Multi-junction solar cells made by assembling semiconductor materials with different bandgap energies have hold the record conversion efficiencies for many years and are currently approaching 50%. Theoretical efficiency limits make use of optimum designs with the right lattice constant-bandgap energy combination, which requires a 1.0–1.15 eV material lattice-matched to GaAs/Ge. Nevertheless, the lack of suitable semiconductor materials is hindering the achievement of the predicted efficiencies, since the only candidates were up to now complex quaternary and quinary alloys with inherent epitaxial growth problems that degrade carrier dynamics. Here we show how the use of strain-balanced GaAsSb/GaAsN superlattices might solve this problem. We demonstrate that the spatial separation of Sb and N atoms avoids the ubiquitous growth problems and improves crystal quality. Moreover, these new structures allow for additional control of the effective bandgap through the period thickness and provide a type-II band alignment with long carrier lifetimes. All this leads to a strong enhancement of the external quantum efficiency under photovoltaic conditions with respect to bulk layers of equivalent thickness. Our results show that GaAsSb/GaAsN superlattices with short periods are the ideal (pseudo)material to be integrated in new GaAs/Ge-based multi-junction solar cells that could approach the theoretical efficiency limit. Theoretical efficiency limits make use of optimum multi-junction designs with the ideal lattice constant-bandgap energy combination but, sometimes, lack of suitable, easy to control semiconductor materials hinders their implementation. For instance, in the standard (Al)InGaP/(In)GaAs/Ge solar cell structure, the addition of a lattice-matched sub-cell tuned to the 1.0–1.15 eV spectral range provides such an optimum multi-layer design3. Under standard AM1.5 G conditions, detailed-balance calculations predict 44.4% efficiency for a 3-junction AlInGaP(1.9 eV)/GaAs(1.4 eV)/1.0 eV solar cell and 47.7% for a 4-junction AlInGaP(1.9 eV)/GaAs(1.4 eV)/1.0 eV/Ge(0.66 eV) solar cell. Both designs would easily leave behind the 50% limit when operated under concentration4. After the two consecutive world efficiency records set by Solar Junction CA5, which were preceded by strong efforts in optimizing single-junction cells6, GaInNAs in combination with Sb has gained a great interest as such 1.0–1.15 eV material. The fabricated GaInP/GaAs/GaInAsNSb solar cells had an efficiency of 44.0% under concentration, still well below the theoretical predictions, and was limited by epitaxial growth problems which are intrinsic to quaternary and quinary materials. These problems seriously affect carrier dynamics and are likely the reason for the lack of success in achieving ultimate solar cell performance beyond the 50% barrier7. In this work, we show how the use of GaAsSb/GaAsN short period superlattices (SL) with type-II band alignment might solve these problems at once.In the solar cell community, there is a quest for surpassing the 50% efficiency psychological barrier, which implies that half of the light energy coming from the Sun would be transformed into electric power. The solar cell efficiency tables9. This is why strain-balancing was shown before long to be a critical issue in developing efficient solar cells involving nanostructures such as quantum wells11. Therefore, materials lattice-matched to GaAs/Ge and with a 1.0 eV or 1.15 eV bandgap are being extensively investigated. Among them, dilute nitride semiconductor alloys, such as GaInNAs or GaAsSbN, can fulfill both requirements and be used for this purpose12. In these highly mismatched alloys, the addition of small amounts of N leads to a dramatic reduction of the bandgap, which is explained in the framework of the band anti-crossing (BAC) model as the result of a strong interaction between the localized N states and the conduction band of the matrix13. However, GaAsSbN alloys show important potential advantages over GaInNAs, because the surfactant effect of Sb atoms facilitates the two-dimensional growth of the material14. It also has the unique property of allowing an independent tuning of both conduction and valence band energies by controlling the N and Sb contents, respectively15. Besides, GaAsSbN can remain lattice-matched to GaAs if the condition [Sb]≈2.8 × [N] is fulfilled16, since Sb compensates the tensile strain induced by N. The GaAsSbN alloy has already been applied to solar cell technology, both as a thick layer20 and as a capping layer over InAs quantum dots22. Nevertheless, the obtained solar cell performance is not satisfactory up to now. This is due to the fact that GaAsSbN faces important epitaxial growth problems such as alloy disorder, phase separation (because of its large miscibility gap), clustering, difficult composition control (3 group-V atoms competing for the same lattice position), or N-related point defects and localized electronic states 25. Therefore, even within the narrow optimum growth window, achieving a low background carrier density and a long carrier lifetime and diffusion length remains still challenging in this quaternary alloy26.Monolithic multi-junction engineering confronts an issue of paramount importance: the different sub-cells have to maintain a very low stress level during epitaxial growth, avoiding the introduction of misfit dislocations, which would degrade the device performance28 and effective bandgap tunability through period thickness. Moreover, independent conduction and valence band edge manipulation makes it possible to reproduce nominal bandgap energies of the quaternary alloy using only half the amount of Sb and N. An overall reduction of the N content should result in an overall reduction of N-related defects in the structure and, therefore, an improved crystal quality. Other SL structures based on dilute nitrides, such as GaAsN/InAsN, GaAsN/GaAsBi and GaAsBiN/GaAs have been already proposed as suitable for photovoltaic applications and studied theoretically31, while GaAsN/InGaAs SLs have already been realized32. However, the use of SLs might also bring a major drawback, which is carrier trapping and ultimately recombination in the SL. This would result in a lower effective mobility33, which degrades carrier transport and results in a severe reduction of the quantum efficiency.The only way to overcome these problems in the growth of the quaternary alloy is to resort to new growth approaches. In this work, we show that an effective way to obtain a (pseudo)material of extremely high crystal quality and fully stoichiometric is by splitting the quaternary into two ternaries and proceed by growing a SL structure; the spatial separation of N and Sb atoms dramatically reduces miscibility problems. The SL structures can be fabricated with type-I or type-II band alignment (electrons confined in GaAsN and holes in GaAsSb) offering additional advantages over the bulk counterparts, such as long carrier lifetimes Our results show that this is not the case in the type-II GaAsN/GaAsSb system when the thickness of the SL period is reduced to 6 nm. For such thin stacks, strong quantum tunneling comes into play producing devices with the same quantum efficiency at zero and reverse biasing, i.e. achieving a complete carrier collection under photovoltaic conditions.SL-Sb), GaAs/GaAsN (sample SL-N), GaAsSbN/GaAs (sample SL-I with expected type-I confinement) and GaAsSb/GaAsN (sample SL-II with expected type-II confinement). A fifth sample with a 200 nm-thick GaAsSbN bulk layer (sample bulk) was grown as a reference to complete the series. A scheme of the epitaxial structure and the expected band structure of samples SL-I and SL-II are shown in Fig. In the first series of samples, different SL structures containing 18 periods with a constant period thickness of 12 nm (6 nm + 6 nm) as active layer are compared. The total thickness of the SL is 200 nm and they consist of: GaAsSb/GaAs . Dark field 002 representative images of samples SL-Sb and SL-N allow estimating the Sb and N composition to be 3.25% and 1.20% in the respective layers, considering a completely pseudomorphic epitaxy as observed by TEM. These two values fulfill the lattice matching condition for GaAsSbN on GaAs, as it is evidenced by the symmetrical position of the main SL peaks with respect to the substrate peak. We also observe that the secondary peaks are considerably less intense in SL-Sb than in SL-N, meaning that the SL-Sb sample has worse periodicity, likely due to Sb segregation in this type of structures. Assuming that there is no Sb-N interaction during growth that could modify the composition, lattice matching is expected from the nominal growth parameters also in the rest of the samples. However, in the SL-I and bulk HR-XRD spectra, the main peak appears shifted towards the tensile region of the spectrum. This indicates that the composition is altered from that of the ternaries due to the concomitant presence of N and Sb in the growth front. This effect is particularly strong in the bulk sample.All samples from this set were investigated by high-resolution x-ray diffraction (HR-XRD). Figure SL-II where we find a perfectly lattice-matched spectrum implying that the expected contents were incorporated and the overall strain precisely compensated. Moreover, the narrower main peak in the SLs as compared to the bulk structure indicates a better strain and composition homogeneity, which means that clustering effects are significantly reduced in the SL structures. Remarkably, the secondary peaks are also narrower and more intense in SL-II as compared to SL-I reflecting the higher interface quality when Sb and N are incorporated separately, in agreement with what was observed by TEM.The main motivation in this work is to explore the alternate introduction of Sb and N atoms in the growth surface to avoid the interaction between both species. We expect that the composition in the pseudo-quaternary structure can consequently be accurately controlled. Figure SL-II emission peak energy with respect to the bandgap of GaAs  is 280 meV. This fits almost perfectly with the combined energy shifts observed for the ternary samples SL-Sb (27 meV) and SL-N (250 meV). This is a quite unique property of this system by which tuning of the valence and conduction bands, and thus the bandgap energy value, can be done setting independently the Sb and N concentrations. Such independent control is hard to reproduce in the bulk quaternary alloy. All samples were fabricated using the same nominal ternary concentrations and, yet, the sample bulk significantly redshifts from the nominal bandgap value. Finite differences calculations shown below suggest that quantum confinement size effect in the 12 nm period SLs is only ~39 meV, what would only partially explain the PL peak difference of 55 meV as compared to the bulk. The redshift of the PL peak energy and the tensile position of the HR-XRD central peak shown in Fig. SL-I sample), which was suppressed in the SL-II sample using alternate deposition of the ternary compounds.The higher control over composition achievable with the type-II SL as compared to the type-I SL or the bulk is an important feature for energy tuning of the bandgap in multi-junction solar cell applications. Figure SL-I and bulk samples have similar decay dynamics, clearly different from those of sample SL-II. A multi-exponential fitting analysis is necessary to describe the decay dynamics across the full-time range and can be found as Supplementary Table SL-II becomes three times slower (decay constant changes from ~15 to ~49 ns). The existence of this significantly longer radiative lifetimes at the PL peak energy for sample SL-II strongly supports the predominance of type-II band alignment and recombination. This is additionally supported by the calculated SL-I/SL-II ratio between the electron-hole wave