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Considering the specific inhibitory effect of juglone on Parvulin and the higher sensitivity of AfuRbp deficient mutants to this chemical compared to the parental strain, it can be concluded that juglone may act as a specific inhibitor of the AfuRBP. More detailed studies on recombinant AfuRBP may verify this claim.
|
study
| 100.0 |
Maternal and child health-related indicators comprise two of the eight development goals in the United Nations Millennium Development Goals (MDGs) (i.e., reducing child mortality and improving maternal health) . This plan aims to reduce child mortality and improve maternal health (1990–2015) by calling for the following changes: a reduction by two-thirds in the mortality of children under 5 years of age, a reduction of three-quarters in maternal mortality, and universal reproductive health by 2015. In September 2000, China officially became a signatory to the MDGs and included women and children as the focus groups in the Healthy China 2030 Planning Outline. In 2010, the World Health Organization (WHO) evaluated the regional and worldwide achievements of the MDGs . A scoring system based on 10 indicators was employed, and the results showed that the worldwide achievements in the MDGs were not satisfactory. Specifically, three of the four maternal and child health-related evaluation indicators failed to show adequate progress. As stated in the final report of the United Nations (the Report of MDGs 2015), the MDGs have not been fully achieved, and inequality still persists. This statement was followed by the target of the Sustainable Development Goals (SDGs) (i.e., reducing cases such as international inequalities). In September 2015, the member states of the MDGs re-signed the SDGs, including Reducing Health Inequality at Home and Abroad .
|
review
| 99.7 |
Equality-related research has developed rapidly over the past 30 years. In the 1980s, only approximately one dozen papers on equity were published each year . By 2015, a total of 3521 Chinese and English documents on equity/equality in health were published, indicating that policy makers, project sponsors and non-governmental organizations paid more attention to the need for increased research in equality in health. Many of the policy statements and findings from the WHO strongly call for a reduction in the disparities in maternal and child health between countries and different socioeconomic groups within countries [5–7]. The World Development Report 2006 published by the World Bank noted that the inequality of opportunity between countries was staggering, not only in terms of inequality in survival opportunities, but also in education, health and the use of infrastructure and other public services . Relevant foreign studies have shown that the coverage rate and service quality of antenatal care are significantly higher in urban areas than in rural areas [9, 10]. Women with higher levels of education are more likely to choose caesarean delivery for childbirth and receive more antenatal care . Additionally, children in poor households are more prone to growth retardation, being underweight, anaemia, and diarrhoea . Health equality in practice has been actively explored in foreign countries, and a series of related measures have been formulated; these measures have mainly included changes in the public health service model by integrating health resources, expanding health service areas and strengthening supervision and management. A series of measures has contributed to the improvement of health equality . One study has shown a distinct difference in women’s and children’s health in Asian countries, with up to 33-fold differences in the under-five mortality rate (U5MR) between Japan and Afghanistan and 67-fold differences in the maternal mortality rate (MMR) . The prevalence of this health inequality was a concern of Marie-Paule Kieny, Deputy Director-General of the WHO , who noted that the current primary task was to ensure the continued health improvement of vulnerable groups by monitoring health inequalities in developing countries.
|
review
| 99.9 |
The condition of maternal and child health equality is not optimistic in China, which is the largest developing country. China has fully committed to the MDGs and has achieved 13 MDG targets over the past 15 years. The under-five child mortality rate dropped from 61.0% in 1991 to 12.0% in 2013, the gap in the child mortality rate between urban and rural areas narrowed from 1:3.4 to 1:2.4, the maternal mortality rate declined from 88.8 per 100,000 in 1990 to 23.2 per 100,000 in 2013, and the maternal mortality rate between rural and urban areas narrowed from 1:2.2 to 1:1.1 . However, an obvious gap in key maternal and child health indicators still exists between urban and rural areas and among different regions. A notable difference remains in the mortality rates of newborns and children under 5 years of age between rural and urban areas. Differences can also be seen among various regions. According to data from the China Health Statistical Yearbook, the MMR and U5MR in the western region are 2.6 and 3.1 times higher, respectively, than the rates in the eastern region . A study in China’s poorest rural areas showed infant mortality rates (IMRs) that were approximately 5 times higher in China’s poorest rural areas compared to the richest regions (123 and 26 per thousand in the poorest and richest areas, respectively) . China’s 10-year follow-up survey showed that the U5MR among the poorest people (accounting for one-fifth of the population) was 6 times the U5MR among the richest people (accounting for one-fifth of the population). The U5MR was only 10% in the richest big cities but was 64% in poor rural areas. An approximately three-fold difference was found in the malnutrition rate of children under 5 years of age between urban and rural areas. The incidence of childhood stunting was 17.3% in rural areas and only 4.9% in urban areas, and the incidence of low birth weight infants was 9.3% in rural areas and only 3.1% in urban areas .
|
review
| 96.4 |
Despite inequalities in international and domestic maternal and child health, research in this area is still relatively scarce. After literature searches of the Web of Science, Engineering Village, Wiley Online Library, Science Direct, Springer Link, VIP, Wangfang Data, and CNKI databases, we found only 30 articles focusing on the equality of maternal and child health. Moreover, studies related to the theory of equality of maternal and child health services started later in China. An analysis of the Chinese literature indicated that related studies gave priority to a cross-sectional design (e.g., a study of the current situation and the equity of the intervening measures to promote maternal and child health coverage in China , an analysis of the MMR, child mortality and impact factor levels , and an analysis of the equality of basic public health services between different regions ). Fewer longitudinal studies have been performed (e.g., an analysis of the equality allocation of maternal health care resources in China between 2005 and 2009 ); moreover, these studies have focused on analysing the health input dimensions and the disparity in the MMR in urban and rural areas between 1996 and 2006 . Moreover, studies on the developing equality trend for only one outcome indicator lack a comprehensive analysis of the equality trend in multiple indicators of maternal and child health outcomes and the causes of death.
|
review
| 99.9 |
In this study, several representative indicators of maternal and child health outcomes were selected based on place of residence and gender strata; from these data, a longitudinal assessment was conducted on equality and the tendencies of China’s maternal and child health outcomes with a distributive difference analysis on the maternal death causes and causes of death in children under 5 years of age. The aim of the study is to suggest strategies and measures to improve the equality of maternal and child health outcomes in China.
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study
| 99.94 |
The data were collected from China’s 2000–2013 maternal and child health surveillance system, which was nationally and originally collected from maternal and child death records. The data were reported from maternity and child care institutions in 336 locations and were investigated by level. We selected the following maternal and child health outcome indicators: incidence of birth defects (IBD), MMR, under 5 mortality rate (U5MR), and neonatal mortality rate (NMR). We calculated the estimated values, sample size and standard error for the causes of death based on location (urban and rural areas) and gender.
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study
| 99.94 |
The indicators in the questionnaire were selected based on a comprehensive literature review and expert consultation. Ultimately, disease and death outcomes were selected to explain the equality of maternal and child health outcomes in China. The disease outcome dimension included the IBD, which referred to the ratio of the number of annual IBD cases to the number of births that occurred in that year in the jurisdiction. The death outcome dimension included the MMR, NMR, and U5MR; the MMR refers to maternal mortality due to all causes from pregnancy up to 42 days after giving birth (except accidents), the NMR refers to live births born after 28 weeks of pregnancy (i.e., the ratio of deaths within 28 days after birth to the number of births), and the U5MR refers to the probability of death before the age of 5 years in children born in a given year. Focused analyses were performed on the cause of maternal mortality and the cause of under-five mortality. In this study, the causes of maternal death included postpartum haemorrhage (PH), puerperal infection (PI), pregnancy-induced hypertension (PIH), medical complications (MC) and amniotic fluid embolism (AFE); the causes of death in children under the age of 5 years included premature birth and being underweight (PBU), birth asphyxia (BA), diarrhoea, and pneumonia, as well as others. The maternal and child health outcomes included in this study are negative indicators, with index definitions and formulas consistent with the definitions and contents in the monitoring and investigation lists of national maternity and child care institutions.
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study
| 99.94 |
In the current study, the latest HD*Calc software (developed by McGill University) recommended by the WHO was used to measure health disparities. The between group variance (BGV) of the absolute measure and the Theil index (T) of the relative measure were adopted for horizontal and vertical monitoring of China’s inequality in maternal and child health. The Slope function was used to analyse the BGV and T trends in various indicators between either the place of residence or gender from 2000 to 2013.
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study
| 100.0 |
The absolute inequality reflected the degree of the difference in health between two subgroups and had the same dimensions as the health indicators. The relative inequality was the difference in the health proportion between the subgroups and was used to compare indicators with different dimensions. The variables were unordered for place of residence and gender; within the stratified indicators, both the BGV in the absolute inequality monitoring method and the T in the relative inequality monitoring method were used to assess the stratified variables based the equity of the unordered variables. Therefore, both methods were selected to measure and calculate the equity of maternal and child health outcome indicators in China. The T and BGV methods were used to consider and discuss equality in the studies of An R , Hajizadeh M , and An Q .
