Nordcan.R: a new tool for federated analysis and quality assurance of cancer registry data.

Aim of the article: We present our new GDPR-compliant federated analysis programme (nordcan.R), how it is used to compute statistics for the Nordic cancer statistics web platform NORDCAN, and demonstrate that it works also with non-Nordic data. Materials and methods: We chose R and Stata programming languages for writing nordcan.R. Additionally, the internationally used CRG Tools programme by International Agency for Research on Cancer (IARC/WHO) was employed. A formal assessment of (GDPR-compliant) anonymity of all nordcan.R outputs was performed. In order to demonstrate that nordcan.R also works with non-Nordic data, we used data from the Netherlands Cancer Registry. Results: nordcan.R, publicly available on Github, takes as input cancer and general population data and produces tables of statistics. Each NORDCAN participant runs nordcan.R locally and delivers its results to IARC for publication. According to our anonymity assessment the data can be shared with international organizations, including IARC. nordcan.R incidence results on Norwegian and Dutch data are highly similar to those produced by two other independent methods. Conclusion: nordcan.R produces accurate cancer statistics where all personal and sensitive data are kept within each cancer registry. In the age of strict data protection policies, we have shown that international collaboration in cancer registry research and statistics reporting is achievable with the federated analysis approach. Undertakings similar to NORDCAN should consider using nordcan.R.

Association of modifiable lifestyle with colorectal cancer incidence and mortality according to metabolic status: prospective cohort study.

Background: Metabolic syndrome has been linked to an increased risk of colorectal cancer (CRC) incidence and mortality, but whether adopting a healthy lifestyle could attenuate the risk of CRC conferred by metabolic syndrome remains unclear. The aim of the study is to investigate the individual and joint effects of modifiable healthy lifestyle and metabolic health status on CRC incidence and mortality in the UK population. Methods: This prospective study included 328,236 individuals from the UK Biobank. An overall metabolic health status was assessed at baseline and categorized based on the presence or absence of metabolic syndrome. We estimated the association of the healthy lifestyle score (derived from 4 modifiable behaviors: smoking, alcohol consumption, diet, physical activity and categorized into "favorable," "intermediate", and "unfavorable") with CRC incidence and mortality, stratified by metabolic health status. Results: During a median follow-up of 12.5 years, 3,852 CRC incidences and 1,076 deaths from CRC were newly identified. The risk of incident CRC and its mortality increased with the number of abnormal metabolic factors and decreased with healthy lifestyle score (P trend = 0.000). MetS was associated with greater CRC incidence (HR = 1.24, 95% CI: 1.16 - 1.33) and mortality (HR = 1.24, 95% CI: 1.08 - 1.41) when compared with those without MetS. An unfavorable lifestyle was associated with an increased risk (HR = 1.25, 95% CI: 1.15 - 1.36) and mortality (HR = 1.36, 95% CI: 1.16 - 1.59) of CRC across all metabolic health status. Participants adopting an unfavorable lifestyle with MetS had a higher risk (HR = 1.56, 95% CI: 1.38 - 1.76) and mortality (HR = 1.75, 95% CI: 1.40 - 2.20) than those adopting a favorable healthy lifestyle without MetS. Conclusion: This study indicated that adherence to a healthy lifestyle could substantially reduce the burden of CRC regardless of the metabolic status. Behavioral lifestyle changes should be encouraged for CRC prevention even in participants with MetS.

Climate change affected the spatio-temporal occurrence of disasters in China over the past five centuries.

Climate change may contribute to the spatio-temporal occurrence of disasters. Long-term studies of either homogeneous or heterogeneous responses of historical disasters to climate change are, however, limited by the quality and quantity of the available proxy data. Here we reconstruct spatio-temporal patterns of five types of disasters in China during the period AD 1368-1911. Our analyses of these time series reveal that warmer temperatures decreased the occurrence of disasters in the monsoon-affected parts of central-east China, but it increased the frequency and intensity of disasters along the boundary of arid and humid conditions in parts of southwest and northeast China, probably driven by the interplay among monsoon, westerlies, polar vortex and variation of temperature. Moreover, we show that drought and flood events had cascading effects on the occurrences of locust outbreaks, famine and human epidemics. Our findings suggest that climate can contribute to the spatio-temporal occurrence of disasters, and therefore may contribute to an improvement of China's regional to national risk management of future climate and environmental change.

