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This article proposes a new likelihood-based panel cointegration rank test which extends the test of Örsal and Droge (2014) (henceforth panel SL test) to dependent panels. The dependence is modelled by unobserved common factors which affect the variables in each cross-section through heterogeneous loadings. The data are defactored following the panel analysis of nonstationarity in idiosyncratic and common components (PANIC) approach of Bai and Ng (2004) and the cointegrating rank of the defactored data is then tested by the panel SL test. A Monte Carlo study demonstrates that the proposed testing procedure has reasonable size and power properties in finite samples. [ABSTRACT FROM AUTHOR]

The Empirical Bayes (EB) before-after study is used extensively for reliable safety evaluation. The EB method has the advantage of addressing confounding factors, including the regression-to-the-mean phenomenon and change of traffic volume. The EB method can also address the time trend effect by two approaches, i.e., the Yearly Multiplier (YM) and the Simple Crash Ratio of a Reference group (SCRR). However, the use of the YM without adjusting the over-dispersion parameter may induce a biased estimation of the Bayesian inference. This study aims to provide the systematic evaluation of the two approaches for correcting the time trend. To achieve this, a numerical example and its sensitivity analysis are presented. The bias due to the use of the YM is also measured based on the empirical data from Korean freeways. The findings of this study show the EB method with SCRR would be a useful approach as a time trend correction approach, especially when the reference group has experienced a considerable time trend. [ABSTRACT FROM AUTHOR]

Highlights • Agreeableness was described most often for both men and women. • Positive personality words were used more often than negative words for all factors. • The usage frequencies were higher for men than women for four factors except openness. • Gender differences showed some reduction over time. Abstract Using the American corpus and the English fiction corpus from Google Books databases, this study examined the frequencies of Big-Five personality adjectives used to describe the two genders between 1800 and 2000. Both gender similarities and differences were found. For both genders, adjectives related to agreeableness were used most often and those related to neuroticism least often. The usage frequency of agreeableness showed a steady decline, whereas extraversion and openness (and, to some extent, neuroticism) showed increases first and then leveled off. In terms of gender differences, the overall frequencies were higher for men than women for agreeableness, extraversion, conscientiousness, and neuroticism, but there was no gender difference for openness. Gender differences showed some reduction over time. [ABSTRACT FROM AUTHOR]

Background and aims. Cancer has emerged as the leading cause of death in human populations. The contribution of alcohol has been highly suspected. The purpose of this paper was to analyze the time trend of digestive cancers in Romania, in terms of mortality rates (1955-2012), and incidence rates (2008-2012), and the alcohol consumption data (1961-2010), aiming to find out if there is any association. Methods. The data on six more common digestive cancers mortality rates (1955-2012) and incidence rates (2008-2012) were obtained from the historical and recent country statistics and publications of International Agency for Research on Cancer (IARC)/World Health Organisation (WHO), as age-standardized rate expressed per 100,000 population (ASRw). Data on alcohol consumption were obtained from the statistics and publications of WHO and United European Gastroenterology (UEG), as liters of pure alcohol/year. Results. Between 1955-2012, the ASRw of mortality registered an increase of the cancers of the esophagus in M (from 2.03 to 3.90), and of colorectal cancer in both sexes (from 4.65 to 18.20 in M, and from 4.57 to 9.70 in F). Between 1980-2012, an increasing trend of mortality was registered, in both sexes, for the cancers of the pancreas (from 5.50 to 9.30 in M and from 2.92 to 5.10 in F) and liver (from 1.77 to 11.00, in M, and from 0.83 to 4.20 in F). In terms of incidence, between 2008-20012, an increasing trend of ASRw was registered for the cancers of the esophagus in M (from 3.90 to 4.30), gastric cancer in M (from 15.90 to 16.30), colorectal cancer in both sexes (from 27.60 to 34.50 in M and from 19.00 to 20.20 in F), pancreatic cancer in F (form 5.20 to 5.90), and liver cancer in M (from 8.10 to 9.20). Alcohol consumption per capita (liters pure alcohol/year) increased in the same period, from an average of 5 in 1961, to 12.8 in 2003-2005, and to 14.4 in 2008-2010. Conclusions. Given the parallel increase of some digestive cancers and alcohol consumption registered in our area, alcohol could represent more than a coincidence. [ABSTRACT FROM AUTHOR]