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study
| 99.94 |
The BGV in the absolute inequality monitoring method is a commonly used statistic that measures the degree of discrepancy between groups and reflects the degree of deviation between a random variable and its mathematical expectation (i.e., average value). The variance is the average of the sum of the squares of the difference between individual data. In many practical problems, the study of variance (i.e., the degree of divergence) is a significant measure, with a larger BGV indicating greater inequality. The Theil index in the relative inequality monitoring method measures and calculates the relative inequality for the subgroups of the population that do not exist in the natural sequence. The T increases with an increase in the relative inequality; thus, a larger T indicates higher relative inequality without an upper limit. The Theil index shows the relative meaning rather than the absolute meaning. Therefore, T was mainly used to compare different indices in this study.\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \boldsymbol{B}\boldsymbol{G}\boldsymbol{V}={\displaystyle \sum_{\boldsymbol{j}-\boldsymbol{1}}^{\boldsymbol{J}}{\boldsymbol{P}}_{\boldsymbol{j}}}{\left({\boldsymbol{y}}_{\boldsymbol{j}}-\boldsymbol{\mu} \right)}^{\boldsymbol{2}} $$\end{document}BGV=∑j−1JPjyj−μ2
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study
| 100.0 |
Pj is the population size of group j, yj is the average health level of group j, and μ is the average health level of the entire population.\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ \boldsymbol{T}={\displaystyle \sum_{\boldsymbol{j}-\boldsymbol{1}}^{\boldsymbol{J}}{\boldsymbol{p}}_{\boldsymbol{j}}}{\boldsymbol{r}}_{\boldsymbol{j}}\boldsymbol{In}{\boldsymbol{r}}_{\boldsymbol{j}}\times \boldsymbol{1000} $$\end{document}T=∑j−1JpjrjInrj×1000
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other
| 99.9 |
Three indicators in the death outcome dimensions (MMR, NMR and U5MR) showed an annual declining trend. Conversely, the IBD showed an upward trend from 109.79 persons per 10,000 perinatal infants in 2000 to 145.06 persons in 2013; an IBD of 153.24 persons per 10,000 perinatal infants was found in 2011 (Fig. 1).Fig. 1Trends in China’s maternal and child health outcomes from 2000 to 2013
|
study
| 99.9 |
The following results were found in the comparison between urban and rural areas from 2000 to 2013: the BGV and T ranges for the IBD were [0.308, 452.413] and [0.007, 10.778], respectively, the BGV and T ranges for the MMR were [0.04, 366.723] and [0.022, 103.032], respectively, and the BGV and T ranges for the NMR were [3.24, 66.422] and [54.37, 110.764], respectively. The disparity of the MMR between the urban and rural areas was the lowest (T = 7.246) in 2013, whereas the disparity of the U5MR between urban and rural areas was the highest (T = 88.611). From 2000 to 2013, there was a decreasing trend in the disparity of all indicators with the exception of an upward trend in the disparity of the IBD between the urban and rural areas. The BGV (Slope BGV = -32.24) and T (Slope T = 7.87) of the MMR declined fastest and showed the largest range of decline, whereas the U5MR equality trend between the urban and rural areas showed slower improvement (Fig. 2).Fig. 2Disparity trends in China’s maternal and child health outcomes between urban and rural areas from 2000 to 2013
|
study
| 100.0 |
With the exception of the widening of the gender disparity in the IBD from 2000 to 2013, the development trends observed for gender disparity (Slope BGV = -0.06, Slope T = -0.21) in the U5MR and NMR were relatively stable (Slope BGV = -0.01, Slope T = 0.23). The BGV and T ranges for the IBD in the analysis stratified by gender from 2000 to 2013 were [38.875, 299.463] and [1.675, 6.595], respectively. The BGV and T ranges for the U5MR were [0.640, 4.000] and [0.210, 6.855], respectively. Finally, the BGV and T ranges for the NMR were [0.023, 1.102] and [0.025, 3.255], respectively. The gender disparity in IBD was largest in 2013 (T = 6.225), whereas the gender disparity in NMR was the lowest (T = 3.255) (Fig. 3).Fig. 3Gender disparity trends in China’s maternal and child health outcomes from 2000 to 2013
|
study
| 99.94 |
Based on the average values of various indicators, the sequence of urban maternal death among the five causes of death (OH, PI, PIH, MC and AFE) from 2000 to 2013 was as follows: MC (49.97%), OH (25.99%), AFE (12.44%), PIH (10.69%) and PI (1.34%). The sequence of rural maternal causes of death in 2000–2013 was as follows: OH (39.83%), MC (36.11%), PIH (11.31%), AFE (10.99%) and PI (2.06%) (Fig. 4).Fig. 4Disparity trends in maternal causes of death between urban and rural areas in China from 2000 to 2013
|
study
| 100.0 |
Based on the overall developing trend from 2000 to 2013, the most obvious reduction in urban-rural differences in the maternal cause of death was OH (Slope BGV = -14.61, Slope T = -20.84). No significant changes were observed for the remaining indicators. With the exception of short-term fluctuations in individual years, the rural-urban differences in PI, PIH, MC and AFE were maintained at a low level. In 2013, the T of PIH was the largest (13.1), whereas the T of the other death causes was relatively small, with a distribution of [3.0, 13.1] (Fig. 4).
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study
| 100.0 |
From the average values, the sequence of the causes of death in children under 5 years of age in urban areas was as follows: other causes (54.46%), BA (17.83%), PBU (17.11%), pneumonia (9.41%) and diarrhoea (1.18%). The sequence of the causes of death in children under the age of 5 years in rural areas was as follows: other causes (47.67%), PBU (17.36%), pneumonia (16.59%), BA (14.24%) and diarrhoea (4.43%) (Fig. 5).Fig. 5Disparity trends in causes of death of children under the age of 5 years between urban and rural areas in China from 2000 to 2013
|
study
| 99.94 |
In 2013, a maximum rural-urban difference was found for diarrhoea in the different places of residence (T = 249.429). Conversely, the differences in PBU and BA were both relatively small (T = 38.945 and 51.244, respectively). The trend showed that the Slope BGV and T values for PBU, diarrhoea and pneumonia were less than 0, indicating that the urban-rural differences were narrow; however, the Slope BGV for the urban-rural differences in BA and the other causes of death trended in the opposite direction of the T values (Fig. 5).
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study
| 100.0 |
Based on the average values, the sequence of the causes of death in boys under 5 years of age was as follows: other causes (48.05%), PBU (17.76%), BA (15.36%), pneumonia (14.93%) and diarrhoea (3.09%). The sequence of the causes of death in girls under 5 years of age was as follows: other causes (51.42%), PBU (16.80%), BA (15.25%), pneumonia (14.14%) and diarrhoea (3.38%). Thus, the same sequence was observed for boys and girls (Fig. 6).Fig. 6Gender disparity trends in causes of death of children under the age of 5 years in China from 2000 to 2013
|
study
| 99.94 |
In 2013, the gender-based T of PBU, BA, and pneumonia was approximately 2, whereas the gender-based T for diarrhoea and other causes of death was greater than 6. Based on the overall trend from 2000 to 2013, no obvious gender-based change across the five causes of death was found; the absolute values of the Slope T and BGV were both less than 1, although great fluctuation was observed in the values (Fig. 6).
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study
| 100.0 |
The results generally show agreement between the longitudinal equality trends in the various indicators represented by BGV and T, but some differences may exist. The BGV in PI indicated a decreasing longitudinal trend in urban-rural differences, whereas the T showed that the longitudinal trend in urban-rural differences increased. Additionally, the Slope BGV of the urban-rural differences in BA and other causes of death showed an opposing trend compared with that of the T value, which was similar to relevant research results. For example, Hajizadeh M and others used T and BGV to monitor equality in maternal and child services between six administrative regions and found that the T of skilled birth attendance in the different administrative regions decreased by 0.2 per year, whereas the BGV showed an upward trend .
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study
| 99.94 |
With the implementation and development of China’s major health projects, basic public health services and related maternal and child health special work throughout the country, China’s maternal and child health services are running at a high level . Based on comparisons with historical data, the MMR, IBD, NMR and U5MR are decreasing annually. With the constant development towards equality in basic public health services , the equality of China’s maternal and child health outcomes has also improved. Regarding the equality between urban and rural areas from 2000 to 2013, improvement was found in the equity of three of the four outcome indicators. The degree of equality based on the place of residence and gender strata showed that the MMR increased overall and that the urban-rural differences in the U5MR and NMR decreased significantly. According to our interviews with officials in the health bureau to assess their actual health situations, various regions have rationally allocated maternal and child health resources and actively provided maternal and child health services in recent years. Furthermore, the efficiency has been enhanced and more attention has been paid to equity to achieve full coverage of basic services and wide coverage of special services. The most obvious change was the reduction in urban-rural differences.
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other
| 93.44 |
The urban-rural differences in the construction mechanisms used to achieve equality in basic public health services in China’s maternal and child health field has narrowed. Specifically, the reduction in maternal and child health differences between urban and rural areas is mainly embodied in two aspects. First, the increased government investment in maternal and child health care projects in rural areas has effectively narrowed the difference in maternal and child health services between urban and rural residents. For example, our interview with health officials in Hubei Province showed that the “rural maternal subsidy for institutional delivery” from the central government to Hubei Province in 2014 represented an annual increase of 13%. Second, significant attendance by local government in the construction of maternal and child health care institutions in rural areas is intended to strengthen the coordination of urban and rural maternal and child health care. For example, apart from the increasing financial subsidies and material support for maternity and child care institutions in rural areas, the local government in Datong County, Qinghai Province, has paid more attention to the selection of personnel for the maternity and child care institutions in these areas. Datong County has gradually established three levels of professional training and support mechanisms for maternal and child health hospitals at the county (city), township, and village clinic (institution) levels. Every year, superior maternal and child health care institutions will send expert groups to provide operational guidance and related training to inferior maternal and child health care institutions. Regarding the increase in support for rural areas, especially the institutions at and below the county level, the government should increase support to areas where the socioeconomic status is relatively low (especially remote and lacking rural areas). This approach may improve or increase related maternal and child health (MCH) services, initiate projects to develop maternal and child health care institutions in these areas, transfer project-promoting financial support to take advantage of multiple forms, such as transfer payments, develop maternal and child support projects to explore the long-term development mechanism of maternal and child health institutions and consolidate the achievement of the equalization of basic public health services.
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other
| 99.9 |
Of the evaluated indicators, IBD showed the highest overall level and a deeper degree of inequality. The increasing trend in IBD and the enlarged difference between groups may be due to technological progress, such as the development of medical examination technology, which facilitates the detection of birth defects. Furthermore, the development of statistical methodology has allowed more recording of birth defect statistics.
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other
| 99.0 |
In terms of inequality, the difference between urban and rural areas increased by 40% between 2000 and 2013. From the results, we noted that the inequality in IBD reached its peak after a compulsory premarital check was cancelled in 2003. Therefore, the decline in premarital medical examinations may also be a cause of the increased inequality in IBD. A premarital medical check-up plays an important role and is the primary threshold for the prevention and control of birth defects in China ; specifically, there is a greater preventive impact of premarital medical check-ups in rural, remote, and socio-economically underdeveloped areas . Additionally, the recognition and support of local governments for premarital medical examinations are more significant for the reduction in IBD and enhancement of IBD equality . Attention should be paid to the function of primary preventive methods to control birth defects, including premarital examinations, while continuously implementing functions such as the “pre-pregnancy eugenic health check” and “neonatal screening in poor areas”. Depending on the condition, regions can also expand the services of these projects based on their own needs and provide partially paid services to maximize their effectiveness.
