two days of dietary recall in making estimates representative of the US non-hospitalized population. Our results could reflect the change in flavonoid consumptions in population. Our study had several limitations. The observational analysis only revealed an association . Notably, dietary flavonoid intake did not include the intake of flavonoid supplements, contributing to the limitations of our results. As discussed above, there are possible health risks associated with excess flavonoid intake. Future studies should include dietary and supplemental flavonoid intakes.In summary, in comparison to being in the first quartile of dietary flavonol intake, being in the second, third, and fourth quartile was inversely associated with cancer-related mortality. Potential protective effects of dietary flavonol intake against cancer death was observed, especially in participants aged 50 or above, males, whites, former smokers, people who used to drink, mild drinkers, people without hyperlipidemia, and people with hypertension. Total dietary intakes of peonidin, naringenin, and catechin were inversely associated with the mortality of cancer. The nomogram based on the dietary intake of flavonols was clinically applicable to estimating the possibility of cancer-related death. Regarding the perspective of public health, our results may provide new insight into assessing cancer mortality risk based on dietary flavonol intake and establishing future personalized dietary recommendations amongst people with unhealthy lifestyles. However, further evidence from randomized controlled trials is still needed to assess the health benefits of flavonoids.


The pleiotropy was evaluated by MR-Egger intercept test and MR-PRESSO. Finally, the leave-one-out analysis was performed to evaluate the robustness of the MR results. We found that there was a negative causal effect of the age at last live birth on BC  and positive effect of the age at menopause on BC . Additionally, there were null effects of the age at menarche , the age at first sexual intercourse  and the age at first birth  on BC. All these results were reliable and stable. In conclusion, the present study showed that younger age at last birth and older age at menopause could increase the risk of BC.Several studies have shown that female reproductive factors are associated with breast cancer (BC), but the results differ. We conducted two-sample MR in the present work. The raw data applied in the MR study were all from the Genome-wide association study (GWAS) database. The causal effect of reproductive factors on breast cancer were mainly estimated by the standard inverse variance weighted (IVW) method. Cochran’s Q test and I Breast cancer (BC) is a common tumor in women, and it is also the main cause of death in women caused by cancer according to Global Cancer Statistics 2020; it was estimated there were about 2.3 million incident cases and 685,000 deaths ,2. In thFemale reproductive factors are heritable traits that vary widely between individuals. They are associated with many chronic diseases and cancers . PreviouMendelian randomization is a novel epidemiological method for causality investigation, which has gained increasing attention in the last decades and widely used in many studies . To our A two-sample MR was conducted in the present study by Single nucleotide polymorphisms (SNPs) obtained from GWAS summary data. Reproductive factors were selected as exposure, while BC was selected as outcome. There are three assumptions that should be met for SNPs selected as instrumental variables (IVs) in MR analysis : firstlyhttps://gwas.mrcieu.ac.uk/datasets/” (accessed on 1 November 2022). The GWAS summary data for age at menopause were derived from a large-scale genomic analysis including 69,360 women of European ancestry and 2,418,696 associated SNPs were identified [Five reproductive factors demonstrated by previous studies were involved in the present study. The IV with regard to the age at menarche was extracted from a GWAS study, which consisted of 182,416 women of European descent from 57 studies and 2,441,816 single nucleotide polymorphisms (SNPs) were included . IVs on entified . The sump < 5 × 10−8) were extracted as the potential instrumental variables (IVs). Then, to avoid biases caused by linkage disequilibrium (LD) [2 (r2 < 0.001), and a number of bases between two SNPs (kb > 5000) were set. The MR-PRESSO was performed