Abstract: Polybrominated diphenyl ethers (PBDEs) have been banned or voluntarily withdrawn from commerce worldwide. Declining levels of PBDEs in humans have been reported elsewhere, but not in Korea. We monitored 7 individual PBDE congeners (BDE‐28, BDE‐47, BDE‐99, BDE‐100, BDE‐153, BDE‐154, and BDE‐183) in 103 human serum samples collected in 2006. The arithmetic mean and median values for the sum of the 7 PBDEs (∑PBDEs) were 7.13 and 6.70 ng/g lipid, respectively. In addition, 6 pooled human serum samples collected in 2006, 2007, 2009, 2011, 2012, and 2013 were analyzed. A decrease in PBDE levels was observed, as reflected by the median value of ∑PBDEs from 5.98 in 2006 to 2.98 ng/g lipid in 2013 as well as in the pooled samples. The levels of individual congeners also decreased but at different declining rates. Based on these results and previously reported data, a definite decline in PBDE levels in the Korean metropolitan population could be observed from 2001 to 2013, providing the first evidence in Korea of the same decline observed elsewhere in the world. Environ Toxicol Chem 2018;37:2323–2330. © 2018 SETAC [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to investigate possible changes in the demographic and clinical characteristics of Japanese patients with eating disorders using a consecutive series of patients who presented at Kyoto University Hospital between 1963 and 2004. We also studied cultural factors related to eating disorders over time. Method: We completed a retrospective review of a cohort of patients using a checklist based on the DSM‐5 diagnostic criteria. Patients seen from 1963 to 1974 (Period I, n = 26), 1975 to 1984 (Period II, n = 97), 1985 to 1994 (Period III, n = 540), and 1995 to 2004 (Period IV, n = 700) were compared. Results: In this study, patients with restrictive eating appeared in the early 1960s. Patients with binge eating and purging behaviors appeared in the mid‐1970s and thereafter increased over time. The number of patients with anorexia nervosa and bulimia nervosa dramatically increased in Period III. The proportion of patients with binge eating increased, while the proportion of patients with restrictive eating decreased over time. All patients with anorexia nervosa in the 1960s had fat phobia and disturbed body image, but none of them reported dieting for slimness. Discussion: The prevalence and clinical characteristics of patients with eating disorders significantly changed across the four time periods. In terms of cultural factors, present findings suggest that factors beyond industrialization, modernization and westernization may be necessary for the development of eating disorders, and these factors may change with the times. [ABSTRACT FROM AUTHOR]

Total diet samples collected from seven regions throughout Japan in 2016 were analysed for polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and dioxin-like polychlorinated biphenyls (DL-PCBs), known collectively as dioxins. This led to estimates of the latest dietary intake of these contaminants for the general Japanese population (≥1 year old). The average daily intake of dioxins for a person weighing 50 kg, calculated at non-detected congener concentrations assumed to be equal to zero, was estimated to be 0.54 pg TEQ (toxic equivalents) kg−1 body weight (bw) day−1. This value is well below the tolerable daily intake of 4 pg TEQ kg−1 bw day−1 for dioxins in Japan. The average intake was highest from fish and shellfish, followed by meat and eggs. The TEQ contribution of the fish and shellfish group to the total dietary TEQs was significant (89%). The DL-PCBs accounted for about 67% of the dioxin intake. The latest dioxin intake level was compared with previous estimates from total diet study results obtained annually since 1998 to determine the time trends in the dietary intake of dioxins in Japan. Overall, the average dioxin intake appeared to be decreasing gradually during the period of study. The previous average intakes of dioxins ranged from 0.58 to 1.9 pg TEQ kg−1 bw day−1. The latest average intake was the lowest since 1998 and was about one-third of the average intake in 1998. This decreasing trend in the dietary intake of dioxins was mainly influenced by the decreased dioxin intakes from two food groups, fish and shellfish, and meat and eggs. [ABSTRACT FROM AUTHOR]

