Assessing the fidelity of intervention components enables researchers to make informed judgements about the influence of those components on the observed outcome. The ‘Implementing work-related Mental health guidelines in general PRacticE’ (IMPRovE) trial is a hybrid III trial aiming to increase adherence to the ‘Clinical Guidelines for the diagnosis and management of work-related mental health conditions in general practice’. IMPRovE is a multifaceted intervention, with one of the central components being academic detailing (AD). This study describes the fidelity to the protocol for the AD component of the IMPRovE intervention.All AD sessions for the trial were audio-recorded and a sample of 22% were randomly selected for fidelity assessment. Fidelity was assessed using a tailored proforma based on the Modified Conceptual Framework for fidelity assessment, measuring duration, coverage, frequency and content. A descriptive analysis was used to quantify fidelity to the protocol and a content analysis was used to elucidate qualitative aspects of fidelity.A total of eight AD sessions were included in the fidelity assessment. The average fidelity score was 89.2%, ranging from 80 to 100% across the eight sessions. The sessions were on average 47 min long and addressed all of the ten chapters in the guideline. Of the guideline chapters, 9 were frequently discussed. The least frequently discussed chapter related to management of comorbid conditions. Most general practitioner (GP) participants used the AD sessions to discuss challenges with managing secondary mental conditions. In line with the protocol, opinion leaders who delivered the AD sessions largely offered evidence-based strategies aligning with the clinical guideline recommendations.The IMPRovE AD intervention component was delivered to high fidelity. The sessions adhered to the intended duration, coverage, frequency, and content allowing participating GPs to comprehend the implementation of the guideline in their own practice. This study also demonstrates that the Modified Conceptual Fidelity Framework with a mixed methods approach can support the assessment of implementation fidelity of a behavioural intervention in general practice. The findings enhance the trustworthiness of reported outcomes from IMPRovE and show that assessing fidelity is amenable for AD and should be incorporated in other studies using AD.Australian New Zealand Clinical Trials Registry ACTRN 12620001163998, November 2020.The online version contains supplementary material available at 10.1186/s43058-023-00531-2. Contributions to the literatureThis study demonstrates the value of utilising mixed methods to assess fidelity of a complex behavioural intervention.This study identifies the strengths (and limitations) of the Modified Conceptual Framework for Implementation Fidelity as a valid and comprehensive method to assessing fidelity.This study supports the use of this methodology in future studies that assess the implementation fidelity of complex behavioural interventions in general practice.Behavioural interventions aim to facilitate change in a participant’s behaviour with potential for improving health outcomes . These tThere is currently limited consensus on the key elements involved in studying intervention fidelity in randomised controlled trials, including trials of multifaceted behavioural interventions , 7–9. FoThe IMPRovE trial aimed to assess the effectiveness of a multifaceted intervention on the implementation of the ‘Clinical guideline for the diagnosis and management of work-related mental health conditions in general practice’. It investigated the effectiveness of a multifaceted intervention, comprising academic detailing (AD), enrolment in a digital community of practice and the provision of resources, on guideline adherence. . The firIn this paper, we describe the extent to which the AD component of the IMPRovE trial, was delivered according to its pre-defined process and intended function .We utilised the Conceptual Framework for Implementation Fidelity, as proposed by Carroll et al.  and modiMeasurement of adherence to the IMPRovE AD plan includes duration, frequency, coverage and content, as outlined in Table All AD sessions that were delivered within the IMPRovE intervention were audio-recorded. A minimum of 20% of the AD sessions delivered by each opinion leader were chosen for assessment, with 22.8% of all the delivered AD sessions eventually selected. This sample of AD sessions was selected through stratified random sampling, stratified by opinion leader (in order to not bias the sample to any particular opinion leaders’ adherence and to adequately represent each opinion leader who delivered the AD session) and by state. Randomisation was conducted by an independent statistician after all the AD sessions were delivered.We used a mixed method triangulation design, giving equal weight to both quantitative and qualitative data collected and analysed to provide an integrated understanding of the breadth and depth of adherence to the planned design of the AD sessions –17. A prQuantitative scoring criteria for the fidelity assessment were based on the adherence component of an adapted model of the Modified Conceptual Framework for Implementation Fidelity , 10, whiAcademic detailers were employees of the National Prescribing Service (NPS) MedicineWise, an Australian not-for-profit organisation with extensive experience in delivering educational outreach sessions to GPs on therapeutics. Their role during the AD session was to run the session and help facilitate discussion. GP opinion leaders were clinicians well-versed in compensation schemes. They were nominated by project partners, thus demonstrating