to identify any potential outliers. The Steiger filtering test was also performed to avoid the reverse causality. Finally, weak IVs with an F-statistic < 10 were excluded and then the remaining SNPs were selected as IVs for further MR analysis.Firstly, significant SNPs (ium (LD) , a linka2 statistics were used to assess heterogeneity [P-value < 0.05.The causal effect of reproductive factors on BC were mainly estimated by the standard inverse variance weighted (IVW) method , while togeneity . The pleogeneity . All datF-statistic of these SNPs are all greater than 10, fulfilling the assumption of strong relevance for MR studies. Detailed information about all SNPs is shown in After removing the SNPs which were palindromic with intermediate allele frequencies, weak IVs and IVs that explain more of the variance in the outcome than in the exposure, there were 64,173,57,41,6 SNPs with regards to age at menarche, AFS, AFB, age at last live birth and age at menopause that were extracted for further MR. The p = 0.484). The MR Egger , simple mode  and weighted mode  also verified this result, indicating that the age at menarche has no causal association with BC.We firstly assessed the causal effect of age at menarche on BC. The results are summarized in p = 8.010 × 10−8) (p = 1.404 × 10−3), weighted median , simple mode  and weighted mode  methods. The heterogeneity tested by Cochran’s Q test and I2 statistics showed that heterogeneity existed , but no pleiotropy , and the leave-one-out test showed that the results were reliable and stable  , and thid stable A. Based p = 0.284), and this is confirmed by other MR analysis methods, including MR Egger , weighted median , simple mode  and weighted mode , which also indicates that there was null causal effect of AFS on BC.We next evaluated the causal association between AFS and BC. The results are also summarized in p = 0.404), and similar results were analyzed by other MR methods including MR Egger  and simple mode  (p = 0.002); weighted median also verified the results  (p = 0.768), and the MR-Egger intercept  and MR-PRESSO [Finally, we assessed the causal association of age at birth on BC. The causal relationship assessed by IVW showed there was null causal effect of AFB on BC  . Interes= 0.020) , indicatMultiple studies have investigated the association between female reproductive factors and BC, but discrepancies existed in the reported results. Some findings suggest that early menarche increases the risk of breast cancer ,14,16,28Numerous studies demonstrated that the older the age at first birth, the higher the risk of BC, particularly for ER-positive tumors ,31,32. HIt is well established that younger age at first sexual intercourse is a risk factor for cervical cancer ,36. HoweALB and the risk of BC are not fully elucidated. Some studies found a positive association between ALB and BC ,38. OtheMenopause marks the end of a woman’s reproductive life span and the cessation of endogenous hormone production. Previous studies have consistently suggested that late age at menopause is a risk factor for BC ,42,43,44Compared to previous studies, our study included several notable advantages. First, the study broadens the scope of the existing literature by including multiple large-scale GWAS summary statistics. Moreover, a key strength of this study was that the MR analysis method we conducted is not vulnerable to confounding factors, ensuring the reliability of the causal association between reproductive factors and BC risk.However, we acknowledge some limitations to our study. First, the data we included were derived from questionnaires and have recall bias. Second, our data was not stratified by age and BC type, so the effect of reproductive factors on different types of BC risk in women of different ages could not be obtained. Third, the genetic instruments comprising SNPs significantly associated with age at first sexual intercourse consisted of both genders; however, the outcome GWAS data of BC were made up of female data only. The MR analyses could have been improved if gender composition of exposure and outcome are the same.According to our study, young age at last birth and older age at menopause could increase the risk of BC, while age at menarche, age at first sexual intercourse and age at first birth are not causally associated to breast cancer. These conclusions can provide a reference for family planning.


