Since 2005, the Australian Government has subsidized the production and distribution of Low Aromatic Fuel (LAF) as a deterrent against petrol (gasoline) sniffing in remote Indigenous communities. LAF is used in place of unleaded petrol as a fuel for vehicles and other engines. This paper reports findings from an independent evaluation of the LAF rollout.Forty one Indigenous communities were surveyed between 2010 and 2014, with each community being visited twice at a two yearly interval. Quantitative data on prevalence of petrol sniffing were collected, as well as qualitative data on the acceptability of LAF, evidence of substitution for inhaled petrol with other drugs, and programs such as recreational, training and employment opportunities. Prevalence rates of sniffing per 1000 population for each survey year and community were calculated by dividing the total number of sniffers by the population aged 5–39 years and multiplying by 1000.p < 0.05). LAF was widely accepted, although acceptance was often qualified by a belief that LAF harmed engines. Anecdotal reports suggest that the fall in petrol sniffing may have been offset by increased use of cannabis and other drugs, but the relationship is not one of simple cause-and-effect, with evidence that an increase in cannabis use in communities commenced before the LAF rollout began. Provision of services in communities has improved in recent years, but many programs continue to be inadequately resourced.Between 2011–12 and 2013–14, the total estimated number of people sniffing petrol declined from 289 to 204, a fall of 29.4%. At both times, the median petrol sniffing prevalence rate was lower in communities with LAF than in communities without LAF. In 17 of the 41 communities, comparable data were available over a longer period, commencing in 2005–06. Fifteen of these communities stocked LAF over the entire period. In these communities, the median rate of petrol sniffing declined by 96%, from 141.6 per 1000 population in 2005–06 to 5.5 in 2013–14 (The rollout of LAF appears to have contributed to reducing petrol sniffing and associated harms in Australian Indigenous communities. This paper presents findings from an evaluation of the impact of introducing government-subsidized Low Aromatic Fuel (LAF) as a deterrent to petrol sniffing  in a national sample of 41 Indigenous communities in Australia, most of them in remote regions.Volatile substance misuse (VSM) has been described as ‘an under-recognized and underestimated global public health issue’ , particuWorld Health Report 2003 reported that, among 40 countries for which lifetime inhalant usage data was available for the 1990s, 10 countries reported rates of 10% to 20% of the youth populations examined, 15 reported rates between 5% and 10%, and 16 reported rates below 5%  and they steal baskets to sell. Young people get cranky with older family members when there’s no gunja. I was told by an old lady recently that she was pushed over by young people wanting food and money.Of much greater concern than these behaviors in many communities were the high levels of concern regarding alcohol and cannabis. For analytical purposes, interviewees’ qualitative assessments regarding the impact of both of these substances were coded in one of three categories: (a) substance reported as not present in the community, (b) substance reported as present, but not a cause for concern, (c) use of substance reported to be heavy and/or a major concern. In the case of cannabis, a fourth category was also created, to cover communities in which fieldworkers reported conflicting assessments of the presence and/or severity of associated cannabis-related problems. In around two-thirds of the 41 communities , cannabis use was reported as being heavy and/or a major cause for concern. In just over half of the communities , alcohol use was described as heavy and/or a major cause for concern. In 14 communities (34.1%), fieldworkers reported heavy use and/or major concerns with both alcohol The decline in petrol sniffing, together with evidence of high levels of alcohol and cannabis use.point to a possibility that some petrol sniffers may have substituted other substances for petrol. In 14 communities (34.1%), fieldworkers were told that the decline in petrol sniffing appeared to have led to an increase in use of cannabis, alcohol, or other drugs more generally. Few observers, however, drew a direct causal link. In many communities, the growth in cannabis use preceded the decline in petrol sniffing, and was generally attributed to a number of interconnected factors, including its ready availability, its social acceptability in the community, and the boredom of many young people. In six communities, informants told fieldworkers that, in general, alcohol, cannabis, inhalants including petrol and, sometimes, other drugs, were all regarded as interchangeable; if you could not access one, you would find another.All the kids I sniffed with stopped but they are smoking gunja now… When I left petrol I was smoking gunja, when I left gunja I was drinking.As a young person in one community put it:To compare levels of concern with alcohol and cannabis in the 18 communities that recorded a decline in petrol sniffing between 2011–12 and 2013–14 with levels of concern in those communities that recorded no decline, levels of concern were dichotomized, with ‘heavy use and/or major concerns’ as one category, and ‘not present, present but not a concern, or conflicting reports’ as the other category. The results are shown in Table p = 1.00). Similarly there was no association between communities reporting use of other inhalants in 2013–2014 and a decline in petrol sniffing between 2011–12 and 2013–14 . In the case of alcohol problems, however, there was a strong association, though possibly not in the direction that might have been anticipated. Far from a decline in petrol sniffing being associated with an increase in alcohol problems, communities reporting a decline in petrol sniffing between the two survey times were less likely than other communities to report heavy alcohol use and/or major concerns with alcohol problems .Table Efforts to deal with petrol sniffing and other drug-related problems in remote Indigenous communities have long been hampered by inadequate intervention services, inadequately resourced youth and recreation programs, and a dearth of training and employment opportunities. Our study found evidence of improvements in access to intervention services. Fieldworkers were asked to document the availability or otherwise of personnel with either mental health or AOD  qualifications. In our 2007–08 study of 20 communities, 30% of communities had access either to a regular visiting service or an on-site service. By 2013–14, the proportion had risen to just over half (51.3%) of the 41 communities surveyed.Youth, sport and other recreational activities in communities ranged from being virtually non-existent (four communities) to apparently adequately funded and satisfactory (nine communities), with the majority (26 communities) falling in between these two extremes – that is, activities were in place, but the programs struggled in the face of problems of funding, staffing and/or facilities. The Shire now has a manager of the Youth Program on the Lands and there are two experienced youth workers in the community running the local program. There are activities every day after school times utilising the basketball court, rec hall, drop-in centre, gym, oval and pool (in summer). There are movie nights and discos a couple of evenings a week.Functioning programs created their own energy, as the following report demonstrates:Unfortunately, the following field report describes a more typical scenario than the one above. It comes from a community of about 350 people located a little over 300 km from Alice Springs:There is no dedicated youth centre building. The basketball court is the centre of activity. The toilets don’t work properly. The youth worker has renovated an air-conditioned shipping container as an art and craft space for little kids. The kitchen is currently unusable and he cooks at home. He is trying to renovate the complex so that at the end of the year it is in a fit condition for his next year or the next person. He is very tired, working 70-hour weeks and has no phone or internet at home. He feels very supported by CAYLUS  but feels that the Shire is very unsupportive.There was a continued sense of things happening - there were locals employed in various roles in the agencies and the shop. [One program] had 325 on the books and 47 in jobs aged 16-60 yrs. Training run in last 12 months included Cert 2 in Tourism, Cert 2 in Indigenous Housing and Cert 2 in Hospitality.Similarly, in a few communities employment and training activities appeared to be opening up genuine opportunities for young people. Here is a fieldworker’s report from a community in Far North Queensland:There was a particular emphasis on a group of young people aged 16-25, and 13 had travelled to Tully for leadership training – ten of these were regular attenders and there were plans that included work with elders recording stories and catering, repairing a damaged park, a youth newsletter, development camps and designing their own uniform. It is planned that this group will be the core of the Youth Hub. The program is now more compliance-based and if people don’t work they don’t get paid. Most people have to do 20 hours per week with some up to 30.There are not many job opportunities at [name of community]. RASAC  employs half a dozen community members and the store, clinic, school, aged care, Catholic Care, Money Mob, the internet centre and the Well Being Centre also employ people. Skill Hire, the RJCP provider, has 150 people on their books. They cannot provide work for everyone for 20hrs/week so they give them activities - women have been picking up tyres from the tip, painting them and using them as garden beds, the men have recently completed landscaping at the school and now are cleaning up the yards. Skill Hire organizes training for workers in connection with the activities they undertake. As one of the Skill Hire coordinators put it ‘they get trained to death - they have bobcat certificates, excavator tickets - but nowhere to use them’.More typical, unfortunately, was the situation described in another community:dearth of training programs;dearth of employment opportunities;where employment opportunities are in principle available – for example, in nearby mines – disqualification of otherwise eligible young people because of issues such as prior drug offences, current drug use, or licence cancellations;absence of basic literacy and numeracy skills; andlack of motivation on the part of young people.With exceptions in a few communities, attempts to generate employment opportunities for young people were found to be plagued by one or more of the following problems:Each one of the above points raises issues that reach beyond the scope of this paper or our inquiry. It is important to note, however, that this is the context within which attempts to address