their leadership amongst their peers. Opinion leaders provided a peer’s voice during the session, facilitating greater engagement from participating GPs . They haQualitative data were analysed using a conventional content analysis approach  which isAll AD sessions were scored using the fidelity coding assessment sheet  treat the person according to their situation; (ii) offer care that is within your scope of practice and use your network to provide collaborative care; and (iii) good work is good for recovery (going to work is part of the recovery).Additional File We were able to demonstrate high fidelity (89.2% on average) in the delivery of the AD component of the IMPRovE intervention using the Conceptual Framework for Implementation Fidelity, as proposed by Carroll et al.  and modiHigh fidelity has been characterised as 80–100% adherence, with less than 50% adherence representing ‘low fidelity’ of intervention delivery . InterveOur high fidelity scores were due to adequate intervention duration, the guideline being discussed frequently, as well as a good coverage of the content delivered throughout the AD sessions. There were however a number of departures from the original academic detailing protocol, and some insights of why these departures occurred are presented below.The sessions were delivered within the intended duration of 50 min ± 10 min. However, it should be noted that in the sample, three of the eight sessions had durations outside the intended range. For sessions with shorter durations, GPs being better versed and confident in guideline recommendations and thereby requiring less time to go over points may have impacted session duration. For sessions with longer durations, these factors may include more intensive discussions about challenges faced by the GPs’ practices, GPs having more questions about clinical guideline recommendations requiring more time for the opinion leader GP to answer, or opinion leaders being unprepared, which may have resulted in more administrative activities at the start of sessions.Throughout the sample of eight AD sessions, more GPs chose the case study for managing a patient with a secondary mental condition. This suggests GPs face a greater challenge or interest in the management of secondary mental health conditions. This may imply that, when educating GPs about work-related mental health conditions, more resources should be allocated towards discussing secondary mental health conditions to assist GPs with diagnosis and management of these kinds of mental health conditions.  It shoulThis study holds the view that interventions should be tailored for participants in different settings, whilst not so flexible that it compromises validity . For insAD was one component in a multifaceted behavioural intervention. There are several interacting factors that may have influenced delivery of the AD session, apart from what could be gleaned from a review of the sessions. These factors will be understood in greater depth and explained through a whole of trial process evaluation. This process evaluation for the study will be published separately.Our approach to fidelity assessment had many advantages. Firstly our data collection, through recording the zoom sessions, was unobtrusive and meant that the researchers did not influence the results. Secondly, content analysis presents a systematic procedure that is easily replicable. Thirdly, it is a highly flexible method requiring little resources to conduct. Finally, this study reinforced the value of utilising a mixed method study design to assess complex behavioural intervention fidelity, allowing us to draw on results from both quantitative and qualitative datasets to inform our understanding of AD fidelity. This research method is not common practice for assessing behavioural intervention fidelity , 23, butThere were however several limitations. Firstly content analysis can be reductive and subjective; however, this was minimised with three researchers assessing fidelity. Secondly, the sample size of eight AD sessions was small. However, we coded the recommended minimum coding of 20–40% of sessions for fidelity studies chosen from a random and stratified sample (by academic detailer and by State) across the delivery of an intervention , to adeqAs there is no consistent approach for assessing fidelity of multifaceted behavioural interventions, future research could focus on creating a consistent, validated method for assessing the fidelity of behavioural interventions in general and of AD sessions in particular. Recent modifications have been suggested for the Modified Conceptual Framework for Implementation Fidelity, such as accounting for adaptations brought by implementers or users to how an intervention was originally designed . TherefoAlthough the use of the framework to assess intervention fidelity has not fully been established, in this study , 26–28, Results from this study should give confidence that the AD portion of the IMPRovE trial intervention was delivered with high fidelity across all AD sessions. As such, there is greater confidence that the IMPRovE trial outcomes reported in the future will be the result of the AD sessions being delivered according to the protocol. High fidelity delivery also allows for a more accurate evaluation of the efficacy of this intervention on trial outcomes.Additional file 1. The IMPRovE trial.Additional file 2. Assessment sheet used for the fidelity coding.Additional file 3. The case studies of the primary mental health patient or secondary mental health patient seen.Additional file 4. Frequency with which clinical questions were discussed in the AD sessions.Additional file 5. Key messages delivered in AD sessions.