Many of the studies that analyze the future impact of climate change on mortality assume that the temperature that constitutes a heat wave will not change over time. This is unlikely, however, given the process of adapting to heat changes, prevention plans, and improvements in social and health infrastructure. The objective of this study is to analyze whether, during the 1983–2013 period, there has been a temporal change in the maximum daily temperatures that constitute a heat wave (T threshold ) in Spain, and to investigate whether there has been variation in the attributable risk (AR) associated with mortality due to high temperatures in this period. This study uses daily mortality data for natural causes except accidents CIEX: A00-R99 in municipalities of over 10,000 inhabitants in 10 Spanish provinces and maximum temperature data from observatories located in province capitals. The time series is divided into three periods: 1983–1992, 1993–2003 and 2004–2013. For each period and each province, the value of T threshold was calculated using scatter-plot diagram of the daily mortality pre-whitened series. For each period and each province capitals, it has been calculated the number of heat waves and quantifying the impact on mortality through generalized linear model (GLM) methodology with the Poisson regression link. These models permits obtained the relative risks (RR) and attributable risks (AR). Via a meta-analysis, using the Global RR and AR were calculated the heat impact for the total of the 10 provinces. The results show that in the first two periods RR remained constant RR: 1.14 (CI95%: 1.09 1.19) and RR: 1.14 (CI95%: 1.10 1.18), while the third period shows a sharp decrease with respect to the prior two periods RR: 1.01 (CI95%: 1.00 1.01); the difference is statistically significant. In Spain there has been a sharp decrease in mortality attributable to heat over the past 10 years. The observed variation in RR puts into question the results of numerous studies that analyze the future impact of heat on mortality in different temporal scenarios and show it to be constant over time. [ABSTRACT FROM AUTHOR]

Aims: Our aim was to assess causes of death and temporal changes in excess mortality among patients with new-onset type 2 diabetes in Skaraborg, Sweden.Methods: Patients from the Skaraborg Diabetes Register with prospectively registered new-onset type 2 diabetes 1991-2004 were included. Five individual controls matched for sex, age, geographical area and calendar year of study entry were selected using population records. Causes of deaths until 31 December 2014 were retrieved from the Cause of Death Register. Adjusted excess mortality among patients and temporal changes of excess mortality were calculated using Poisson models. Cumulative incidences of cause-specific mortality were calculated by competing risk regression.Results: During 24 years of follow-up 4364 deaths occurred among 7461 patients in 90,529 person-years (48.2/1000 person-years, 95% CI 46.8-49.7), and 18,541 deaths in 479,428 person-years among 37,271 controls (38.7/1000 person-years, 38.1-39.2). The overall adjusted mortality hazard ratio was 1.47 (p < .0001) among patients diagnosed at study start 1991 and decreased by 2% (p < .0001) per increase in calendar year of diagnosis until 2004. Excess mortality was mainly attributed to endocrine and cardiovascular cause of death with crude subdistributional hazard ratios of 5.06 (p < .001) and 1.22 (p < .001).Conclusions: Excess mortality for patients with new-onset type 2 diabetes was mainly attributed to deaths related to diabetes and the cardiovascular system, and decreased with increasing year of diagnosis 1991-2004. Possible explanations could be temporal trends of earlier diagnosis due to lowered diagnostic thresholds and intensified diagnostic activities, as well as improved treatment. [ABSTRACT FROM AUTHOR]

Aims: To identify how efforts to control the diabetes epidemic and the resulting changes in diabetes mellitus, type II (T2D) incidence and survival have affected the time-trend of T2D prevalence.Methods: A newly developed method of trend decomposition was applied to a 5% sample of Medicare administrative claims filed between 1991 and 2012.Results: Age-adjusted prevalence of T2D for adults age 65+ increased at an average annual percentage change of 2.31% between 1992 and 2012. Primary contributors to this trend were (in order of magnitude): improved survival at all ages, increased prevalence of T2D prior to age of Medicare eligibility, decreased incidence of T2D after age of Medicare eligibility.Conclusions: Health services supported by the Medicare system, coupled with improvements in medical technology and T2D awareness efforts provide effective care for individuals age 65 and older. However, policy maker attention should be shifted to the prevention of T2D in younger age groups to control the increase in prevalence observed prior to Medicare eligibility. [ABSTRACT FROM AUTHOR]

