Since the discovery of the two-dimensional (2D) carbon material, graphene, just over a decade ago, the development of graphene-based field effect transistors (G-FETs) has become a widely researched area, particularly for use in point-of-care biomedical applications. G-FETs are particularly attractive as next generation bioelectronics due to their mass-scalability and low cost of the technology’s manufacture. Furthermore, G-FETs offer the potential to complete label-free, rapid, and highly sensitive analysis coupled with a high sample throughput. These properties, coupled with the potential for integration into portable instrumentation, contribute to G-FETs’ suitability for point-of-care diagnostics. This review focuses on elucidating the recent developments in the field of G-FET sensors that act on a bioaffinity basis, whereby a binding event between a bioreceptor and the target analyte is transduced into an electrical signal at the G-FET surface. Recognizing and quantifying these target analytes accurately and reliably is essential in diagnosing many diseases, therefore it is vital to design the G-FET with care. Taking into account some limitations of the sensor platform, such as Debye–Hükel screening and device surface area, is fundamental in developing improved bioelectronics for applications in the clinical setting. This review highlights some efforts undertaken in facing these limitations in order to bring G-FET development for biomedical applications forward. The unique properties of graphene, including excellent conductivity, rapid electron transport, large surface area, and biocompatibility [The discovery of Graphene in 2004 by Novoselov and Geim  brought tibility ,2, make tibility . The devtibility . Biosenstibility . For exaRecent advances in the microfabrication techniques have led to the development of next-generation bioelectronic devices, including silicon nanowires ,8,9,10, G-FET biosensors are particularly attractive in point-of-care diagnosis due to their miniaturization, potential for large-scale manufacture at low-cost, rapid and inexpensive assays, and reduced need for skilled personnel. Moreover, G-FET biosensors offer the benefits of high sensitivity, lower detection limits, low cost, and high throughput detection compared to the existing enzyme-linked immunosorbent assay (ELISA), Polymerase Chain Reaction (PCR), and fluorescence methods, which are time consuming and require expensive and complex optical imaging devices and sophisticated image recognition software . It is fThis review is organized to emphasize the recent developments in affinity-based G-FET biosensors. We will briefly discuss the properties of graphene functionalization techniques in the context of bioelectronics in 2sp-hybrised carbon [2/g), a trait which is particularly advantageous in biosensing applications [7 cm2·V−1·s−1 in graphene that has been decoupled from bulk graphite, to be as high as 105 cm2·V−1·s−1 in suspended graphene devices [3 cm2·V−1·s−1 for CVD graphene on a SiO2 substrate. Moreover, graphene material can be manufactured in large quantities and relatively cheaply, therefore making it a suitable substrate for large-scale electronic device manufacturing [Graphene, or single atomic thick carbon, is the first purely two-dimensional (2D) material to be obtained . Graphend carbon . The 2D ications . Graphenications . Experim devices , and aboacturing .K and K’ points in the Brillouin zone. At the point where they meet, depicted by the Dirac voltage (VD) in Vg–IDS measurements, the Fermi level passes across. This Fermi level can be tuned and adapted because of doping by external influences, such as electron deficient (p-doping) or electron rich (n-doping) molecules [D to a more positive voltage (p-doping) or to a more negative voltage (n-doping). The VD can therefore be monitored and utilized as a means of sensing biological molecules. The electronic properties, such as the VD, carrier mobility, and resistance, can be influenced by many external sources, these include: applying an electrical field, charged moieties near the graphene’s surface, or by chemically modifying the surface, such as chemical binding to the graphene both covalently and non-covalently [Graphene consists of two energy bands, the valence band (VB) and the conductance band (CB), which hold holes and electrons, respectively . The arrolecules , therefovalently .2/Si or epitaxial graphene) is plasma etched away to form a channel [Graphene FETs are generally fabricated using micro fabrication techniques, such as photolithography coupled with metal evaporation or physical vapor deposition (PVD), to pattern and develop the device contacts. The graphene is either then transferred from a copper substrate used for its growth (CVD graphene) or from exfoliated graphene on to a patterned device . Alterna channel . Many G-The channel is then modified to detect target biomarkers by immobilizing bioreceptors onto the graphene channel. This can be done directly (adsorption) or through a linker molecule. The immobilization of a highly specific bioreceptor  to the graphene surface induces chemical specificity towards the target biomarker. Such receptors may include amino acids, enzymes, antibodies, aptamers, or indeed any selective and specific molecule . However2sp carbon atoms makes the graphene surface a