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study
| 82.7 |
Cause of death statistics are important epidemiological data and are the main source of information for the formulation of health policy and the determination of health resource allocation and disease intervention focuses . Approximately 50 years of historical data are available in the death cause registration report in China . At present, the four main case management systems for the national death cause registration report are as follows: Death Cause Registration System of the Ministry of Health , National Disease Surveillance Points System, the National Maternal and Child Health Monitoring System (NMCHMS) and the National Death Cause Registering and Reporting System (i.e., the system described herein). Most of the documentation on maternal mortality and deaths in children under 5 years of age is sourced from the National Maternal and Child Health Monitoring System (as in this study).
|
study
| 99.8 |
The different sequences in the causes of death reflect an unfair outcome. The results of this study show similar sequences in the causes of death within the U5MR for different genders, whereas the U5MR and MMR differ between urban and rural areas. When comparing Figs. 2 to 3, we found that the gender differences in the IBD, U5MR, and NMR for the same year were smaller than the urban and rural differences; additionally, no gender difference is found in pregnant women. Therefore, this study focused on the analysis of urban-rural differences in an effort to reduce the overall differences; this approach was likely to reduce the urban-rural differences in maternal and child health.
|
study
| 100.0 |
To reduce the number of deaths in children under 5 years of age in medical institutions, attention should be paid to perinatal diseases, and effective measures, such as neonatal asphyxia resuscitation technology, should be promoted. Respiratory diseases should also be considered, especially pneumonia, which is not only a common disease in children under the age of 5 years but is also a common cause of death in children in medical institutions . Therefore, regulating the use of antibiotics is essential. Additionally, more attention should be placed on cardiac congenital malformations, the physical examination process should be standardized for children, and dedicated auscultation should be performed to find cardiac congenital malformations as early as possible. Both the timely treatment of children and the selection of an appropriate time for cardiac surgery are effective measures.
|
other
| 99.9 |
From the survey of global maternal death causes, OH is the major cause of maternal mortality in Asia . The OH equality data from 2000 to 2013 illustrate significant improvement in the urban-rural gap (from 267.7 to 5.5). In this study, the major causes of OH were uterine inertia, placental factors, damage to the uterine and birth canal, and coagulation defects . The recent awareness, prevention and control of OH through constant and strengthened rural basic medical and health institutions in China and symptomatic treatment training of the causes of OH have enabled rural maternal health care institutions to implement maternal referrals in a timely manner and administer effective treatment . These improvements have gradually narrowed the urban-rural gap. Additionally, the urban-rural gap in deaths caused by PIH is related to the socioeconomic status, extent of education, and living conditions of pregnant women with and without PIH, among others. Therefore, China’s health sectors actively provide grass-roots maternal health services to promote equality in public health services, increase publicity efforts, encourage rural maternal women to receive timely antenatal examinations and increase the number of antenatal examinations; overall, this work will effectively control PIH and other common diseases during pregnancy.
|
study
| 99.94 |
The data in this study were mainly obtained from the official authority data of China’s Maternal and Child Health Surveillance Network, and accepted sensitive outcome indicators were selected. However, the network’s lack of individual cases and structural and procedural indicators may lead to a deficiency in the comprehensiveness of the data. Although this lack could be a limitation of this study, the purpose of this study was to provide the government with a policy basis through a macro-level equality analysis; therefore, the use of official data had an appropriate effect. In the future, we will perform a case study based on a macro-level equality analysis and consider building a more comprehensive index system to enrich relevant research results.
|
study
| 95.4 |
From 2000 to 2013, general improvement in the equality of maternal and child health was found in China. Within the overall performance, greater differences were found between urban and rural areas than between genders. However, there is still a need for improvement. In particular, there is an increasing gap in IBD between urban and rural areas. Therefore, seizing crucial links, actively exploring appropriate technology to reduce the overall IBD and improving the range of inequality issues are essential. Additionally, improved health equality must be consolidated and the urban-rural gap in MMR and U5MR must be narrowed by focusing on differences in the causes of death between urban and rural areas.
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other
| 99.9 |
Hypertension is a major risk factor for cardiovascular diseases and is responsible for 14% of all annual deaths globally . The prevalence of hypertension varies across occupational groups, possibly affected by differences in the working environment. One work-related factor that might impose a risk for hypertension is lifting . Heavy lifting causes acute large increases in blood pressure (BP) . These increases in BP during heavy lifting are explained by the constriction of the vessels due to contraction of muscle fibers surrounding the vessels as well as the pressor reflex, both leading to an increased peripheral resistance and thereby also an increased BP . Thus, because some workers perform occupational lifting for several hours per day, many days per week, higher BP or hypertension is likely to occur . Yet, scientific knowledge of the relation between heavy occupational lifting and hypertension is limited. Previous studies investigating this relation have found occupational lifting to increase risks for myocardial infarction and ischemic heart disease in population studies including both sexes and workers from white- and blue-collar occupations. However, one study, only including males from blue-collar occupations did not find increased risk for ischemic heart disease from occupational lifting . As the study by Petersen and colleagues found the risks from lifting to be most pronounced among workers with low occupational physical activity (OPA) but high exposure to lifting, it seems that investigations of associations between occupational lifting and risk for hypertension benefit from populations including both sexes and a variety of occupations.
|
review
| 99.8 |
Conversely, heavy lifting might also impose beneficial effects on BP, since resistance training involving heavy lifting has been shown to reduce resting BP . Additionally, it is also unknown whether effects of exposure to heavy occupational lifting differ between participants with and without preexisting hypertension. A Danish survey from 2016 concludes that 22% of the Danish workforce are exposed to occupational lifting during ≥25% of their working hours. Likewise, 32% of European workers report to carry or move heavy loads regularly during working hours (6th survey in Eurofound). Thus, an investigation of the association between occupational lifting and risk of hypertension in population studies including both sexes and both blue- and white-collar occupations, might uncover a potential for prevention of cardiovascular diseases for a quite large proportion of the working population.
|
study
| 99.94 |
The aim of this study is to explore associations between heavy occupational lifting and hypertension in the Copenhagen City Heart Study. Associations will be investigated both cross-sectionally and prospectively, among randomly selected citizens from two districts of Copenhagen, Denmark.
|
study
| 99.94 |
For the cross-sectional analysis, the primary null-hypothesis is that there is no association between heavy occupational lifting and hypertension. For the prospective analysis, the primary null-hypothesis is that there is no association between heavy occupational lifting at baseline and increased resting systolic BP (SBP) 10 years later.
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study
| 99.94 |
This study will use data from the Copenhagen City Heart Study, which have been collected via health examinations and questionnaires in five examinations, namely 1976-1978, 1981-1983, 1991-1994, 2001-2003, and 2011-2014, on random population samples from two districts of Copenhagen. The sample of the first examination consisted of approximately 20,000 people in the age range of 20 to 93 years. The samples of the other examinations consisted of all previously invited people plus a new sample of people, who were younger than 20 years at the time of the first examination. In the first examination, 73.58% responded (14,223/19,329), this dropped to 49.50% (6237/12,599) in the fourth examination . The dataset contains person-based information on health, as well as a large variety of biological, environmental, and lifestyle-related factors. This study will include data from the third, fourth, and fifth examination of the Copenhagen City Heart Study for the analysis of the association between heavy occupational lifting and hypertension without inclusion of effect of time. Using a cross-sectional design, we will investigate the association between heavy occupational lifting and hypertension, defined as using antihypertensive drugs or having a measured SBP ≥140 mm Hg or DBP ≥90 mm Hg. Furthermore, in a prospective design, we will investigate the association between heavy occupational lifting and risk of becoming an SBP case across a time span of approximately 10 years. An SBP case will be defined as the shift from not using antihypertensive drugs in examination n to use of antihypertensive drugs in examination n+1 or an above median delta value of SBP (SBP in examination n+1−SBP in examination n). Analyses of associations both cross-sectional and prospectively hold the potential of evaluating associations both with and without inclusion of the effect of time.
|
study
| 99.94 |
Inclusion criteria for the prospective analysis will be (1) that the participant answered the question regarding level of OPA at the third examination and/or fourth examination (n); (2) that he or she was normotensive at examination n; and (3) that he or she participated in the BP measurement and gave a valid answer to the questions regarding antihypertensive drug usage in examination n and n+1.
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study
| 99.94 |
We believe that potential effects of heavy occupational lifting on BP may be concealed, reversed, or otherwise distorted by effects from antihypertensive drugs. The reason for excluding participants with hypertension at baseline from the prospective analysis is that they either are treated with antihypertensive drugs at examination n or, due to being detected as hypertensive at the health examination, are likely to receive treatment with antihypertensive drugs in the time period between examination n and examination n+1.
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study
| 99.94 |
In all 3 examinations, the self-reported information on level of OPA was obtained by asking the question: “Please describe your level of OPA within the past year” with the following response categories: “(1) predominantly sedentary; (2) sitting or standing, some walking; (3) walking, some handling of material; (4) heavy manual work.” If answering 3 or 4, an additional question regarding heavy occupational lifting was applied. The question was: “Do you lift heavy burdens?” with the response categories: “(1) yes and (2) no.” Participants will be classified as exposed to heavy occupational lifting by answering “yes” to the question concerning heavy burdens, and those participants answering 1, 2, and 3 or 4 in combination with not lifting heavy burdens will be classified as the reference group.
|
study
| 100.0 |
Between the examinations of data collection, we do not have any information about their exposure to OPA or lifting. However, for the prospective analysis, a measure of the stability of exposure was accounted for by cross-tabulating the self-reported exposure at examination 3 by exposure at examination 4 and also the self-reported exposure at examination 4 by exposure at examination 5. Among those participants responding to the self-reported exposure to OPA at examinations 3 and 4, 13.4% (329/2459) stated to be exposed to heavy lifting in examination 3 and 12.0% (295/2459) in examination 4. Among those participants responding to the self-reported exposure to OPA at examinations 4 and 5, 8.29% (146/1762) stated to be exposed to heavy lifting in examination 4 and 6.81% (120/1762) in examination 5. An evaluation of the agreement (Cohen kappa) between exposure to heavy occupational lifting in examinations 3 and 4 was .30, and the agreement between exposure to heavy occupational lifting in examinations 4 and 5 was .40, indicating a fair agreement between exposure to heavy occupational lifting across examinations (see Tables 1-4) .
|
study
| 100.0 |
In the prospective analysis, the primary outcome will be classified as an SBP case. The SBP case definition is the shift from no use of antihypertensive drugs in examination n to use of antihypertensive drugs in examination n+1 or an above median delta value of SBP (SBP in examination n+1−SBP in examination n).
|
study
| 99.94 |
Previously a number of factors have been shown to be associated both with occupational workload and BP. Thus, those factors will be included as covariates: sex (male or female) ; age (categories of <40, 50-59, 60-69, 70-79, and >80 years) ; body mass index (BMI; categories of <18.5, 18.5-24.9, 25.0-29.9, and ≥30kg/m2) calculated from objectively measured body height and weight; smoking (categories of nonsmoking and currently smoking) ; length of education (categories of uneducated, low educated up to 3 years, vocationally educated 1-3 years, higher educated, and academically educated) ; for the prospective analysis only, additional adjustment for vital exhaustion, split in 4 categories defined elsewhere (0, 1-4, 5-9, and 10-17) ; self-rated cardiorespiratory fitness (categories of lower, similar, and higher cardiorespiratory fitness compared with peers of same sex and age) ; SBP at baseline (categories of 80-89, 90-99, 100-109, 110-119, 120-129, 130-139, and ≥140 mm Hg) ; and DBP at baseline (categories of 40-49, 50-59, 60-69, 70-79, 80-89, and ≥90 mm Hg).
|
study
| 100.0 |
The overall significance level will be set at .05. A Bonferroni correction will be applied, due to the similarity of the two proposed hypotheses, which means that each of the two primary hypotheses will be tested at a significance level of P=.025. Secondary analyses will be regarded as exploratory and will therefore not be tested for statistical significance, but the precision will be reported by 95% CI. They may influence the interpretation of findings of the primary analyses.