Moreover,the analysis of the supramolecular self-assembly of one of the β-turn-containingpeptide models in the solid state reveals that it forms a supramolecularhelical arrangement while maintaining the β-turn structure.The results here presented provide the basis for the use of this azepanequaternary amino acid as a strong β-turn inducer in the searchfor novel peptide-based bioactive molecules, catalysts, and biomaterials.β-Turns are one of the most common secondary structuresfoundin proteins. In the interest of developing novel β-turn inducers,a diastereopure azepane-derived quaternary amino acid has been incorporatedinto a library of simplified tetrapeptide models in order to assessthe effect of the azepane position and peptide sequence on the stabilizationof β-turns. The conformational analysis of these peptides bymolecular modeling, NMR spectroscopy, and X-ray crystallography showedthat this azepane amino acid is an effective β-turn inducerwhen incorporated at the  This quaternary amino acid displays a set ofproperties that make it especially suited for its application as peptidesecondary structure inducer. There are not many studies on the abilityof seven-membered quaternary amino acids to constrain peptide conformationson their own, i.e., without the synergistic effect of additional restrictedresidues.55 The azepane heterocycle in 1 also enablesthe incorporation of structural diversity and functionality in theconstrained peptides through the Alloc-protected nitrogen, for example,fluorescent dyes or affinity labels for visualization and immobilization.In addition, it contains two chiral centers, which can be easily definedin the synthesis step opening the possibility of studying the effectof chirality in the induction of secondary structure elements. Infact, we have reported the synthesis of the four possible diastereoisomersof the 2-oxoazepane derivative III.53 In a previous report, we have also demonstrated that theazepane 1 is an effective inducer of 310 helicesin short alanine-based pentapeptide models.56 In this article, we report the induction of single β-turnsby this quaternary amino acid in the shortest possible peptide model.We present a study of the key factors governing the folding of thepeptide chain into a β-turn, such as the position of the constrainedamino acid in the sequence and the compatibility with proteinogenicamino acids in the remaining central position of the turn.We have previously described the stereoselectivesynthesis of aquaternary azepane amino acid from commercial ornithine derivatives1.53 The 1 were first analyzed using moleculardynamics (MD) simulations with the Amber 10 suite of programs.57 Simplified tetrapeptide systems were used inwhich the N-terminal amino acid (i) was replaced by an acetyl group and the C-terminal(i + 3) by a N-methylamide. Theβ-turn induction was evaluated through its characteristic topographicparameters, i.e., H-bond distance COi–NHi+3 and the backbone dihedral angles of thecentral residues. We first studied the influence of the position ofthe constrained amino acid within the central residues of alanine-basedtetrapeptide models. As a reference, it is worth mentioning that theconformational properties of alanine-based short peptides have beenanalyzed in depth both theoretically and experimentally, showing astrong tendency for extended conformations.60 When the azepaneresidue was incorporated at the i + 1 position, molecularmodeling results showed that the 100% of the conformers within a 3kcal·mol–1 window from the global minimum stabilizetype I or III β-turns. At the i + 2 position,the global minimum also displays a β-turn, but there is anotherfamily of conformers within a 3 kcal·mol–1 windowin which the characteristic β-turn H-bond is not present (seethe Supporting Information for details).Thus, MD studies suggest that the incorporation of 1 atthe i + 1 position is preferred over that at the i + 2 position, with a higher degree of β-turn induction.This is in agreement with the preferred position for other constrainedamino acids, as the restriction in the dihedral angles imposed bythese residues at such position facilitates the β-turn nucleation.62The conformational preferencesof tetrapeptide models incorporatingthe azepane amino acid i + 1 position,we next evaluated the effect of the amino acid side chain at position i + 2, again using MD simulations. Calculations were performedin tetrapeptide models incorporating the azepane residue at the i + 1 position and the 20 proteinogenic amino