alcohol and other drug problems, including petrol sniffing and the rollout of LAF, are played out.The study demonstrates that the introduction of LAF has been accompanied by a significant decline in the prevalence of petrol sniffing. In 15 communities for which data is available over an extended period from 2005–06 to 2013–14, and which stocked LAF during the entire period, the median prevalence rate of petrol sniffers declined from 141.6 per 1000 population to 5.5. Among the 41 study communities in the recent study, communities with LAF had prevalence rates lower than communities without LAF (5.6 compared with 11.0 in 2013–14). Although the differences were not statistically significant, this is an outcome of small absolute numbers of sniffers in communities and the small number of communities, leading to high variability.It is not possible, on the basis of these findings, to ascribe the decline in petrol sniffing entirely to the introduction of LAF. The rollout of LAF was not conceived as a trial or research exercise, but rather as a policy initiative under which LAF has been made available to communities as and when they request it and demonstrate a need. Consequently, there are no control communities with which to compare prevalence. Among the 17 communities for which long term data are available, in only two of them was LAF not available – hardly a basis for comparison. Among the 41 communities in the more recent study, as indicated above, 28 communities had LAF at the time of both data collections, eight had no LAF at either time, and the remaining five communities changed their LAF status during the course of the study. Comparison of those having LAF with those not having it, as shown above, suggests that LAF has reduced prevalence of sniffing, but other contextual differences may well have contributed to the observed outcomes.Fuel Standard (Petrol) Determination 2001. The analysts reported that, in their opinion, the fuel tested would have no adverse environmental or engine operating effects; on the contrary, the low content of sulphur, benzene, other aromatics and olefin meant that use of the fuel would entail an environmental and health benefit. It would also, in their view, enhance engine efficiency [The quantitative evidence of a decline is corroborated by the testimony of community residents and service providers, among whom there is a widely shared belief that LAF has been a major factor in reducing petrol sniffing. Similar observations were made by several witnesses to a 2012 Senate inquiry into legislative options for supporting the rollout of LAF . Supportficiency .how best to counter misconceptions requires ongoing attention.From a policy point of view, the persistence of beliefs about adverse effects of LAF on engines, despite evidence to the contrary, and despite considerable efforts already made by government and other agencies to dispel misconceptions, poses an ongoing challenge that cannot be addressed simply by pointing to the objective evidence. Shared beliefs have consequences regardless of their objective validity. Our study found one instance of a community that actually stopped using LAF because some people in the community believed that it was damaging outboard motors. The question of The study found evidence of a belief in some communities that reductions in petrol sniffing may have led to substitution with other drugs, including other inhalants and cannabis. Given that much drug use by young people – in remote communities as elsewhere – takes the form of opportunistic polydrug use, this is not surprising. The findings, however, do not support a simple cause-and-effect interpretation. Changes in drug use patterns are normally a product of many causal factors. In the case of Indigenous Australian communities, the apparent widespread, heavy consumption of cannabis that has given rise to the concerns reported in this study predates the introduction of LAF. As several studies have reported, the availability and consumption of cannabis in remote Indigenous communities increased dramatically from the mid-1990s, driven by rising demand and highly organised profiteering mainly by sources outside the communities themselves , 36. Morless likely than other communities to report heavy alcohol use and/or a major concern with alcohol problems. It is not immediately clear why this should be so, and the question warrants further examination. While decisions on whether or not to sniff petrol, drink alcohol or use other drugs are taken by individuals, the mechanisms available for managing alcohol and other drug use in local communities operate through families, communities and states/territories, as well as individuals. Levels of petrol sniffing, alcohol-related problems and other drug use may, to some extent at least, be different aspects of a single attribute which can be tentatively conceptualized as ‘community capacity’. A useful extension of the findings of this study would be to examine the relationship between petrol sniffing, other drug use, and community capacity.Communities reporting a decline in petrol sniffing were, however, At the same time, caution is needed in interpreting these results. While the reported levels of petrol sniffing are quantitative estimates, the data on cannabis, alcohol and other drugs are all, as indicated earlier, qualitative and anecdotal.The improvements in both the quantity and quality of alcohol and other drug services in communities reported in this study, and the limited improvements in provision of youth and recreation services, are to be welcomed. However, the findings also point to a continuing pattern of unstable and often inadequate funding and other resource problems in these programs, and the need for ongoing improvements.The main limitation of the study is the absence of an adequate sample of control communities. Among the 17 communities for which long term data are available, only two did not have LAF throughout the period under review. Among the larger sample of 41 communities, the eight communities that did not have LAF at either data-collection time furnish a basis for comparison, but do not constitute a matched group of control communities. A second limitation is the absence of population projections for two data collection times – 2007-08 and 2013–14. As a result, it was necessary to base population estimates for these years on census returns for 2006 and 2011 respectively. A third limitation is our reliance on proxy respondents for estimates of petrol sniffing prevalence. Finally, interpretation of statistical findings was constrained by small numbers.The support for the use of LAF in remote Indigenous communities as a deterrent to petrol sniffing by successive Australian governments is an example of an adequately funded program that has enjoyed broad political support, and consistency in application. Insofar as governmental decisions to support the provision of LAF to individual communities are taken in response to requests from those communities, it is also an example of government policy complementing community initiatives. The findings from this and earlier studies of the LAF rollout demonstrate the benefits to be derived from this approach to policy-making. LAF is not a ‘magic bullet’ for eradicating petrol sniffing. Further research is needed to identify the conditions under which LAF is and is not effective in reducing petrol sniffing. From thepoint of view of policy and programs, it is vital that the continuing need for other programs and services, also demonstrated in this study, be addressed if the gains in reducing petrol sniffing are to be consolidated.


In April 2016, a Virginia dentist who had recently received a diagnosis of idiopathic pulmonary fibrosis (IPF) and was undergoing treatment at a specialty clinic at a Virginia tertiary care center contacted CDC to report concerns that IPF had been diagnosed in multiple Virginia dentists who had sought treatment at the same specialty clinic. IPF is a chronic, progressive lung disease of unknown cause and associated with a poor prognosis  (median = 47% [range = 19%–55%]). Pulmonary function test results were not available for one patient. One of the living patients who did not complete an interview underwent a lung transplant 3 years after diagnosis. No tissue specimens were available for analysis.Among 894 patients treated for IPF at the tertiary care center, nine (1%) were identified as dental personnel, including eight dentists and one dental technician. All patients were male and were treated during 2000–2015. Five were white, one was black, and the race of three was unknown. At the time of pulmonary consultation, the median patient age was 64 years (range = 49–81 years) . States Three patients were former smokers, one had never smoked, and smoking history was unknown for five . A telepDuring September 1996–June 2017, nine (1%) of 894 patients treated for IPF at a single tertiary care center in Virginia were identified as dental personnel. Each patient presented for care during 2000–2015. Seven of the patients had died. This is the first known described cluster of IPF occurring among dental personnel. Although no clear etiology exists for this cluster, it is possible that occupational exposures contributed to the development of IPF.During 2016, dentists accounted for an estimated 0.038% of U.S. residents  for “other interstitial pulmonary diseases with fibrosis”https://www.osha.gov/SLTC/respiratoryprotection/index.html). If respiratory protection is used, a written respiratory protection program should be implemented as required by the Occupational Safety and Health Administration Respiratory Protection Standard, including training, fit testing, and maintenance and use requirements (https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_id=12716&p_table=STANDARDS).The living patient who was interviewed reported occupational exposures to known respiratory hazards  yet did not wear National Institute for Occupational Safety and Health-certified respiratory protection. It is possible other patients in this case series had similar experiences. Dental personnel who perform tasks that result in occupational exposures to known respiratory hazards should wear adequate respiratory protection if other controls  are not practical or effective  is a chronic, progressive lung disease of unknown cause and is associated with a poor prognosis. IPF has been associated with certain occupations; however, no published data exist regarding IPF in dental personnel.A unique cluster of nine cases of IPF was identified among dental personnel treated at a tertiary care center in Virginia during 2000–2015. No clear etiology has been identified, but occupational exposures are possible.During 2016, approximately 650,000 dental personnel were estimated to be employed in the United States, including 122,330 dentists. This cluster of IPF cases reinforces the need to understand further the occupational exposures of dental personnel and the association between these exposures and the risk for developing IPF so that strategies can be developed for prevention of potentially harmful exposures.