potential candidate for covalent bonding [−1 using the diazonium functionalization chemistry [−1 using an epitaxial G-FET functionalized using the APTES method [2sp nature of the carbon atoms. As a result, the 2sp hybridization will be converted to 3sp hybridization [The functionalization of graphene with a linker molecule can be performed through covalent binding to the carbon atoms of the hexagonal matrix or by non-covalent binding to the graphene by electrostatic and/or weak Van der Waals forces . A wide  bonding . Covalen bonding  and hydr bonding  by plasm bonding , such as bonding . Other c bonding  and sila bonding . Tehranihemistry . TeixeirS method . Althougdization , which ddization .2sp nature of the carbon atoms is not affected. Therefore, the electronic and structural properties are not severely disrupted [Non-covalent functionalization is dominated by the physisorption of molecules to the graphene through weak Van de Waals forces . More spisrupted , making isrupted . Chen etisrupted . Furtherisrupted ,38,39,40isrupted , platinuisrupted , palladiisrupted , and zinisrupted . Metal nisrupted . Cai et isrupted . Nucleic acids such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and microRNA (miRNA) play a major role in human physiology, and therefore they also play a major role in many diseases. As a result, rapid and highly sensitive detection methods of nucleic acid abnormalities or expression are considered extremely important for disease diagnosis . G-FETs DNA, a double stranded polynucleotide, contains the entire genetic code of an individual, therefore assessing an individual’s genetic makeup can not only aid in the diagnosis of many diseases, but also contains information regarding an individual’s predisposition to genetic diseases and cancers. The DNA nucleotide is made up of a phosphate group, which makes the backbone of the DNA polynucleotide, a sugar (2-deoxyribose), and a nucleobase . These nucleotides arrange in specific sequences through phosphodiester bonding between nucleotides to make up the genome, which stores and transmits genetic information. A complementary strand of DNA then binds via the hydrogen bonding of the nucleobases (A with T and G with C) to make it a double-stranded helix . Since D2 substrate with 45 nm thick Cr/Au contacts by an electrolysis bubbling method. Using a PBASE linker, the 22-mer DNA probe was attached to the graphene surface. It was reported that the Dirac peak of the graphene shifted increasingly at each stage of functionalization , otherwise known as a single nucleotide mutation in the DNA sequence . These mAn important factor in designing a molecular biology test is sensitivity and the linear dynamic range. Both can be influenced by many factors, including but not limited to: graphene quality, a probe’s affinity for the target, the efficiency of hybridization and the surface coverage of the capture probe, and the surface-to-volume ratio. Although graphene inherently has an extremely high surface-to-volume ratio, it can still be a limiting factor when improving the sensitivity of the G-FET. However, it is not impossible to enhance the surface-to-volume ratio further, and, as a result, the sensitivity . Dong et2/Si substrate with Cr/Au/Cr contacts, and applied a polydimethylsiloxane (PDMS) microfluidic to avoid contact interference in the signal. Using the well documented streptavidin-biotin binding mechanism, the 41-mer DNA probe was immobilized upon the graphene surface. A biotinylated bovine serum albumin (BSA) was absorbed onto the channel, and streptavidin was then bound to that biotinylated BSA. The DNA probe  was then introduced, and was able to immobilize upon the channel via binding to one of the three remaining binding sites on the streptavidin. On exposing the eight G-FETs to 100 fM of the target miRNA, a noticeable negative shift was observed due to the electron doping effect of DNA hybridization on the graphene channel. Xu et al. also confirmed the selectivity of their devices by applying a control nucleotide to the sensor. The response seen for the control nucleotide was negligible when compared to the response exhibited by the hybridization event, which occurred between the probe and the target miRNA  probe. PNA is essentially the same as DNA, however due to the exchange of the deoxy-ribose and phosphate backbone for a peptide backbone it is essentially a neutral form of DNA. However, PNA is still able to exhibit an effect on the graphene’s doping due to the electron-rich nucleobase. Therefore, it is still possible to note a shift in the VImmunoassays are biomolecular recognition tests commonly used to determine the presence of biomarkers in a solution and potentially quantify them. More specifically, immunoassays are analytical techniques which rely on biorecognition by antibody-antigen interactions. Therefore, the techniques are based on the specificity and affinity of the antibody for the respective antigen . ImmunosLei and co-workers reported the successful detection of a protein biomarker in whole blood, which is specific to heart failure, using a platinum nanoparticle (PtNP) decorated rGO-FET immunosensor technology. The binding of brain natriuretic peptide (BNP) to anti-BNP was able to be detected through liquid gated measurements at 100 fM. Adding to this, the BNP was able to be