The Faroe Islands in the North Atlantic consist of several small islands, and numerous small freshwater ponds can be found on most of them. These ponds are inhabited by species-poor aquatic communities. Faroese ponds are thus simple systems which lend themselves well to studying diversity of water insects and their interactions with the environment, which ultimately contributes to our understanding of patterns of biodiversity. In this study, we systematically collected water beetles and water boatmen from 57 ponds on the islands Streymoy and Eysturoy to obtain information on species distributions, diversity, and community composition, as well as their relationship with habitat characteristics. We found six small species of Dytiscidae and Haliplidae (Coleoptera) and two species of Corixidae (Heteroptera). There was a higher species diversity in shallower ponds, and community composition differed according to pond size. Geographical location and isolation between ponds did not influence diversity and community composition. We thus conclude that the distribution of water beetles and water boatmen in the Faroes is explained by habitat characteristics, specifically size and depth of the pond.2 and >50,000 m2. Environmental variables such as pond size, temperature, pH, and depth were measured, and distance to nearest neighboring pond was calculated as a measure of isolation. The sampling yielded 1522 individuals of eight species, with species richness of the ponds ranging between zero and six. Pond size (shoreline length) did explain differences in community composition, whereas water depth explained differences in diversity indices with lower diversity in deeper ponds. We found species-specific relations between abundance and shoreline length, e.g., H. fulvus and H. palustris being restricted to larger ponds. Lastly, water beetle and water boatmen communities in Faroese ponds are discussed in the light of island biogeography and species distributions in the North Atlantic islands.Water beetles of the families Dytiscidae and Haliplidae (Coleoptera) as well as water boatmen (Heteroptera: Corixidae) are well-studied groups in Northern Europe. In the Faroe Islands, their diversity is much lower than in the British Isles and Fennoscandia. Here, we first describe the communities of water beetles and water boatmen in Faroese ponds and, secondly, assess whether community compositions are driven by habitat characteristics or dispersal abilities of species. To this end, we sampled 57 ponds, ranging between <50 m The interplay between dispersal ability, environmental tolerance, and intra- and interspecific interactions determines the distribution of species and, depending on available resources (biotic and abiotic), abundance and species richness at various spatial and temporal scales. To work on geographical ecology is to search for patterns , and it Salmo trutta L.) and three-spined stickleback (Gasterosteus aculeatus L.), are present in some of the larger ponds, Coleoptera and Corixidae often are the top predators. Species richness of water beetles and water boatmen is much lower than in the British Isles and Fennoscandia [The North Atlantic islands, from the British Isles and northwards, represent a gradient of increasing isolation (distance from source area) and environmental harshness, and many groups of land and freshwater species decrease in species richness along this gradient . The Faroscandia . Whetheroscandia ,4,5,6.Elodes pseudominuta Klausnitzer, previously recorded as Elodes minuta (Linnaeus).In the Faroes, water beetles and water boatmen have mainly been recorded as part of wider collection effort without targeting these species. Only few ecological studies have been conducted of inland waters in the Faroes. These studies were either concentrated on one lake or on a restricted part of the ecosystem, such as a seasonal study of the benthic community in Leynavatn and analyses of phytoplankton community composition in eleven lakes . Brown , howeverWater beetles of the families Haliplidae and Dytiscidae (Coleoptera) and water boatmen (Heteroptera: Corixidae) are trophically similar and can be considered a discrete ecological guild . They arOur first (I) objective was to describe the water beetle and water boatmen communities in ponds and lakes in the Faroes.Our second (II) objective was to determine whether those communities are shaped by habitat characteristics  or as a result of stochastic distribution events .We hypothesized that the species which have successfully colonized the islands are characterized by good dispersal ability and hardiness in terms of environmental tolerance. As a consequence, we expected a high degree of geographical and ecological overlap between the species. Thus, patterns in distribution, species richness, and community composition should be strongly affected by environmental variables such as pH, pond size, water temperature, and altitude.Lastly, and assuming that communities are shaped by environmental variables, our third (III) objective was to determine the relative importance of these on species diversity.Hereby, we hypothesized that pond size is an important variable, as shown by ,20,21. A2 [The Faroes consist of 18 islands and several islets situated in the North Atlantic (approx. 