Quantitative-Profiling Method of Serum Steroid Hormones by Hydroxylamine-Derivatization HPLC-MS.

A sensitive and rapid high performance liquid chromatography-mass spectrometry (HPLC-MS) method was developed and validated for simultaneous quantification of ten steroid hormones, including estrogens, androgens, progesterones, and corticosteroids four classes of steroids. The following ten steroid hormones were analyzed: progesterone, 21-deoxycortisol, estrone, 4-androstenedione, testosterone, dihydro-testosterone, androstenone, dehydroepiandrosterone, corticosterone and cortisone. Stable deuterated isotopes were used as internal standards for quantification. Sample preparation with and without derivatization were performed after liquid-liquid extraction, and the corresponding results were compared according to sensitivity and selectivity. Hydroxylamine derivatization was found to improve the ionization efficiency of the analytes for electrospray ionization MS analysis. The gradient of mobile phase and experimental parameters for HPLC separation were optimized. The lower limits of quantification were in the range of 0.05-5 ng mL-1 with wide linear range for the ten steroid hormones. The intra-day precision < 11.1% and recovery of 84.5-120% with negligible matrix effect were achieved, where within the acceptance limits of the FDA guideline. Total HPLC-MS analysis time was 6 min. This method enables simultaneous quantification of steroids in human serum. It will be helpful for the serum steroid profiling in order to understand various endocrinology diseases.

Theory of Mind Development in School-Aged Left-Behind Children in Rural China.

The current study aimed to investigate differences in theory of mind between left-behind children and non-left-behind children in rural China and to examine the potential protective role of general reasoning ability in left-behind children's theory of mind. Participants included 213 children aged 7.10-13.67 years (111 boys and 102 girls, M = 10.51 years, SD = 1.33), 101 of whom were left behind in rural areas by one or both migrating parents for at least 6 months. The Strange Stories task, a second-order false belief task, and a faux pas task were used to measure children's theory of mind, and Sessions B and C in Raven's Standard Progressive Matrices were used to test children's general reasoning ability. The results showed that left-behind children scored lower on both the faux pas task and Strange Stories task. Additionally, on second-order false belief understanding, left-behind boys performed worse than non-left-behind boys, while left-behind girls scored higher than non-left behind girls. Moreover, children's general reasoning ability moderated the relationship between parental migrant status and children's faux pas understanding: For children with high levels of general reasoning ability, left-behind children performed similarly to non-left-behind children, while for children with low levels of general reasoning ability, left-behind children scored lower than non-left-behind children, indicating that general reasoning ability buffered the negative effect of being left behind on children's theory of mind development. The implications of these findings for training directed at left-behind children are discussed.

Scale-dependent climatic drivers of human epidemics in ancient China.

A wide range of climate change-induced effects have been implicated in the prevalence of infectious diseases. Disentangling causes and consequences, however, remains particularly challenging at historical time scales, for which the quality and quantity of most of the available natural proxy archives and written documentary sources often decline. Here, we reconstruct the spatiotemporal occurrence patterns of human epidemics for large parts of China and most of the last two millennia. Cold and dry climate conditions indirectly increased the prevalence of epidemics through the influences of locusts and famines. Our results further reveal that low-frequency, long-term temperature trends mainly contributed to negative associations with epidemics, while positive associations of epidemics with droughts, floods, locusts, and famines mainly coincided with both higher and lower frequency temperature variations. Nevertheless, unstable relationships between human epidemics and temperature changes were observed on relatively smaller time scales. Our study suggests that an intertwined, direct, and indirect array of biological, ecological, and societal responses to different aspects of past climatic changes strongly depended on the frequency domain and study period chosen.

Spatio-temporal dynamics of a fish predator: Density-dependent and hydrographic effects on Baltic Sea cod population.

Understanding the mechanisms of spatial population dynamics is crucial for the successful management of exploited species and ecosystems. However, the underlying mechanisms of spatial distribution are generally complex due to the concurrent forcing of both density-dependent species interactions and density-independent environmental factors. Despite the high economic value and central ecological importance of cod in the Baltic Sea, the drivers of its spatio-temporal population dynamics have not been analytically investigated so far. In this paper, we used an extensive trawl survey dataset in combination with environmental data to investigate the spatial dynamics of the distribution of the Eastern Baltic cod during the past three decades using Generalized Additive Models. The results showed that adult cod distribution was mainly affected by cod population size, and to a minor degree by small-scale hydrological factors and the extent of suitable reproductive areas. As population size decreases, the cod population concentrates to the southern part of the Baltic Sea, where the preferred more marine environment conditions are encountered. Using the fitted models, we predicted the Baltic cod distribution back to the 1970s and a temporal index of cod spatial occupation was developed. Our study will contribute to the management and conservation of this important resource and of the ecosystem where it occurs, by showing the forces shaping its spatial distribution and therefore the potential response of the population to future exploitation and environmental changes.