distinguished from whole blood proteins, namely, human serum albumin and D-Dimer. Furthermore, BNP was successfully detected in a whole blood sample treated with a microfilter, reported in In 2017, Zhou et al. demonstrated the development of a G-FET for the real-time monitoring of carcinoembryonic antigen (CEA) detection, a biomarker for cancer. Zhou and co-workers reported a detection limit of 100 pg/mL (0.5 pM), far exceeding that of the clinical diagnostics cut-off value. Anti-CEA was immobilized to the G-FET through PBASE, and subsequently the binding of CEA was detected by chronoamperometry. An increase in the drain current was observed, correlating with increasing CEA concentration, as depicted in D), is highly dependent on buffer concentration [D are generally unable to be detected, as the charges within the graphene channel are unaffected [D decreases with increasing buffer concentration [D, and making it difficult to use antibodies as the capture molecule [Even though many immuno-based sensors have been reported in the literature, it is still challenging to reach ultra-high sensitivities because of Debye–Hükel screening . Debye–Hntration . Therefoaffected . As depintration . The Debmolecule .This issue has been addressed by many by only utilizing the antigen binding fragment (Fab) of the antibody. This decreases the distance of the antigen antibody interaction from the surface from approximately 10–15 nm for the whole antibody to approximately 3–5 nm for the Fab, allowing for the use of higher ionic strength buffers ,59. ManyKim et al. reported research addressing this issue. The research directly compared the performance of an aptamer-based G-FET and an antibody-based G-FET for protective antigen (PA), a target analyte for detecting anthrax. A single-stranded DNA aptamer (PA65 5–12) and anti-PA were used. A comparison of the range of detection, sensitivity, and limit of detection proved the aptamer-based sensor to have an overall better performance to the antibody based sensor, as depicted in For over a decade, considerable scientific effort has been directed towards the development of G-FETs for biosensing applications. This review highlights the recent developments in G-FET biosensors, with an emphasis on nucleic acid-based sensors. Label-free G-FETs have shown sensitivities as low as attomolar, far lower than those usually exhibited by other semiconductor technologies or current bioanalytical methods, attesting to G-FET biosensors as a potential platform towards clinical applications. There are, however, challenges faced in the development of G-FET biosensors. One of these limitations is device sensitivity due to the Debye–Hükel phenomenon and limited surface area. These issues were highlighted in The Debye–Hükel phenomenon becomes a hindrance in developing highly sensitive G-FET biosensors, as high ionic strength buffers are needed for the analyte solutions. This decreases the Debye screening length, and as a result decreases the sensitivity of the G-FET to target analytes outside of this length. Therefore, although the field of G-FET technologies is rapidly improving, the development of immunoFETs is hindered by Debye-screening. However, significant R&D efforts have focused on bypassing this issue through the development of nucleic acid-based sensors, aptasensors, and antigen binding fragment (Fab) modified G-FETs. The use of aptamers and Fabs as biorecognition molecules decreases the distance of the interaction from 10–15 nm to 3–5 nm, well within the debye-screening length of 7.4 nm that is seen for 0.01× PBS solution. The development of aptamers and Fabs have led to a biorecognition technology which can replace antibodies and will possibly drive forward the development of immunoFET technologies.The second issue is the surface area of the G-FET sensor. Although graphene has an inherently high surface area, it was reported that this feature could be further improved, and as a result the sensitivity could be increased. This was possible through decorating the G-FET surface with metal nanoparticles, increasing the binding sites for the biorecognition element, and therefore the target analyte.It is clear that graphene has many superior qualities when compared to other semi-conductor technologies. However, the majority of these measured characteristics and aforementioned G-FET sensors have only been achieved using the highest of quality samples within a laboratory setting. To date, most of the work has focused on R&D efforts, as although rapidly improving, these exceptional properties still remain difficult to obtain in a mass-scale manufacturing process . Deokar Furthermore, to develop efficient G-FET biosensors with high accuracy, precision, reproducibility, and lower detection limits, it is vital to improve the biomolecular immobilization strategies. Therefore, more functionalization chemistries need to be identified. The exploration of various bioreceptors, such as aptamers and antibody fragments, would certainly increase their sensitivity. Moreover, the nano-bio interfaces in G-FET sensors should be investigated in more detail. The real-time detection and stability of such sensors also needs to be analyzed in detail to enable the commercialization of G-FET biosensors that exhibit long-term stability and superior performance for clinical practice.