Background and Aim: Considering the importance of cutaneous leishmaniasis in Iran, this study was conducted to present the epidemiological characteristics of patients with cutaneous leishmaniasis, the time trend and the mapping of the disease in the cities under the supervision of Shiraz University of Medical Sciences. Materials and Methods: Data was collected from the Heath deputy of Shiraz University of Medical Sciences and Health Centers of cities from 2005 to 2014; and was analyzed using Excel and SPSS19 software. Chi square test and Poisson regression were used for analysis. Results: The incidence of the disease increased from 109 cases per 100,000 in 2005 to 218 in 2008 and decreased to 110 in 2014. The 0-9 age group was the most vulnerable and housewives were the most involved occupational group. Most people had a wet wound. The hands were the most affected. The highest incidence of disease was in the autumn. Zoonotic Cutaneous Leishmaniasis (ZCL) was the dominant type. Cutaneous leishmaniasis was more in northern than southern regions of the province in the recent years. Conclusion: In the last years of the study, unlike in the early years, the incidence of disease in the northern region of the province was more than the southern regions. This finding could be a warning signal that the disease could be relocating and spreading in areas where the disease was not endemic before. [ABSTRACT FROM AUTHOR]

Background and purpose: Lower-extremity amputations (LEAs) in people with diabetes are associated with reduced quality of life and increased health care costs. Detailed knowledge on amputation rates (ARs) is of utmost importance for future health care and economics strategies. We conducted the present cohort study in order to estimate the incidences of LEA as well as relative and attributable risk due to diabetes and to investigate time trends for the period 2008-2012. Methods: On the basis of the administrative data from three large branches of German statutory health insurers, covering ~34 million insured people nationwide (about 40% of the German population), we estimated age-sex-standardized AR (first amputation per year) in the populations with and without diabetes for any, major, and minor LEAs. Time trends were analyzed using Poisson regression. Results: A total of 108,208 individuals (diabetes: 67.3%; mean age 72.6 years) had at least one amputation. Among people with diabetes, we observed a significant reduction in major and minor ARs during 2008-2012 from 81.2 (95% CI 77.5-84.9) to 58.4 (55.0-61.7), and from 206.1 (197.3-214.8) to 177.0 (169.7-184.4) per 100,000 person-years, respectively. Among people without diabetes, the major AR decreased significantly from 14.3 (13.9-14.8) to 11.6 ([11.2-12.0], 12.0), whereas the minor AR increased from 15.8 (15.3-16.3) to 17.0 (16.5-17.5) per 100,000 person-years. The relative risk (RR) comparing the diabetic with the nondiabetic populations decreased significantly for both major and minor LEAs (4% and 5% annual reduction, respectively). Conclusion: In this large nationwide population, we still found higher major and minor ARs among people with diabetes compared with those without diabetes. However, AR and RR of major and minor LEAs in the diabetic compared with the nondiabetic population decreased significantly during the study period, confirming a positive trend that has been observed in smaller and regional studies in recent years. [ABSTRACT FROM AUTHOR]

Sports with high numbers of athletes and acute injuries are an important target for preventive actions at a national level. Both for the health of the athlete and to reduce costs associated with injury. The aim of this study was to identify injuries where injury prevention should focus, in order to have major impact on decreasing acute injury rates at a national level. All athletes in the seven investigated sport federations (automobile sports, basketball, floorball, football (soccer), handball, ice hockey, and motor sports) were insured by the same insurance company. Using this insurance database, the incidence and proportion of acute injuries, and injuries leading to permanent medical impairment (PMI), at each body location, was calculated. Comparisons were made between sports, sex, and age. In total, there were 84 754 registered injuries during the study period (year 2006‐2013). Athletes in team sports, except in male ice hockey, had the highest risk to sustain an injury and PMI in the lower limb. Females had higher risk of injury and PMI in the lower limb compared to males, in all sports except in ice hockey. This study recommends that injury prevention at national level should particularly focus on lower limb injuries. In ice hockey and motor sports, head/neck and upper limb injuries also need attention. [ABSTRACT FROM AUTHOR]