acids at the i + 2 position. MD studies suggested that the azepane derivativeis a strong β-turn inducer, except when it is combined withGln, Arg, and Asp at the i + 2 position. In thesecases, less than 50% of the conformers within a 3 kcal·mol–1 window from the global minimum display a β-turnstructure. The presence of polar residues tends to destabilize theβ-turn due to competing H-bond formation between the side chainand the peptide backbone (see the Supporting Information for details). Taking these results into account, we selected a representativeset of amino acids to prepare a library of Boc-Aze(Alloc)-Xaa-NHMetetrapeptide models, where Xaa was chosen to be alanine, valine, leucine,or phenylalanine (residues with a high tendency to adopt β-turns)as well as serine, lysine, or glycine (with a medium tendency towardβ-turns). This small library covers from hydrophobic aliphaticand aromatic residues to polar ones, displaying different side chainbranching patterns. Additionally, we also prepared the correspondingalanine-based tetrapeptide model Boc-Ala-Aze(Alloc)-NHMe to experimentallyassess the influence of the azepane position in the reverse turn induction.With the azepane fixed at the 2-8 were obtained through peptide coupling betweenthe azepane residue 1 for amide protons equal to or lower than 3 ppb·K–1  are indicative of such NHs participating inan intramolecular H-bond.64 In contrast, solvent-exposedamide protons typically display values over 4 ppb·K–1, while values within 3–4 ppb·K–1 arenot conclusive. 1H NMR spectra forcompound 2 at different temperatures, as well as theplot of the chemical shift variation with temperature (Δδ/ΔT). The observed linear correlation was used to calculatethe temperature coefficient for all the amide protons. For compound 2, only NHi+3 has a temperaturecoefficient compatible with the presence of an intramolecular H-bond,suggesting the adoption of a β-turn in solution. It is worthpointing out that the splitting of the NH signal corresponding tothe i + 1 residue at the lowest temperature is likelydue to rotamers of the N-Alloc group, which coalescewhen the temperature increases.The conformational preferences in solution oftetrapeptide models 2, the temperature coefficients for all the amide protonsin derivatives 3–8 and 10 were extractedfrom VT-NMR experiments . Compounds 3 (Ala), 5 (Leu), and 7 (Ser) show the same behavior as the glycineanalog 2. Only the NHi+3 protonparticipates in an intramolecular H-bond, suggesting the stabilizationof the β-turn structure. They all contain a β-methylenegroup in the side chain, thus providing the necessary flexibilityfor the adoption of the β-turn structure. For compounds 4 , 6 (Phe), and 8 (Lys), theNHi+3 temperature coefficient falls inthe uncertainty range. Although we cannot fully conclude the formationof the β-turn in solution, the temperature coefficients forPhe (6) and Lys (8) are close to 3 ppb·K–1, suggesting some degree of β-turn folding.The valine-derived tetrapeptide model 4 clearly showsdistinct behavior, with the NHi+2 formingan intramolecular bond. This is compatible with the stabilizationof a γ-turn instead of a β-turn. γ-Turns are thesecond most common reverse turn in proteins after β-turns, formedby three consecutive residues with a H-bond between the COi and the NHi+2.65 Thus, this result demonstrates that branchingat the β-position of the side chain seems to destabilize theβ-turn conformation.Following the same protocol as that for compound 10 with the azepane residueat the i + 2 position, both NHi+2 andNHi+3 have temperature coefficients inthe uncertainty range, so there is no strong evidence of the formationof either a γ- or β-turn. Comparing the NMR data of 3 and 10, the incorporation of the constrainedamino acid at the i + 1 position seems to be morefavorable for the stabilization of the β-turn, in line withthe data obtained from the molecular modeling studies.For compound 2 and 3. N-methylamide moiety (residue i + 3) and the Boccarbonyl oxygen (residue i), characteristic of aβ-turn. Both β-turn structures are quite similar as observedwhen the two crystal structures are superimposed . In contrast, the supramolecular arrangement observedin the crystal structure of peptide derivative 3 belongsto the tetragonal system. It forms supramolecular right-handed helicalassemblies with small internal pores  and COi+1 of moleculeA and the NHi+1 and NHi+2 of molecule B, respectively  seems to largelydisrupt the β-turn. We have also paid attention to the supramolecularself-assembly