In Cox-regression analysis, double lung transplant and white race of the lung donor showed to have a significant survival advantage. Since double lung transplant, those who are younger and have lower Lung Allocation Score (LAS) at the time of transplant have a survival advantage, we suggest double lung transplant as the procedure of choice, especially in younger sarcoidosis subjects and with lower LAS scores.Sarcoidosis commonly affects the lung. Lung transplantation (LT) is required when there is a severe and refractory involvement. We compared post-transplant survival rates of sarcoidosis patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). We also explored whether the race and age of the donor, and double lung transplant have any effect on the survival in the post transplant setting. We analyzed 9,727 adult patients with sarcoidosis, COPD, and IPF who underwent LT worldwide between 2005–2015 based on United Network for Organ Sharing (UNOS) database. Survival rates were compared with Kaplan-Meier, and risk factors were investigated by Cox-regression analysis. 469 (5%) were transplanted because of sarcoidosis, 3,688 (38%) for COPD and 5,570 (57%) for IPF. Unadjusted survival analysis showed a better post-transplant survival rate for patients with sarcoidosis ( The lung is the organ most commonly involved and the disease is characterized by frequent pulmonary exacerbations and remissions, particularly within the first 2 to 5 years of the diagnosis3. There is a known difference in prevalence according to race, with Caucasians having a 0.85% lifetime risk of developing sarcoidosis, while this risk for African Americans is 2.5%4. Racial differences in disease severity are also observed. African Americans have a more acute and severe presentation in contrast to a typically slow insidious process in European Americans5.Sarcoidosis can affect all age groups but is more frequent in middle age populations, and women are two times more likely to have the disease6. The selection of the best treatment option is based on the degree of lung involvement, ranging from mild interstitial pulmonary disease to severe disabling pulmonary fibrosis and pulmonary hypertension3. Eligible patients with severe lung involvement, refractory to medical therapy, are referred for lung transplantation (LT).Medical treatment of symptomatic sarcoidosis is based on immunomodulation. Corticosteroids are usually the first line of therapy, but other medications including methotrexate, leflunomide, infliximab and other anti-TNF agents are commonly used7. Lung transplantation has been recommended in patients with advanced chronic obstructive pulmonary disease (COPD), bronchiectasis, cystic fibrosis (CF), primary pulmonary hypertension, idiopathic pulmonary fibrosis (IPF), sarcoidosis, and other end stage interstitial lung diseases8. Advanced COPD and IPF are the most common indications for lung transplants worldwide7. Advances in lung transplant techniques, post-transplant patient care, and immunosuppressive therapies during the last 30 years have significantly improved survival9. The median survival of adults who undergo lung transplantation is reported to be 5.6 years, with an unadjusted survival rate of 53% at 5 years, and 31% at 10 years10. The highest post-lung transplant survival rate per specific disease occurs in CF patients, with a 67% survival rate at 5 years11. Meanwhile 5 year survival is reported to be 45% for COPD and 44% for IPF patients12. There are limited information regarding survival rates following LT in patients with sarcoidosis13. Taimeh et al. recently found no difference in lung transplant outcomes between sarcoidosis and non-sarcoidosis lung transplant recipients in the last 30 years14. However, given the significant improvement in LT outcome in the last 10 years, the sarcoidosis survival after LT may have also been improved. Moreover, information on the factors that influence on sarcoidosis survival in lung transplantation are still unclear. The aim of this study was to compare the post-transplant survival rates of sarcoidosis patients with the two most common indications for LT: COPD and IPF. We also explore whether some independent factors, such as race of the donor, age of the donor and double lung transplant have any effect on the survival of sarcoidosis patients in the post transplant setting.Since the first successful lung transplant was performed in 1983, thousands procedure have been performed worldwideth, 2005, to December 30th, 2015 based on the United Network for Organ Sharing (UNOS)/OPTN standard transplant analysis and research files database. All methods were conducted in accordance with pertinent guidelines and regulations. We used open resource de-identified national dataset, therefore no Institutional Review Board (IRB) or informed consent was required. From the same dataset, all subjects with diagnosis of COPD and IPF were selected for survival rate comparisons. The variables of interest were age, sex, race, body mass index (BMI), and outcomes including death and re-transplantation.We analyzed adult sarcoidosis subjects who underwent LT in the United States from December 30p < 0.05) and Kaplan-Meier curves were plotted to depict ordinality of any found differences. A cox regression model was performed to find if variables including age of transplant recipient, age of donor, race of donor, double lung transplant, Lung Allocation Score (LAS), cold ischemic time , mechanical ventilation, and male gender are independently associated with mortality in sarcoidosis subjects. We developed multivariate analysis model based on variables which have previously been used by Taimeh’s et al.14. Factors were selected based on clinically important variables which was found in previous study. Missing data in the 10-year dataset was also studied, and collinearity between covariates was also explored. A second cox regression model was performed only in the overall black population to determine if the race of the donor had a persistent effect on the outcome. Moreover, a separate cox regression model was performed in non-white patients. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated. All analyses were performed in R (version 3.2.2) and the Survival package (version 2.38-3) and results were considered significant at P < 0.05.A log-rank test was utilized to determine if there were any statistically significant differences in survival between the three groups of interest  were transplanted because of advanced sarcoidosis, 3688 (37.9%) for COPD and 5570 (57.3%) for IPF.p =  < 0.0001) or IPF . About half of the sarcoidosis subjects were female, similar to what was observed in COPD but not in IPF, where an overall significant difference was observed (p =  < 0.0001), as most IPF subjects were male. In the sarcoidosis group, 64% (302) of the subjects were African American while 90% (3346) and 82% (4582) were European American in the COPD and IPF group, respectively. Finally, lung re-transplant rates were relatively low but statistically significantly higher in patients with IPF.Table p < 0.001, log-rank test). Figure p < 0.001, log-rank test).The survival analysis in the three groups showed a better survival rate for patients with sarcoidosis compared with patients with COPD and IPF  in the US17, However, IPF causes severe pulmonary fibrosis and advanced lung disease in almost all subjects, while fibrotic lung disease develops in up to 20% of patients with sarcoidosis18.Sarcoidosis comprised only a 4.8% of subjects when compared to other transplant indications, such as COPD and IPF in the last 10 years. It has not been changed in the last 30 years19. Recently, we reported that the overall mortality rate of sarcoidosis was eight times higher in African Americans than in European Americans5.The significant higher prevalence of females and African Americans in the sarcoidosis group highlights the gender and race disparities. Females and African Americans are more susceptible to sarcoidosis for still unknown reasons. African Americans also suffer from higher severity of disease and have a higher mortality rateet al. could not demonstrate any association between donor age and race, and survival in the sarcoidosis cohort14. We can hardly compare these studies together for several reasons. We analyzed the outcomes of lung transplant in the last 10 years to achieve the current status. We also aimed to compare sarcoidosis patients who underwent lung transplantation with the two most common causes for lung transplant: COPD and IPF. Taimeh et al. analyzed a 30-year cohort for their analysis, comparing sarcoidosis to all non-sarcoidosis subjects. In the last 30 years, significant improvement in outcome of lung transplant has been achieved including surgical techniques, post-operative care and immunosuppressive therapy. Those factors may affect the outcome results between two studies. We considered this may be a major driven factor to see an association between donor age and race with a better outcome in sarcoidosis subjects in the current study.In contrast with our study, Taimeh et al.20 that was 56% at 5 years. Interestingly, sarcoidosis subjects had a better unadjusted survival compared to COPD and IPF subjects in Kaplan–Meier analysis. The Cox regression analysis revealed that better survival in sarcoidosis subjects was secondary to their younger age, higher number of double lung transplant and receiving lungs from European-American donors. Sarcoidosis patients were on average 8 years younger than their COPD and IPF counterparts, and this was an independent risk factor in the adjusted survival analysis. The effect of age on lung transplant outcome has been studied before. Gutierrez and colleagues showed that subjects with advanced age who underwent lung transplant have