62° N and 7° W) about 675 km W of Norway, 300 km NW of Shetland, and 450 km SE of Iceland. The total land area is 1396 km2 . The cli2 have been identified and mapped, including some smaller ones [2, and only 28 waterbodies had a surface area larger than 50,000 m2. Those, and some which are smaller and deeper, can be defined as lakes, according to Richardson et al. [A total of 2293 waterbodies with a surface area of more than 100 mler ones ,37. The n et al. ; howeverBeing heavily influenced by surface runoff, ponds and streams in the Faroes differ from continental waterbodies in permanency and water level fluctuations. In the Faroes, smaller ponds and streams tend to dry out from time to time during summer, and others fluctuate considerably in size.2, 100–999 m2, 1000–9999 m2, 10,000–99,999 m2, and >100,000 m2). Of those, 57 ponds , and to avoid any possible stratification effects, the water samples for pH and temperature measurements were taken at a distance from the bank where the pool surface was assumed to be unprotected from wind. The depth of the ponds was measured in the deepest part of the sampled area, and type of bottom substrate and amount of aquatic vegetation were estimated and noted. Time constraints did not permit us to ascertain presence of fish (trout and stickleback) in a systematic manner, but casual observations of fish were noted in ten ponds . In addition, altitude, longitude, latitude, pond size, and shoreline length (pond perimeter) were obtained through the GIS software Mapinfo 6.5 . As a meStatistical analyses were performed in R 4.2.1 .0), Shannon diversity (N1), and Shannon evenness  according to Borcard et al. [As a measure of alpha diversity, we calculated species richness  . In casemetaMDS and envfit in the vegan package. Bray–Curtis was used as dissimilarity distance measure.The effects of geographical location , water temperature, altitude, water depth, sediment depth, shoreline length, and distance from nearest neighboring pond (near_dist) (explanatory variables) on the community composition (response variables) were tested with a PERMANOVA (function adonis2 in the vegan package) and visualized with nonmetric multidimensional scaling (NMDS) using the functions To evaluate the importance of shoreline length on species distributions, we plotted species abundances as well as diversity indices against log-transformed shoreline length. The dependence of species richness on environmental variables was analyzed with generalized linear models (function glm in stats package ) with thArctocorisa carinata (C. Sahlberg), Callicorixa wollastoni (Douglas & Scott), Haliplus fulvus (Fabricius), Hydroporus pubescens , Hydroporus erythrocephalus (Linnaeus), Hydroporus palustris (Linnaeus), Boreonectes multilineatus , and Agabus bipustulatus (Linnaeus). Two additional species of Dytiscidae, Hydroporus nigrita (Fabricius) and Hydroporus memnonius Nicolai, have previously been recorded in the Faroes [A total of 1522 individuals (1246 water beetles and 276 water boatmen) were found in this study, belonging to eight different species: e Faroes ,47 but wt-test: t = 0.8729, df = 54.22, p = 0.387), Shannon diversity , and Shannon evenness . However, H. fulvus only occurred in ponds on Eysturoy.Local species richness varied between 0 and 6 . There wB. multilineatus as the most abundant and by far the most widely distributed species  co-occurred with all other species, and species with a low frequency  co-occurred with few of the other species.There was a positive relationship between abundance and number of ponds occupied (frequency), with  species . The twoB. multilineatus, H. fulvus, and H. palustris were associated with ponds with a longer shoreline, whereas the other five species tended to be found in smaller ponds  and water depth being significant explanatory variables , Table 2er ponds . Due to er ponds .Species number and Shannon diversity were highest in the smaller ponds a,b, wherH. fulvus and H. palustris only occurred in ponds with a longer shoreline, B. multilineatus was fairly evenly distributed over ponds with varying shoreline lengths, and the remaining five species were mainly found in ponds with shorter shoreline (There were species-specific relations to shoreline length . H. fulvhoreline .H. fulvus) were geographically widely distributed. This is in line with previous reports of species poverty of water beetles and water boatmen [Our first (I) objective of the study was to describe the community of water beetles and water boatmen in Faroese ponds. Species richness was low, with only eight species found of ten previously reported species. On average, there were two to three species per pond, and all but one species  objective was to determine whether water beetle and water boatmen communities were shaped by habitat characteristics of the ponds  or the result of different dispersal abilities of the species . We had predicted that environmental variables were more important drivers of community composition than variables related to dispersal abilities, and this was supported by our results. Shoreline length (a proxy for pond size) and water depth were the significant variables in explaining the community composition in the ponds.Lastly (III), we wanted to determine the effects of those variables on species diversity. We had predicted that diversity would be influenced by pond size, but that was not supported by our results. Water depth, but not shoreline length, was correlated with all three diversity indices.In the British Isles, the total number of species of the three aquatic insect families included in this