behavior of two β-turn-containing peptide modelsin the solid state. When alanine is incorporated at the i + 2 residue, the tetrapeptide model self-assembles into a supramolecularright-handed helical structure, stabilized by a defined network ofintermolecular H-bonds along with the characteristic β-turnintramolecular H-bond. The results here presented therefore providethe basis for the use of azepane quaternary amino acids as effectiveβ-turn inducers with widespread potential applications in thedevelopment of novel bioactive molecules, catalysts, and biomaterials.The stabilization of the peptide secondarystructure elements isof interest to achieve a fundamental understanding of complex protein–proteininteractions in the search of novel therapeutic agents. In particular,β-turns are some of the most common secondary structures foundin proteins. They play a key role in protein folding and stabilizationas well as in protein–protein and peptide–protein recognition.Moreover, they are an attractive scaffold with relevant applicationsin peptide-based catalysis and in supramolecular materials. The useof constrained quaternary amino acids is one of the most common strategiesused to induce reverse turns in short peptide sequences. In this context,we have previously reported the stereoselective synthesis of a novelazepane-derived quaternary amino acid.1 in dry THF (9 mL) was treated with H-Gly-NHMe·TFA , (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate, and triethylamine .After the mixture was stirred at room temperature for two days, thesolvent was evaporated to dryness. The crude was dissolved in EtOAcand washed successively with 10% aq. soln. citric acid (2×),10% aq. soln. NaHCO3 (2×), H2O (1×),and brine (1×). The organic phase was dried over MgSO4 and evaporated to dryness. The residue was purified by centrifugalthin-layer chromatography using a gradient from 200:1 to 10:1 of MeOH/CH2Cl2, yielding 2 as a white, amorphoussolid . HPLC: tR = 6.26min (gradient from 15% to 95% CH3CN/0.1% formic acid inH2O/0.1% formic acid over 10 min). 1H NMR : δ 7.96 , 7.44 , 6.95 , 5.93,5.27 ,5.18 ,4.53 , 3.70 , 3.52–3.56 , 3.35 , 3.09 , 2.58 , 2.27 , 2.22, 1.69 , 1.65 , 1.51 ,1.43 , 0.82 . 13C{1H} NMR :δ 173.6 and 169.3 (CONH), 155.3 , 155.6 , 155.1 , 133.5 , 116.4 , 78.7 , 64.8 , 63.4 (4-C), 47.2, 46.9 , 45.6 , 45.3 , 42.4 (α-C),39.1 (3-C), 30.2 , 30.5 , 28.0 , 25.1 (N–CH3), 20.6 , 20.1 ,13.0 (3-CH3). MS (ES+): m/z = 427.19 [M + H]+, 853.43 [2M+H]+. Elementalanalysis: calcd (%) for C20H34N4O6 C 56.32, H 8.04, N, 13.14. Found (%): C 56.25, H 8.08, N13.19.A solutionof the azepane-derived amino acid 1 in dry CH2Cl2 (7 mL) was treated with (benzotriazol-1-yloxy)tris(dimethylamino)phosphoniumhexafluorophosphate , H-Ala-NHMe·HCl, and triethylamine . Afterthe reaction mixture was stirred at room temperature for 15 h, thesolution was diluted with EtOAc and washed successively with 10% aq.soln. citric acid (2×), 10% aq. soln. NaHCO3 (2×),H2O (1×), and brine (1×). The organic phase wasdried over Na2SO4 and evaporated to dryness.The residue was purified on a silica gel column using EtOAc/hexane(8:1) as solvent, yielding 3 as a white, amorphous solid. HPLC: tR = 10.99 min (gradientfrom 5% to 80% CH3CN/0.05% TFA in H2O/0.05%TFA over 20 min). Caution! The use of BOP as couplingreagent is discouraged because of the formation of carcinogenic HMPA,with PyBOP being a convenient alternative. 1H NMR : δ 7.83 , 7.80 , 7.62 , 7.00 , 6.94 , 5.92 ,5.26 ,5.18 ,4.52 , 4.24 , 4.23 , 3.58 , 3.45 ,3.29 , 3.11 , 3.01 ,2.56 , 2.30 , 2.07 , 1.68 , 1.63 ,1.46 , 1.42 , 1.21 , 0.82 , 0.80 . 13C{1H} NMR: δ 173.1 and 172.5 (CONH), 155.8 and 155.4, 155.7 and 155.2 ,133.6 , 116.7 , 116.5, 78.9 , 78.8 , 65.0, 63.7 (4-C), 48.2 , 47.7 , 47.1 , 45.5 , 45.3 , 40.8 (3-C), 30.0(5-C), 28.2 , 25.5 (NCH3), 20.8 , 20.1 , 17.6 , 13.3 , 13.2 . MS (ES+): m/z = 441.2 [M + H]+, 463.3 [M + Na]+, 881.7 [2M+H]+, 903.5 [2M+Na]+. Elementalanalysis: calcd (%) for C21H36N4O6 C 57.25, H 8.24, N 12.72. Found (%): C 57.08, H 8.07, N 12.80.A solutionof the azepane-derived amino acid 2–8 and 10 at 7–10mM concentration in DMSO-d6 were preparedand transferred to an NMR tube. 1H NMR spectra were acquiredat different temperatures (25–85 and 10 °C steps). Thevariation of the amide proton chemical shifts was plotted against the variation of temperature , and the data fitted to a straight line. The slope of the equationrepresents the temperature coefficient .Solutions of compounds 2 (1.5 mg) was dissolved in MeOH (1 mL) andthe mixture was put in a crystallizing dish, resulting in spontaneouscrystallization after 12 days at 4 °C in a closed jar. X-raydiffraction was performed at the BL13-XALOC beamline at ALBA Synchrotronwith the collaboration of ALBA staff.Purecompound 3 (5 mg) was dissolved in MeOH (5 mL)and the mixture was put in a crystallizing dish, resulting in spontaneouscrystallization after 20 days at 4 °C in a closed jar. X-raydiffraction was performed in a Bruker MicroStar 2.7 kW, with a four-circlegoniometer, with κ-geometry, and Bruker CCD detector, usingCuKα radiation.Pure compound