function’s overlap , which is ~3. Slower carrier recombination shall lead to an enhanced carrier extraction and, therefore, an improved photocurrent. Remarkably, in this sample, not only the PL band is narrower but the integrated PL emission is the most intense despite the longer carrier lifetime  decay curves measured at the PL peak energy provide further details about the carrier confinement within each sample. As shown in Fig. see Fig. 35. This 36. The lowest energy critical point obtained thereof is associated with the optical transition between electron and hole ground states. As shown in Fig. In order to investigate the formation of minibands and the effective bandgap tunability through the SL period thickness, four additional samples were grown: 200 nm-thick type-II SLs with the same N and Sb contents as the previous set of samples, but different period thickness: 3 nm, 6 nm, 12 nm and 20 nm. HR-XRD measurements indicate that all the samples are lattice-matched to GaAs and that the period thicknesses agree with the nominal values: 3.1 nm, 6.4 nm, 12.6 nm and 19.1 nm, respectively. Tuning in relevant spectral regions shall be demonstrated at room temperature. Thus, the effective bandgap energies from these SLs have been obtained from photoreflectance (PR) measurements at room temperature, shown in Fig. SL-I12), two GaAsSb/GaAsN type-II SL structures with 12 nm (SL-II12) and 6 nm (SL-II6) period, a bulk GaAsSbN layer (bulk) and a GaAs reference sample (GaAs) for comparison. The Sb and N-containing samples were all grown under the same nominal fluxes. Comparing the EQE of devices based on low-dimensional structures and bulk layers with the same effective bandgap is not straightforward. On one hand, the total intrinsic region thickness should be the same to do the comparison under the same transport conditions for a given bias. On the other hand, the volume (thickness) of the absorbing material  should also be the same or else the absorptance or the total light absorption would not be directly comparable from one device to the other. Moreover, the different dimensionality of the structures will give rise to a different density of states and absorption coefficient α. Thus, to establish a fair comparison between the performance of devices of different quantity of absorbing material, we introduce an effective thickness. As the bulk sample contains twice as much Sb and N than the SLs, we can define the bulk materials as having double effective thickness with respect to the SLs, i.e. L′ = 2 L. The EQE curves for the bulk sample have been normalized as if it had the same effective thickness than the SL: L′/2. Such value of the EQE is calculated from the absorptance, expressed as (1 − e−αL), at half-thickness. The details of the normalization method can be found in the supplementary material. The EQE curves obtained at 0 V and −3 V are shown in Fig. 37. Therefore, we can define the carrier collection efficiency at 0 V as the ratio EQE(0 V)/EQE(−3 V)37. It can be observed that the bulk sample and the two SLs with 12 nm period provide significant conversion efficiencies in the technologically relevant 1.15 eV spectral region.Efficient carrier transport through the epitaxial structure is mandatory to assess the performance of these SL structures as solar sub-cells. We have investigated the external quantum efficiency (EQE) at room temperature of five p-i-n diodes with different 750 nm-thick active regions: one GaAsSbN/GaAs type-I SL structure with 12 nm period . This enhancement shall be attributed to the increase of the joint density of states, reported for dilute nitrides, arising from a larger electron effective mass and thus a better matching to the hole band dispersion42.Figure SL-II12 sample than in SL-I12 as shown in Fig. SL-II12 and SL-I12 devices also exemplifies the potential drawback of a non-optimized SL structure suffering from slow carrier extraction dynamics. In both samples, EQE increases with the reverse bias limiting severely its application in solar cells. In this case, the carrier extraction at 0 V is not efficient enough because the weak electronic coupling for a 12 nm period prevents carrier tunneling through the SL barriers in the presence of the built-in electric field. However, it can be easily restored by reducing the period from 12 to 6 nm as shown in Fig. SL-II6) shows a normalized EQE which not only is the largest of all samples, but is virtually the same at 0 V as at −3 V. This means improved carrier collection at 0 V and a large overlap of the SL minibands across the structure. A quantum treatment of the transport along the SL43 is out of the scope of this work but, as a first approximation, we have calculated the transmission coefficient based on analytic expressions using the transfer matrix approach44. In such framework, the electronic transmission through a finite array of barriers represents the ability of a confined electron to be transmitted through the periodic structure. Figure SL-II6 sample strongly suggest that vertical transport is more efficient than radiative and non-radiative recombination under photovoltaic conditions, though the situation at the operating voltage of the solar cell (positive voltage) could be different and still has to be analyzed.Regarding the 12 nm period SLs, both the normalized and raw EQE are larger in the Overall, Fig. Strain-balanced GaAsSb/GaAsN SLs grown on GaAs are shown to overcome the unavoidable growth problems related to the quaternary GaAsSbN alloy that affect both thick layers and GaAsSbN/GaAs SLs. The spatial separation of N and Sb atoms gives rise to a superior composition and effective bandgap control, as well as to an improved crystal quality and interface abruptness. Moreover, the new structures allow additional tuning of the effective bandgap through the period thickness due to quantum confinement. The type-II band alignment results in long radiative lifetimes that are beneficial for carrier extraction. Remarkably, despite the long carrier lifetimes, the new structures show a strongly enhanced luminescence compared to thicker quaternary bulk layers having twice as much active material. A significant EQE at 1.15 eV is demonstrated, as well as efficient carrier transport by tunneling though the SL minibands for period thicknesses of ∼6 nm. For these thin periods, a strong net enhancement of EQE over equivalent bulk counterparts is demonstrated under photovoltaic conditions. In this SL with the optimum design, however, the absorption edge is 50–100 meV over the target value due to the effect of quantum confinement, so the N and Sb contents should be slightly increased to compensate for that. All these characteristics make short period GaAsSb/GaAsN SLs the ideal (pseudo)material candidate to be monolithically series-connected in ultimately efficient GaAs/Ge-based multi-junction solar cells.+ substrates under As4 overpressure conditions. Each sample consists of a 250 nm-thick n-doped GaAs buffer layer, a 200 nm or 750 nm-thick undoped active layer grown at 470 °C at a growth rate of 1 ML/s, and a 50 nm-thick p-doped GaAs layer deposited on top. The device configuration is therefore a p-i-n junction. The nominal n and p-type doping concentration was 2·1018 cm−3. The Sb flux was supplied from a Knudsen effusion cell whereas the atomic N flux came from a radio-frequency plasma source using a 0.1 sccm flow of pure N2. The growth was in-situ monitored by reflective high energy electron diffraction (RHEED) which allowed the verification of a two-dimensional growth mode throughout the whole structure.The analyzed samples were all grown by solid source molecular beam epitaxy in a Riber 32 system using GaAs (001) n2 at 10 MHz. Multi-exponential deconvolution analysis was done taking into account the system response measured with a 980 nm ps laser. Time resolution after system response deconvolution is ~200 ps. The optical analysis was completed with PR measurements. PR was performed at room temperature using the 325 nm line of a 15 mW He-Cd laser as pump beam (chopped at 777 Hz), the monochromatic (1/8 m-spectrometer) probe beam from a 150 W QTH lamp, and a cooled InGaAs-photodetector.TEM was used to obtain dark field 002 images, which were acquired in a JEOL 2100 microscope operating at 200 keV. HR-XRD rocking-curve scans using the Cu-Kα1 line (1.54056 Å) were performed with an X’Pert Pro Pan’alytical commercial system. Low temperature (15 K) PL measurements were carried out using a He-Ne laser with a power of 3 mW. The emitted light was dispersed through a 1 m-spectrometer and detected using a liquid-nitrogen cooled Ge-detector and standard lock-in techniques. TR-PL experiments were performed at low temperature exciting the sample with 405 nm pulsed laser light. Decay curves were recorded by a time correlated single photon counting system based on a fast-infrared photomultiplier attached to a 0.3 m-focal length spectrometer. The average excitation power density was 0.6 W/cm13, with the specific values for the electron effective mass and BAC parameters described elsewhere45. Regarding the GaAsSb layers, their bandgap energy and band offsets were estimated using experimental results for GaAsSb pseudomorphically grown on GaAs46. The hole effective mass was obtained from a linear interpolation between the binaries.The calculation is based on finite differences methods. Single band effective mass approximation was used with input parameters for the Sb and N contents obtained from the HR-XRD spectra of the ternary samples, and the period thickness estimated from the TEM measurements of each sample. The bandgap energy and band offsets of GaAsN were obtained considering the BAC predictions in first order perturbation theory3PO4-H2O2-H2O (1:1:8) solution. The p-type contact, deposited on top of the mesa, was Au/Au-Zn/Au (100/800/2000 Å). A common n-type contact consisting on Au-Ge/Au (800/2000 Å) was evaporated on the substrate side. The contacts were exposed to an annealing process at 400 °C during 1 minute.The thickest samples (750 nm active layer) were processed in 200 μm-diameter mesa-etched devices using standard fabrication techniques. The mesa structures were defined by wet etching using a HPhotocurrent measurements were carried out using light from a QTH lamp which was dispersed through a 0.34 m monochromator and directed through the optical path to the sample. A K230 Keithley sourcemeter as well as a K617 Keithley electrometer were employed. To obtain the EQE, the photocurrent data was first converted into responsivity dividing by the power per unit area of the QTH lamp  multiplied by the diode top metal-free area. Finally, responsivity was converted to EQE multiplying by the photon energy divided by the electron charge.The parameters used in the calculation for the bandgap energies, effective masses and band offsets are those used in the electronic band structure calculations. Calculations were done separately for electrons and holes transmitted through 12 consecutive barriers at flat band condition.All data generated or analyzed during this study are included in this published article (and its Supplementary Information files).Supplementary Information. Strain-balanced type-II superlattices for efficient multi-junction solar cells