These graphene temperature sensors act as resistance temperature detectors, showing a quadratic dependence of resistance on the temperature in a range between 283 K and 303 K. The observed resistance change of the graphene temperature sensors are explained by the temperature dependent electron mobility relationship (~T−4) and electron-phonon scattering. By analyzing the transient response of the SLG temperature sensors on different substrates, it is found that the graphene sensor on the SiN membrane shows the highest sensitivity due to low thermal mass, while the sensor on SiO2/Si reveals the lowest one. Also, the graphene on the SiN membrane reveals not only the fastest response, but also better mechanical stability compared to the suspended graphene sensor. Therefore, the presented results show that the temperature sensors based on SLG with an extremely low thermal mass can be used in various applications requiring high sensitivity and fast operation.Micro-fabricated single-layer graphenes (SLGs) on a silicon dioxide (SiO The observed superior physical properties of graphene, such as high electron mobility3, mechanical strength5, optical properties7, and thermal conductivity9, have attracted much attention from the research community for a variety of applications12. Although various physical properties of single-layer graphene (SLG) have been measured and predicted14, its thermal properties, such as thermal conductivity, have been continuously investigated to date15. The higher thermal conductivity of graphene in comparison with metals and carbon nanotubes (CNT)16 has led to active research opportunities in thermal management and energy storage applications17. At nanoscale, the performance of electronic devices suffers from elevated temperatures as a result of self-heating, so graphene’s outstanding thermal properties are considered to be suitable for both instrumentation and integrated microelectronic applications18. Recently developed techniques for fabricating complex graphene structures in micro/nano scale21 make graphene a great candidate for temperature sensor applications due to its excellent electrical properties, outstanding mechanical strength, and high thermal conductivity.Graphene is a monolayer of carbon in a honeycomb lattice. Since being isolated from graphite by the micromechanical cleavage method in 2004, the physical properties of graphene have been studied extensively22 and biomedical sensors24. In resistance-based temperature sensors, the initial resistance  and the temperature coefficient of resistance (TCR) are essential parameters for temperature measurement. Commercially available RTDs have a resistance range of 100 Ω to 1000 Ω at 0 °C. For most metals used in RTD applications, the TCR is about 10−3 C−1. A higher TCR value means a higher sensitivity. Thus, lowering the TCR or increasing the thermal mass of a sensor helps to reduce the noise, but lowers the sensitivity.To use graphene as a temperature sensor, the relationship between electrical resistance and temperature needs to be characterized to determine viable applications. A linear relationship between temperature and electrical conductivity can lead to use as a resistive temperature detector (RTD) like metals, while a non-linear relationship can lead it to be used like a thermistor, similar to ceramics or semiconductors. Increasing demands for faster operation speed, improved temperature measurement resolution, and miniaturization capabilities have triggered a search for new materials in temperature sensing applications, such as bolometers18. However, complicated carrier scattering by large densities of defects and residual oxygen contamination in GO and r-GO sheets limits their resistance based applications27. In this paper, we present micro-patterned SLGs placed on silicon dioxide (SiO2)/Si, a silicon nitride (SiN) membrane, and a Si wafer with etched rectangular pits for their use as temperature sensors. After describing the details of the fabrication processes, the device characteristics are investigated by using the 4-wire measurement technique to observe the relationship between electrical resistance and temperature on the SLG temperature sensors on the various substrates. Also, the effects of carrier scattering on the mobility of graphene on different substrates28 are taken into account to explain the observed results.Although SLG has good electrical and thermal properties, no significant temperature sensing application has been studied. Meanwhile, reduced Graphene Oxide (r-GO) and hybrid graphene-GO membranes have been used as temperature sensorset al.29. Graphene layers grown on Cu foils