an increased mortality rate even after adjusting for expected advanced age-related mortality21. Our study also showed that age and race of donors are independently associated with post transplant survival in sarcoidosis subjects. Sommer and colleagues could not find significant difference in 1-year survival rate when using of donor lungs of aged population (≥70 years old). But, noted significantly lower forced expiratory in 1 second values in subjects with lung transplantation of aged donor lungs in IPF recipients22. Obviously, our 10 years follow up study has higher power to show survival effect of aged donor lungs on post transplantation survival.Our observation of 53% survival of sarcoidosis subjects at 10 years post-lung transplant is better than previously report by Walker 23. Further investigation is needed to determine the nature of the relationship between donor and recipient race and survival in LT.Recipients of lungs from Caucasian donors had better survival. We speculate that socioeconomic factors influence on this observation. To our knowledge, no other studies have reported a survival advantage related to race and ethnicity of donor lungs. However, studies in kidney transplant patients have found that recipients of African American kidney donors had lower graft survival24. According to our analyses, sarcoidosis patients with a lower LAS at the time of transplant should have a higher post-LT survival. Therefore, a new scoring system should be developed to determine the most appropriate time for lung transplantation for patients with advanced refractory sarcoidosis.Our analysis showed that higher lung allocation scores are associated with worse post-LT outcomes in sarcoidosis. LAS has been universally used to prioritize LT candidates by balancing expected post-transplant survival and predicted waitlist mortalityDouble lung transplant was associated with higher survival in our study. It was performed in higher percentage in sarcoidosis subjects compared to IPF and COPD, perhaps due to severe bilateral lung involvement, presence of bronchiectasis, and pulmonary hypertension. Our study suggests that double lung transplantation should be the procedure of choice in sarcoidosis patients.et al. previously25. They found granulomatous reaction recurrence in 7 (23%) out of 30 sarcoidosis subjects who undergone lung transplant in Cleveland Clinic, Ohio, USA. However, they found no impact of granulomas recurrence on overall outcomes. Schultz and colleagues also reported that 7 (28%) of 25 subjects who undergone lung transplant for sarcoidosis in Copenhagen, Denmark showed recurrence of granulomas in new lungs with no impact of outcomes26. UNOS does not provide information concerning recurrence of sarcoidosis in post-transplanted patients. Therefore, we would not able to analyze rate of sarcoidosis recurrence after lung transplantation. This topic requires further investigation.Sarcoidosis recurrence after lung transplantation is an important topic. We reported no significant increasing risk for re-transplantation among sarcoidosis subjects when compared to others. The rate of re-onset of sarcoidosis after lung transplant was reported by Banga A This study consists of a big cohort comprised of 9,727 patients that underwent lung transplant because of sarcoidosis, COPD and IPF, in a period of 10 years. To our knowledge, this is the first time that the role of the ethnicity of the donor was analyzed as an independent factor for the outcome in lung transplantation.Despite the use of the largest available database for lung transplantation, our study has several limitations. We are unable to analyze the impact of many other variables that play a role in post lung transplant survival including nutritional status, psychological factors, adherence to medications, pre existent pulmonary arterial hypertension (PAH), spirometric values including total lung capacity (TLC), and other co-morbidities. Even though PAH may be a potential cofounder in post lung transplant outcome, we had no access to PAH data of subjects from UNOS database. Moreover, only a total of 912 subjects were African-American among 9,727 patients (9.4%). This represents an important limitation because we were not able to analyze the correlation between African-American recipients undergoing lung transplant from African-American donors. A more powered sample size is required to further investigate the impact of other ethnicities in the outcome of lung transplant.Sarcoidosis patients have a reasonable survival rate and re-transplant rate that are comparable with other common LT indications such as COPD and IPF. Given that double lung transplant is associated with better survival in sarcoidosis subjects, and those who are younger and have a lower LAS score at the time of transplant have a survival advantage, we would suggest double lung transplant as the procedure of choice, especially in younger sarcoidosis subjects and preferably those with lower LAS scores.


On the other hand, questions on previously unseen or niche topics take a while to get a good answer. This is particularly the case with questions about current updates to or the introduction of new application programming interfaces (APIs). In a hyper-competitive online market, getting good answers to current programming questions sooner could increase the chances of an app getting released and used. So, can developers anyhow, e.g., hasten the speed to good answers to questions about new APIs? Here, we empirically study Stack Overflow questions pertaining to new Android APIs and their associated answers. We contrast the interest in these questions, their answer quality, and timeliness of their answers to questions about old APIs. We find that Stack Overflow answerers in general prioritize with respect to currentness: questions about new APIs do get more answers, but good quality answers take longer. We also find that incentives in terms of question bounties, if used appropriately, can significantly shorten the time and increase answer quality. Interestingly, no operationalization of bounty amount shows significance in our models. In practice, our findings confirm the value of bounties in enhancing expert participation. In addition, they show that the Stack Overflow style of crowdsourcing, for all its glory in providing answers about established programming knowledge, is less effective with new API questions.Stack Overflow is a popular crowdsourced question and answer website for programming-related issues. It is an invaluable resource for software developers; on average, questions posted there get answered in minutes to an hour. Questions about well established topics,  The social coding movement and the phenomenon of crowdsourcing have made eminently useful software development resources and services available at low cost. The Stack Overflow question and answer site and various Open Source Software forges, like GitHub, are transformative resources; they enable the creation, promulgation, and archiving of new knowledge and artifacts on an as-needed basis. They are often also very responsive: most questions on Stack Overflow are answered within minutes, and pull requests get reviewed, merged, and released into the codebase of large projects within days. In fact, Stack Overflow and Open Source work quite well as a coupled, interdependent system, with the former providing almost instantaneous documentation for the latter, and developers of the latter serving as askers and answerers in the former’s gift economy. This system is critically predicated on both a short turnaround time and the existence of enough knowledgeable users to provide needed expertise. As soon as one or both of those conditions are unmet, the programming and documentation resources get decoupled.et al., the mean time to an answer is between 17 and 47 minutes, depending on subject area The “involving” class consists of questions that explicitly state the new API, but the question does not address it directly. An example of such a question is:Question ID: 11485026, Linked API: SeekBarTitle: Seekbar creating EditTexts and then getting entries for further useThis code creates a seekbar and makes the seekbar create as many EditText fields as the slider is at / remove ones that would be too much. This code is in OnActivityCreated […]SeekBar), but it is not clear that the question is entirely about the new API itself. We found that the difference between these two groups is often small, but still worth separating.As shown, the “involving” question above does explicitly mention the new API  in the case study are in either the “involving” or “explicitly about” groups, we have confidence that our models can be used for inference. To assuage potential concern about the difference between the “involving” and “explicitly about” groups, we sought to identify a control that can be used to separate between the two groups. This case study shows that Stack Overflow users indeed ask questions about new APIs, and we can conclude that Stack Overflow users actually do use and care about new APIs; in other words, the new APIs are not merely mentioned in passing within the post. In addition, it provides confidence that our linking strategy indeed prioritizes true positive links, as false positives are rare. Meeting these core assumptions allows us to use the models we build for inference.i.e., textual variables and user-defined tag count. Column 3 introduces a variable that is not in control of the question asker (QNComments), API-related variables , and variables related to the bounty .F.QQualityLabelGood) receive more answers (0.049). For text-based, non-code variables , we see negative effects . As these variables serve as proxies for textual complexity, this is expected. Stack Overflow emphasizes