Our continuing quest to improve the performance of polymer composites under moist and saltwater environments has gained momentum in recent years with the reinforcement of inorganic nanoparticles into the polymer. The key to mitigate degradation of composites under such environments is to maintain the integrity of the fiber/matrix (F/M) interface. In this study, the F/M interface of carbon/vinyl ester composites has been modified by coating the carbon fiber with polyhedral oligomeric silsesquioxane (POSS). POSS is a nanostructured inorganic-organic hybrid particle with a cubic structure having silicon atoms at the core and linked to oxygen atoms. The advantage of using POSS is that the silicon atoms can be linked to a substituent that can be almost any chemical group known in organic chemistry. Cubic silica cores are ‘hard particles’ and are about 0.53 nm in diameter. The peripheral organic unit is a sphere of about 1–3 nm in diameter. Further, cubic structure of POSS remains intact during the polymerization process and therefore with appropriate functional groups, if installed on the fiber surface, would provide a stable and strong F/M interface. Two POSS systems with two different functional groups; namely, octaisobutyl and trisilanolphenyl have been investigated. A set of chemical and mechanical procedures has been developed to coat carbon fibers with POSS, and to fabricate layered composites with vinyl ester resin. Interlaminar shear and low velocity impact tests have indicated around 17–38% improvement in mechanical properties with respect to control samples made without the POSS coating. Saltwater and hygrothermal tests at various environmental conditions have revealed that coating with POSS reduces water absorption by 20–30% and retains the composite properties. Although carbon fiber reinforced polymer composites are widely used in various industries, their usage in marine applications is somewhat limited ,2,3. To et al. [Modification of the fiber surface has been considered as a method of improving the fiber/matrix bonding ,11,12. Set al.  have shoTo address this issue, we are investigating nanoscale inclusion at the carbon fiber surface. Nanoparticles, such as POSS, should be ideal for such coating of the fiber since the physical dimension of POSS is in nanometer range and is expected to enhance bonding at the interface. POSS is an inorganic-organic hybrid nano silica engineered to strengthen composites, as well as, promote hydrophobicity, which is ideal for marine applications. The advantage of using POSS is that silicon atoms can be linked to a substituent that can be almost any chemical group known in organic chemistry. POSS chemically bonded with thermoset polymers either enhances or reinforces the mechanical and thermal properties of the neat material system . Recent ® bag. Each Ziplock® bag was filled with 240 mL of acetone, then the air bubbles were removed prior to sealing the Ziplock® bag. The plies were soaked in acetone for 16 hours in order to remove the sizing from the fiber surface. Acetone was evaporated in a cooling oven preheated to 100 °C.Two types of carbon/vinyl ester nanocomposites were manufactured; one with 1.0 wt % loading of octaisobutyl-POSS (Octa), and the other with 0.2 wt % of trisilanolphenyl-POSS (TriS). POSS particles were procured from Hybrid Plastics . As-received carbon fiber cloth  was cut into panels of 12 in × 12 in and placed in stacks of 6 plies into a ZiplockA liquid media was produced to de-agglomerate POSS particles and provide a medium for attaching the particles to the carbon fiber. The manufacturer specified two solvents; hexane for Octa and ethanol for TriS. The POSS product and respective solvent were mixed by a VDI-24 homogenizer at 2400 rev/min for 5 minutes. The amount of solvent in each batch was of sufficient quantity such that the fiber plies could be fully soaked. Weight percent of POSS was calculated based on the weight of the carbon fiber to be coated. Since the homogenizer was not able to completely de-agglomerate the particles, the admixture was then subjected to ultrasound cavitation to achieve appropriate dispersion of POSS particles. The solution was submerged in a 5.5 °C cooling bath and was sonicated for an hour and 30 minutes at 45% amplitude using the VCX 500 Vibra Cell Liquid Processor.® bag with 40 mL of the solution for each 6 in × 6 in ply. In case of each 12 in × 12 in ply, 140 mL of the solution was used. To ensure complete soaking, air bubbles were removed prior to sealing the bags. Each Ziploc® bag was then secured to a standard massage pad set on high vibration mode for a duration of three hours. Residual solvent was then evaporated by keeping it in an cooling oven (preheated to 100 °C) for 30 minutes. Coated carbon fibers were next used to fabricate composite panels.To coat carbon fibers with POSS, fiber plies were individually inserted in a ZiplocTraditional hand lay–up method followed by compression molding was used to fabricate the various categories of panels. Three categories of composite panels were fabricated using Derakane 8084 vinyl ester resin (J.I. Plastics 19233 Plank Road Zachery. LA 70791). The three types of panels were: (i) - fiber coated with 1.0 wt % octaisobutly; (ii) - fiber coated with 0.2 wt % Trisilanolphenyl; and (iii) - control panels with acetone treated carbon fiber. The resin was formulated as specified by the manufacture, namely, Ashland Inc. The process began with pouring of resin on the mold face. A single ply was stacked on top followed by the addition of resin spread over the entire ply. This sequence was repeated until all the required plies had been applied. The top mold plate was stacked at the end completing the hand lay-up operation. The mold was then clamped and allowed to cure. After curing for 24 hours the mold was debulked, and the panel was machined to extract samples for mechanical and hygrothermal analyses.Short beam shear tests were carried out on a Z050 Zwick/Roell machine at a crosshead speed of 1.3 mm/min at ambient temperature. ASTM D2344 standard was followed to conduct the short beam shear tests. Span-to-thickness ratio was maintained at 4. Sample dimensions were 30 mm (length) × 10 mm (width) × 5 mm (thickness). Five specimens were tested in each category.Low velocity impact tests were conducted using a Dynatup 8210 machine with a 12.5 mm diameter hemispherical tup. Impact energy was 30 J. The weight of the crosshead was 6.39 kg . SpecimetM is the weight at time t and 0M is the initial dry weight [For durability tests, composite samples were exposed to saltwater at room temperature, saltwater at 40 °C, and 85% humidity at 50 °C for six weeks. Thirty-six short beam shear specimens were used in this investigation. Specimens from each category of panels were weighed prior to immersion. Samples were weighed periodically to measure the rate of water absorption. Initially, the samples were weighed every 3–4 days followed by wider intervals up to a week. Water absorption was higher initially, and then leveled off as the samples became saturated. Percentage of weight change was determined as:y weight ,20. AfteIn an attempt to assess the success of coating, SEM micrographs of fiber surfaces were examined as shown in Two types of mechanical tests were performed to see if there was any improvement in properties due to POSS coating of the fiber. Short beam shear and low velocity impact tests were conducted. Short beam shear tests were meant to measure the interlaminar shear strength of the composite. Since the span/depth ratio was low the tests allowed specimens to fail under in-plane shear. Short beam shear tests were done according to ASTM standard. Representative load-displacement curves for three categories of samples are shown in versus time curves from the impact tests are shown in vs. time curve [i.e., time required to reach the peak load) but longer propagation time. However with Octa and TriS samples, it is observed that there is also a initial fracture region before the load reaches the peak. This initial fracture region is followed by pre-initial fracture as indicated in In the next step, samples were tested under low velocity impact. As the tup tends to penetrate during impact, energy is absorbed and dissipated from the point of impact. Absorption of energy will depend on delamination, matrix cracking, and interface separation. On the other hand, tensile wave speed through the composite will dictate the rate of dissipation of energy. Tensile wave speed through the composite in turn will depend on the modulii of the matrix and fiber, F/M matrix interface, and density of the composite. In other words performance under low velocity impact, in addition to energy absorption characteristics of the composite, will also reflect the integrity of the F/M interface modified by POSS. Load and energy me curve . The curme curve  and thisversus time for all three curves are seen to be leveling off at constant values between 26 and 29 joules. The point where the load returns to zero or the energy curve levels off to a constant value is denoted as total point (TP). The energy corresponding to TP represents the total energy absorbed by the panel and indicates the end of the impact events. The total energy absorbed at 29 joules impact level for three categories are shown in The energy i.e., under HM50, it is observed that none of the specimens absorb any moisture as data points hover around the 0.00% line  than the neat (0.85%). But that was not the case with TriS, it still absorbed less water (0.68%) than the neat. Amount of water absorption was 20% less compared to neat as indicated in the table. This again shows clearly that TriS coating is very effective in enhancing the durability of carbon/vinyl ester composites under salt water environment.Having demonstrated that POSS improves mechanical properties in dry conditions, composite samples similar to those of short beam shear coupons were exposed to moist environments. For six weeks, composite samples were immersed in three different environments: saltwater at room temperature (SWRT), saltwater at 40 °C (SW40), and in 85% humidity at 50 °C (HM50). In each environment, a total of 36 specimens were exposed comprising of 12 samples from each type of panel: Neat, Octa, and TriS. The moisture absorption data for all categories of samples are shown in 00% line . A compaIn an attempt to assess the degradation of strength after environmental exposure, samples were tested in short beam shear at two stages; one category was tested immediately after the end of six week period while specimens were still wet (SW40_Wet), and the other was dried for two weeks at ambient temperature (SW40_Dry) and then tested. Although short beam shear tests were performed after all three environmental exposures, test data for SW40 are shown in this paper. Since the performance of TriS samples were most significant, short beam shear data for TriS only are shown in A chemical procedure has been developed to install POSS on the carbon fiber surface. The procedure is simple and involves a few low cost steps. SEM and EDS studies have demonstrated that the treatment of the fiber surface is indeed successful. Two types of POSS, namely, octaisobutyl and trisilanolphenyl have been investigated. Mechanical tests have indicated that both interlaminar shear strength and low velocity impact strength have improved by the reinforcement of POSS. However, the improvement was more significant with TriS in each case since TriS had compatible functional groups attached to its core silica molecule.Environmental exposure experiments have revealed that water uptake during a six week period of time was minimal. Although water absorption was insignificant, it has been shown that composites with TriS performed the best under each of the exposure conditions. Mechanical tests, such as short beam shear test, of samples after exposure to environmental conditions have shown that there is no degradation in shear strength. In some cases, it has rather shown some improvement. This was true with neat, as well as with POSS reinforced composites. However, improvement with POSS was consistent as it was observed under dry conditions. It also suggests that while under environmental exposure, the resin was in fact curing rather than deteriorating within the six week time period, especially at elevated temperature. This explains the minimum amount of water absorption and slight increase in shear strength. Follow up experiments with post cured specimens have confirmed the assertion.