by the CVD method were transferred to a Si substrate covered with a 250 nm thick thermally grown SiO2 layer . Then, the synthesized graphene layers were characterized by Raman spectroscopy31. The measured Raman spectrum clearly shows the G (~1598 cm−1) and 2D (~2712 cm−1) bands with the rarely observed D band near 1350 cm−1, which verifies that the synthesized graphene is a high quality layer. Also, mono-layer graphene was identified by the peak intensity ratio of the 2D band to the G band greater than one, and the full width at half maximum of 2D peak less than 40 cm−1 34.We adapted the process of chemical vapor deposition (CVD) growth of graphene and the transfer method on a substrate from Gunes 2/Si, a SiN membrane, and a Si wafer with etched rectangular pits. After being transferred, the graphene was micro-patterned by a photo-lithography process as shown in Fig. 2 film was used as a substrate. The CVD graphene layer was transferred to the substrate. Then, a thin layer of positive photoresist (PR) was spun, UV exposed, and developed. Then, the exposed graphene was removed by oxygen plasma at 300 W for 10 seconds and the resulting pattern is shown in Fig. The graphene temperature sensors were fabricated on three different surfaces to investigate the scattering effects due to the graphene/surface boundaries on the resistance change as a function of temperature. The synthesized graphene layers were transferred to SiO38. Patterning the graphene device was similar to the graphene on the SiO2/Si. The graphene on the SiN membrane device was constructed with the fabrication process flow as shown in Fig. 2/Si substrate, resulting in a faster measurement. However, the surface roughness is much higher than that of SiO2/Si substrate.To investigate the surface boundary related scattering effects between graphene and the substrate, a graphene device was integrated on a low stress SiN membrane. The SiN membrane was fabricated using an anisotropic wet chemical etching (KOH) as explained previously2/Si substrate was prepared. The pits were fabricated by patterning rectangular boxes (10 × 20 μm2 boxes) using photolithography on the SiO2/Si substrate. The patterned SiO2 was etched with a buffered oxide etchant followed by KOH silicon anisotropic etching. The SLG was transferred on the wafer with etched boxes, and the sensor patterns and electrical contacts were printed over the boxes. Then oxygen plasma at 300 W for 10 seconds was used to etch the exposed graphene as shown in Fig. Surface boundary scattering and defects play a key role in the electrical conductivity of graphene. To reduce the surface effects, a suspended SLG device was prepared. To fabricate the suspended graphene device, rectangular pits on a SiO39. A schematic of a graphene device as a temperature sensor is shown in Fig. μA was used throughout the experiments. The temperature increase due to self-heating at room temperature in this work was less than 0.01 °C. A temperature controlled chamber (water bath) was used to measure the temperature and resistance relationship of the graphene device as shown in Fig. To measure the resistance of the micro-fabricated SLGs on the three different substrates, we used the 4-wire measurement techniqueThe device resistance depends on the conduction electrons. By increasing the chamber temperature the number of electrons will be increased and their mobility will be decreased. A schematic view of the graphene device at low and high temperature is shown in Fig. 2/Si, the SiN membrane, and the suspended substrate are shown in Fig. 2) denoted by the red lines in Fig. 2 ≈ 1. While most metals show linear resistance change behavior as a result of temperature change, thermistors (most semiconductors) show non-linear  resistance changes. In our result, the graphene resistor shows the resistance change is proportional to T2. The electrical conductivity of SLG40 is proportional to the temperature dependent carrier density and mobility of its electrons11: σ = 1/ρ = qnμ, where q is charge, n is the carrier density, and μ is the mobility of the mobile charge. The defects in graphene and the boundaries between the graphene and substrate contribute to carrier scattering, which are directly related to carrier mobility42. These defects can be introduced during the fabrication process, and different boundary conditions can be created by the varying geometry/size and substrate of the device. The significant contribution of interfacial scattering in graphene to electrical properties, like phonon-boundary scattering and graphene contact scattering, have been reported43. For the single layer graphene, it is reported