Was mandatory quarantine necessary in China for controlling the 2009 H1N1 pandemic?

The Chinese government enforced mandatory quarantine for 60 days (from 10 May to 8 July 2009) as a preventative strategy to control the spread of the 2009 H1N1 pandemic. Such a prevention strategy was stricter than other non-pharmaceutical interventions that were carried out in many other countries. We evaluated the effectiveness of the mandatory quarantine and provide suggestions for interventions against possible future influenza pandemics. We selected one city, Beijing, as the analysis target. We reviewed the epidemiologic dynamics of the 2009 H1N1 pandemic and the implementation of quarantine measures in Beijing. The infectious population was simulated under two scenarios (quarantined and not quarantined) using a deterministic Susceptible-Exposed-Infectious-Recovered (SEIR) model. The basic reproduction number R0 was adjusted to match the epidemic wave in Beijing. We found that mandatory quarantine served to postpone the spread of the 2009 H1N1 pandemic in Beijing by one and a half months. If mandatory quarantine was not enforced in Beijing, the infectious population could have reached 1,553 by 21 October, i.e., 5.6 times higher than the observed number. When the cost of quarantine is taken into account, mandatory quarantine was not an economically effective intervention approach against the 2009 H1N1 pandemic. We suggest adopting mitigation methods for an influenza pandemic with low mortality and morbidity.

Validation of the gravity model in predicting the global spread of influenza.

The gravity model is often used in predicting the spread of influenza. We use the data of influenza A (H1N1) to check the model's performance and validation, in order to determine the scope of its application. In this article, we proposed to model the pattern of global spread of the virus via a few important socio-economic indicators. We applied the epidemic gravity model for modelling the virus spread globally through the estimation of parameters of a generalized linear model. We compiled the daily confirmed cases of influenza A (H1N1) in each country as reported to the WHO and each state in the USA, and established the model to describe the relationship between the confirmed cases and socio-economic factors such as population size, per capita gross domestic production (GDP), and the distance between the countries/states and the country where the first confirmed case was reported (i.e., Mexico). The covariates we selected for the model were all statistically significantly associated with the global spread of influenza A (H1N1). However, within the USA, the distance and GDP were not significantly associated with the number of confirmed cases. The combination of the gravity model and generalized linear model provided a quick assessment of pandemic spread globally. The gravity model is valid if the spread period is long enough for estimating the model parameters. Meanwhile, the distance between donor and recipient communities has a good gradient. Besides, the spread should be at the early stage if a single source is taking into account.

Reconstruction of a 1,910-y-long locust series reveals consistent associations with climate fluctuations in China.

It is becoming increasingly clear that global warming is taking place; however, its long-term effects on biological populations are largely unknown due to lack of long-term data. Here, we reconstructed a 1,910-y-long time series of outbreaks of Oriental migratory locusts (Locusta migratoria manilensis) in China, on the basis of information extracted from >8,000 historical documents. First by analyzing the most recent period with the best data quality using generalized additive models, we found statistically significant associations between the reconstructed locust abundance and indexes of precipitation and temperature at both annual (A.D. 1512-1911) and decadal (A.D. 1000-1900) scales: There were more locusts under dry and cold conditions and when locust abundance was high in the preceding year or decade. Second, by exploring locust-environment correlations using a 200-y moving window, we tested whether these associations also hold further back in time. The locust-precipitation correlation was found to hold at least as far back as to A.D. 500, supporting the robustness of this link as well as the quality of both reconstructions. The locust-temperature correlation was weaker and less consistent, which may reflect this link being indirect and thus more easily moderated by other factors. We anticipate that further analysis of this unique time series now available to the scientific community will continue to provide insights into biological consequences of climate change in the years to come.

Periodic climate cooling enhanced natural disasters and wars in China during AD 10-1900.