Prudent use of antibiotics is important to prevent antibiotic resistance in humans and in animals. For this reason politicians demanded a decrease of total antibiotic use and of use of critically important antibiotics in animal husbandry in the Netherlands. In the dairy sector the use of antibiotics almost halved in the years 2009–2015, with a decrease of the use of critically important antibiotics to very low levels.To realize a sustainable decrease in antibiotic usage, the mindset towards the subject was considered crucial. Based on several models from social psychology, the RESET Mindset Model was used. This model contains the most important cues to change human behaviour, being Rules and regulations, Education and information, Social pressure, Economics, and Tools. To change behaviour of groups in order to reach a tipping point, it is of utmost importance to not choose among the different cues, but to use them all.In order to decrease antibiotic usage in dairy cattle in the Netherlands several actions, obliged as well as voluntary, were undertaken. An independent veterinary medicine authority was founded that became active for all animal sectors. In the dairy sector a national database on antibiotic usage called MediRund was developed, which made transparency and benchmarking on antibiotic usage at the national and the herd level possible. Several other activities are described, such as herd health and treatment plans, selective dry cow therapy, and the strong limitation on the use of critically important antibiotics. Antibiotic usage at the herd level, referred to as the ‘antibiotic number’, became an important and socially accepted herd level parameter.The actions undertaken worked through different cues, all part of the RESET Mindset Model. As such, different types of dairy farmers sensitive to different types of cues were motivated to change their behaviour.Antibiotic usage in dairy cattle in the Netherlands decreased significantly by intense cooperation between the most important stakeholders in the dairy chain, taking communication seriously and applying the RESET Mindset Model. Since the second world war, antibiotics became widely available to cure bacterial diseases, which had an enormous impact on lifetime expectancy of people suffering from bacterial infections. Antibiotics were also used in animals, initially to cure diseases, later also to prevent diseases and as growth promoters , which lStaphylococcus aureus (MRSA) and extended spectrum beta-lactamase producing bacteria (ESBLs) in animals [In 2008 antibiotic usage in animal husbandry became a political issue in the Netherlands. Whereas antibiotic usage in humans was relatively low compared to other European countries, antibiotic usage in the Dutch livestock industry was relatively high , 7. Afte animals  antibiot animals . At the At that time it was clear that, although the dairy sector was not the sector in which most antibiotics were used or that seemed to have a big antibiotic resistance problem, there were some issues there too that had to be solved . In DeceThe use of antibiotics in the dairy sector decreased by 47% in the period 2009–2015, with a decrease in the use of critically important antibiotics to very low levels , as presIn this review paper we use the strategy of the TAUC as an example to show how the RESET Mindset Model can be used to change behaviour of dairy farmers. The specific issues involved in the communication process and the decisions that were made were described, as was the approach to change the mindset of dairy farmers and veterinarians towards reduction of antibiotic usage in dairy cattle in the Netherlands.An important step in the success model of the reduction of veterinary antibiotic use in the Netherlands  was thatBased on the Theory of Planned Behaviour , 22, theIt is clear that the different cues of the RESET Mindset Model are interrelated, and that people are often motivated by the various cues simultaneously. Nevertheless, for practical reasons, different cues will be discussed separately below.Generally rules are intended to force you to perform a desired behaviour. Compulsory behavioural change is enforced by regulations and restrictive provisions . Thus, iEducation is a very strong method to increase internal motivation. Internal motivation is not easy to influence, but once it is done, it still is not easy to change, which we then consider a positive effect. Veterinarians generally tend to overestimate the effect of the educational approach, based on the assumption that once the technical arguments are given, farmers take rational decisions and will act accordingly , 19. TheProbably the most important factor in changing behaviour is social pressure. Most people would do anything in their power to become and remain part of a certain group. The urge to belong is an important motivator for behavioural change . VeterinOne of the ways to externally motivate people is through changing circumstances that have economic consequences. Many advisors think money is the only factor influencing farmers’ decisions. Although this is seldom true, economic consequences undoubtedly are important in a free-market economy. That may be either way, positive as well as negative, profits and costs, bonuses and penalties, which have been mainly described for bulk milk somatic cell count (BMSCC) . EconomiOne of the important factors influencing circumstances are technical facilities that make it easier to perform the desired behaviour. These tools can also be design solutions or nudges, that unconsciously steer people in the right direction, without them being aware . Using tThe main goal of the TAUC was to improve the antibiotic resistance situation through decreasing the amount of antibiotics administered while increasing prudent antibiotic usage. There were some specific conditions that had to be fulfilled such as limiting the use of critically important antibiotics and banning the preventive use of antibiotics as in applying blanket DCT. To realize these goals, several activities were initiated, of which two were obligatory for all farmers: transparency of antibiotic use at the herd level, and implementation of a herd health and treatment plan . These oNAT) as well as at the farm level (DDDAF), and was specified for specific types of antibiotics, age groups and application methods, as described earlier by Santman-Berends et al. [To make antibiotic usage transparent at the herd level calculation of the Defined Daily Dose of Antimicrobials (DDDA) was introduced basically indicating the number of days of antimicrobial treatment per animal per year. The DDDA was calculated at the national  , with whMost of the antibiotics used in dairy cattle are administered via the intramammary route. In the Netherlands this accounted for approximately 70% of total antibiotic usage of which roughly 1/3 in mastitis treatment and 2/3 in DCT . BecauseE. coli, while no association was found with other antimicrobials [Apart from the quantitative approach of total antimicrobials used the types of antibiotics received specific attention. The relation between antibiotic usage and antibiotic resistance has been shown in general  as well crobials , 46. Antcrobials . Veterincrobials . If infecrobials .A final important aspect of antibiotic use in the dairy industry is residue handling. Liquid milk and milk that is processed are monitored very well, leading to a very low percentage of positive findings. In the past, however, very little attention was given to residues in waste-milk. This milk, that contained antibiotic residues in approximately 70% of samples  was ofteTo reduce the use of antibiotics in dairy cattle, the RESET Mindset Model was applied, trying to use as many cues as possible to motivate dairy farmers as well as veterinarians to change their behaviour towards antibiotic use. These activities are summarized in Table F) with the accompanying signaling and action thresholds, and obligatory action plans when needed also had their direct effect on farm. The guidelines on the use of antibiotics at drying off, and the herd health and treatment plans were, although obligatory, also examples of structured management approaches that were considered helpful by some farmers and veterinarians [The R was first of all fulfilled by the quantitative reduction goal set by the government. This goal, however, was intangible for the individual dairy farmer and veterinarian. The earlier described 1-to-1 relationship between farmer and veterinarian , the oblinarians .The E of education and information was used in many studies done under Dutch circumstances and the scientific publications of these studies , 42, 43.F or the ‘antibiotic number’ as farmers call it became one of the parameters dairy farmers know and that many of them consider an important characteristic.One of the ways the S is reflected is in a changed social environment of farmers. In most western countries society has changed in a few generations form a mainly agricultural society to one in which farmers are a minority. That has had its consequences on the way the general public thinks of farming and also on the way farmers think of farming. Those changes occur very slowly and differ from region to region but they do occur. The emotional impact of farmers standing up at meetings to tell about their experiences in hospital where they were isolated for suspicion on MRSA because they came from a farm is an indication of that. The transparency of the total antibiotic usage in dairy farms may also have had an effect on social pressure. Veterinarians and other advisors on herd health, such as representatives from the food industry, considered antibiotic use an important parameter and talked about alternative approaches for disease prevention. The DDDAThe effect of social pressure is visible once farmers proudly tell in public meetings they have a low antibiotic number and are among the best in the benchmark. The obliged herd health and treatment plan forces farmer and veterinarian to work together and works also as social pressure for both of them . Other hThe E of economics started having its effect after the initial fear for the effect of using less antibiotics, specifically in DCT, had disappeared. At the herd level using less antibiotics at drying off had minimal effects of the incidence of mastitis but did have an effect on the use of dry cow antibiotics  and the F using the colour codes described. These tools had their effect through other cues, but also directly as technical devices facilitating the desired behavioural change.The T of tools was applied through the above discussed herd health and treatment plans, the guidelines of antibiotic use of the WVAB and on antibiotic use in selective DCT, and the MediRund data that were visualized in their DDDAAll the described activities together Table  combinedAntibiotic usage in dairy cattle in the Netherlands decreased significantly by intense cooperation between the most important stakeholders in the dairy industry, taking communication seriously and applying the RESET Mindset Model.