that n is proportional to T2 11. The mobility depends not only on temperature, but also on various scattering mechanisms, such as defects, phonons, surfaces, and edges44. On the scale of our devices , it is a challenge to experimentally identify which scattering mechanism dominates and how it affects electron mobility as a function of temperature. According to previous numerical studies, the electron mobility of SLG considering various scattering mechanisms in a temperature range between 200 K and 350 K was reported to be proportional to T−2 ~ T−4 40, and is limited by electron-phonon scattering in SLG45. The electron mobility in our device is deduced to be proportional to T−4 from the T2 dependent resistance in the range of 283 K to 303 K.The resistance change of the graphene devices in a temperature controlled chamber was measured. The water bath temperature was increased from 10 °C to 30 °C in 5 °C increments. The water bath temperature stayed at each temperature for 2 hours. The 2 hour dwell time at each temperature increment was used for the sensor inside the chamber to reach equilibrium with the water bath temperature. The measured results for the graphene devices on the SiO16 and a very low thermal mass46, the temperature of graphene reaches the bulk silicon temperature quickly. The bulk silicon is in thermal equilibrium with the acrylic device holder and the air inside the chamber  is valid, because the temperature equilibrium characteristics between the apparatus and graphene are the same for each temperature of the water bath. The temperature dependent resistance of graphene is measured from 10 °C to 30 °C because the apparatus starts to physically distort above 35 °C. It was an unexpected experimental fact. The physical distortion of the apparatus applies a mechanical stress on the graphene, causing resistance fluctuations. This response to the mechanical stress shows that graphene is a piezoresistor. The piezoresistive properties of the graphene causes a proportional resistance change due to the applied deformation and strain49.The resistance of graphene continues to increase at a fixed water bath temperature. It takes more than 2 hours for the resistance of the graphene to reach a steady state value in the water bath. This delay in reaching the steady state value may be due to the apparatus of the device holder. The device holder is made of bulky acrylic plates, which the entire device is mounted on. Since the thermal mass of the apparatus is high, it takes a long time  to reach a steady state value with the water bath temperature. The Si substrate is in thermal contact with the acrylic plate and quickly reaches the temperature of the acrylic plate. It takes more than 2 hours for the acrylic plate to reach the water bath temperature. Because graphene has a very high thermal conductivityber Fig. . Althoug2/Si, the SiN membrane, and the suspended architecture are estimated to be 1.25, 2.15, and 1.90, respectively. So, the graphene on the SiN shows the highest normalized resistance sensitivity, while the graphene on SiO2/Si is the lowest one.In addition, in Fig. 50, the temperature response of the graphene follows the response of the SiN membrane. The response of the graphene on the SiN membrane is slower than that of one without the PDMS due to the PDMS thermal mass. The metal sensor made of a 100 nm-thick nickel film on the SiN membrane shows the third fastest response. Compared to graphene, the metal layer has a higher thermal mass, causing a slower response than the graphene layer. The suspended graphene sensor shows the second slowest temperature response. The high thermal conductivity of graphene is expected to lead to a fast response to environmental temperature changes. However, the graphene sensor is suspended across the Si substrate with a suspended length of 20 μm equilibrates with the substrate, causing the slower response. This is because the substrate was mounted on an acrylic plate, which has a higher thermal mass. The slowest response is shown for the graphene sensor on the SiO2/Si substrate mounted on an acrylic plate due to having the highest thermal mass among the five configurations. The graphene temperature sensor on the SiN membrane has not only the fastest response, but also better mechanical stability compared to the suspended graphene sensor. Therefore, the optimal configuration of a graphene based temperature sensor would be the graphene sensor on a SiN membrane.Furthermore, the effect of the substrate on the device temperature transient response for five different configurations have been investigated as shown in Fig. 51 as shown in Fig. sccm, was