|
other
| 73.75 |
Logistic regression will be used to estimate the odds of becoming a case from examination n to n+1 as a function of heavy occupational lifting. For the cross-sectional analysis, there will be a possibility of 3 observations per participant, 1 from each examination. For the prospective analysis, there will be a possibility of 2 observations per participant, 1 from the third to the fourth examination and one from the fourth to the fifth examination. The cross-sectional analysis will be controlled for sex, age, BMI, smoking, and education. The prospective analysis will, in addition to the variables of the cross-sectional analysis, be controlled for self-rated cardiorespiratory fitness, vital exhaustion, and BP at baseline. Self-rated cardiorespiratory fitness and vital exhaustion will only be included as covariates in the prospective analysis where the main point of interest is new cases and not prevalent cases as in the cross-sectional analysis. Generalized estimating equations will be used to estimate the parameters. Observations from the same person will be treated as repeated measurements. A first order autoregressive correlation structure is assumed. Should the estimated covariance matrix fail to converge, then we will resort to a variance component correlation structure.
|
study
| 100.0 |
Table 5 shows the expected numbers of observations, participants, and “cases” that will be included in the primary analyses. It also shows the variance inflation factor, which is a function of the assumed intraperson correlation and the mean numbers of observations per participant.
|
study
| 99.94 |
aA case in the primary analysis will be defined as the shift from no use of antihypertensive drugs in examination n to use of antihypertensive drugs in examination n+1 or an above median delta value of systolic blood pressure (systolic blood pressure in examination n+1-systolic blood pressure in examination n).
|
study
| 99.94 |
Statistical power of detecting an association between heavy occupational lifting at examination n and antihypertensive drug usage or an above median delta of systolic blood pressure (SBP) at examination n+1, as a function of the underlying odds ratio between exposed and unexposed participants in the target population.
|
study
| 99.94 |
The statistical powers of the primary hypotheses are given in Figures 1 and 2. The calculations are based on the above assumptions, the propagation of error formulas, the central limit theorem, and a two-tailed significance level at P=.025, for each of the two hypotheses.
|
study
| 99.9 |
It has been suggested that each mm Hg increase in resting SPB is associated with an approximately 3.5% increased risk of death due to ischemic heart disease (IHD) . It has moreover been suggested that the relative effect of a 1 mm Hg increase is quite independent of the level of SBP; a change in SBP from 120 to 121 would, for example, cause the same relative risk increase as a change from 139 to 140 . From this viewpoint, it would be of interest to estimate the expected effect of heavy occupational lifting on resting SBP in a linear regression model and thereby obtain an estimate that could be directly translated into relative risks of death due to IHD. There are, however, some problems with this approach:
|
study
| 99.9 |
If occupational lifting is associated with risk of hypertension and we exclude participants who are treated for hypertension, then the participants who had been most affected by their occupational lifting status would be more likely to be excluded than the ones who had been least affected, and this would bias the estimation toward unity.
|
study
| 99.9 |
It was the above mentioned problems that made us refrain from linear regression in the primary analyses. We recognize, however, that a conservative estimation of the effect of heavy occupational lifting on resting SBP in a linear regression model may provide meaningful information if the bias is taken into account in the interpretation of the results. We will therefore conduct a secondary analysis, in which the association between heavy occupational lifting and SBP will be investigated, first cross-sectionally and then prospectively (change in SBP [mm Hg] from examination n to examination n+1), by use of linear regression. Observations from participants who are treated with antihypertensive drugs or other types of heart medications will be excluded from an analysis similar to the primary analysis and performed both cross-sectionally and prospectively.
|
study
| 100.0 |
Generalized estimating equations will be used to estimate the parameters. Observations from the same person will be treated as repeated measurements. A first-order autoregressive correlation structure is assumed. Should the estimated covariance matrix fail to converge then we will resort to a variance component correlation structure. The expected difference between the exposed and the nonexposed will be estimated and presented with a 95% CI, based on the empiric SE.
|
study
| 99.94 |
It is presently not known if and how a person’s resting BP is influenced by occupational lifting activities. It is therefore of interest to also regard potential effects of occupational lifting on mean arterial pressure, DBP, and pulse pressure. For this reason, we will repeat the linear regression analyses described above on each of these outcomes. Furthermore, a prospective analysis will be applied where the outcome will be classified as a DBP case, similar to the analysis aforementioned relating occupational lifting to the risk of becoming an SBP case. The DBP case will be defined by the shift from no use of antihypertensive drugs in examination n to use of antihypertensive drugs in examination n+1 or an above median delta value of DBP (DBP in examination n+1−DBP in examination n).
|
study
| 99.94 |
According to our primary assessment of exposure, the exposed group would consist of participants whose work entailed heavy occupational lifting combined with walking, some handling of material, or heavy manual work. The comparison group would consist of the rest of the occupationally active participants, regardless of their type of occupational activity. We want to know how sensitive our analyses are to the choice of comparison group after adjustment for the included covariates. To shed some light on this issue, we plan to perform an additional set of linear regressions on SBP. In these particular analyses, we will split the comparison group into three different subgroups and thereby create an exposure variable with 4 instead of 2 categories. The statistical models, covariates, and inclusion criteria will otherwise be the same as they are in our previously defined linear regression analyses. The results will be presented as outlined in Table 6.
|
study
| 100.0 |
In our primary cross-sectional analysis, we will define hypertension as the use of antihypertensive drugs or a measured consultation SBP ≥140 mm Hg or DBP ≥90 mm Hg . We recognize, however, that the cut-points could have been defined differently, eg, SBP ≥160 mm Hg or DBP ≥100 mm Hg ; SBP ≥180 mm Hg or DBP ≥110 mm Hg ; and SBP ≥130 mm Hg or DBP ≥80 mm Hg .
|
study
| 99.94 |
We want to know whether the OR for hypertension as a function of heavy occupational lifting is sensitive to the definition of hypertension. We will therefore conduct two additional cross-sectional logistic regression analyses, which will be performed in the same way as the primary cross-sectional analysis but with the cut-points SBP ≥160 mm Hg or DBP ≥100 mm Hg and SBP ≥130 mm Hg or DBP ≥80 mm Hg instead of the traditional SBP ≥140 mm Hg or DBP ≥90 mm Hg.
|
study
| 100.0 |
A potential effect of occupational exposures might be more pronounced among people who are likely to be occupationally active throughout the approximately 10-year period that passes between the baseline and follow-up examinations than it is among people who have fulfilled the requirements for old-age pension (65 years of age) or early retirement (60 years of age) at the time of the follow-up examination. It is therefore possible that this study is more relevant among participants who are younger than 50 years at baseline than it is among those who are 50 years or older. For this reason, we will perform a sensitivity analysis in which the sample is stratified by age at baseline (≥ vs <50 years). The outcome, statistical model, inclusion criteria, and covariates will otherwise be the same as they were in the primary prospective analysis.
|
study
| 100.0 |
As previously mentioned, we believe that any potential effect of occupational lifting on SBP may be concealed, reversed, or otherwise distorted by effects from antihypertensive drugs and other types of heart medications. It is, however, relevant to investigate the effect of the decision to exclude participants who were treated for antihypertensive drugs from sensitivity analysis 1 and, therefore, we will repeat the steps of that analysis, without the exclusion of medically treated participants.
|
study
| 99.94 |
Data from the fourth and fifth examinations of the Copenhagen City Heart Study will be included for the cross-sectional and long-term associations between heavy occupational lifting and cardiac damage in a nested design. Early subclinical structural changes of the heart will be recognized by advanced echocardiographic analyses. We will compare participants exposed to heavy occupational lifting (cases) with matched participants who are not exposed to heavy occupational lifting (controls) both in the cross-sectional and longitudinal study. Controls will be matched on age and sex. Echocardiographic assessment will focus on early subclinical changes in cardiac structure primarily assessed by cardiac mass, indices of diastolic function, and global strain assessments. Analyses will be adjusted for confounders, including hypertension, diabetes, and BMI. With 200 exposed and 200 unexposed participants included in the echocardiographic analyses, we will have 80% power to detect a between-group difference of 1 in global longitudinal strain (equal to 5% difference based on an expected mean of 20) with a significance level (alpha) of 1.25%. The choice of alpha is adjusted to allow for comparison over several parameters of subclinical structural changes.
|
study
| 100.0 |
In the third examination in 1991-1994, 10,135 out of 16,560 (61.20%) participants attended; in the fourth examination in 2001-2003, 6237 out of 12,599 (49.50%) participants attended; and in the fifth examination in 2011-2015, 4550 out of 9765 (46.59%) participants attended. On the basis of the inclusion criteria of responding to the level of OPA, 5031 observations were excluded from examination 3; 2600 from examination 4; and 1621 from examination 5. Hence, the final populations for the cross-sectional and prospective analysis are assumed to include less than 7166 participants in the cross-sectional analysis and less than 1850 participants in the prospective analysis (Figure 3), due to the additional inclusion criteria of measured BP and use of antihypertensive drugs. The information on BP and use of antihypertensive drugs will be provided after submission of this protocol paper.
|
study
| 100.0 |
The population which will be included in the analysis will be set by the criteria for inclusion, described previously. Therefore, it is assumed that fewer participants will be included in the analysis than the amount of participants answering on the level of OPA, described in Tables 7 and 8.
|
study
| 99.9 |
Cross-sectionally, the participants responding to the level of OPA were 9.8 years younger (mean age 49.0 years among the participants answering on the level of OPA and 58.8 years among the attending), had a higher level of education than the attending participants (13.87% [1619/11,670] participants responding to the level of OPA were noneducated and 20.69% [4328/20,922] among the attending), and a higher proportion of the participants responding to the level of OPA stated to be exposed to heavy occupational lifting (14.04% [1638/11,670] among the participants responding to the level of OPA and 8.48% [1774/20,922] among the attending participants).
|
study
| 100.0 |
Prospectively, the participants answering on the level of OPA were 11.0 years younger (mean age 48.0 years among participants responding to the level of OPA and 59.0 years among the attending). The smokers were 2.31 percentage points higher (38.96% [2311/5932] of the participants responding to the level of OPA were current smokers and 36.65% [6930/18,908] among the attending); they had a higher level of education than the attending participants (12.39% [735/5932] of the participants responding to the level of OPA were noneducated and 19.76% [3737/18,908] among the attending). A higher proportion of the participants responding to the level of OPA stated to be exposed to heavy occupational lifting (17.52% [1039/5932] among the participants responding to the level of OPA and 8.34% [1576/18,908] among the attending participants), and a higher proportion of the participants responding to the level of OPA stated to have a level of cardiorespiratory fitness similar to their peers (57.67% [3421/5932] among the participants responding to the level of OPA and 45.57% [8617/18,908] among the attending).
|
study
| 100.0 |
These nonsignificant differences between the attending participants and participants responding to the level of OPA in the cross-sectional and prospective populations may affect the prevalence of hypertension. The younger age of the participants responding to the level of OPA as well as their higher proportion of being educated might lower the prevalence of hypertension among these participants compared with those attending . Conversely, may those participants responding to the level of OPA have a higher prevalence of hypertension due to their higher exposure to heavy occupational lifting than among the attending participants. In the prospective population, the small difference in proportion of participants stating to have a level of cardiorespiratory fitness similar to their peers, is not believed to affect the prevalence of hypertension, as the proportion of participants stating to have a higher level of cardiorespiratory fitness than their peers is similar among those participants responding to the level of OPA and those attending.