Preoperative antibiotic prophylaxis in relation to the risk of infectious complications, however, has never been studied.The additional value of perioperative antibiotic prophylaxis in preventing infectious complications after emergency cholecystectomy for acute cholecystitis is a much-debated subject in the surgical community. Evidence-based guidelines are lacking, and consequently the use of antibiotic prophylaxis varies greatly among surgeons and hospitals. Recently, high-level evidence became available demonstrating that preoperative antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis. Patients with mild or moderate acute cholecystitis, as defined according the Tokyo Guidelines, will be randomly assigned to a single preoperative dose of antibiotic prophylaxis  or no antibiotic prophylaxis before emergency cholecystectomy. The primary endpoint is a composite endpoint consisting of all postoperative infectious complications occurring during the first 30 days after surgery. Secondary endpoints include all the individual components of the primary endpoint, all other complications, duration of hospital stay, and total costs. The hypothesis is that the absence of antibiotic prophylaxis is noninferior to the presence of antibiotic prophylaxis. A noninferiority margin of 10% is assumed. With a 1-sided risk of 2.5% and a power of 80%, a total of 454 subjects will have to be included. Analysis will be performed according to the intention-to-treat principle.The PEANUTS II trial is a randomized, controlled, multicenter, open-label noninferiority trial whose aim is to determine the utility of The PEANUTS II trial will provide evidence-based advice concerning the utility of antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis.NTR5802. Registered on 4 June 2016.Netherlands Trial Register, The online version of this article (doi:10.1186/s13063-017-2142-x) contains supplementary material, which is available to authorized users. Acute calculous cholecystitis is a frequently encountered disease in surgical practice that generally mandates emergency cholecystectomy. Although this is considered to be a low-risk procedure, the complication rate is not negligible. The most common complication is a postoperative infection, either at the surgical site or a distant site, occurring in approximately 17% of patients [The Working Party on Antibiotic Policy in the Netherlands (Stichting Werkgroep Antibioticabeleid) issued guidelines for perioperative antibiotic prophylaxis in Dutch hospitals . Accordielective cholecystectomy for uncomplicated cholelithiasis, high-level evidence is available demonstrating that prophylactic antibiotics do not reduce the incidence of postoperative infections [emergency cholecystectomy the continuation of antibiotic prophylaxis after surgery is disputable [In patients undergoing fections –9. For tsputable . This stIf the present study demonstrates that omitting antibiotic prophylaxis does not increase the postoperative infection rate, the use of antibiotics for this indication can be dropped as a whole. If so, the role of antibiotic prophylaxis in surgery of the entire upper gastrointestinal tract will become questionable. A decrease of antibiotic use on such a scale may result in a large reduction of needless medical activities, costs, and bacterial resistance. The latter is a growing issue in contemporary medicine and has emerged as one of the eminent public health concerns nowadays .The Perioperative Antibiotic Use in the Treatment of Acute Inflammation of the Gallbladder (PEANUTS II) trial is designed to assess whether preoperative antibiotic prophylaxis is indicated to prevent postoperative infectious complications in patients undergoing emergency cholecystectomy for acute calculous cholecystitis. The hypothesis is that the absence of antibiotic prophylaxis does not lead to an increase in infectious complications.The PEANUTS II trial is a randomized, controlled, multicenter, open-label noninferiority trial. Patients will be randomly allocated to receive either no antibiotics or a single dose of antibiotic prophylaxis before emergency cholecystectomy Fig. .Fig. 1FlAll patients presenting with acute calculous cholecystitis to one of the participating hospitals will be assessed for eligibility. Patients are eligible if diagnosed with mild or moderate acute calculous cholecystitis as defined according the Tokyo Guidelines  Table 11. The inThe primary endpoint is a composite endpoint consisting of all postoperative infectious complications occurring during the first 30 days after surgery. Table https://nl.tenalea.net/amc/ALEA/; Academic Medical Center, Amsterdam, The Netherlands) and stratified according to center. Computer-generated permuted block randomization with varying block sizes is being used with a maximum block size of six patients. The sequence of the different blocks is predetermined by an independent programmer and concealed to all investigators.Patients will be randomly assigned to the treatment group (antibiotic prophylaxis) or the nontreatment group (no antibiotic prophylaxis) as shown in the flowchart in Fig. To confirm the diagnosis, all patients presenting with suspected acute calculous cholecystitis will undergo standard laboratory workup and ultrasound examination of the abdomen or contrast-enhanced computed tomography if ultrasound results are inconclusive. When patients are eligible for inclusion and informed consent is obtained, randomization will take place. Patients in the treatment group will receive 2000 mg of first-generation cephalosporin administered intravenously 15–30 minutes before surgery. Patients in the nontreatment group will not receive any antibiotic prophylaxis. Cholecystectomy should be performed within 24 h after randomization. Figure Cholecystectomy will be performed laparoscopically using the four-trocar technique according to the guidelines of the Dutch Society of Surgery, which includes the critical view of safety techniques . The surPatients will be discharged on the basis of their clinical condition and at the discretion of the treating physician. If patients in either group develop infectious complications, antibiotic therapy will be started. All events will be recorded.Each patient will receive an anonymous study number that will be used for the study record forms and the database. On admission, baseline characteristics, including age, sex, body mass index, comorbidity, American Society of Anesthesiologists physical status score, clinical data , will be collected and documented by the admitting physician or  study coordinator Fig. . Data reA data and safety monitoring board (DSMB) consisting of three independent members has been appointed to assess patient safety. The first meeting will take place after 20 patients are included and subsequently once per every 50 included patients. The DSMB has unblinded access to all data.http://www.toetsingonline.nl).An adverse event is defined as an undesirable experience of a subject during the study, regardless of whether it is considered related to the intervention. Participating physicians will report all adverse events to the study coordinator immediately on occurrence. The study coordinator will list all adverse events and will present these to the DSMB for every 30 randomized patients. All adverse events will be reported to the Dutch Central Committee on Research Involving Human Subjects using the committee’s online module  on June 4, 2016. Written informed consent will be obtained from each participant before any trial-related procedures are carried out.The PEANUTS II trial is being conducted in accordance with the Declaration of Helsinki and Dutch law regarding research involving human subjects (Wet Medisch Wetenschappelijk Onderzoek met Mensen). The study protocol  was approved by the Medical Research Ethics Committee (MEC-U) of the St. Antonius Hospital, Nieuwegein, The Netherlands, on November 24, 2015. Secondary approval was obtained from the executive boards of all participating centers. The study protocol was retrospectively registered (after enrollment of the first participant) with the Netherlands Trial Register at The present study protocol is written according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 statement for reporting a clinical trial protocol [A recently published randomized controlled trial showed a postoperative infectious complication rate of 17% in patients with mild and moderate acute calculous cholecystitis undergoing laparoscopic cholecystectomy [Dichotomous data and counts will be presented as frequencies. Continuous data will be presented as means with standard deviations or, in cases of skewed distribution, as medians with interquartile ranges.After the last patient has completed follow-up, raw data will be presented to an adjudication committee to determine whether the endpoints meet the protocol-specified criteria. Each member of the adjudication committee is blinded to the treatment allocation and will assess the potential endpoints individually. Disagreement will be resolved in a plenary consensus meeting. After consensus is reached on each individual endpoint for each patient, final analysis will be performed by an unblinded independent statistician. This analysis will be performed according to the intention-to-treat principle, which means that all randomized patients will be included in their initially assigned study arm, regardless of adherence to the protocol.U test will be used. Noninferiority will be demonstrated if the upper limit of the two-sided 95% CI of the difference of the proportion of the primary endpoint between the two groups is lower than the noninferiority margin. The effect will be measured by the absolute risk difference, and the precision will be quantified by means of the 95% CI. The formal statistical hypothesis regarding noninferiority will be tested by the Westlake-Schuirmann test, with the noninferiority margin set at 10% and a one-tailed p value < 0.025 considered statistically significant. For all other tests, a two-tailed p value < 0.050 is considered statistically significant. In general, for the primary endpoint, we do not expect data to be missing; if so, missing data will not be imputed.For nominal data, the chi-square test or Fisher’s exact test will be used; for continuous data, the Mann-Whitney n = 227) of the total number of patients have been randomized and have completed the 1-month follow-up. The Peto approach will be followed, which includes that the study will be stopped only for benefit or harm in case of a p value < 0.001 [The DSMB will perform a formal interim analysis for superiority with respect to the primary endpoint when 50%  does not reduce the risk of infectious complications [Preoperative antibiotic prophylaxis in relation to the risk of infectious complications, however, has never been studied. We therefore designed the PEANUTS II trial with the aim of determining the utility of preoperative antibiotic prophylaxis in patients undergoing emergency cholecystectomy for acute calculous cholecystitis.Whether antibiotic prophylaxis has any additional value in preventing infectious complications after emergency cholecystectomy is a much-debated subject in the surgical community. Evidence-based guidelines are lacking, and, as a result, the use of antibiotic prophylaxis varies greatly among surgeons and hospitals. Recently, high-level evidence became available demonstrating that ications . PreoperThe PEANUTS II trial has a noninferiority design. The hypothesis is that the absence of antibiotic prophylaxis will not lead to an increase of postoperative infectious complications. In the nontreatment group, either an increase of the infectious complication rate or no effect will be seen. Because it is very improbable that the absence of antibiotic prophylaxis will lead to a decrease of infectious complications, and thus deviation is possible in only one direction, a noninferiority design is best suited to answering this primary question.The best design for a therapeutic trial is a placebo-controlled, double-blind trial, but because treatment of acute cholecystitis is often performed in an acute setting outside regular working hours, such a design is difficult to organize. Therefore, an open comparative design was chosen. We believe that blinding and placebo are not of absolute importance, because the primary outcome of the study is an objective criterion with a clearly defined  definition. In addition, all potential endpoints will be assessed individually by the members of the adjudication committee, who are blinded to the treatment allocation. Only after reaching consensus on each individual endpoint for each patient will final analysis be performed by an unblinded independent statistician.Patients with grade III (severe) acute cholecystitis are septic and require antibiotic treatment in addition to appropriate organ support , 15. ThiIf this study demonstrates that omitting antibiotic prophylaxis does not increase the postoperative infection rate in patients with acute cholecystitis, the role of antibiotic prophylaxis in surgery of the entire upper gastrointestinal tract will become questionable. A decrease in the use of antibiotics may result in a large reduction of bacterial resistance, the latter being an increasingly serious threat to global public health .Recruitment commenced in March 2016 and is anticipated to run until March 2019. As of August 20, 2017, 158 patients had been randomized, and 7 hospitals were participating in the trial. The study results will be communicated via publication.