A graphene/poly(methyl methacrylate) (PMMA) closed cavity resonator with a resonant frequency at around 160 kHz has been fabricated. A six-layer graphene structure with a 450 nm PMMA laminated layer has been dry-transferred onto the closed cavity with an air gap of 105  Graphene has aroused much attention from the research and industrial community since it was discovered  due to iThe unique mechanical and electrical properties of graphene also show that it is an interesting material for ultrasonic sensing. The large Young’s modulus of graphene suggests that graphene-based membranes can be easily designed to reach a high resonant frequency, typically in the range of megahertz ,21,24,25To date, there has been limited study of graphene-based resonators reported to cover the ultrasonic frequency range between 20 kHz and 1 MHz. To achieve a relatively lower ultrasonic frequency range (below 1MHz), a larger size of graphene-base membranes is required, which increases the complexity of graphene transfer and the difficulty in suspending the graphene-based membrane over the substrate without collapse. To address these two problems, an ultrasonic transducer [In this work, a fully clamped graphene/PMMA closed cavity resonator at a resonant frequency less than 200 kHz will be presented. To avoid the membrane being transferred on the supporting ring and assembled onto the substrate afterwards, a one-step graphene dry transfer process has been developed by our group . A six-lt and R is the radius of the membrane; An optical image of the graphene/PMMA ultrasonic closed cavity resonator is shown in The fabrication process of the graphene/PMMA closed cavity ultrasonic sensor is shown in lication . In thisThe graphene/PMMA ultrasonic resonator has been actuated mechanically, electro-statically and electro-thermally to characterize its dynamic behavior. For the mechanical actuation, the graphene/PMMA ultrasonic resonator has been placed and attached to the piezoelectric disk. By applying a voltage to the piezoelectric disk, ultrasound vibration has been generated and actuated the substrate of the resonator. For the electro-static actuation, silver paste has been attached to the graphene layer to work as the top electrode. The patterns etched into the silicon with the resistivity of 1–10 For mechanical actuation, the varying AC voltage from 0.2 V to 3 V and a constant 1 V DC voltage with a frequency sweep from 150 kHz to 220 kHz have been applied to the piezo-disk. The frequency response of the membrane is shown in For electro-static actuation, the voltage of constant 1 V DC and varying AC voltage from 4 V and 9 V with a frequency sweep between 120 kHz to 200 kHz have been applied between the membrane and substrate. The frequency response of the graphene/PMMA membrane is shown in For electro-thermal actuation, the frequency response of the resonator actuated by increasing 1 V to 9 V AC and 1 V DC voltage applied to the silver paste on the graphene/PMMA membrane with the frequency range from 140 kHz to 220 kHz is illustrated in The vibration amplitude of the graphene/PMMA membrane over the closed cavity is shown in The dynamic behavior of the graphene/PMMA closed cavity ultrasonic sensor is summarized in oftening ,33,34 anoftening .In mechanical and electro-static actuation, the change in frequency shift and quality factor versus the input signal has been detected to be relatively small compared to the electro-thermal case, as shown in In the case of the electro-thermal actuation, the change in quality factor can be temperature-related. The frequency shift at resonance is evident in the frequency response c. The reAs shown in The change in the quality factor has been studied in the resonator under the electro-thermal actuation. The quality factor has been measured to increase from around 36 to 40 when the AC voltage rises from 2 V and 3 V. A decrease in the quality factor has been observed when the AC voltage