study, Haliplidae, Dytiscidae, and Corixidae, is 173  , of whicNectoporus sanmarkii (Sahlberg), Agabus uliginosus L. and Colymbetes dolabratus (Paykull)) have not been recorded in the Faroes [H. fulvus occurs in both Iceland and the Faroes, although species of the family Haliplidae are claimed to have a relatively low dispersal ability [A. carinata, is also found in Iceland [Dytiscus L. or Colymbetes Clairville and that A. bipustulatus is the largest species (10–11 mm), whereas the others (including the two previously recorded species not found in present study) are all in the range 3.5–4.5 mm in size.Presumably, Faroese species have arrived from the British Isles and Fennoscandia, but only a small fraction  of the relevant species pools of these two source areas has succeeded in colonizing the Faroes. Considering the dispersal ability of many members of the family Dytiscidae, one would expect more species to have reached the islands than those presently occurring there. That at least some of the species apparently absent in the Faroes are capable of reaching remote islands is suggested by the fact that three of the five Dytiscidae species found in Iceland (e Faroes . On the  ability . Of the  Iceland . It is a2 pond in northern Sweden [2 in Newfoundland [Even the highest number of species (six) found in any single pond is low compared to studies in other northern regions, e.g., 32 species of Dytiscidae found in a 500 mn Sweden  and 27 Coundland . Howeveroundland . Thus, loundland , which cEnvironmental variables, namely, pond size (shoreline length) and water depth, shaped the composition of water beetle and water boatmen communities in Faroese ponds. This is in line with the findings of several studies in other parts of the world. In his study on aquatic beetle communities of ponds in Southern Germany, Flechtner  found poNaturally, ponds differ from each other in many ways and not only with respect to the variables measured in this study. The permanency of a pond and the predictability of changes are important factors influencing species composition ,58,59. AAnother variable we did not measure systematically was predation pressure by fish, which was shown to be an important driver of aquatic communities ,62,63. D2—only one sampled pond was smaller than 50 m2—and we might have seen a positive relationship between pond size and species richness if we had included more smaller ponds into our sampling scheme. Nilsson and Svensson [2. Peak abundances varied between species in our study. H. fulvus and H. palustris abundances peaked in ponds with a size of >1000 m2 and B. multilineatus abundance in ponds of 200–300 m2 in size, whereas the remaining five species were most abundant in ponds of sizes around 100 m2.Positive relationships between pond size and species richness have been documented . In our Svensson  state thDiversity of water beetles and water boatmen was lower in deeper ponds, which is in agreement with the general rule of thumb stated by Nilsson  that “thHaliplus fulvus and Hydroporus palustris were only encountered in the larger ponds, with low abundances and with few (1–3) other species present. Their occurrence in the larger ponds is consistent with observations in other regions of the world, where they are more confined to lakes than to ponds. Both these species have wide geographical distributions [B. multilineatus exhibited the highest evenness of occupancy with respect to pond size, and by far the highest overall abundance and frequency, probably occurring all over the Faroes. This is consistent with the association between local abundance and regional distribution [A. bipustulatus deviates from it, and A. carinata and H. pubescens had wider distributions than some species with similar mean abundances. However, the low abundance found in A. bipustulatus may be an underestimate as it has been reported that few Agabus individuals are obtained when net sampling is applied, as they stay hidden during the day [H. fulvus, H. palustris, and H. erythrocephalus, all with reasonably high local abundances, are not found more often, though it can be noted that two of them are “large-pond species”.ibutions ,14, whicibutions . B. multribution ,65, and ribution . The spe the day  and the


Physical activity is important for healthy aging, but few older adults achieve the goal of 150 min per week of moderate activity. The purpose of this study was to employ a robust statistical approach in the analysis of the factors related to physical activity in a diverse sample of older adults. A secondary analysis of factors associated with calculated MET-h/week was conducted in a sample of 601 African Americans, Afro-Caribbeans, European Americans, and Hispanic Americans age 59 to 96 living independently in the community. Age, education, social network, pain, and depression were the five variables that accounted for a statistically significant proportion of unique variance in the model. The strongest correlation to total MET-h/week was with depression. Directionality of the relationship between these variables and physical activity is complex: while pain and depression can reduce physical activity, activity may also help to reduce pain and depression. Additionally, of note is that many of these factors may be modified, calling for the design and testing of individual, group, and community level interventions to increase physical activity in the older population. Physical activity is important