MET exon 14 splicing has been revealed in lung cancers and is a promising therapeutic target. Because we have limited knowledge about the natural history of MET mutant tumors, the current study was aiming to determine the clinical and pathological characteristics in non-small cell lung cancers (NSCLC).Recurrent MET exon 14 skipping. Patients with MET exon 14 skipping displayed unique characteristics: female, non-smokers, earlier pathology stage and older age. MET exon 14 skipping indicated an early event as other drivers in lung cancer, while MET copy number gain was more likely a late event in lung cancer. Overall survival (OS) of patients harboring MET exon 14 skipping was longer than patients with KRAS mutation. Almost four-fifths of the lung tumors with MET exon 14 skipping had EGFR and/or HER2 gene copy number gains. EGFR inhibitor showed moderate antitumor activity in treatment of a patient harboring MET exon 14 skipping.Twenty-three patients (1.3%) were positive for MET status with clinical pathologic characteristics and mutations in EGFR, KRAS, BRAF, HER2, and ALK. Quantitative Real-Time PCR was used to detect MET gene copy number gain. Immunohistochemistry (IHC) was also performed to screen MET exon 14 skipping. Clinicopathological characteristics and survival information were analyzed.From October 2007 to June 2013, we screened 1770 patients with NSCLC and correlated MET exon 14 skipping was detected in 1.3% (23/1770) of the Chinese patients with NSCLC. MET exon 14 skipping defined a new molecular subset of NSCLC with identifiable clinical characteristics. The therapeutic EGFR inhibitors might be an alternative treatment for patients with MET mutant NSCLC. EGFR mutations and ALK/ROS1 fusion, respectively [Lung cancer is the leading cause of cancer deaths worldwide. Non–small cell lung cancer (NSCLC) comprises over 80% of all lung tumors. With better understanding of the major genetic alterations and signaling pathways involved of lung cancer, it has been classified into various subsets with different molecular and clinicopathologic characteristics . Target-ectively , 3. Evenectively –7.MET, encoding the proto-oncogene tyrosine kinase c-MET, is the receptor for hepatocyte growth factor (HGF). The activation of this kinase by amplification and overexpression could promote cancer [MET amplification is uncommon in NSCLCs and was observed in 2%–4% of previously untreated patients [MET targeted therapies are currently undergoing early-phase clinical trial evaluations in lung cancer patients [e cancer –10. MET patients , 9, 11. patients , 13.MET gene exon 14 skipping was identified as a potential driver mutation in lung and colon tumors [MET inhibitor (crizotinib or cabozantinib) in several independent early-phase trials, suggesting that MET might be a novel druggable target in lung cancers [MET exon 14 skipping have not yet been described. These results provide us with an impetus to understand the natural history of MET mutant tumors.Recently, n tumors . Strikin cancers –18. The MET exon 14 skipping is a novel oncogenic driver in lung cancers by clinical and pathological characteristics. This new molecular subset of patients had distinct features, allowing clinicians to select enriched subpopulations for genotyping and with whom randomized prospective clinical trials of targeted therapies could be efficiently performed.Here, we demonstrated that From October 2007 to June 2013, we screened out 1770 qualified patients in this study cohort, including 1305 adenocarcinomas, 48 adenosquamous carcinomas and 417 squamous cell carcinomas. There were 991 (56.0%) male patients and 779 (44.0%) female patients. Ages below or above 60 years old were almost equally distributed. Seven hundred and seventy-nine patients were current smokers or former smokers; nine hundred and ninety-one patients were non-smokers. Obviously, most adenocarcinomas were female and non-smoking patients. Squamous cell carcinomas predominantly occurred in male and smoking patients. More detailed information was illustrated in Table MET exon 14 skipping was detected in 23 patients (1.3%), which was the fourth most frequently identified driver in NSCLCs  of non-smoking lung adenocarcinomas (NSLAD) harbored MET exon 14 skipping .MET exon 14 skipping had EGFR and/or HER2 gene copy number gains. Among 19 invasive lung cancers, 94.7% of MET mutant tumors showed EGFR and/or HER2 gene copy gains, but none of the cases with AAH/AIS harbored EGFR or HER2 gene copy alterations  cohort [We showed that 18 of 23 (78.3%) lung tumors with ) cohort .MET exon 14 skipping defined a novel genetic subset of NSCLC. Patients with MET exon 14 skipping displayed unique characteristics: female, non-smokers, earlier pathology stage and older age (Table MET exon 14 skipping (Table in situ (AIS) were observed in 17.4% (4 of 23) of MET positive tumors, indicating that it was an early event as other drivers in lung cancer. In contrast to patients with MET exon 14 skipping, patients with MET copy number gain were more prone to have late stage disease, poor differentiation, and acinar/solid/invasive mucinous adenocarcinoma , KRAS (5.6%), HER2 (21.9%), BRAF (15%), ALK (2.9%), RET (5.6%), and pan-negative (10.3%) lung adenocarcinomas, indicating that mutant MET alone might be insufficient to transform normal cells but depend on other genetic alterations progressing into more aggressive carcinoma subtypes.The proportion of precancerous or early lesions (AAH/AIS/Lepidic) (38.1%) in MET compared with 48.2 months for EGFR (P = 0.152), 41.2 months for KRAS (P = 0.088), 39.4 months for ALK (P = 0.462), and 35 months for HER2 (P = 0.13). The median overall survival (OS) was 70 months for MET compared with 67.2 months for EGFR (P = 0.841), 60 months for KRAS (P = 0.016), 52.7 months for ALK (P = 0.95), and 49.4 months for HER2 (P = 0.321)  was 46.2 months for MET exon 14 skipping in our cohort, a 68 year-old non-smoker with MET, EGFR, and HER2 gene copy number gains in his tumor had relapsed. The patient showed a stable disease response to EGFR inhibitor Iressa, and the status had been maintained for 12 months  for treating patients harboring MET exon 14 skipping [MET inhibitor. The response rate was 83.3% (nine of 12 lesions) and the median progression free survival was five months (range of two to 13 months). The antitumor activity shown in early phase clinical trials strongly supports MET exon 14 skipping as a bona fide target of the MET inhibitor. However, the responses to the MET inhibitor are quite heterogeneous. There still remains a substantial amount of tumor cells that are intrinsically resistant to the MET tyrosine kinase inhibitor. The molecular basis of the response heterogeneity is largely unknown, and no biomarker is available for predicting a response.Garrett M.F. et al. demonstrated that NIH-3T3 cells stably expressed mutant erations . It is iskipping –18, 23. MET exon 14 skipping in our cohort had EGFR and/or HER2 gene copy number gains. Whether this observed consequence was a coincidence or an intrinsic connection remained unclear. One patient harboring MET exon 14 skipping simultaneously with EGFR, HER2 gene copy number gains received Iressa and maintained his disease for 12 months. It might be difficult to Figure out which alternation of genes played a more important role. Specific MET inhibitors should be an excellent choice according to the reported data; EGFR-TKIs, however may come to rescue as a replacement, especially when patients have had EGFR gene alternations. Since these three genes are essential in cell signaling, affecting various kinds of activities in cells such as survival, proliferation and invasion, completely understanding of the interaction of these genes is a necessity, and further experiments are urgently demanded. Future possible therapeutic strategy may hide in this network by double or triple targeting these molecules.Remarkably, almost four-fifths of the patients with MET exon 14 skipping defined a new molecular subset of NSCLC with identifiable clinical characteristics. These patients are typically older, female, and non-smokers who might benefit from MET targeted therapy. Most of the lung tumors with MET exon 14 skipping had EGFR and/or HER2 gene copy number gains. Additionally, the therapeutic EGFR inhibitors might be an alternative treatment for patients with MET mutant NSCLC.In summary, TTF1, P63, Nepsin A and CK5/6. DNA and RNA were collected as previously reported [From October 2007 to June 2013, a total of 1770 frozen surgically resected NSCLC tumor tissues, including 1305 lung adenocarcinomas, 48 adenosquamous carcinoma and 417 squamous cell carcinomas, were prospectively collected in the Department of Thoracic Surgery of Fudan University Shanghai Cancer Center. This study was approved by the Institutional Review Board of the Fudan University Shanghai Cancer Center. All patients provided written informed consent. Two pathologists (Y.L. and X.X.S.) confirmed the diagnosis by H&E staining and verified by immunohistochemistry as reported , 20.EGFR, KRAS, HER2, BRAF, CTNNB1, PIK3CA, ALK, RET, ROS1, NRG1, FGFR1, FGFR2, and FGFR3 was detected. MET (exon 13 to 21) was PCR amplified using cDNA for direct sequencing and exon 14 deleted cases were verified by sequencing of the PCR product of MET exon 13 to 15. Primers were shown in MET gene copy number gain as previously reported [As previously reported , 19–21, reported .MET , P40 , and TTF-1  antibodies.Standard 5-μm formalin-fixed paraffin-embedded sections were subjected to IHC analysis using anti-Clinical and pathologic data were prospectively collected for analyses, including age at diagnosis, sex, smoking history, histologic type, pathologic TNM stage, tumor size, and tumor differentiation. Patients were observed in clinic or by telephone for disease recurrence and survival from the date of diagnosis. Of the 1770 NSCLC patients, 56 patients who were incidentally found to have pleural metastasis were excluded from survival analysis. Seventy-nine patients of loss to follow-up were also excluded. A total of 1635 NSCLC patients were included for analysis with a median follow-up time of 32.83 months.p < 0.05.Associations between mutations and clinical and pathologic characteristics were analyzed by the χ2 test or Fisher's exact test. Survival curves were estimated using the Kaplan-Meier method, with differences in survival assessed by the log-rank test. Data were analyzed using Statistical Package for the Social Sciences Version 19.0 Software (SPSS Inc.). The two-sided significance level was set at