|
study
| 100.0 |
This study aims to contribute to the knowledge of risk for hypertension from heavy occupational lifting, and possibly thereby contribute to the prevention of cardiovascular disease by giving recommendations for participants exposed to heavy occupational lifting.
|
study
| 99.94 |
In the primary prospective analysis, the power would be insufficient if the outcome had been defined as hypertensive (yes or no). Therefore, we chose a case definition which included both hypertension and an above median increase in SBP of the study population from examination n to n+1. The proposed analyses have some limitations, such as the self-reported exposure to occupational lifting and level of cardiorespiratory fitness. Previous studies show that self-reported exposure to occupational lifting may be affected by recall bias . Also the collection of BP only in consultation during rest is a limitation due to the lower prognostic value than obtained by monitoring of 24 hours BP or BP during sleep . Furthermore, a previous study has shown occupational lifting to reduce the odds for having prolonged working hours ; however, this is not possible to adjust for in this analysis due to the lack of information on amount of weekly working hours. It could also be speculated that the range and variety of the exposure to occupational lifting could be limited due to the Danish Working Environment Authority guideline for occupational lifting , stating that carrying, lifting, pulling, and pushing of nonliving burdens below 3 kg are not classified as heavy lifting, and workers should not lift or carry burdens heavier than 20 kg.
|
study
| 100.0 |
Some of the strengths in the proposed analysis are the follow-up time of 8 to 10 years and the determination of hypertension based both on the use of prescription medicine and the resting BP in mm Hg. This limits the risk of classifying a participant as false negative (eg, using antihypertensives and therefore having a resting BP below the threshold). Another strength is the randomly selected study population.
|
study
| 99.94 |
Since one-third of the workforce in Europe reports to carry or move heavy loads regularly during working hours (6th survey in Eurofound) and hypertension is a major risk factor for cardiovascular disease and mortality [1;2], a positive association between occupational lifting and risk for hypertension could reveal a potential for improved prevention for hypertension by reducing exposure to occupational lifting in the population. This could, for example, be achieved by using technical lifting devices and automatization of manual work tasks currently requiring heavy lifting. This is particularly the case because a positive association could be considered as a reflection of a physiological mechanism and therefore must be assumed to apply for the majority of humans exposed to occupational lifting. Conversely, a negative association would not be assumed as a reflection of a physiological mechanism before the negative association had been verified in populations not subject to restrictive regulations of occupational lifting, as employees in Denmark are. Moreover, a null finding would also propose a need for additional investigations of this association in populations with wider ranges of exposure to occupational lifting. Since these proposed analyses will be applied to a randomly selected adult population and is planned to be verified in another randomly selected adult Danish population, these results may be generalized to the Danish adult population engaged in work including occupational lifting.
|
study
| 99.94 |
Middle East respiratory syndrome coronavirus (MERS-CoV), discovered in 2012, can cause fatal respiratory disease in humans. Although MERS-CoV might have originated in bats, dromedary camels (Camelus dromedarius) are a natural host and likely source of human MERS-CoV infection (1,2). Camel trade is a major driver of MERS-CoV movement between Africa and the Arabian Peninsula (3), where most human cases have occurred. Rajastan, India, is a large breeding center for dromedaries, some of which are exported to Pakistan and Bangladesh. Seropositive dromedaries have been identified in Pakistan, but little is known about MERS-CoV in other parts of South Asia (4). In Bangladesh, camels are bred on farms and imported from India for sale in seasonal markets for ritual slaughter during religious festivals. Imported camels go directly to urban markets to be sold by traders and are a separate enterprise from farmed camels.
|
study
| 99.94 |
During the September–October 2015 festival of Eid-ul-Adha, we collected and tested for coronaviruses the specimens of 36 dromedary camels at an urban farm and 19 camels and 18 fat-tailed sheep at an urban market in the capital city of Dhaka (Table; Technical Appendix). The testing was conducted as part of the US Agency for International Development’s PREDICT program, which conducts surveillance in humans and animals for novel and select known zoonotic viruses, including MERS-CoV. We obtained information for each camel’s origin and age from market registries or breeders’ records. We also assessed and recorded the sex and apparent health status of each camel at specimen collection, at which time we collected blood, 2 nasal swab specimens, and 2 rectal swab specimens from each animal. We placed 1 set of each swab in lysis buffer (Nuclisens; bioMérieux, Marcy-l’Étoile, France) and 1 in viral transport medium. We separated and froze serum samples. We extracted total nucleic acid by using EasyMag (bioMérieux) and performed cDNA synthesis by using SuperScript III first-strand synthesis supermix (Invitrogen, Carlsbad, CA, USA) according to the manufacturer’s instructions. We performed pancoronavirus PCR targeting the RdRp gene (5) and MERS-CoV real-time PCR targeting the upstream envelope protein gene and nucleocapsid protein genes N2 and N3 (6). We screened serum samples by using a MERS-CoV ELISA (7) and confirmed the results by using a MERS-CoV pseudoparticle neutralization test (8).
|
study
| 100.0 |
Of the 36 camels on the farm, 24 were born there. The remaining 12 and all 19 market camels were imported from India (Table). All specimens tested negative for coronaviruses, including MERS-CoV, by PCR. ELISA showed 98.6% specificity and sensitivity compared with the pseudoparticle neutralization test. We detected MERS-CoV antibodies in 31% (95% CI 19%–45%) of camels; adults had a higher seroprevalence (36% [95% CI 22%–52%]) than juveniles (9% [95% CI 0.2%–41%]). Imported camels had a significantly higher seroprevalence (52% [95% CI 33%–70%]) than domestically bred camels (4% [95% CI 0.1%–21%]). Among the 5 seropositive farm camels, 1 was a domestically bred adult, whereas the other 4 were adults from India. Camels in the market had a higher seroprevalence (63% [95% CI 38%–85%]) than those on the farm (14% [95% CI 5%–30%]). All sheep serum samples were negative for MERS-CoV antibodies.
|
study
| 100.0 |
The findings of a higher MERS-CoV seroprevalence in adult camels (9) and the seronegativity in sheep are consistent with other studies (8). Only adult camels were found in the market. The finding of an adult seropositive camel, born on the farm, suggests that it was infected locally. No records indicate intermingling between farmed camels and those in markets. The finding of only 1 seropositive camel originating in Bangladesh suggests that if infection or exposure occurred on the farm, either viral circulation was limited or other seropositive camels had since been sold or removed. Juveniles are more likely to be actively infected than adults, and the limited juvenile sample size might explain our lack of virus detection among them (9).
|
study
| 100.0 |
Our findings suggest transmission of MERS-CoV has occurred among camels in Bangladesh, extending the previously reported range of this virus (up to ≈1,900 km east of Pakistan). Exactly where or when imported camels became infected is unclear. To date, no human cases of MERS-CoV have been reported in South Asia. The possibility of having MERS-CoV–infected camels in Dhaka, a populous city with ≈18 million persons, presents a potential risk for human outbreaks. Insufficient surveillance, behavioral differences in human–camel interactions compared with Middle Eastern societies, or differences in virus strains or human susceptibility might explain the lack of observed cases. Improved surveillance of camels along camel trade routes, camel herds in Dhaka, and persons who have close contact with camels will help assess the transboundary movement and the risk for zoonotic transmission in Bangladesh. Given the ubiquity of MERS-CoV in dromedary camels, the predictable seasonal movement of camels into Dhaka, and a higher incidence of infection in persons with frequent contact with camels (10), targeted public health messaging that promotes handwashing after contact with camels and avoidance of exposure to camel excreta might help reduce the risk for zoonotic MERS-CoV transmission.
|
study
| 99.94 |
Electronic and optoelectronic materials deployed in complex, three-dimensional (3D) structures can offer qualitatively expanded levels of functionality compared to those in their corresponding two-dimensional (2D) planar counterparts. Many examples demonstrate clearly the value of 3D structures in achieving unique properties with simple constituent materials1–5. Progress in this area is often limited by the relatively small range of choices in controlled, reliable, reproducible strategies for producing 3D geometrical forms in advanced functional materials6–11. Among the most recently introduced methods is a scheme in which compressive buckling associated with a stretched elastomeric substrate guides the mechanical assembly of elaborate 3D mesostructures, some with designs reminiscent of those achieved in macroscale structures by origami/kirigami, with specified shapes and with sizes that can span several orders of magnitude in characteristic dimensions, down to the submicron regime in lateral features and to a few tens of nanometers in thickness12–15. These ideas leverage an intimate interplay between materials and microstructural mechanics, with diverse examples of use with silicon membranes, metallic electrodes, and polymer films in hundreds of different 3D geometries13–16. Full, quantitative modeling of the mechanics forms an essential aspect of design in all such cases; without such theoretical guidance, the buckling process itself can lead to cracking and/or defect formation in the constituent materials in ways that can deteriorate their properties. Physical toughness and materials structure geometries are, therefore, critically important in maximizing the diversity of realizable 3D structures.
|
review
| 99.9 |
Atomically thin, 2D materials have a well-established set of excellent mechanical properties, some of which, for graphene, are unmatched; these characteristics have direct and essential relevance in the context of 3D assembly17–19. In fact, recent work demonstrates that graphene can be built into common, kirigami-type structures and in mechanical metamaterials such as stretchable electrodes, springs, and hinges20,21. The assembly approaches in these cases, however, rely on externally imposed forces, with limited ability to address complex, 3D architectures and/or functional systems that form naturally in a parallel fashion with the requisite heterogeneous collection of patterned materials.
|
study
| 99.9 |
Here, we explore the use of 2D materials in functional, 3D systems formed via geometry transformation guided by compressive buckling, with a focus examples in constructs that provide 3D photodetection/imaging capabilities by use of light sensing elements that incorporate monolayer MoS2 and graphene, each of which offers an extraordinary combination of electrical, mechanical and optical properties relevant for present purposes. Specifically, graphene offers the best set of parameters for flexible, transparent conductors, with potential to replace indium–tin–oxide in flat panel displays and touch screens22,23. Additionally, MoS2 is of great interest for its excellent semiconducting properties at atomic thicknesses24–26. Owing to a direct band gap of 1.9 eV in monolayer MoS2, this material is well-suited for applications in the unique photodetecting systems27–32. Realizing 3D arrays of MoS2/graphene photodetectors involves first optimizing the parameters for assembly of origami-inspired 3D shapes (an octagonal prism, an octagonal prismoid, and a hemisphere) using finite-element analysis (FEA). The set of assembly parameters defined in this way serves as starting points for experimentally constructing the targeted 3D shapes, with integrated devices, by compressive buckling. Here, MoS2 and graphene serve as the channel and electrodes, respectively, in ultrathin semiconductor photoresistor supported by a layer of polymer. The resulting system forms spontaneously, and without external application of targeted forces, from a 2D planar geometry into a 3D configuration that allows tracking of both the direction and intensity of incident light. As an additional feature, the atomically thin MoS2 and graphene yield optically transparent devices, such that light passing through the device can be detected at two sensing locations (the entry and exit sites), thereby providing further information of relevance to divergence angle.