for healthy aging ,2. RegulDespite the known health benefits associated with regular physical activity, older adults seldom meet physical activity guidelines. Thus, it is not surprising that research studies, both qualitative and quantitative, undertaking to identify barriers and motivators influencing activity participation by older adults are abundant in the scientific literature. A systematic review conducted by Notthoff, Reisch and Gerstorf  in 2017,Gomes  studied Understanding what factors affect physical activity levels among older adults from different ethnic groups can inform the development of interventions to encourage and support regular physical activity among older adults. Therefore, the objectives of this study were to identify factors associated with different amounts of physical activity among a large, diverse sample of older adults living independently in the community using robust statistical methods that account for multicollinearity among many of these factors.A secondary analysis of the physical and psychosocial correlates of physical activity was conducted using data from the Healthy Aging Research Initiative (HARI) an in-depth survey of the health and well-being of multiethnic community dwelling older adults in South Florida. Participants were drawn from three metropolitan areas encompassing Miami-Dade, Broward, and Palm Beach counties ,12. The The HARI database contains information on 698 participants, of which 601 had complete data on their physical activity level and the related physical and psychosocial variables of interest. This included 115 African Americans, 142 Afro-Caribbeans, 217 European Americans, and 127 Hispanic Americans ranging in age from 59 (approaching 60) to 96. All were living independently in the community, able to walk at least 6 m independently, or with the aid of a cane or walker, and had a Mini-Mental State Examination score ≥ 23 . InterviSociodemographic variables included age, sex, years of education, ethnic group membership, years living in the United States, and receipt of Medicaid based upon income level qualifications. Cognition was measured using the Mini-Mental State Exam . PsychosActivity was calculated from three variables derived from Health and Retirement Study  items meSociodemographic, cognitive, psychosocial, physical, and behavioral variables were selected for analysis from the HARI database with the goal of building the most parsimonious and best fitting model to predict the older adult participant’s reported frequency and intensity of physical activity. To build this model, elastic net (EN) regression was used. EN is a regularization technique that combines the strengths of both ridge regression and least absolute shrinkage and selection operator (LASSO) regression models. This is especially important in cases of high multicollinearity where ordinary least squares (OLS) models may yield unstable and unreliable parameter estimates. Additionally, EN outperforms OLS when you have a high number of predictors compared to the number of participants. This occurs because OLS models also have higher variability as the number of predictors increases ,36.With ridge regression, the traditional OLS model is adjusted to both the sum of squared residuals as well as to the penalty size related to the number of predictors made to the parameter estimates, in order to shrink them towards zero. For ridge regression the λ parameter represents the regularization penalty. LASSO, least absolute shrinkage and selection operator, is quite similar conceptually to ridge regression. It also adds a penalty for non-zero coefficients, but unlike ridge regression which penalizes the sum of squared coefficients , LASSO penalizes the sum of their absolute values . As a result, with higher values of λ many coefficients are exactly zeroed under LASSO, which is never the case in ridge regression. Elastic net (EN) first emerged as a result of critique of LASSO, whose variable selection can be too dependent on the data and thus unstable. The solution is to combine the penalties of ridge regression and LASSO to get the best of both worlds . Cross-vThe age of the participants in this study ranged from 59 (one participant approaching the 60th birthday) to 96 years old with an average age of 74.3 years. All of the participants had lived in the United States for at least one year with an average of 55.5 years. On a pain scale of 0 to 10, the average reported pain was low (2.9). However, there were 94 participants who reported their average pain at or above an eight out of ten. BMI ranged from 16 to 48 with an average of 29. The average activity index was 4.4 METS-h/week.p < 0.001), years of education (p < 0.001), years in the US (p < 0.001), cognition (p < 0.001), functional activity (p < 0.001), and calculated activity index (p < 0.002). European Americans reported statistically significantly higher average physical activity levels (4.8) than African Americans (4.1), Afro-Caribbeans (4.7) or Hispanics (3.6) .As can be seen in p = 0.001), years of education (p = 0.002), social engagement (p < 0.001), social network (p < 0.001), resilience (p < 0.001), depression (p < 0.001), anxiety (p < 0.003), SF-36 mental health summary score (p < 0.024), cognition (p = 0.002), pain (p = 0.004), BMI (p < 0.001) self-health rating (p = 0.011), and functional activity (p < 0.001). Participants who reported lower physical activity tended to be older, have less years