changes from 3 V to 8 V. A small increase in the quality factor was measured when the AC voltage increased from 8 V to 9 V, as shown in The mode shapes at the resonant frequencies obtained by different actuation methods are shown in The overall tension and strain can be derived from Equation  and the This is the first time that a graphene-based closed cavity ultrasonic resonator has been fabricated and actuated in the atmosphere successfully. Using the graphene dry transfer method with Kapton tape as the supporting frame, developed by our group, a graphene/PMMA closed cavity sensor at a resonant frequency of around 160 kHz has been fabricated. The graphene/PMMA closed cavity resonator has been actuated mechanically, electro-statically and electro-thermally. The amplitude of the membrane has been observed to be linear with AC voltage for the mechanical and electro-static actuation and quadratic with AC voltage for the electro-thermal actuation. The membrane has been observed to exhibit a  mode at the resonant frequencies. The membrane can be tuned by up to 4% by varying the AC voltage via the electrodes connected to the graphene/PMMA membrane, and a nonlinear frequency shift under electro-thermal actuation has been detected. The strain in the membrane under the three actuation methods has been estimated to be around 0.08%. The device shows the possibility of applying graphene as an ultrasonic detector and opens a door to the fabrication of graphene-based ultrasonic sensors at a lower ultrasonic frequency of less than 200 kHz.


N,N′-bis(3-aminopropyl)ethylenediamine) and 4A-3P -1,3-propanediamine) crosslinked with terephthaloyl chloride (TPC) on a crosslinked polyacryonitrile (PAN) support through interfacial polymerization (IP). The presence of multiple hydrophobic –CH2– groups in the structures of the aliphatic amines 4A and 4A-3P develops hydrophobic sites in the hydrophilic polyamide active layers of the membranes. In addition, 4A has two secondary amino groups separated by ethylene (–CH2–CH2–) groups, whereas in 4A-3P, the two secondary amino groups are separated by propylene (–CH2–CH2–CH2–) leading to variation in the structural features and performance of the two membranes. Both membranes were fully characterized by several membrane characterization techniques and applied for OSN/SRNF using both polar  and non-polar (n-hexane and toluene) solvents. Different dyes  were used as model solutes during the filtration experiment. The 4A-3P-TPC@crosslinked PAN showed n-hexane and toluene flux of 109.9 LMH and 95.5 LMH, respectively. The Congo red (CR) showed the highest rejection, reaching 99.1% for the 4A-TPC@Crosslinked PAN membrane and 98.8% for the 4A-3P-TPC@Crosslinked PAN membrane.Given the huge significance of organic solvents in several industrial processes, the use of membranes for recovering the solvents has evolved into an industrially viable process. The current work has been focused on studying the effect of minor changes in the chemistry of the reacting monomers on the organic solvent nanofiltration/solvent resistance nanofiltration (OSN/SRNF) performance of the membranes. The two aliphatic amines with varying aliphatic chain lengths between primary and secondary amines were selected for this purpose. Based on the structure of the resultant active layer, the Janus nanofiltration performance of the membrane was evaluated. The two membranes, 4A-TPC@crosslinked PAN and 4A-3P@crosslinked PAN were fabricated by using two different tetra-amines, 4A ( Hence, the chemical industries are constantly improving their processes to (i) meet the stringent environmental regulations and (ii) increase their profit2. Among the chemical industries, the pharmaceutical industries are heavily dependent on the consumption of organic solvents, where organic solvents account for 80–90% of the total mass in the process3. The most common solvent wastes generated by pharmaceutical companies include methanol, dichloromethane, toluene, acetonitrile, and chloroform. Among the different organic solvent wastes, methanol waste has been estimated to reach 44.8 × 106 kg per year. Compared to conventional processes such as distillation and adsorption, membrane-based separations are less energy intensive, eco-friendly, have a footprint, cost-effective for product isolation and concentration4.Organic solvents are of prime significance in several industrial processes, ranging from pharmaceuticals to petrochemicals. The reuse of highly precious organic solvents is of utmost economic