conciseness in question asking (https://stackoverflow.com/help/how-to-ask); as these variables represent question lengths, it is not surprising that longer questions receive fewer answers. We see that questions linked to new APIs (F.Added) receive more answers (0.076), when controlling for other relevant variables. This is a positive result for Stack Overflow—new APIs are a topic of interest to developers, and one would hope that their needs for the most current documentation is met. However, we see that questions with higher documentation need (QNeed) receive less answers (−0.014).We see that high quality questions  all have significant positive values. In addition, our data shows that there are far fewer unique people who answer questions that reference new APIs  than those who answer questions that are not about new APIs —this may be due to new APIs requiring specific knowledge that is not yet widespread. Thus, due to a lack of knowledgeable individuals, answers come slower.For the former case, the explanation could be that questions with new APIs are harder to answer, and thus answers come slower. This is supported by the fact that question text variables which serve as a proxy for complexity (F.Added coefficient is −0.216).For the latter case, the explanation could be as follows. Questions with a first good answer after 2 days are harder to answer; otherwise, they would likely have received a faster answer (median time to first good answer in our data is 17 minutes). In addition, our data shows that of questions that are answered only after 2 days , only 46% are answered within 1 month. This result is more nuanced than what has been discussed in the past; questions that are hard enough to not receive an answer within 2 days often take longer than 1 month to answer—a far cry from the median answer time of 17 minutes. However, users want to document new APIs—this is supported by prior work that shows Android classes are highly documented, and generally done so quickly . Thus, fhttps://meta.stackexchange.com/q/130046/when-should-i-vote). However, the general consensus is that a question should be upvoted when it is useful, clear, and (or) shows research effort. It may be that an eminently useful question with no immediately obvious solution takes longer to answer. To our knowledge, there is no comprehensive  work on the social reasoning behind high Stack Overflow question scores. Thus, this explanation is one of a potential many; the underlying social mechanism behind high scoring questions could be the subject of future work.For both time to answer models, we see that good quality questions take longer to answer. This is initially puzzling; if a question is of high quality, should it not be easier to answer? Recall that our metric for question quality is a function of question score. The mechanism that drives higher scores is complex and has been discussed in length by users , we see that questions with higher need receive slower answers (0.045). For the second model (first good answer within 2 days), We see a positive effect of question quality, indicating that higher quality questions receive higher quality answers, even when controlling for time to answer. This is in agreement with prior work . We see QTitleLength, QBodyNWords, QBodyCHarsOfCode), we see negative effects. This suggests that decreased conciseness is associated with lower answer quality.For significant text-based variables , there was no significant effect of bounty amount on any outcomes tested.We also tested the inclusion of bounty amount into the models to see if higher reputation value bounties receive benefits compared to lower reputation value bounties (not shown in tables). In all forms individually tested , users are instructed to “make sure your answer provides [the specific answer for a given question]—or a viable alternative”. In manual inspection of questions and answers for new APIs, answers often provide semi-orthogonal solutions to the same stated problem. When solving programming tasks, there are often many methods of accomplishing the same goal, and having multiple solutions provides a wider breadth of information and thus understanding as to how a given API works. We find the same is true in the case of the bounty; bounties increase the number of answers that a question receives, a beneficial effect. Thus, we conclude the bounty incentive works as intended in attracting more answers.Our results show that questions referencing new APIs receive more answers, when controlling for other relevant variables, a net positive for Stack Overflow that strives to provide timely, quality answers to questions. As stated by the Stack Overflow answering guidelines (e0.133 = 1.142 or 14.2%), this may still be an issue if the question is asked, e.g., close to the end of a work day, or if the solution is especially time critical. However, for new API questions which receive a first good answer after 2 days, we see a hastening effect; good news for Stack Overflow users.Our results also show that new API questions receive a slower first good answer, given that the answer comes within 2 days. This is a potential point of concern for Stack Overflow. Though the effect is relatively small in raw value , though slower answers for those questions answered within 2 days (0.045). In all, this is good news for Stack Overflow, as although answers may come slower for under-documented APIs, the answers they do receive are of higher quality.In all cases, adding a bounty has a beneficial effect, increasing the number of answers, decreasing time to first good answer, and increasing answer quality. Interestingly, however, the bounty amount has no significant effect for any outcomes tested, for any operationalization of bounty amount tried. We acknowledge that the lack of a statistically significant operationalization does not necessarily equate to finding evidence that the bounty amount does not matter. However, we are still interested in discussing potential reasons behind this lack of significance, and do so below.This lack of significance may elucidate an underlying phenomenon: Stack Overflow answerers may not care much about being “paid” extra for their work, as long as they are paid at all. Or, it could be that questions which receive a bounty are inherently more difficult to answer—those who answer these questions may be more expert and thus have more reputation to begin with, so the additional bounty payoff is negligible to them. Another explanation could be that the payment provides little to no motivation, and the increased benefits are due to the increased visibility the bounty provides. Further studies, including interviews and surveys of Stack Overflow users, are needed to distinguish among those alternatives.e.g., a system that automatically detects underserved questions and randomly places them into a special section for a limited amount of time. However, Nisbett and Valins’ overly sufficient justification hypothesis [e.g., altruism), and when removed, can act against intrinsic motivation. On Stack Overflow, this means that removing the bounty and replacing it with an equivalent system that offers no reward may result in a negative response. Others have also discussed the bounty incentive in their work [If bounty visibility is the only reason that associated questions receive beneficial effects, one may consider replacing the bounty with, pothesis  seems toeir work , 25, 32 Our findings suggest that in practice, one can put a bounty on their question and receive a large speed increase (71.1%), with the additional benefits of receiving more, higher quality answers. As we found the reputation reward for the bounty does not seem to matter, we believe putting up the minimal reward (50 reputation) is likely sufficient.e.g., discrepancies when posts are migrated between sections within the Stack Exchange network). As we found these issues to affect a minority of our data (<1%), we do not believe this is a large threat. In addition, due to how the data dump is structured, it is expensive to calculate reputation scores at the time each question or answer is initially posted, as this requires calculating a cumulative sum for each user in our data across all their posts for all time. As we have 22,366 posts in our considered data, this calculation time is prohibitive. Thus, we use reputation scores at the time of the dump.In addition to threats outlined in above sections, we acknowledge a number of threats to validity. First, our data is primarily from the Stack Overflow provided data dump. As mentioned, we found a number of issues in the provided data  can also be seen as a threat. However, we log transform our answer time outcome variable in all models, which acts to reduce the effect of the long tail on model fit. As a result, we do not believe these threats are debilitating.As shown in t of a post being made, and test varying values of t. Or, we could define an API as new if it has only been added in the most recent framework update. Our choice has the drawback that some APIs may be defined as “new” by our method that are old in raw value; if an API was introduced in API level 1 and is not modified for all time, we would still consider this API as new. To mitigate this threat, we include various time variables  designed to absorb the variance introduced by these old (in raw time) APIs, and thus do not believe this threat affects our results significantly.In this work, we identify an API as “new” if it has not been modified between the time of its introduction and the time the question is asked, for reasons described in Data. We acknowledge that this is only one of many choices for this definition. For example, we could define an API as new if it was added within some time e.g., remain up-to-date with