of education, and reported lower social engagement, networking, resilience, mental health, self-health rating, and higher levels of depression, anxiety, pain, and BMI compared to the moderate to high physical activity groups.The next step in building our predictive model was to assess differences in physical activity level across the demographic, cognitive, psychosocial, physical and behavioral variables that emerged from prior qualitative analysis of a smaller sample of diverse older adults  and fromAfter identifying the potential differences by ethnic group and activity level, these variables in combination were included in a predictive model to account for the variability reported in the activity index as measured by MET-h/per week. Elastic net regression (EN) utilized cross validation to obtain the best, most parsimonious and stable, model. A repeated tenfold cross-validation with a 0.1 standard error was used to identify the most appropriate shrinkage parameter (λ) as the final selection criteria for the most appropriate model. The EN model suggested the best fitting λ = 1 and LASSO penalty = 0.180 and retained eleven variables that accounted for 22.2% of the variability in predicting the MET-h/week. Six of these accounted for unique variance while the other five did not and were removed from the model.β) set to zero essentially removing them from the model. As mentioned earlier, this is the variable selection technique of importance. The six variables retained through this regularization process were age, social network, depression, cognition, pain and BMI which accounted for a statistically significant proportion of unique variance . Of the six variables identified by the EN regression, five variables accounted for a statistically significant proportion of unique variance (p = 0.05), age, years of education, social network, depression, and pain.p < 0.001). As can be seen in this table, even though these variables were retained by the EN there are still significant relationships between many of the predictors such as depression and education , depression and social network , and pain and depression .A Pearson correlation was conducted on the five variables that accounted for a statistically significant proportion of unique variance in the EN. There were statistically significant correlations with total MET-h/week see . The strp < 0.001) accounted for a significant proportion of unique variance in predicting the MET-h/week (R2 = 0.165). Depression accounted for the largest proportion of unique variance in the model.These five variables were then refitted using OLS regression to obtain the unpenalized standardized and unstandardized coefficients. As can be seen in The purpose of this secondary analysis was to examine factors associated with physical activity in a diverse older population. Unique to this study was the use of rigorous analytical techniques to build the most parsimonious, best fitting model predicting older adults’ levels of physical activity. This is particularly important in instances of a large number of variables with high multicollinearity. This study used elastic net regression analysis combining the penalties for both ridge regression and LASSO to investigate the underlying factors that predict physical activity in older adults. For example, instead of just studying ethnic differences in physical activity, we went further and identified the key significant predictors, many of which were highly correlated with ethnicity.Additionally, when controlling for variability accounted for by these underlying factors, the unique variance accounted for by ethnicity alone becomes nonsignificant. The elastic net regression technique is less affected by multicollinearity between these underlying components and ethnicity and therefore allowed us to get a clearer view of these critical underlying components. While a number of published studies have addressed the question of factors influencing older adults’ physical activity levels, none have employed the large range of instruments/tools, used this robust statistical analysis, and included older adults from multiple ethnic groups as done in this study.Other published studies conducted in older adults have targeted population groups in countries such as Ireland , JamaicaSome of the findings from this study, including the impact of age, depression, and social network , have been confirmed in the literature. McKee, Kearney and Kenny , for exaSimilar to the findings from the present study, other studies investigating older men and/or women have identified education, age, social support, and depression as factors contributing to physical inactivity. For example, age, education and social support along with current health and employment status, were identified as being associated with physical activity among older men residing in Jamaica . Higher Some studies have also reported pain as a factor that influenced physical activity. Among a group of 409 older adults living independently in Scotland, using logistic regression and then regression modelling, Crombie and colleagues  showed tIn one of the few studies aimed at identifying factors associated with physical activity that included multiple ethnic groups, advanced age and fewer years of education (as in the present study) were linked with inactivity in a group of 2912 middle- and older-aged (40 years and older) American Indian, African American, Hispanic and European