The purposes of this study were: firstly, to estimate time trends in the prevalence of prescription antibiotic consumption between 2003 and 2014; secondly, to identify the factors associated with the probability of consuming antibiotics during this period in elderly persons in Spain.We analyzed data collected from the Spanish National Health Survey in 2003 , 2006 , and 2012  and from the European Health Interview Survey for Spain in 2009  and 2014 . Antibiotic consumption was the dependent variable. We also analyzed sociodemographic features, self-perceived health status, lifestyle habits, comorbid diseases, and disabilities using logistic regression models.The prevalence of antibiotic consumption increased from 2003 to 2014 in both sexes. The variables that predicted antibiotic consumption  were secondary education , visits to a general practitioner , hospitalization , therapy with > 4 non-antibiotic drugs , instrumental activities of daily living , and activities of daily living . In contrast, age > 85 years was associated with low antibiotic consumption in both men (OR 0.81) and women (OR 0.88).The prevalence of antibiotic prescription has increased in Spain in the last decade. Our study identified several factors that appear to affect antibiotic consumption in elderly persons, with potential implications for healthcare providers. Antibiotics reduce the burden of common infectious diseases and usually play an essential role in many medical interventions because of their therapeutic benefits and their impact on public health throughout the world . HoweverSimilarly, previous studies have shown over prescription of these drugs outside hospitals which is associated with more frequent use of healthcare services for treatment of specific conditions ,8 and a The objectives of the present study were: a) to analyze time trends in the prevalence of consumption of prescription antibiotics among elderly persons in Spain between 2003 and 2014; and, b) to identify the sociodemographic features, self-rated health status, comorbidity, lifestyle habits, and disabilities associated with antibiotic consumption during this period in elderly persons in Spain.We conducted a nationwide, descriptive, cross-sectional epidemiological study on the consumption of antibiotics by persons aged ≥65 years old in Spain. We used individualized secondary data drawn from the 2003, 2006, and 2012 Spanish National Health Surveys (SNHS) –16 and tThe 2003 survey included 21,650 adults of both sexes interviewed between April 2003 and March 2004, the 2006 survey included 29,478 adults of both sexes interviewed between June 2006 and June 2007, and the 2012 survey included 20,007 persons interviewed from July 2011 to June 2012. Data from the years 2009 and 2014 were obtained from the EHIS, which was proposed by the European Commission to EU Member States and conducted by the Spanish National Statistics Institute under the aegis of the Spanish Ministry of Health, Social Affairs, and Equality (SMHSAE). The methods of the EHIS are the same than those used in the SNHS. The data collection period ranged from April 2009 to March 2010, and a sample of 22,188 subjects aged 16 or over was selected. The 2014 survey included 22,842 adults of both sexes interviewed between January 2014 and January 2015. A detailed description of EHIS methodology can be found elsewhere ,18.For the purposes of the current study, we included answers from adults of both sexes aged ≥65 years from all the surveys. The variables included can be compared because the same questions were asked in all 5 surveys.The information to create the dependent variables was obtained from the answers "yes" or "no" to the question “Have you taken antibiotics in the last 2 weeks?” Respondents who answered “yes” were then asked the question “Were they prescribed for you by a doctor?” Those who answered yes to the first question, regardless of the answer to the second one, were considered consumers of antibiotics.The independent variables were the primary sociodemographic characteristics of the population, namely, age, marital status, and educational level. To identify subjects with an associated chronic condition, we used the self-reported affirmative answer to the presence of any of the following physician-diagnosed diseases : arterial hypertension, hypercholesterolemia, respiratory disease (asthma and chronic bronchitis), heart disease, diabetes, and cancer. The variables related to lifestyle and health profile used in the study were current smoking (yes/no), consumption of alcoholic beverages within the 2 weeks prior to the survey (both defined as dichotomous variables), body mass index, and leisure time physical activity . Self-perceived health was analyzed as a dichotomous variable (very good and good/fair or poor and very poor).In order to assess the use of healthcare resources, respondents were asked about visits to the primary care physician (in the preceding 4 weeks [yes/no]), hospitalization (in the previous 12 months [yes/no]), and visits to the emergency department (in the previous 12 months [yes/no]). They were also asked if they had taken any type of non-antibiotic medication in the previous 2 weeks .Finally, information regarding functional disability was obtained from questions targeting distinct physical tasks in 2 functional domains that had been validated and used in previous studies ,20, as f2 test was used for the bivariate comparison of proportions, and statistical significance was set at p < 0.05 (2-tailed).We calculated the prevalence of total antibiotics consumption for each of the 5 surveys according to the study variables. All data analyses were performed separately for women and men. Pearson’s χTo estimate the independent effect of each of the variables on the consumption of antibiotics, we also obtained the corresponding adjusted odds ratio (AOR) by means of multivariate logistic regression analysis. All variables with a significant association in the bivariate analysis were included in the multivariate analysis, along with those variables that were considered relevant in the scientific literature. Two models were generated to identify factors associated with the overall consumption of antibiotics in men and women.2 test, logistic regression). Statistical significance was set at a 2-tailed α<0.05.Estimates were made by incorporating the sampling weights and using the “svy” (survey command) functions of STATA , which enabled us to incorporate the sampling design into all our statistical calculations  and 20,117 women (57.09%), of whom 52.36% were aged 65–74 years, 36.42% were aged 75–84 years, and 11.22% were aged ≥85 years.Consumption of antibiotics increased significantly during 2003–2014 in both sexes, 5.6% in men (p = 0.002) and 6.21% in women (p = 0.001). By age, consumption increased in women aged 65–74 years and 75–84 years. During the years 2009 and 2012, statistically significant values were recorded for the age ranges 65–74 years and ≥ 85 years, respectively (p<0.05) in both sexes .Data consumption in men, according to sociodemographic characteristics, lifestyle, and health-related study variables are shown in Chronic diseases were significantly associated with consumption of antibiotics during each year of the study period (p<0.05), although no significant increases were recorded.The results of the multivariate analysis are shown in When the consumption pattern among women was analyzed, the variables that were independently and significantly associated with a greater probability of antibiotic use were age 75–84 years , educational level, visits to the general practitioner (GP), hospitalization, polymedication with ≥ 4 nonantibiotic drugs , and disability (ADL and IADL).As for elderly men, the health profile analysis showed that educational level, visits to a GP, taking 4 or more non-antibiotic medications , ADL, and IADL were all significantly associated with more frequent consumption of antibiotics.To assess the time trend in the consumption of antibiotic during the period 2003–2014 and after adjusting for differences in socioeconomic data and health status, antibiotic consumption increased by 66% between 2003 and 2014 in elderly women , whereas antibiotic consumption among Spanish elderly men increased by 46% during the study period .Our study revealed an increase in antibiotic consumption from 2003 to 2014 in elderly persons in Spain. We found that variables associated with higher consumption were secondary education, visits to a GP, hospitalization, taking ≥ 4 non-antibiotic drugs, and difficulty in performing IADL and ADL. In contrast, age ≥ 85 years was associated with low consumption in both sexes.Our study supports previous reports of increases in consumption of antibiotics in elderly ,21. IncrWe observed a variation in prevalence in 2009, probably because the purchasing power of elderly persons decreased during the economic recession and prescriptions were more closely controlled, thus potentially leading to misuse of medication ,28.Our results showed that antibiotic consumption increased in both sexes and are consistent with previous studies ,22,26,29In some cases, gender differences can be explained by the greater frequency of symptomatic infections of the urinary tract in women than in men and the over-use of primary healthcare services by women ,30.Clostridium difficile)[Previous studies ,29,31,32ifficile).Low educational level  was alsoPrevious studies have shown that visiting a GP was associated with increased consumption of antibiotics by the elderly ,10,31,32Hospitalization is also a risk factor for consumption of antibiotics in terms of the admitting complaint, disease burden, iatrogenic infections associated with urinary catheters, and emergence of multidrug-resistant infections ,31.In general, although concomitant use of multiple drugs is very common among elderly persons in developed countries, data on the prevalence of polypharmacy in the literature also vary widely between studies. This practice can mask symptoms of infection , thus hampering diagnosis and necessitating prescription of broad-spectrum antimicrobial drugs to provide full antibiotic coverage . ParadoxOur results also showed that functional disability increased the probability of antibiotic consumption. There are several explanations for this finding. Disability is associated with increased severity of infection in persons aged > 80 years and could be an atypical manifestation of infection in elderly persons  . In addiFirst, we used a self-reported measure of antibiotic consumption, which may have limited the assessment of antibiotic prescription. Nevertheless, even though individuals can overestimate or underestimate their antibiotic consumption, surveys are extremely useful for investigating patterns, frequencies, and longitudinal trends of antibiotic consumption . Second,The current study found an increase in antibiotic consumption in Spain between 2003 and 2014. Factors associated with higher consumption were secondary education, visits to a GP, hospitalization, taking ≥ 4 non-antibiotic drugs, and poor functional status. Our results have clear implications for health services in Spain. At national level, health services and hospitals should develop joint programs focused on appropriate antibiotic prescription and development of programs to monitor consumption in elderly people. Further, the creation of programs to monitor antimicrobial use, and identification of factors associated to increase of consumption should be carried out. At a community level, in primary health care, health care professionals could increase elderly education to prevent inappropriate antibiotic consumption, and identify factors associated to increase GP visits.S1 Table(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.