the current trends [Though documentation metrics are split by API level and attached to posts based on time, we do not split function invocation counts by API level; they are aggregated across all levels. To split function invocation counts by API level would require far more data from the Google Play store, and may not be possible due to the fact that application developers often update their products to target newer APIs to, t trends , 58. Thee.g., Kincaid et al. [i.e., we do not want to data peek; we do not want to remove a variable that we initially hypothesized as important after we found out it is not significant—this would be a disaster for inferential robustness). Though this may be seen as a threat, this variable was not significant in any of our models, and thus we do not interpret it in any discussions. It is possible that the inclusion of this variable may cause issues in estimation due to, e.g., multicollinearity. However, we take extreme care to make our models robust for inference, including reducing multicollinearity as much as possible, as described in Methodology. As a result, we do not believe the inclusion of this variable negatively affects our findings.We note that our measure of “structural complexity” through counting HTML tag switches is not supported by prior work. We hypothesized its importance based on theories of language complexity used by, d et al. . Due to In this work, we studied Stack Overflow questions referencing new APIs, which we know have longer latency to an acceptable answer. Specifically, we sought to elucidate the factors affecting answer count, their latency, and their quality when the questions refer to new Android APIs.Overall, we found that questions referencing new APIs receive more answers, after controlling for confounds, but there are subtleties in this overall result. Namely, among questions with a first good answer within 2 days, those referencing new APIs receive slower answers. On the other hand, among questions with a first good answer after 2 days, questions referencing new APIs receive faster answers. We see no significant effect of new APIs in identifying answer quality, but APIs with higher documentation need are more likely to receive a higher quality answer.Questions with a bounty receive benefits across all variables of interest, though bounties can only be placed after 2 days. Based on these findings, we discussed what a question asker can do to receive benefits for our outcomes. In general, adding a bounty is the most efficient way to receive more, faster, and higher quality answers. However, the bounty reputation value does not appear to be significant in any context. We hypothesized potential reasons behind this insignificance. Due to the complexity of the bounty system and its introduction of many overlapping confounds, to our knowledge there is no prior work on the exact mechanism behind the bounty’s effectiveness, and why the amount is insignificant when controlling for confounds. This could be the subject of future work.To our knowledge this is the first study that specifically focuses on questions referencing new APIs, and we use a novel metric to determine documentation need. These two points provide different descriptions of Stack Overflow’s ability to maintain currentness in terms of API documentation. In addition, we believe we are the first to find that the bounty amount does not seem to matter when controlling for many relevant confounds. We have identified both shortcomings and places where Stack Overflow excels in terms of maintaining currentness, and show that the bounty indeed accomplishes its intended effect. We hope our findings motivate others to identify and provide solutions for potential deficiencies in Stack Overflow, positively affecting software development as a whole.


Graphene, a two-dimensional material, has a wide range of unique properties and could be used in the development of varieties of mechanic, electronic and photonic devices, therefore methods to synthesis large-area high-quality graphene films are urgently required. Chemical vapor deposition (CVD) has been of particular interest recently due to its simplicity and low cost. However, because of the mismatch of thermal expansion coefficients, high densities of wrinkles are commonly observed. Despite their prevalence and potential impact on large-scale graphene properties, relatively little is known about their structural morphology and formation mechanism. In this article, morphologies of graphene obtained by CVD are experimentally investigated by an atomic force microscope (AFM) and results show that the profiles of wrinkles are much larger than they should be. By using theoretical methods and molecular dynamics simulations (MD), we find internal molecules created during CVD process which supply additional pressure is the main mechanism. Graphene is widely supposed to be a material to enable new development of many modern technologies6 which involves the potential applications in mechanic, electronic and photonic devices10. However, wrinkling is a ubiquitous phenomenon in 2D membranes that severely weaken the performance of graphene. In spite of very fast improving methods on manufacturing graphene, a large-area high-quality wrinkle-free graphene has yet to emerge. The practical difficulty to use graphene in devices is that the available methods for growing graphene contain high density of wrinkles11. Systematically understand the mechanism of wrinkle formation can help controlling its morphology and further eliminating wrinkles.Graphene as a two-dimensional (2D) material has many unique physical and mechanical properties, including highest strength, elastic stiffness, in-plane electrical conductivity and thermal conductivity15. Despite their prevalence and potential impact on large-scale graphene properties, relatively little is known about their structural morphology and formation mechanism17. In this letter, we use AFM to characterize surface morphology of graphene wrinkles and find morphology of graphene wrinkles measured by AFM is not real. The widths of wrinkle are much wider than theory and simulation results that cannot be understood. By using MD simulations and theoretical methods, we quantitatively studied the unexpected mechanism of wrinkles.Due to its low cost and efficiency, CVD has been widely adopted to manufacture graphene. A particular issue for graphene obtained by CVD is the presence of high density of wrinkles. These are formed by differential thermal expansions, as the metal contracts more than the graphene during cooling process, leaving an excess area of graphene18 which were grew on copper foil substrate at temperatures up to 1000 °C. Generally copper foil has a positive thermal expansion coefficient of 16.5 × 10−6/K, however, graphene has an negative in-plane thermal expansion coefficient of −8 × 10−6/K19. This contrast leads to a compression strain about 2.45% between graphene films and copper substrate after reduced to room temperature. The binding between graphene and copper is weak and graphene can slip on copper surface21, as a consequence the strain distribution is no longer uniform, typically, wrinkles can be easily found in large strain areas. In order to obtain more quantitative morphological information about wrinkles, AFM in tapping mode was adopted to investigate profiles of wrinkles. We first used conventional AFM tips with the typical diameter of ~10 nm in tapping mode to measure heights and widths of graphene wrinkle. We measured 10 graphene wrinkles, the typical measured profiles can be found in Fig. 22. To avoid the effect and obtain more accurate profiles of graphene wrinkles, high resolution super sharp tips (Hi’Res-C14/Cr-AU from Micromasch) with tip spike radius of ~1 nm and spike height 100–200 nm are used in the paper. Figure W ≤ 40 nm, heights of graphene wrinkles are 3.4 nm ≤ h ≤ 11 nm. The profiles of wrinkles in the article are consistent with the previous results16 but the unexpected morphologies and mechanisms are not clear.Single layer graphene samples were obtained by CVD methods23 between graphene foil and copper substrate can be used to verify the accuracy of the measured morphology. We do this in the framework of the elastic theory, generalized to account for bending energy (Eb) and adhesion energy (Ea). In this model, the total energy consists of two parts: the bending energy stored in the graphene and the adhesion energy that represents the atomic interactions (binding) between graphene and copper substrate. The only unknown inputs to the model are the height and width of wrinkles.The binding energy (Γ)Eb can be simply written as D = 1.2 eV = 0.192 nN·nm24 is the bending stiffness graphene, b represents length of wrinkle along its axis, h is height of wrinkles and W is half width of wrinkles. The adhesion energy (Ea) between graphene and copper can be calculated as Ea = bΓW, where Γ represents the binding energy between graphene and copper per unit area. In the equilibrium state Eb−Ea = 0. By using the experimental measurements of h and W, the obtained adhesion energy Γ ≤ 0.0034 J/m2. Recently, Γ has been determined by experiments and first principle calculations. The reported value 0.397 J/m2 ≤Γ ≤ 0.72 J/m221, which is at least 2 orders of magnitude large than the results we estimated. These observations, taken together, clearly demonstrate that the profiles of graphene wrinkles measured by AFM are not real, however, little is known about the factors determining the profiles of wrinkles so far. Morphologies may depend on the process of CVD growth and environment; however, previous studies haven’t already yielded insight into the mechanism.According to the measured results, profiles of wrinkles can be reasonably assumed to satisfy k = 100 