Aims: The aim was to investigate the time trends in educational, occupational, and income-related inequalities in leisure time physical inactivity in 2006, 2010, and 2014 in northern Swedish women and men. Methods: This study was based on data obtained from the repeated cross-sectional Health on Equal Terms survey of 2006, 2010, and 2014. The analytical sample consisted of 20,667 (2006), 31,787 (2010), and 21,613 (2014) individuals, aged 16–84. Logistic regressions were used to model the probability of physical inactivity given a set of explanatory variables. Slope index of inequality (SII) and relative index of inequality (RII) were used as summary measures of the social gradient in physical inactivity. The linear trend in inequalities and difference between gender and years were estimated by interaction analyses. Results: The year 2010 displayed the highest physical inactivity inequalities for all socioeconomic position indicators, but educational and occupational inequalities decreased in 2014. However, significant positive linear trends were found in absolute and relative income inequalities. Moreover, women had significantly higher RII of education in physical inactivity in 2014 and significantly higher SII and RII of income in physical inactivity in 2010, than did men in the same years. Conclusions:The recent reduction in educational and occupational inequalities following the high inequalities around the time of the great recession in 2010 suggests that the current policies might be fairly effective. However, to eventually alleviate inequities in physical inactivity, the focus of the researchers and policymakers should be directed toward the widening trends of income inequalities in physical inactivity. [ABSTRACT FROM AUTHOR]

Purpose: To investigate differences in prostate cancer incidence between two distinct Swiss regions from 1996 to 2013 stratified by age group, grade, and T-stage.Methods: The dataset included 17,495 men living in Zurich and 3,505 men living in Ticino, diagnosed with prostate cancer between 1996 and 2013. We computed age-standardized incidence rates per 100,000 person-years using the European Standard Population. Trends were assessed using JoinPoint regression analysis Software.Results: Age-standardized incidence rates were generally higher in Zurich compared to Ticino but the difference decreased over time. Incidence rates increased significantly up to 2002 in Zurich and 2007 in Ticino and then decreased. A statistically significant increase was observed for men aged < 65 years, for grade 3 tumors, and for T-stage 2 and 3 tumors. The largest decrease was seen for grade 1 tumors. Furthermore, the incidence of tumors of unknown grade or T-stage decreased significantly in both regions.Conclusions: The trends in prostate cancer incidence rates were similar in both regions, although on a higher level in Zurich compared to Ticino. However, the difference decreased over time. The distribution of T-stage and grade did not explain the difference in incidence rates. Different use of opportunistic screening may play a role. [ABSTRACT FROM AUTHOR]

Background: To describe, with aid of geo-mapping, the effects of a risk-based capitation model linked to cariespreventive guidelines on the polarization of caries in preschool children living in the Halland region of Sweden. Methods: The new capitation model was implemented in 2013 in which more money was allocated to Public Dental Clinics surrounded by administrative parishes inhabited by children with increased caries risk, while a reduced capitation was allocated to those clinics with a low burden of high risk children. Regional geo-maps of caries risk based on caries prevalence, level of education and the families purchasing power were produced for 3-6-year-old children in 2010 (n = 10,583) and 2016 (n = 7574). Newly migrated children to the region (n = 344 in 2010 and n = 522 in 2016) were analyzed separately. A regional caries polarization index was calculated as the ratio between the maximum and minimum estimates of caries frequency on parish-level, based on a Bayesian hierarchical mapping model. Results: Overall, the total caries prevalence (dmfs > 0) remained unchanged from 2010 (10.6%) to 2016 (10.5%). However, the polarization index decreased from 7.0 in 2010 to 5.6 in 2016. Newly arrived children born outside Sweden had around four times higher caries prevalence than their Swedish-born peers. Conclusions: A risk-based capitation model could reduce the socio-economic inequalities in dental caries among preschool children living in Sweden. Although updated evidence-based caries-preventive guidelines were released, the total prevalence of caries on dentin surface level was unaffected 4 years after the implementation. [ABSTRACT FROM AUTHOR]