continuously flown through a chamber (400 cm3), where the sensor is placed. Figure 52. Besides the doping effect, the resistance of the graphene sensor increases at the elevated temperatures as shown in Fig. The graphene temperature sensor can be affected by surrounding environments. For example, the humidity modulates the resistance of the graphene sensorMicro-patterned SLG devices were fabricated and characterized as temperature sensors, showing the characteristics of temperature response between those of metals and thermistors. The quadratic dependence of resistance on the temperature for the fabricated graphene sensors was analyzed using the temperature-dependent carrier density and electron mobility model. The graphene sensor placed on the SiN membrane reveals not only the fastest response and the highest sensitivity due to the low thermal mass, but also better mechanical stability compared to the suspended graphene sensor. As a result, the suggested SLG on a SiN membrane can be an efficient temperature sensor for use in various fields requiring highly sensitive and fast operation.μm-thick copper foil  was loaded in the CVD reactor and pumped to the base vacuum pressure (<10−4 Torr). The copper foil was vertically placed on a substrate holder in the central isothermal growth zone of the reactor during the growth process. The temperature of the chamber was ramped up to 1060 °C with a mixture of Ar (2000 sccm) and H2 (30 sccm) at the processing pressure of 470 Torr. The copper foil was typically annealed for 2 hours. The furnace temperature was then decreased to the process temperature of 1020 °C with pure 30 sccm H2 gas only at 570 mTorr. When the temperature reached 1020 °C, graphene layers started to grow on the copper foil when a methane/hydrogen gas mixture (CH4 = 40 sccm and H2 = 100 sccm) and 2000 sccm Ar as a carrier gas were introduced to the reaction chamber at 600 mTorr for 30 min. The reaction chamber was then cooled down to room temperature with an average rate of 14 °C/min under the same Ar/H2 gas flow rates without methane.The CVD reactor we used is a horizontal quartz tube, which is 2400 mm long and 152 mm in diameter. This quartz tube was placed in a 1500 mm long six-zone furnace. A 25 μm-thick PMMA  was spin-coated on the as-synthesized graphene on copper foil at 3000 rpm for 100 seconds. The PMMA was baked in an oven at 120 °C for 10 minutes. Because the CVD process grew graphene layers on both sides of the copper foil, graphene layers the other side (no PMMA) of the copper foil were removed by oxygen plasma (60 W power for 10 minutes). The copper foil was then removed by floating the sample on a copper etchant  for 40~60 min. To rinse the graphene after copper etching, the PMMA/graphene was removed from the etchant and placed in two subsequent DI water baths for 20 min each. After the DI water rinsing, the PMMA/graphene layer was transferred onto a SiO2 (300 nm)/Si (100) wafer. Then, the PMMA was removed by acetone in an ultrasonic bath for 20 min, leaving the SLG on the SiO2/Si wafer. The single layer graphene on the SiO2/Si wafer was then rinsed in a 30% HCl solution at 60 °C for 30 min to remove residual Fe+3 ions. As a result, the high-quality graphene layer with a low defect density was prepared on the SiO2/Si substrate on a large scale  membrane, and a silicon wafer with etched rectangular pits were patterned by a photo-lithography process. During the lithography process, the photoresist (PR) remaining on the graphene was removed by acetone after patterning the graphene. Since the surface and parts of the graphene were damaged during the removal of the PR, the PR on patterned graphene was not removed. Then, this remaining PR was used to support the suspended graphene over the pits  with a 100X lens  and a 532 nm laser (~1 mW) polarized by a GX-AN360 (Olympus) filter. Each spectrum was obtained by 10 acquisitions in 10 s of accumulation time. Three to six analyses were performed at various places on each sample.Graphene layers grown on Cu foil by the CVD method were transferred on the SiOElectrical contacts to external electrical measurement units were made using silver paint  and 40 AWG copper wire  on the graphene contact pads in a wire bonding fashion. It should be noted that typical silver epoxy  may dissolve or make a poor electrical contact with the graphene based on the observations during the experiments. Despite this occasional malfunction, the 4-wire measurement eliminated any lead resistance (graphene traces and conductive epoxy) from contributing to the temperature sensor resistance.


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.