eV/Å2 was applied to each end of graphene in order to fix the both ends. Finally the whole model were relaxed under a constant tempereture T = 300 K, as a result, many wrinkles with variety of profiles were formed on copper substrate.To better understand the unexpected morphology of graphene wrinkles, we performed several MD simulations to help understanding the machanism. The model itself is a stack of a rectangular copper substrate  using MD simulations. h (blue triangle) and W (black rectangle) are plotted in Fig. ɛ. From these results, we see that h is nearly linear dependent on strain over the entire strain range examined. On the other hand, W first increases with strain and then decreases with the further increase of strain. The maximun value of W is less than 2.7 nm. To understand the evolution of wrinkle, we ploted the typical cross-sectional profiles in Fig. h and W increase with strain; (II) The cross-section of wrinkles transited from arch shape to mushroom shape, at this time, h still increases with increases strain, however, W decreses with strain; (III) With further increasing strain, wrinkles of graphene collapsed due to the fluctuation of temperature or other influence, such as mechanical loads, electrostatic interaction and environmental disturbance. The simulation results are contradict with the experimental observes in the letter and previous reports16.Because of the merge of wrinkles and Fig. 25. At the stage of ripple structure, the bending energy is equal to the binding energy, resulting in a stable structure. As the strain increase, unstable mushroom shape structure are formed. For a given mushroom shape structure, the binding energy increases with length, while the bending energy is almost constant, mostly proportional to the number of sharp bends. When beyond the critical strain, unstable mushroom shape structure collapses to form mulilayer folds due to the fluctuation of temperature or other disturbances such as mechanical loads, electrostatic interaction and environmental disturbance in order to reduce the free energy of system26.The profiles of wrinkles can be easily understood at a qualitative level, as arising from the competition between elastic bending energy and van der Waals binding energyT = 1 K are plotted in supplementary Fig. Temperature effects on profiles of wrinkles are also investigated in the article. MD culculations carried at U) can be written as followsD represents the bending stiffness of single layer graphene, α is a Lagrangian multiplier. The first term represents the total free energy; the second term is the boundary conditions.To estimate the maximum width of wrinkles, we turn to theoretical analysis. The insert of Fig. θ = 0, cosθ = 1 and calculate the gradient of Eq.  = 0. Finally one can obtain the following relationshipTaking account of fixed boundary conditions, i.e. at the end of wrinkles mentclass2pt{minimθ = θ0 is the inflection point of wrinkles at which the curve changes from being concave (concave downward) to convex (concave upward), or vice versa, obviously W), the width of wrinkle (W − ΔW), the height of wrinkle (d) can be written as the followingUsing Eq. , the exc221 and D = 0.192 nN·nm24, theoretical results can be used to interpret simulation finds. Both theory results based on the Eqs .Substituting the experimental obtained values of Γ=0.72 J/m the Eqs –6) and  and 221The theoretical results can fit and predict the MD results very well, however, neither of them can explain experimental observations, so there must be some other mechanisms need to be seriously considered. It is crucial to understand the details of the growth process. We note that directly grow graphene on copper involving a surface catalyzed process which is generally attributed to the low solubility of carbon (<0.001 at.%) in copper and the surface diffusion of carbon atoms on copper substrate. First expose copper substrate to the mixture of methane and hydrogen gas. Depending upon the temperature, methane pressure, methane flow and hydrogen partial pressure, methane decomposes to form hydrogen and carbon atoms. Finally, aggregation of carbon atoms on Cu surface form graphene nucleation centers and form graphene films consequently.27, so there are a lot of molecules between graphene and copper substrate. In order to involve this effect, we built MD models with various number of interlayer molecules and calculated the final morphology. To be simplified, we only consider hydrogen as the interlayer molecules. Figure T = 300 K, the calculation model contains three parts, upper cyan graphene, interlayer hydrogen molecules and lower red copper substrate. Morphologies of graphene wrinkles with different numbers of interlayer molecules can be found in Fig. The key factor during the CVD process is that there may be some molecules (mainly hydrogen molecules and hydrocarbon molecules) dissolve in the copper substrate, after cooling to room temperature, precipitation of hydrogen molecules happens. However graphene is impermeable to molecules even hydrogen moleculesIn the present work, we report the unexpected morphology of graphene wrinkles on copper substrate. In order to systematically understand mechanisms of the unexpected phenomenon, we performed several MD simulations without interlayer molecules. The calculated widths of wrinkles are largely smaller than the experimental observed. In addition, a theoretical model based on Lagrangian multiplier method was proposed which fits and predicts the simulations results well. However, both the MD results and theory results are contradicted with experimental observed. Based on the above analysis, we performed inter-molecules MD calculations. The obtained results are consistent with the experimental observations. The interlayer molecules can supply additional pressure that enlarges both width and height of graphene wrinkle.Supplementary Information


We theoretically and experimentally demonstrate a significantly large modulation efficiency of a compact graphene modulator based on a silicon waveguide using the electro refractive effect of graphene. The modulation modes of electro-absorption and electro-refractive can be switched with different applied voltages. A high extinction ratio of 25 dB is achieved in the electro-absorption modulation mode with a driving voltage range of 0 V to 1 V. For electro-refractive modulation, the driving voltage ranges from 1 V to 3 V with a 185-pm spectrum shift. The modulation efficiency of 1.29 V · mm with a 40-μm interaction length is two orders of magnitude higher than that of the first reported graphene phase modulator. The realisation of phase and intensity modulation with graphene based on a silicon waveguide heralds its potential application in optical communication and optical interconnection systems. A silicon modulator converts an applied external electrical signal into variations in the fundamental characteristics of light  in an optical waveguide4. In general, there are two primary types of modulation, intensity modulation and phase modulation, which are suitable for short-reach interconnects and long-haul communication, respectively6. The purpose of the electro-optical modulator is to tune the light intensity and phase at the working wavelength. For a Mach-Zehnder optical modulator, the electro-optical effect of the modulation arms may result in the shifts of the transmission spectral, thus the change of the light intensity and phase would happen. The variation in light intensity make it possible for the generation of the amplitude-modulation signal. While the situation that the spectral shift with a π phase will be suitable for phase modulation7. For high-speed data transmission in integrated silicon photonic systems, the main approach to modulate optical signals is based on doped silicon p–n junctions8. However, this kind of modulator suffers from a large footprint, high energy consumption, and high insertion loss due to its relatively weak electro-refractivity, which requires millimetre device sizes to achieve a phase shift of π10. Modulation efficiency (Vπ * Lπ) is the key parameter for evaluating performance of an electro-optical modulator, which describes the driving voltages and the device size required for the operational wavelength ideally drops to zero due to interference. The conventional carrier depletion based silicon optical modulators have a typical modulation efficiency of (5–30) V ⋅ mm11. In order to lift up the modulation efficiency, the other types of electro-optic materials have been assembled into the silicon waveguide, such as the metal-insulator-silicon modulator based on surface plasmonic polaritons (SPPs) and the organic-silicon hybrid (SOH) modulator, with the modulation efficiency coming up to 0.5 V ⋅ mm13.Silicon photonics has become one of the leading technological solutions for integrated photonics with its merits of low cost and CMOS compatibility. In particular, silicon modulators have been extensively studied as essential components of optoelectronic circuits14. Graphene-based devices hold great potential for enhancing the modulation efficiency with their advantages of compact footprint, low operation voltage, and ultrafast modulation speeds across broadband wavelengths. These properties of graphene have been exploited in electronic and photonic devices such as the electro-absorptive optical graphene modulator based on doped silicon waveguides26. An optical modulator with a graphene monolayer on a single silicon waveguide was first demonstrated in 201119, and subsequently, a graphen,e modulator based on a micro-ring silicon waveguide was also exhibited, thereby demonstrating the potential of graphene integration with silicon waveguides25. Moreover, graphene modulator employing hybrid plasmonic effect was proposed