Background: Phase I trials are designed to determine the safety, tolerability, and recommended phase 2 dose of therapeutic agents for subsequent testing. The dose-finding paradigm has thus traditionally focused on identifying the maximum tolerable dose of an agent or combination therapy under the assumption that there is a non-decreasing relationship between dose-toxicity and dose-efficacy. The dose is typically determined based on the probability of severe toxicity observed during the first treatment cycle. A novel endpoint, the total toxicity profile, was previously developed to account for the multiple toxicity types and grades experienced in the first cycle. More recently, this was extended to a repeated measures design based on the total toxicity profile to account for longitudinal toxicities over multiple treatment cycles in the absence of within-patient correlation. Methods: In this work, we propose to extend the design in the presence of within-patient correlation. Furthermore, we provide a framework to detect a toxicity time trend (toxicity increasing, decreasing, or stable) over multiple treatment cycles. We utilize a linear mixed model in the Bayesian framework, with the addition of Bayesian risk functions for decision-making in dose assignment. Results: The performance of this design was evaluated using simulation studies and real data from a phase I trial. We demonstrated that using available toxicity data from all cycles of treatment improves the accuracy of maximum tolerated dose identification and allows for the detection of a time trend. The performance is consistent regardless of the strength of the within-patient correlation. In addition, the use of a quasi-continuous total toxicity profile score significantly increased the power to detect time trends compared to when binary data only were used. Conclusion: The increased interest in molecularly targeted agents and immunotherapies in oncology necessitates innovative phase I study designs. Our proposed framework provides a tool to tackle some of the challenges presented by these novel agents, specifically through the ability to understand patterns of toxicity over time, which is important in the cases of cumulative or late toxicities. [ABSTRACT FROM AUTHOR]

Education is a central determinant of adolescent health. School absences and bullying involvement jeopardize wellbeing, mental health, and educational attainment. We analyzed time trends in school absenteeism over two decades and examined the association of absenteeism with bullying involvement.We analyzed data from the nationwide School Health Promotion study, with self-reported data from Finnish middle school students in grades 8 and 9 (ages 14–17, N = 1 000 970). Questionnaires assessed frequency of illness absences (IA), truancy, frequency of bullying victimization, bullying perpetration, and involvement in both bullying perpetration and victimization. Frequent school absences were defined as occurring on more than 3 days during the prior month (2000–2015), or at least weekly (2017–2019).Frequent IA increased from 12% to 2000 to 22% in 2015. In 2017–2019, frequent IA was reported by 3.5%. Frequent truancy declined from 9% to 2000 to 4% in 2015, and remained at 4% during 2017–2019. Bully victimization was reported at least weekly by 6.9%, perpetration by 5.4% and victimization-perpetration by 1.9% of participants in total. In a logistic regression model, every type of bullying involvement increased odds for both IA and truancy.Since bullying involvement was associated with both IA and truancy, particular concern should be raised for adolescents involved in bullying, and for their social and educational functioning. The concurrent increase in IA and decrease in truancy may reflect destigmatization of mental health problems or other changes in reporting absenteeism. [ABSTRACT FROM AUTHOR]

In most countries, incidence and mortality for Parkinson's disease (PD) have not been monitored by surveillance registries, although it could demonstrate the need for primary and tertiary prevention. To examine 25-year trends in first-time hospitalizations for PD in Denmark and subsequent short and long-term mortality. In a nationwide population-based cohort we identified all 34,947 individuals with a first-time hospitalization for PD from 1995 through 2019. We calculated standardized incidence rates of PD and 1-year and 5-year mortality by sex. Mortality rates were compared with a reference cohort randomly selected from the background population matched on sex, age, and index date. The annual standardized incidence rate of PD was relatively stable during the study period in both men and women. The incidence of PD was higher in men than in women and with the highest incidence in those aged 70–79 years. One and 5-year mortality risk after first-time hospitalization for PD was similar for men and women, and decreased by around 30% and 20%, respectively, between 1995 and 2019. The matched reference cohort had a similar decline in mortality over time. The rate of first-time hospitalization for PD was relatively stable between 1995 and 2019, whereas subsequent short and long-term mortality declined during the period as in the reference cohort. • The incidence of Parkinson's disease was relative stable in Denmark between 1995 and 2019. • The incidence of Parkinson's disease was highest in men and at age 70–79 years. • During the time period one and five year mortality risk decreased in patient with Parkinson's disease. [ABSTRACT FROM AUTHOR]