The clinical picture of IgG4-related sclerosing disease (IgG4-RSD) may mimic lymphoma, and should be in the differential diagnosis of patients with this clinical picture.A 32-year-old female had recurrent swelling of both eyelids for more than 15 years. Examination revealed elastic, firm, swollen lacrimal glands about 2–3 cm in diameter that was not painful. Head and orbits magnetic resonance imaging (MRI) showed mass lesions over the bilateral lacrimal glands, submandibular glands, and left foramen of ovale. The differential diagnosis included lymphoid tissue, inflammatory masses, and lymphoma. Gallium single-photon emission computed tomography/computed tomography (SPECT/CT) showed uptake in the bilateral lacrimal glands, right parotid and bilateral submandibular glands, bilateral perirenal region, mediastinal, prevertebral, paraaortic, lumbar, bilateral pelvic  lymph nodes, anterior aspect of right 3rd rib, and lateral aspect of left 6th rib. CT showed multiple enlarged lymph nodes in the mediastinum, right pulmonary hilum, prevertebral space of the thoracolumbar spine, retroperitoneal paraaortic area, bilateral parailiac areas, and bilateral perirenal spaces. Antinuclear and anti-SSA/SSB antibodies were negative, and the serum IgG4 level was 740 mg/dL . Right parotid gland biopsy showed abundant IgG4-positive plasma cells. Mikulicz disease (IgG4-related sclerosing disease) was diagnosed and she received glucocorticoid treatment. Follow-up CT and MRI showed with resolved eyelid swelling and perirenal mass lesions. Follow-up gallium scan was normal.Gallium SPECT/CT can be a useful tool for initial and follow-up evaluation of IgG4-RSD. Recent studies have indicated the importance of differentiating between IgG4-DS and malignant lymphoma. Characteristic patterns of gallium uptake and on positron emission tomography with [18F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scanning are helpful for diagnosis, detection of involved lesions, and differential diagnosis in patients with IgG4-related disease to avoid unnecessary surgery or incorrect treatment (such as chemotherapy).,5IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz disease (MD), is characterized by elevated serum immunoglobulin G4 (IgG4) and bilateral enlargement of the lacrimal and salivary glands with infiltration of IgG4-positive plasma cells, and lack of systemic inflammation.2A 32-year-old female with childhood asthma has intermittent painless tense bulging of the bilateral upper eye lids for more than 15 years (since 1999). She had no diplopia, orbital pain, blurred vision, dry eyes, or dry mouth. She was informed of benign eyelid lesions in 2000 and 2002 by ophthalmologists. No biopsies were performed, and the lesions resolved with intravenous corticosteroids. However, eye lid swelling recurred after she was tapered off oral steroids. In 2003, MRI was performed, and she was diagnosed with SS. She was treated with methylprednisolone pulse therapy (MTP) for 3 days, after the eyelid swelling completely subsided. However, swelling of the upper eyelids recurred when she was tapered off oral steroids. In 2004, she had to quit her job because of recurrent eyelid swelling. In 2006, she began using Chinese herbal medicines which she stated reduced the eyelid swelling by about 50%. However, in the 3 months before being seen at our clinic, the upper eyelid swelling increased and was severe enough to produce tense bulging.Her mother stated that she has had a cough and wheezing since her infancy, with the need for intermittent bronchodilator and intravenous corticosteroid therapy. She has no known allergies to foods or medications. Both her mother and sister have allergic rhinitis. Bilateral lacrimal gland swelling related to sicca syndrome was suspected.A Schirmer test showed od 2 mm, os 1 mm, but the patient had no complaints of dry eyes or dry mouth. Cranial MRI revealed bilateral lacrimal gland and submandibular gland enlargement with mass infiltration into the bilateral maxillary sinuses and left foramen of ovale Fig. . The posThe patient was treated with low-dose corticosteroids (methylprednisolone 40 mg intravenous) for 2 days. There was no clinical response, so MTP pulse therapy 500 mg daily for 3 days was administered. The eyelid swelling rapidly decreased, and she was able to open her eyes. Three months after treatment, gallium SPECT only showed physiological uptake; no regions of abnormal uptake were noted  persistent symmetrical swelling of lacrimal glands and major salivary glands more than 2 glands and more than 3 months; (b) high serum IgG4 levels more than 135 mg/dL; (c) IgG4-positive plasma cells/IgG-positive plasma cells more than 0.4 in the tissue by immunostaining. If any 2 of these 3 criteria fulfilled including item (a), diagnosis of IgG4-DS can be established. Our case was suspected for IgG4-DS because of the item (a) and (b) of criteria. For differentiating between IgG4-DS and other possible etiologies of diseases, gland biopsy was performed.IgG4-DS has been considered to be a subtype of SS because of certain histopathological similarities, particularly lymphocytic infiltration.,9 Another similar entity, Küttner (KT), a chronic sclerosing sialadenitis that presents with asymmetrical firm swelling of the submandibular glands, is also associated with prominent infiltration of IgG4-positive plasmacytes. In MD, the benign enlargement of lacrimal and salivary glands is persistent, and secretory dysfunction is either minor or not detectable; it also lacks anti-SSA and anti-SSB antibodies. Sialography, sonography, and FDG PET/CT may provide information for differentiation between SS and MD.,11 In our case, initially the lacrimal and salivary swelling, like in SS, occurred repeatedly and disappeared without treatment. Although steroids were effective, swelling of the lacrimal and salivary glands recurred and serum IgG4 levels increased when steroids were discontinued.Complications of MD and various diseases encompassed by IgG4-RSD include autoimmune pancreatitis, retroperitoneal fibrosis, tubulointerstitial nephritis, autoimmune hypophysitis, Riedel thyroiditis, interstitial pneumonitis, prostatitis, lymphadenopathy, inflammatory aortic aneurysm, and inflammatory pseudotumor, all of which exhibit IgG4 involvement in their pathogenesis. IgG4-RSD showed uptake at various sites including hilar, paraaortic, and mediastinal lymph nodes, lacrimal, parotid, submandibular glands, lung, pancreas, and kidney. Thus, the 2 entities showed overlapping regions of gallium uptake. Though in our case pathological studies were not done on all of the gallium-positive lesions, all of the gallium-avid lesions in our case showed complete remission after steroid treatment. The incidental finding of autoimmune pancreatitis was also found to have resolved on follow-up gallium SPECT/CT. SPECT/CT also showed the uptake peripherally to the kidneys as perirenal pseudotumor, not only or instead of tubulointerstitial nephritis. FDG PET has also been studied to evaluate IgG4-RSD.,5Gallium scanning is a nuclear medicine imaging method that is used to evaluate active inflammatory processed. A study of gallium scanning focused on comparison between sarcoidosis and IgG4 disease showed uptake in different patients at variable sites including mediastinal, hilar, supraclavicular, inguinal, submandibular and paraaortic lymph nodes, lacrimal and parotid glands, lung, heart, spleen, kidney, and pancreas. IgG4-RSD relapses are frequent after treatment discontinuation. Relapses usually occur relatively rapidly, but can also occur after a long period of time. Involvement of more than 1 organ or lymph nodes may be associated with poor clinical outcomes.,15Although the efficacy of corticosteroids for the treatment of IgG4-RD has been established, second- or third-line treatments are frequently required.–5,16,17 Gallium scan can find clinically unfound lesions of IgG4-RSD, and probably can differential KT from MD if asymmetric salivary uptake. Although lacrimal uptake probably physiologic, SPECT/CT can offer the differentiation of pathological enlargement in the CT images. Pancreatic uptake can be easily recognized by SPECT/CT. The pattern of FDG uptake on PET/CT has been shown to support a diagnosis of IgG4-RSD. In addition, FDG PET/CT is more sensitive than conventional radiology for detecting early involvement of IgG4-RSD. As compared with FDG PET/CT, gallium SPECT/CT is much cheaper and more readily available, and offers similar diagnostic efficacy. Gallium SPECT/CT may also be superior to PET/CT because it allows differentiation of renal involvement  and perirenal pseudotumor.Gallium scanning with SPECT/CT and FDG PET/CT may be useful for whole body imaging for evaluation the disease distribution, disease status (active or not), localization, pretherapeutic staging, disease recurrence, therapeutic response, and treatment guidance of IgG4-RSD, and also for guiding tissue biopsy for diagnosis confirmation. An increase in serum IgG4 also can be observed in several other conditions, and is thus not specific to the disease.,21 There are also reported cases of mantel cell lymphoma presenting as IgG4-DS, MD complicated with diffuse large cell lymphoma, ocular adnexal lymphoma associated with IgG4+ chronic sclerosing dacryoadenitis, and cases developing non-Hodgkin lymphoma during follow-up of IgG4-RSD.,22–24 Although chronic inflammation and lymphomas are causally related, the mechanism involved is still unclear.,23Only a small number of IgG4-RSD patients present with typical clinical involvement, normal serum IgG4, typical pathological findings, and positive immunostaining.4In our case, the initial impression after CT scan was suspected lymphoma. Biopsy of the lesion and serum IgG4 testing are essential for a definitive diagnosis of IgG4-DS. Gallium scan with SPECT/CT can identify an appropriate biopsy site, evaluate disease status and range of involvement, and treatment response. It is also a complement to other diagnostic and clinical examinations in terms of functional information. Informed consent was agreed.