|
study
| 99.94 |
Figure 1a provides a schematic illustration of the design and assembly process for a 3D photodetector system. Briefly, the complete device results from sequential patterning of an epoxy-based negative photoresist (PR, SU-8), graphene, and MoS2 on an SiO2/Si wafer. Patterned encapsulation using SU-8 yields thick and thin regions designed specifically to aid in guiding the assembly process. Finally, a layer of photoresist (PR) serves to pattern the exposure of selected regions to ultraviolet (UV) ozone. After removing the SiO2 by immersion in an etchant, transfer printing with a flat slab of polydimethylsiloxane (PDMS) delivers the planar device assembly onto a film of polyvinyl alcohol (PVA) such that the topside can be exposed to UV ozone. Subsequent lamination onto a pre-stretched elastomeric substrate, pre-exposed to UV ozone, leads to strong bonding at the regions of SU-8 previously treated with UV ozone. Removing the PR layer leaves a slight physical separation between the device platform and the elastomeric substrate at corresponding regions. Releasing the substrate (Fig. 1a, right) initiates spontaneous assembly of the full 3D structure. The final architecture depends on the relevant design parameters, such as the degree of pre-stretch, the 2D geometry, and the thicknesses of the active and passive layers.Fig. 1Assembly and mechanical analysis of 3D photodetector structures from 2D materials. a Schematic illustration of processes for fabricating the 3D systems. b FEA results describing the formation of arrays of photodetectors based on graphene and MoS2 in the form of an octagonal prism, and corresponding colorized SEM images of the final configuration including MoS2 (green), graphene (light gray), and SU-8 (gray). c, d Similar FEA results for the cases of an octagonal prismoid and a hemisphere. Colors represent the magnitude of the maximum principal strain. e Central angle and radius of a cross-section of the hemisphere in d vs. the released pre-strain. Here, the insets denote an intermediate state (εreleased = 21.4%) and the final state (εreleased = 46%) of pre-strain release, with the dashed and solid lines representing the profiles from FEA and fitting arcs, respectively. f FEA results and analytic predictions of the height of three photodetector structures in b–d. g Computational study of tensile strain applied to the SU-8, graphene, and MoS2 layers vs. pre-strain during the 3D assembly (squares, circles, and triangles denote the octagonal frustum, hemisphere, and octagonal prism, respectively). h Experimentally measured variation in the resistance in graphene during repeated buckling processes
|
study
| 99.94 |
Assembly and mechanical analysis of 3D photodetector structures from 2D materials. a Schematic illustration of processes for fabricating the 3D systems. b FEA results describing the formation of arrays of photodetectors based on graphene and MoS2 in the form of an octagonal prism, and corresponding colorized SEM images of the final configuration including MoS2 (green), graphene (light gray), and SU-8 (gray). c, d Similar FEA results for the cases of an octagonal prismoid and a hemisphere. Colors represent the magnitude of the maximum principal strain. e Central angle and radius of a cross-section of the hemisphere in d vs. the released pre-strain. Here, the insets denote an intermediate state (εreleased = 21.4%) and the final state (εreleased = 46%) of pre-strain release, with the dashed and solid lines representing the profiles from FEA and fitting arcs, respectively. f FEA results and analytic predictions of the height of three photodetector structures in b–d. g Computational study of tensile strain applied to the SU-8, graphene, and MoS2 layers vs. pre-strain during the 3D assembly (squares, circles, and triangles denote the octagonal frustum, hemisphere, and octagonal prism, respectively). h Experimentally measured variation in the resistance in graphene during repeated buckling processes
|
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| 100.0 |
As the 3D shape evolves, the strains induced by bending and twisting must remain below the maximum endurance limit for each layer in the construct, to avoid cracking or other forms of mechanical degradation of the materials. Optimization in this context, with a goal toward realizing the desired geometry (octagonal prism, octagonal prismoid, and hemisphere), involves analytic modeling and full 3D FEA techniques that capture all details of the mechanics. The analysis starts with a precursor device design on the 2D planar surface, which subsequently morphs into a 3D structure via the process of controlled compressive buckling. Precursor designs for the octagonal prism, octagonal prismoid, and hemisphere at the 2D planar surface appear on the left side of panels b, c, and d, respectively, in Fig. 1. Various regions of the precursors adhere strongly (red) or weakly (blue) to the substrate, and some locations are relatively thin (indicated by arrow) to enable localized folding deformations. The strong and weak adhesion occurs at the strongly and loosely attached regions, respectively, of the structure after the dissolution of the PR. The pre-strain values required to form closed 3D shapes depend on the various geometric parameters of the 2D precursors (Supplementary Fig. 1). The values necessary for the cases (Fig. 1) examined here are 111, 38, and 46% for the octagonal prism, octagonal prismoid, and hemisphere, respectively. The 3D shapes evolved under these pre-strain values are in the mid-left parts of Fig. 1b–d. In particular, the design in Fig. 1d enables the formation of an approximate hemisphere, as an example of a non-developable surface that cannot be realized by simple bending/twisting deformations of an unpatterned, 2D membrane. Here, the thin regions play crucial roles, as they allow highly flexible rotation of each constituent ribbon at the outer ends adjacent to the bonding sites. Figure 1e and Supplementary Fig. 2 show that the cross-section of each intermediate state of assembly approaches an arc of evolving central angle, in which this angle increases gradually with increasing degree of release of the pre-strain, reaching 180o at the final state. The heights of three mesostructures increase with the release of the pre-strain, as captured by simple analytic models (Fig. 1f, Supplementary Figs. 1 and 2). As shown in Fig. 1b–d and Supplementary Fig. 3, the strains reach peak values in the locations of the creases (indicated by arrow), where the thickness/length ratio is lower than that in the other regions. By comparison, the strains in the other parts are extremely low. The distributions of strain in the graphene and MoS2, separately shown in the mid-right parts of Fig. 1b–d, exhibit similar trends. The pre-strain values optimized by FEA experimentally yield 3D structures nearly identical to those predicted. The corresponding scanning electron microscopic (SEM) images are in Fig. 1b–d (right). The strain levels created in individual graphene, MoS2, and SU-8 layers of each 3D structure increase during the release of the pre-strain (Fig. 1g). The maximum strain in the graphene and SU-8 layers are 1.2% and ~2.3% for the octagonal prism, which are higher than those in the other structures, consistent with the comparatively high level of pre-strain required for this case. Note that the maximum strains in the graphene and MoS2 layers estimated by FEA are far below their corresponding elastic limits (~6 and 2%, respectively)33–37. The maximum strain in the MoS2 is ≤0.15%, indicating that MoS2 occupies a relatively flat region of the structure and that the strain is bending dominated. It is noteworthy that the maximum strain of MoS2 is much higher in the hemisphere than the other two configurations, due to the non-negligible bending deformations. The resistance of the graphene under repeated buckling and release appears in Fig. 1h. Throughout these cycles, the maximum change in resistance (~15%) occurs in the octagonal prism; changes for the octagonal prismoid and hemispherical 3D structures are relatively small. The reversible behavior observed in all three cases suggests purely elastic mechanical responses.
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System-level operation requires electrical interconnects to external data acquisition equipment, with designs capable of accommodating the 3D transformation and associated buckling processes. Figure 2a shows a 2D precursor that satisfies these requirements, along with the corresponding 3D structure that results after releasing the pre-strain (46%) (Supplementary Movie 1). These traces (as well as interconnects in the active regions of the device) exploit bi-layer graphene sandwiched between two SU-8 layers. As with main part of the system, selective bonding regions result from patterned UV ozone exposure. These traces evolve into their own 3D shapes, in parallel with the central hemisphere. The maximum strain (2.17%) appears in the regions of smallest bending radius, designated as 1 (circled, Fig. 2a). Supplementary Fig. 4 presents the strain distribution for two designated points 1 and 2 located on the interconnects. The maximum strains, as estimated in simulations, are again far below the intrinsic elastic limit of graphene (~6%)33–35. The areal proportion of the regions that undergo significant strain (>2%) is less than 0.2% (Supplementary Fig. 5). Figure 2b presents an SEM image of the resulting 3D system. The hemispherical structure supports three MoS2 photodetectors on each arm, for a total of 48 devices in the entire array, all interconnected with a network of bi-layer graphene traces (Fig. 2c shows a magnified view of SEM (left) and simulated (right) parts of the structure). The resistance of the graphene in the regions of lowest bending radius (where the strain is maximized at 2.17%) is ~20.7 kΩ vs. ~18.3 kΩ in the flat geometry (Supplementary Fig. 6). Such slight variations in resistance have a negligible effect on the overall operation, as they are much lower than the resistance of the photoactive material MoS2 (~1 MΩ).Fig. 2Interconnect design and photoinduced response of MoS2 photodetectors on a 3D hemispherical structure. a FEA of the 3D hemisphere structures before and after compressive buckling, showing the distributions of maximum principal strains in the MoS2 photodetectors and 3D interconnects. b Colorized SEM image of MoS2 photodetectors consisting of MoS2 (green), graphene (light gray), and SU-8 (gray) on the hemisphere with 3D interconnects. c Magnified view of the SEM image in b and corresponding FEA results for the strain distribution. Inset: schematic illustration of the unit device enclosed by the red box in the main image. d I–V characteristics of the 3D photodetector at different bias voltages (laser-beam wavelength = 532 nm, power density = 1000 W m−2). e Photoresponsivity of the MoS2 photodetector at a bias voltage of 3 V for different laser power densities. (Standard deviation of 48 sampling distribution recorded from 48 devices.) f Time-resolved photoresponses of the devices under laser illumination at different power densities. g Variation in photocurrent during repeated buckling processes for the octagonal prism (top), octagonal prismoid (middle), and hemispherical structure (bottom)
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Interconnect design and photoinduced response of MoS2 photodetectors on a 3D hemispherical structure. a FEA of the 3D hemisphere structures before and after compressive buckling, showing the distributions of maximum principal strains in the MoS2 photodetectors and 3D interconnects. b Colorized SEM image of MoS2 photodetectors consisting of MoS2 (green), graphene (light gray), and SU-8 (gray) on the hemisphere with 3D interconnects. c Magnified view of the SEM image in b and corresponding FEA results for the strain distribution. Inset: schematic illustration of the unit device enclosed by the red box in the main image. d I–V characteristics of the 3D photodetector at different bias voltages (laser-beam wavelength = 532 nm, power density = 1000 W m−2). e Photoresponsivity of the MoS2 photodetector at a bias voltage of 3 V for different laser power densities. (Standard deviation of 48 sampling distribution recorded from 48 devices.) f Time-resolved photoresponses of the devices under laser illumination at different power densities. g Variation in photocurrent during repeated buckling processes for the octagonal prism (top), octagonal prismoid (middle), and hemispherical structure (bottom)
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Visible light (532 nm) passed over a representative photodetector induces a photoresponse that can be captured as current–voltage (I–V) characteristics for different illumination intensities (Fig. 2d). The photocurrent (Iph) increases with intensity and with bias voltage, in a manner that is symmetric around 0 V. The linear behavior and symmetric I–V characteristics are consistent with approximately ohmic contacts between the graphene and MoS2 (Supplementary Fig. 7). The maximum ratio of Iph in illuminated and dark states reaches ~427 at an intensity of 103 W m−2 (Supplementary Fig. 8). The photoresponsivity, calculated as Rph=Iph/Pin, where Iph is the photocurrent and Pin is the incident laser power, is 38 A W−1 at an intensity of 0.3 W m−2, and decreases with increasing intensity (Fig. 2e). These observations are qualitatively and quantitatively comparable to the Rph values previously reported in MoS2-based photodetector devices27–32. Time-resolved measurements at different bias voltages (Fig. 2f) indicate that the device responds to the “on” and “off” switching of the laser beam, and its corresponding temporal Iph is quite uniform (1.49, 0.84, and 0.28 µA corresponding to bias voltages of 1, 3 and 5 V, respectively, at 1000 W m−2 power density) through multiple cycles at each bias voltage27–32. The estimated rise (τrise) and decay (τdecay) times of the Iph are 290 ± 130 ms and 420 ± 210 ms, respectively,27,28,31. The time-resolved photoresponses are lower than those of similar devices fabricated on SiO2 substrates (Supplementary Fig. 9), possibly due to the larger number of surface traps at the MoS2/SU-8 interface than at the MoS2/SiO2 interface30,38. The detection mechanism is based on photoresistive behavior, with a response time that is slower than that of devices such as photodiodes or phototransistors30,32. The photodetectors responded 20 times faster when encapsulated with the sandwich structure: Al2O3/MoS2/Al2O3. The high-k dielectric Al2O3 layer significantly reduces interface trap charges and results in a clean, conformal and low roughness interface that also efficiently suppresses Coulombic impurities (Supplementary Fig. 10)39,40. For all cases, the 3D structures (the octagonal prism, octagonal prismoid, and hemisphere) can be reversibly stretched and deformed from 2D to 3D states; the corresponding stability behaviors, as in Fig. 2g, are consistent with robust operation under the high strain levels and cycling. Further, the 3D photodetectors are environmentally stable (Supplementary Fig. 11) and can be formed in high density layouts (up to 10,000 on a single hemispherical surface) across arrays of separate 3D devices that can all be assembled in a single step. The mechanical flexibility of the supporting substrate and the intrinsic deformability of the 3D structures allow such systems to be bent, stretched and twisted in a reversible, non-destructive fashion (Supplementary Figs. 12−14 and Movie 2). These features in stability, manufacturability, and deformability suggest potential for use in practical applications with unique modes of operation.