Background: Detailed knowledge of the evolutionary potential of polymorphic sites in a viral protein is important for understanding the development of drug resistance in the presence of an inhibitor. We therefore set out to analyse the molecular evolution of the HIV-1 subtype B integrase at the inter-patient level in Germany during a 20-year period prior to the first introduction of integrase strand inhibitors (INSTIs). Methods: We determined 337 HIV-1 integrase subtype B sequences (amino acids 1-278) from stored plasma samples of antiretroviral treatment-naïve individuals newly diagnosed with HIV-1 between 1986 and 2006. Shannon entropy was calculated to determine the variability at each amino acid position. Time trends in the frequency of amino acid variants were identified by linear regression. Direct coupling analysis was applied to detect covarying sites. Results: Twenty-two time trends in the frequency of amino acid variants demonstrated either single amino acid exchanges or variation in the degree of polymorphy. Covariation was observed for 17 amino acid variants with a temporal trend. Some minor INSTI resistance mutations (T124A, V151I, K156 N, T206S, S230 N) and some INSTI-selected mutations (M50I, L101I, T122I, T124 N, T125A, M154I, G193E, V201I) were identified at overall frequencies >5%. Among these, the frequencies of L101I, T122I, and V201I increased over time, whereas the frequency of M154I decreased. Moreover, L101I, T122I, T124A, T125A, M154I, and V201I covaried with non-resistance-associated variants. Conclusions: Time-trending, covarying polymorphisms indicate that long-term evolutionary changes of the HIV-1 integrase involve defined clusters of possibly structurally or functionally associated sites independent of selective pressure through INSTIs at the inter-patient level. Linkage between polymorphic resistance- and non-resistanceassociated sites can impact the selection of INSTI resistance mutations in complex ways. Identification of these sites can help in improving genotypic resistance assays, resistance prediction algorithms, and the development of new integrase inhibitors. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess if the gap in mortality between adults with and without diabetes has widened over time in US adults. Methods and study design: This cohort study included 44,041 adults with diabetes from the US National Health Interview Survey between 1986 and 2009 linked to the National Mortality Index data up to 2011. Each participant with diabetes was matched to two participants without diabetes by age, sex, race, survey year, and region of residence (88,082 persons without diabetes). Mortality differences and hazard ratios were calculated for different time periods defined by three methods, according to 1) survey years with original follow-up durations, 2) follow-up calendar years, and 3) survey years with a fixed 3-year follow-up duration. Results: Different methods of defining time periods produced substantially different mortality rates and changing patterns over time. The decline in mortality was higher when time periods were defined according to survey years with original follow-up durations than with the fixed 3-year duration. Different time periods had comparable baseline and attained ages only when the fixed duration was used. With this method, the gap between adults with and without diabetes progressively decreased from 224 (95% confidence interval 188-260) in 1992-1994 to 99 (65-132) per 10,000 person-years in 2007-2009. Hazard ratios declined significantly from 2.12 (1.88-2.38) in 1995-1997 to 1.70 (1.44-2.00) in 2007-2009. Conclusion: The decline in mortality over time was greater among adults with diabetes than those without diabetes. The gap in mortality between adults with diabetes and those without diabetes significantly narrowed in recent years, and was more than halved over the last 15 years. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to present the time trend of suicide rate in people aged 5 years and over in China from 2002 to 2015, and to describe the rural and urban distribution, and population characteristics of suicide rate in recent 13 years. Methods: The data of suicide rate were based on the China Health Statistics Yeabook published by the National Health and Family Planning Commission (formerly as the Ministry of Health) of the People's Republic of China. Poisson regression models were used to test the time trend of the general suicide rate, and region-, gender-and age-specific suicide rates. Results: Since 2002, the suicide rates in urban population, rural population, male and female have decreased significantly. Urban population had higher decreasing trend than rural population, and female had higher decreasing trend than male. Suicide rates in women of reproductive age (15 -49 years) both in rural and urban areas had significantly decreasing trends, and were lower than male with same ages in recent years. There was no statistical difference of the decreasing trend in rural population aged 85 years and over, or young male population in rural area. The annual average suicide rate from 2012 to 2015 was 6. 75/100 000. Rural population, male and the older persons had higher suicide rate. Conclusion: The overall suicide rate decreased over the period of 2001-2015. However, it is still important to carry out suicide prevention program, especially in rural area, and in older persons and young male. [ABSTRACT FROM AUTHOR]