American women . This stIn the final model, a set of five predictors of activity were retained: age, years of education, social activity, depression, and pain. Interestingly, many of these underlying factors are modifiable. The implications of these predictors are discussed in the following paragraphs with an emphasis on those that can be addressed through individual and/or community level intervention.The findings from the current study suggest development of interventions and programs aimed at increasing older adults’ participation in physical activity. While age is not modifiable, depressive symptoms and pain can often be improved with physical activity and social networks can be created or expanded. Tailored activity sessions can be developed and provided to encourage inactive older adults to begin and/or increase physical activity. Education may be key both to helping older adults with depressive symptoms understand that physical activity can help reduce their symptoms and in helping them identify the types of activity that they may find enjoyable. Marques et al.  reportedThe present study, like others, found that pain was also associated with less time spent being physically active. What is not clear is whether older adults understand that sedentary lifestyles can promote and/or worsen some types of pain  and physSocial support and connectedness, identified as a factor influencing participation in physical activity in this study and other studies ,39,41,48A complex group of interacting factors that influences participation in physical activity among older adults clearly exists. While these factors may be challenging to overcome, involvement in physical activity can provide enormous benefits including long-term reduction in pain and symptoms of depression and improved social connectiveness among others. Partnerships among local senior centers, low income housing developments, places of worship, YMCAs, and healthcare providers are crucial in the development of tailored multi-faceted programs for physically inactive older adults especially those experiencing pain and/or depression. These programs can provide health-related education pertinent to the identified medical issues  and assist participants in meeting other participants and in developing specific physical activity-related goals which are known to be associated with sustained involvement.  Program There are several important limitations to this study. The influence of motivation and self-efficacy could not be evaluated as these variables were not in the HARI database. Similarly, the effect of the environmental context on engagement in physical activity was not evaluated. This includes the walkability of the neighborhood, access to safe, user friendly transportation, free or low-cost exercise programs, and the existence of safety concerns that impede neighborhood activity and interaction. Further, the directionality of several of the significant predictors cannot be determined in a cross-sectional study. One example is the interaction of depression and physical activity: those who are depressed are less likely to engage in physical activity but activity has also been cited as an efficient nonpharmacological intervention for depression. The interrelationship between pain and physical activity is another portion of this cycle of pain, depression, and inactivity that affects many older adults .Both the results of this study and the limitations of this work suggest direction for future research. The bidirectionality of the interactions between some of the variables of interest and need to know, for example, in what instances pain or depression precedes/leads to inactivity versus resulting from inactivity, calls for examination of longitudinal data to understand these relationships. The high degree of interaction among many of the factors affecting physical activity suggest that future studies take a multifactorial, holistic approach encompassing all of the known and even suggested predictors to produce a comprehensive model for physical activity in older adults.Four of the five significant predictors of physical activity in the older adults studied are at least partially modifiable, calling for the testing of interventions addressing these factors’ potential effect on physical activity and inactivity. A few suggestions include education regarding the effect of activity on common sources of pain such as arthritis or back pain; encouraging providers to write a “prescription” for a daily walk or workout for those with depression, community outreach to isolated older adults, improving the walkability of neighborhoods, repairing sidewalks, adding trails, and making these areas safe to walk and work out.Age, education, social network, pain, and depression were the five factors that accounted for a statistically significant proportion of unique variance in physical activity in this diverse, community dwelling older population. The bidirectionality of their effect is noted as the presence of pain or depression is associated with lower activity, but physical activity has been shown to reduce pain and depression as well. Longitudinal studies would help understand these relationships. Furthermore, most of these factors are also modifiable, calling for greater efforts to design, test, and implement individual, group, and community level interventions that support physical exercise and encourage older adults to increase their activity.