Recent studies have linked climatic and social instabilities in ancient China; the underlying causal mechanisms have, however, often not been quantitatively assessed. Here, using historical records and palaeoclimatic reconstructions during AD 10-1900, we demonstrate that war frequency, price of rice, locust plague, drought frequency, flood frequency and temperature in China show two predominant periodic bands around 160 and 320 years where they interact significantly with each other. Temperature cooling shows direct positive association with the frequency of external aggression war to the Chinese dynasties mostly from the northern pastoral nomadic societies, and indirect positive association with the frequency of internal war within the Chinese dynasties through drought and locust plagues. The collapses of the agricultural dynasties of the Han, Tang, Song and Ming are more closely associated with low temperature. Our study suggests that food production during the last two millennia has been more unstable during cooler periods, resulting in more social conflicts owing to rebellions within the dynasties or/and southward aggressions from northern pastoral nomadic societies in ancient China.

Climate change induced range shifts of Galliformes in China.

Climate change will cause range shifts of many species in the future. Galliformes might be particularly vulnerable to climate change, as they have low dispersal ability. Little is known about their possible responses to the future climate. We used a generalized additive model to predict the current and future ranges of all 63 Galliformes in China, based on a comprehensive species occurrence database and a combination of climate variables. Other environmental variables (e.g. elevation and human footprint index) were also considered, as well as the latitude and longitude of the occurrences. Principal component analysis was conducted to illustrate the association between environmental variables and Galliformes distributions. Using the Special Report on Emissions Scenarios (SRES) A2 climate change scenario for 2071-2100, we projected that 29 species would have range shifts over 50%, including 13 endemic species. Galliformes at higher elevation face greater range shifts. Northward shifts are greater than those in other directions. We suggest conservationists pay special attention to the 29 Galliformes that face extensive range shifts, especially the endemic species among them.

Periodic temperature-associated drought/flood drives locust plagues in China.

Global warming is currently of great concern. Yet the ecological effects of low-frequency climate variations remain largely unknown. Recent analyses of interdecadal variability in population abundance of the Oriental migratory locust (Locusta migratoria manilensis) in China have revealed negative associations with temperature and positive associations with Yangtze drought and flood frequencies during the past millennium (AD 957-1956). In order to shed new light on the causal relationships between locust abundance, floods, droughts and temperature in ancient China, we used wavelet analysis to explore how the coherencies between the different variables at different frequencies have been changed during the past millennium. We find consistent in-phase coherencies between locusts and drought/flood frequencies, and out-of-phase coherencies between locusts and temperature and between drought/flood and temperature at period components of 160-170 years. Similar results are obtained when historical data of drought/flood frequencies of the Yangtze Delta region are used, despite flood data showing a weak and somewhat inconsistent association with other factors. We suggest that previously unreported periodic cooling of 160-170-year intervals dominate climatic variability in China through the past millennium, the cooling events promoting locust plagues by enhancing temperature-associated drought/flood events. Our results signify a rare example of possible benign effects of global warming on the regional risk of natural disasters such as flood/drought events and outbreaks of pest insects.

Relationship between increase rate of human plague in China and global climate index as revealed by cross-spectral and cross-wavelet analyses.

Plague has caused the death of hundreds of millions of people throughout the human history. Today this disease is again re-emerging and hence is again becoming an increasing threat to human health in several parts of the world. However, impacts of global climate variation (e.g. El Nino and Southern Oscillation [ENSO]) and global warming on plagues are largely unknown. Using cross-spectral analysis and cross-wavelet analysis, we have analyzed the relationship between increase rate of human plague in China during 1871-2003 and the following climate factors (as measured by the Southern Oscillation Index [SOI], Sea Surface Temperature of east Pacific equator [SST] and air Temperature of the Northern Hemisphere [NHT]). We found in the frequency domain that increase rate of human plague was closely associated with SOI and SST. Cross-spectral analysis reveals that significant coherencies between increase rate of human plague and ENSO were found over short periods (2-3 years), medium periods (6-7 years) and long periods (11-12 years, 30-40 years). Cross-wavelet analysis reveals that increase rate of human plague oscillates in phase with SOI, but in anti-phase with SST over periods of 2-4 years and approximately 8 years (6-10 years). These results indicate that ENSO-driven climate variation may be important for occurrences of human plague in China. However, there is a need for a further analysis of the underlying mechanism between human plague in China and ENSO.