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In combination, the assembled layers in these photodetecting devices (the bi-layered graphene, monolayer MoS2, and the 7.5-μm SU-8 layer) exhibit high optical transmittance (~87%) at 550 nm (Supplementary Fig. 15). An array in a 3D format can therefore detect the position and intensity of illuminating light simultaneously, in a manner that cannot be replicated easily with traditional photodetector arrays or those in 2D layouts. Current 2D solutions involve external light-blocking screens (e.g., a wall and a cylinder with a pinhole or a slit), a pair of actuators, and a driving motor connected with microprocessor41,42. Although functional, this multicomponent apparatus cannot be easily scaled to small dimensions. By contrast, the transparency and 3D shape of the systems introduced here allows light to pass through the entire device, to provide measurements both at the point of illumination but also at the point where the light passes out of the structure. The results allow collection of beam directionality and divergence.
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The system in Fig. 3a allows for the demonstration of these capabilities. Here, a laser source (532 nm) and goniometer allow motion of the laser beam in 3D coordinates, to provide incidence at any desired position. An automated measurement unit records the photoresponses of the 48 devices with ~64 Hz device interval (corresponding frame interval ~0.75 s), as in the bottom of Fig. 3a. The devices nearest to the location of illumination (entry or exit point) exhibit the highest photoresponses; those of the other devices decrease with increasing distance from this location owing to scattered light (Supplementary Fig. 16). Only the nine devices nearest to the illumination point respond significantly to the light signal; therefore, the position of the incident light is computed from the known coordinates of these nine devices (with respect to the center of the hemisphere). The calculation is according to1\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{P}}_{\mathrm{I}}({\mathrm{\theta }}_{\mathrm{I}},{\mathrm{\varphi }}_{\mathrm{I}}) = (\mathop {\sum }\limits_1^9 (\theta _n \ast \frac{{I_{{\rm ph},n}}}{{\mathop {\sum }\nolimits^ I_n}}),\,\mathop {\sum }\limits_1^9 (\varphi _n \ast \frac{{I_{{\rm ph},n}}}{{\mathop {\sum }\nolimits^ I_n}})),$$\end{document}PI(θI,φI)=(∑19(θn*Iph,n∑nI),∑19(φn*Iph,n∑nI)),where PI is the spherical coordinate of the incident point, Iph is the photocurrent for the nth device, and θ and φ are the azimuthal and polar angles, respectively. As the laser beam moves, its trajectory can be recorded in this manner, as indicated by the arrow in Fig. 3b. From the initial point X1 (Fig. 3b), a continuous photoresponse spectrum immediately begins up to the final point X3. The responses of the nine nearest photodetecting devices in the recorded data define the location of the beam. Figure 3c shows the estimated positions of the beam (green dot) and the photoresponses of the nearest devices at three locations X1, X2, and X3 (Fig. 3b). These measured movements exactly match the laser movements, as indicated by the arrow (Fig. 3b). The device closest to the incident point delivers the maximum photoresponse (bright red point). Figure 3d shows the interpolated position of the incident laser beam corresponding to location X1 in spherical coordinates originating at the hemisphere center.Fig. 3Operating principles of a 3D photodetection and imaging system. a Schematic illustration and optical images of the system. Inset: magnified view. b Distribution of the devices and movement of the laser beam. c Photocurrent distribution on the hemisphere surface during movement of the laser beam. d Magnified view of the photocurrent distribution at the first position of the laser beam. The illuminating locations of the incident laser beam are estimated by interpolation. e Penetration of the laser beam at two points of the 3D hemispherical surface. f Photocurrent distribution on the hemisphere surface in the scenario of e. g Principle of estimating the incident direction of the laser from the photocurrent map
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Operating principles of a 3D photodetection and imaging system. a Schematic illustration and optical images of the system. Inset: magnified view. b Distribution of the devices and movement of the laser beam. c Photocurrent distribution on the hemisphere surface during movement of the laser beam. d Magnified view of the photocurrent distribution at the first position of the laser beam. The illuminating locations of the incident laser beam are estimated by interpolation. e Penetration of the laser beam at two points of the 3D hemispherical surface. f Photocurrent distribution on the hemisphere surface in the scenario of e. g Principle of estimating the incident direction of the laser from the photocurrent map
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As mentioned previously, the passage of the laser beam through the transparent 3D system provides additional locations for determining the direction of the beam: an exit (P2) in addition to an entry (P1) (Fig. 3e). Figure 3f shows the mapping result for a representative case. As indicated in the bar graphs, the photoresponses of devices nearest to P1 are slightly stronger than those at P2, due simply to partial reflections and absorption (the device surface transmits 87% of the incident light). The direction of the incident beam (P1 → P2) follows from the spherical locations of the P1 and P2 vectors with respect to the hemisphere center. The P1 → P2 direction can be defined in terms of the azimuthal angle θ in the x–y plane and the polar angle φ between the x–y plane and z direction (Fig. 3g). This simple example extends naturally to more complex cases involving movement of the laser beam in θ, φ, and both planes. For present purposes, we explore three scenarios: (1) increasing θ from −45.0° to 45.0° while fixing φ at 90.0°, (2) decreasing φ from 90.0° to 67.5° while fixing θ at 0.0°, and (3) increasing θ from 45.0° to 135° and φ from 67.5° to 112.5°. In each, three combinations of θ and φ are tested, as shown in Fig. 4, with the laser beam incident on top of the 3D system. The direction (P1 → P2) can be expressed in spherical coordinates θ and φ. In all combinations in the three scenarios (nine experiments in total), the θ and φ coordinates calculated from the measured photoresponses match the coordinates directly measured with a protractor scale (Supplementary Fig. 17), as summarized in panels (a)–(c) of Fig. 4 along with the spatial mapping of the photoresponse. Corresponding bar graphs are in Supplementary Fig. 18. Note that although the system can map 360° rotations of θ in the x−y plane, the φ movement is limited by the array geometry, which imposes lower and upper circumferences on the hemispherical surface; see Supplementary Fig. 19. Simple modifications allow up to 45° movement of φ (Supplementary Fig. 20). All measurements and analysis can be performed in real time, as shown in the video clip of the supporting materials (Supplementary Movie 3). Further, the degree of accuracy in determining the position and direction improves with decreases in the distances between photoresistors and in the laser spot sizes (Supplementary Figs. 21 and 22). Moreover, the representative 3D photodetector showed good imaging capability in kHz range (Supplementary Fig. 23).Fig. 4Sensing characteristics of a 3D photodetection and imaging system. a Maps of photocurrent measured across the 3D surfaces. The incident angle θ ranges from −45° to 45° with φ fixed at 90°. The measured θ and φ from the device arrays are shown for comparison. b Similar results with φ ranging from 90° to 67.5° and θ = 0°. c Photocurrent maps of the photodetector array on the 3D surfaces randomly penetrated at two points by the incident laser. The incident angles are (from left to right) θ = 45°, φ = 67.5°, θ = 90°, φ = 90°, and θ = 135°, φ = 112.5°
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Sensing characteristics of a 3D photodetection and imaging system. a Maps of photocurrent measured across the 3D surfaces. The incident angle θ ranges from −45° to 45° with φ fixed at 90°. The measured θ and φ from the device arrays are shown for comparison. b Similar results with φ ranging from 90° to 67.5° and θ = 0°. c Photocurrent maps of the photodetector array on the 3D surfaces randomly penetrated at two points by the incident laser. The incident angles are (from left to right) θ = 45°, φ = 67.5°, θ = 90°, φ = 90°, and θ = 135°, φ = 112.5°
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Exploiting MoS2 and graphene in complex 3D system architectures allows their unique electronic, mechanical, and optical properties to be leveraged in a photodetection and imaging device that can sense both the direction and intensity of illumination, in real time. Similar capabilities cannot be achieved easily, with solid state, integrated operation, by using conventional designs or materials. Key enabling properties of 2D materials in this context include high threshold strains, to avoid fracture even in extreme cases of 2D to 3D transformation, ultrathin geometries, to minimize bending-induced strains that follow from this transformation and optical transparency, to allow simultaneous illumination on the front and backsides of the system. The example presented here might foreshadow other opportunities to engineer unique system-level function by deploying 2D materials in 3D designs.