for higher efficiency and more compact size26. However, the abovementioned graphene modulators are only based on the electro-absorption effect of graphene; these modulators may suffer a severe degradation in the signal-to-noise ratio when applied in long-haul communications. In order to meet the needs of phase-shift keying, Xu et al.23 have theoretically proposed a Mach–Zehnder (MZ) graphene modulator based on the doped silicon waveguide structure via analysing the electro-refractive effect of a graphene phase shifter, which suggests its potential in long-haul high-speed optical communication systems. In order to improve the modulation efficiency, few-layer graphene and novel waveguide structures in graphene based Mach-Zenhder phase modulator have also been discussed28. Furthermore, some other applications based on electro-refractive effect such as tunable polarizer has been demonstrated29. Recently, Mohsin et al.9 experimentally demonstrated electrorefractive graphene phase modulation by utilising a structure comprising double graphene layers. However, the device suffers from a large driving voltage range (−40–40) V and a relatively low modulation efficiency (300 V ⋅ mm).Graphene, a typical 2D material with a single layer of carbon atoms, is emerging as a promising material for photonic applications owing to its unique optoelectronic propert ies9.In this study, we propose a graphene-based silicon MZ modulator which is switchable between the electro-absorption and electro-refractive modes of operation. Both simulations and experimental results show that the modulator affords the advantages of a low driving voltage, compact size, and high modulation efficiency. When the working range is (0–1) V, an extinction ration of 25 dB can be realised for electro-absorption modulation. For electro-refractive modulation, a maximum wavelength shift of 185 pm can be achieved within a driving voltage of (1–3) V. Further, the modulation efficiency is 1.29 V ⋅ mm with a 40-μm interaction length, which efficiency is two orders of magnitude higher than that of the first reported graphene phase modulatorμ) of graphene can be tuned, as described by Eq. vF = 3 × 106 m ⋅ s−1 denotes the Fermi velocity, Vdirac = 0.8 V the voltage offset caused by natural doping, Vg the driving voltage, and η = 5.531 × 1016 m−2 ⋅ V−1 as per the GOS capacitor model.Figure 9.ω, μc, τ and T represent the radian frequency, chemical potential, carrier relaxation time, and temperature. ξ is the energy, kB is the Boltzmann constant. Accordingly, the relative permittivity of graphene changes with variation in the optical conductivity. Consequently, the effective refractive index (neff) of the waveguide also changes, thus allowing phase shift realisation25. Figure The change in the chemical potential of the graphene layer results in variation in the optical conductivity of graphene, which can be described via Kubo formalism as below, owing to the contributions of the intraband and interband partsneff) and the absorption of the GOS modulator for different chemical potentials. The fundamental transverse electric (TE) mode is solved around 2.5. As the chemical potential rises, Re(neff) and the absorption coefficient exhibit three different sets of characteristics, which are classified in three stages. The range of (0–0.28) eV corresponds to the absorption region, wherein the absorption of GOS remains high and both the effective and absorption index change by very little. The step change region, (0.28–0.64) eV, is suitable for amplitude modulation, since there is a significant ‘stepping up’ of absorption index around 0.41 eV. In this region, the effective index of the TE fundamental mode first increases and subsequently decreases, wherein a peak value of neff can be observed around the 0.41 eV chemical potential point. Phase modulation schemes are applicable in the linear region, which lies in the range of (0.64–1) eV, as the absorption is low and the effective index exhibits a linear change.We use COMSOL Multiphysics to analyse the mode distribution and photoelectric interaction in one arm of the MZ structure. Figure 2O3 thin film can be recognized by the color depth of the different materials. The size of silicon waveguide is 498 nm × 218 nm, and the thickness of thin Al2O3 is 10 nm. It is the same with the size of our design.The proposed device is fabricated on a silicon-on-insulator (SOI) platform with ridge waveguides  on top of 2-μm buried oxide (BOX) and an interaction region with a length of 40 μm. Details of the fabrication process can be found in the Methods section. The optical images of the device are shown in Fig. By applying different voltages to the GOS structure, the modulation mode can be switched to achieve either electro-absorption or electro-refractive. Here, the modulation-mode switch is mainly analysed by applying different voltages to a single arm. The simulation results of electro-absorption modulation and electro-refractive modulation are shown in Fig. When the chemical potential is in the range of (0–0.4) eV, corresponding to the absorption region and a part of the step region in Fig. Vpp keeps zero, Vbias equals to Vdirac (about 0.8 V) and Vpp′ is changing from 0 V to 3 V. Figure Vpp′. The static extinction ratio is 36 dB at 0 V, and it decreases with the increase in the applied voltage, which is attributed to the absorption of graphene. Such characteristics extend over a broad range of spectra and are not just limited to the range of (1545–1560) nm displayed in the figure. Figure neff should increase till a chemical potential of 0.41 eV and begin to decrease subsequently, which corresponds to the blue and red shifts of the spectra, respectively.Experiments have been designed to observe the modulation-mode switch of the device. Driving signal is applied to a single arm, which means nge of 155–1560 nmλ) and absorption variation (Δl) as functions of the applied voltage  V, which means that intensity modulation is the preferred mode of operation. In contrast, the slope coefficient of Δλ increases and dominates the region of (1–3) V, thereby indicating that phase modulation is more effective within this voltage range.Figure λ), we can obtain the refractive index change (Δn) and phase shift change (φ) using Eqs λ, L and d represent the wavelength shift, graphene length (40 μm), and free spectral range (6 nm), respectively. With application of the above equations, the observed wavelength shift of 185 pm in the voltage range of (1–3) V corresponds to a refractive index change of 0.0012 and phase shift change of 0.062π.By measuring the shift of wavelength  V ⋅ mm11.For on-chip phase modulators, the product of length L and drive voltage neff) first increases and subsequently decreases as the chemical potential rises from 0 eV to 1 eV, with an inflection point at the chemical potential of 0.41 eV, corresponding to the two-stage wavelength shift and mode switch around 1 V observed in the experiments. Similarly, the absorption is relatively larger in the region of (0–0.41) eV but smaller in the region of (0.41–1) eV, corresponding to the different absorption changes over the voltage range of (0–1) V and (1–3) V in the experiments, which indicates that the chemical potential of 0.41 eV corresponds to the applied voltage of 1 V.Importantly, while our results validate the feasibility of using graphene, they also show exhibit good consistency with the theoretical results. Parameter Re at 300 °C using H2O and trimethylaluminium (TMA) as precursors. The starting material for fabrication is the 8-inch (100) n-type SOI wafer. The SOI wafer was patterned by photolithography with an I-line and electron beam lithography (EBL) mixed. Patterns were then formatted using reactive ion etching (RIE). After the metal crossed shape marks (Ti/Au = 5/60 nm) were deposited for alignment of the following EBL processes. The graphene was grown on Pt film by CVD process and transferred onto the SOI platform by a bubbling method. Then, an EBL was carried out to form the graphene pattern, followed by a reactive ion etching (RIE) process to remove the unwanted graphene. Finally, another EBL was utilized to pattern the electrode pads, followed by an electron beam evaporation (EBE) process (Ti/Pd/Au = 0.5/30/50 nm) and a standard lift-off process.The graphene MZ phase modulator based on silicon waveguide device is realized on Si-on-insulator (SOI) platform with ridge waveguides  on top of 2 μm buried oxide (BOX). TE-polarized light was coupled in using grating couplers optimized for (1530–1570) nm. The relative difference between the lengths of two MZ arms is 91 μm. Subsequently, AlA continuous-wave (CW) laser was employed to generate the optical signal. The polarization was set to TE by a deterministic polarization controller (DPC). The first EDFA after DPC was employed to ensure that enough power was input into the modulator. Different voltages were applied to the electrode of one arm. There was a second EDFA employed to amplify the modulated signal. An optical spectrum analyzer was employed to recieve the output signal with the center wavelength sweeping from 1545 nm to 1560 nm.d = 0.7 nm) layer with anisotropic properties. The relative permittivity of graphene is described by a diagonal tensor. The in-plane component is εxx = εzz = 2.5 − (jσ/ε0ωd), while the surface-normal component εyy is set to 2.5. The offset of 2.5 on the relative permittivity is adopted from the relative permittivity of graphite. As long as the thickness of graphene layer d is sufficiently small, such as 1 nm or 0.3 nm, the simulation produces almost similar results.The proposed structures are simulated with 2D electromagnetic wave frequency-domain method provided by COMSOL Multiphysics. In this model, the graphene layer is represented as a thin (