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| 91.75 |
Monolayer graphene and MoS2 were grown on a Cu foil and a SiO2/Si wafer, respectively, by the low pressure chemical vapor deposition and the metalorganic chemical vapor deposition (MOCVD). The Cu foils (16 × 8 cm2) were inserted in a circular quartz tube and thermally annealed up to 1000 °C in the presence of H2 gas (8 sccm) at 80 mTorr for 2 h. The chamber was then injected with CH4 precursor gas (20 sccm) at 1.6 Torr for 1 h. Subsequently, the quartz tube (heated zone) was allowed to naturally cool at an initially rapid rate, before being gradually raised to room temperature in the presence of H2 gas (8 sccm) at 80 mTorr. Chemical precursors to Mo and S for growth of MoS2 were molybdenum hexacarbonyl (MHC) and dimethyl sulfide (DMS), respectively. The gas phase MHC (0.5 sccm) and DMS (1 sccm) were inserted into the MOCVD quartz tube along with H2 (10 sccm) and Ar (300 sccm), and the tube was heated to 550 °C at 7.5 Torr for 20 h. Raman and photoluminescence (PL) results from MoS2 and graphene are shown in Supplementary Figs. 24 and 25, respectively. The results confirm that MoS2 is monolayer and graphene is double-layer.
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Polymethyl methacrylate (PMMA) was spin-coated on top of the graphene of one side of the Cu foil (the other side was etched out by O2 plasma) and on the MoS2 monolayers to provide support during the transfer process. The Cu foil was etched by floating the PMMA-coated graphene/Cu foil on ammonium persulfate (APS) solution (20 g ℓ−1) for 5 h. After etching the Cu foil, the PMMA/graphene film was floated multiple times on deionized (DI) water to completely wash away the APS residue. Finally, the graphene was transferred to the desired wafer and the PMMA was removed by acetone. The SiO2 on the MoS2 was etched by floating the PMMA-coated MoS2 SiO2/Si wafer on diluted (1%) hydrogen fluoride (HF) solution. Afterward, the HF residues were washed away by floating the PMAA/MoS2 film on DI water in a manner similar to that for the PMMA/graphene film.
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First, SU-8 (2 µm) was spin-coated on an SiO2/Si wafer and patterned according to the desired 3D structure (octagonal prism, octagonal prismoid, or hemisphere). After transferring the graphene, the electrodes were defined in an interdigitated geometry by photolithography and reactive ion etching (RIE) with O2 plasma (40 sccm, 100 W, 5 s). MoS2 was transferred onto the interdigitated pattern of graphene electrodes and the channel regions were defined by photolithography and RIE with CHF3/O2 plasma (35/10 sccm) at 100 W for 5 s. Another SU-8 (5 µm) layer was spin-coated and patterned in a manner similar to that for the first SU-8 layer, but with openings in regions designated for creases. PR was spin-coated and patterned to expose and cover the bonding and non-bonding regions, respectively. Assisted by HF treatment, this fabricated structure was transferred with a slab of PDMS to a tape of PVA. Next, an elastomer substrate (Dragon Skin, Smooth-On) was bi-axially pre-stretched to the optimized strain determined by FEA simulations. The structure on the PVA tape and the pre-stretched substrate were exposed to UV ozone, laminated together and then baked in an oven at 70 °C for 5 min. The PVA was then dissolved in DI water. Finally, the PR was dissolved in acetone, which loosened and/or slightly delaminated the non-bonding regions of the devices from the pre-stretched substrate, facilitating the 3D assembly process upon release of the pre-stretching strain. The sizes of MoS2 photoresistor and the 3D pop-up hemisphere structure are 80 × 80 µm and 3.5 × 1.4 mm (diameter × height), respectively. Detailed descriptions of the 3D hemispherical structure and diagrams of the operating principles are in Supplementary Figs. 26 and 27, respectively.
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Three-dimensional FEA allowed prediction of the mechanical deformations and strain distributions of photodetector structures and the entire circuit system enabled by controlled buckling. Eight-node 3D solid elements and four-node shell elements with a multiple stack design (SU-8/MoS2/Graphene/SU-8 or SU-8/Graphene / SU-8) were used to model the silicone substrate and 2D precursors, respectively. Refined meshes of those elements ensured the computational accuracy. The critical buckling strains and corresponding buckling modes determined from linear buckling analyses were implemented as initial imperfections in the postbuckling calculations to obtain the deformed configurations and strain distributions during the pre-strain release. The simulations of postbuckling process were performed using conventional static analysis in the commercial software ABAQUS. The elastic modulus (E) and Poisson’s ratio (ν) are Esubstrate = 166 kPa and νsubstrate = 0.49 for substrate; Egraphene = 500 GPa and νgraphene = 0.15 for graphene; \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\it{{E}}}_{{\mathrm{MoS}}_2}$$\end{document}EMoS2 = 270 GPa and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\nu _{{\mathrm{MoS}}_2}$$\end{document}νMoS2 = 0.25 for MoS2; and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$E_{{\mathrm{SU}} - 8}$$\end{document}ESU-8 = 4.02 GPa and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\nu _{{\mathrm{SU}} - 8}$$\end{document}νSU-8 = 0.22 for SU-8.
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A laser source of wavelength 532 nm and the diameter of ~315 µm was connected to a tilting stage through an optical fiber. The tilting stage enabled easy adjustment of the incident direction of the laser beam. Electrical measurements of the photodetecting device were performed using a semiconductor characterization system (Keithley 4200). The photoresponse was recorded in real time by using a data acquisition system (DAQ) (Keithley 3706A) and a source meter (Keithley 2612). The raw photoresponse data from the DAQ were input into a program (encoded in MATLAB) to allow visualization of the photocurrent mapping. The program represents the intensity of the photocurrent mapping by a color scale and calculates the direction based on Eq. (1).
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| 99.94 |
Many decades of experimental research in cellular and molecular radiation biology have provided evidence suggesting that DNA damage plays a critical role in a plethora of human pathologies, including cancer, premature aging and chronic inflammatory conditions . In response to both endogenous and exogenous insults (approximately 104–105 lesions induced per cell per day) mammalian cells evolve the DNA damage response and repair pathway (DDR/R) that arouse the immune system, activating DNA damage checkpoints and facilitating the removal of DNA lesions . Dysregulation of the DDR/R pathway is closely linked to several human disorders associated with cancer susceptibility, developmental abnormalities, neurodegenerative disorders and accelerated aging .
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review
| 99.8 |
The DDR is triggered by a wide variety of physico-chemical aberrations in the genome. Depending on the source of damage, diverse lesions in the DNA can be induced, including nucleotide alterations (mutation, substitution, deletion and insertion), bulky adducts, single strand breaks (SSBs) and double strand breaks (DSBs) . Genotoxic agents, such as ultraviolet light from the Sun and IR from e.g., cosmic radiation and medical treatments utilizing X-rays or γ-radiation, mainly cause changes or losses of bases (abasic sites), crosslinks formed between two complementary DNA strands, SSBs and DSBs. Such types of DNA damage can occur separately or in conjunction with one another, resulting in complex DNA damage (clustered lesions). Chemical agents used in cancer therapy can also induce a diversity of DNA lesions, such as intrastrand or interstrand crosslinks. Apart from these environmental agents and genotoxic chemicals, DNA aberrations can also arise from physiological processes such as base mismatches introduced during DNA replication and from the release of reactive oxygen and nitrogen species (ROS/RNS) upon oxidative respiration or through redox-cycling events mediated by heavy metals . Additionally, replication stress resulting from oncogenic signaling may cause genome instability .
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review
| 99.7 |
It is well-accepted that IR can induce cancer even at clinically relevant doses and the relationship between radiation and formation of solid tumors is considered to be linear in the dose range of 0.15–1.5 Gy . Epidemiological data from the Life Span Study of the Japanese Atomic Bomb survivor cohort has provided significant evidence on the causal relationship between IR exposure and carcinogenesis . For low doses (<0.1 Gy), there is a heated debate on the actual relationship between dose and cancer incidence. Even recently the validity of the well-known linear no-threshold (LNT) model has been challenged and many questions are still open regarding if the radiosensitivity of a tissue to malignant transformation increases or decreases with dose and if the actual form of the curve, i.e., linear or curvilinear, etc. .
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review
| 99.6 |
Our knowledge of the mechanistic basis of the strong link between IR and carcinogenesis has been based on early studies using various animal models and it is concluded that radiation tumorigenesis proceeds in a conventional multi-step mode following radiation-induced key gene losses from single-target cells (including possible stem cells) . These genes can be DNA damage response, apoptotic and cell cycle control genes and others. This radiation-induced GI can be transmitted over many generations after irradiation via the progeny of surviving cells . Complex DNA damage and the consequent less precise and/or delayed DNA repair certainly hold a pivotal role(s) in this association between IR and cancer . Last but not least, in order to draw the current picture of the factors contributing to radiation-induced carcinogenesis one should also add the non-targeted effects and the release of clastogenic factors in non-irradiated cells and tissues , as well as the involvement of inflammation and constant triggering of the immune system .
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review
| 99.7 |
Lesions formed in a close proximity (i.e., within a few nm) result in clustered types of DNA damage, also called multiply damaged sites (MDS) and are considered the fingerprint of IR. Clustered DNA lesions can comprise a DSB and several base damages and/or abasic sites in close vicinity. In the case of multiple DSBs, we refer to the idea of complex DSBs . The biological significance of such lesions relates to the inability of cells to process them efficiently compared to isolated DNA damages and the outcome in case of erroneous repair can vary from mutations up to chromosomal instability . Therefore one should wonder if there are any mutational signatures of IR. Only recent evidence, mostly due to availability and affordability of next generation sequencing technologies, indicates that such radiation signatures do exist ; yet previous studies have shown the lack of such associations . Specifically, Behjati et al. have shown a significant increase in small chromosome deletions and balanced inversions in radiation-associated tumors which probably act as driver mutations and explain the carcinogenic potential of IR. More importantly, they suggest that these chromosomal abnormalities originate from the repair of radiation-induced DNA damage via the less accurate pathways of non-homologous (NHEJ) or microhomology mediated end-joining (MMEJ) . Therefore, accepting the claim that IR induces complex DNA damage that is irreparable and leads to mutations or structural abnormalities and subsequently to genomic instability (GI) and cancer, radiation-induced cancers should bear traces of the radiation-related origin of these mutations. Disruption of genome maintenance (i.e., GI) can occur through a variety of mechanisms and it is now considered as a key hallmark of cancer. Hence, there is a great need for improved detection techniques at cellular and tissue level that will provide valuable information for understanding the cellular mechanisms to process clustered DNA lesions .
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review
| 99.8 |
The complexity of DNA damage as discussed above refers to the idea of clustering of several and different DNA lesions within a short DNA region of 10–15 bp. The two main categories of lesions appearing in a cluster are the DSB and non-DSB lesions, usually referred to as oxidatively-clustered DNA lesions (OCDLs). The reader can refer to several comprehensive reviews for the general description of clustered DNA damage , detection methodologies and biological importance. More specifically for the accepted repair resistance of these lesions, including experimental evidence on the increase of the possibility for generation of mutations and chromosomal breaks after erroneous repair of clustered DNA lesions please see . Although within the context of this review we refer to bistranded DNA lesions appearing in both the DNA strands, there is also the possibility of unistranded or tandem lesions appearing in the same DNA strand and several groups have dealt with the processing and biological role of these complex DNA lesions as described in recent reviews .
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review
| 99.9 |
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