significance as it can lower the demand for fresh organic solvents7, which is due to certain salient features of the TFC membranes such as chemical and physical stability, adaptability to different feed compositions, and easy availability with a wide range of pore sizes for a desired application10. TFC membranes consist of a thin selective layer deposited on top of a porous polymeric ultrafiltration support. Generally, the porous polymeric ultrafiltration support is prepared through wet phase inversion by using water as a non-solvent in the process. On the other hand, the active layer is grown on the ultrafiltration support through interfacial polymerization (IP)11. Given the versatility of the IP process, a huge variety of TFC membranes have been fabricated in the literature by either altering the chemistry of reacting monomers or changing the other parameters of IP12.With the development of thin film composite (TFC) membranes, several separation processes have been optimized13. Another group reported the green synthesis of a PA TFC membrane by using polyethylenimine (PEI) as an amine solution cross-linked with TMC on porous PAN support. The IP reaction was carried out using decanoic acid as the organic phase. The membrane was able to reject the majority of the tested dyes with a molecular weight cut-off (MWCO) of 650 g mol−114. Recently, molecule-based design strategies have been explored by the research community for manipulating the pore structure and physicochemical properties of organic solvent nanofiltration/solvent-resistant nanofiltration (OSN/SRNF)15 membranes. In a recent study by Alduraiei et al., fluorine-containing diamine, 5-trifluoromethyl-1,3-phynelenediamine (TFMPD), was crosslinked with TMC and 4,4′-(hexafluoroisopropylidene)bis(benzoyl chloride) (HFBC) during IP. Since the presence of fluorine atoms in the active layer gives a hydrophobic feature to the membrane, the resulting membranes were used for cleaning non-polar solvents. The TFMPD-HFBC membrane showed a toluene permeance of 10 L m−2 h−1 bar−116. Thijs et al. used a novel approach to tune the chemistry of the active layer of the TFC membrane by growing an active layer consisting of polymers of intrinsic microporosity (PIMs). In their work, several amine monomers with 2.5–4 amines per molecule were crosslinked with binaphthalene-based di(acid chloride) through IP on Matrimid support. The fabricated membrane showed an increase in acetonitrile permeance by a factor of 20 compared to a conventional MPD/TMC membrane. By comparing the structure and performance of the different fabricated membranes, the team found that changing the number of amine groups per molecule and altering the length of alkyl chains on binaphthalene-based di(acid chloride) altered the performance of the membranes17. In one such instance, Liu et al. constructed Janus pathways by using cyclodextrin (CD) in the membrane. The presence of CD in the constructed OSN/SRNF membrane allowed passage of both polar and non-polar solvents, which is attributed to the inner hydrophobic cavities and outer hydrophilic spaces of CD18. However, the larger pore size of CD lowers the rejection of the membrane. Similarly, Li et al. developed a Janus membrane by using β-cyclodextrin (BCD) as a monomer during IP on a polyelectrolytes-based interlayer developed through layer-by-layer self-assembly. The membrane was able to permeate both polar and non-polar solvents with permeances reaching 5.8 LMH/bar for methanol and 7.0 LMH/bar for hexane along with a 91.9% rejection of methyl orange19. In another work, Li et al. used m-xylylene diamine (m-XDA) as an aqueous monomer crosslinked with TMC leading to a Janus membrane for the passage of both polar and non-polar solvents. The addition of an additional methylene –CH2– group in m-XDA rendered the hydrophobic features to the hydrophilic polyamide active layer of the membrane20. Hence, minor variations at the molecular level of reacting monomers lead to different structural features targeting a specific application. Therefore, the need of the day is to come up with new membranes with structural, physical and chemical stability by tuning the chemistry of reacting monomers.The variations in the chemistry of the active layers of TFC membranes have led to remarkable applications. Solomon et al. reported a polyamide (PA) TFC membrane by using conventional meta-phenylenediamine (MPD) as an aqueous monomer and trimesoyl chloride (TMC) as a non-aqueous monomer during IP. The membrane was prepared on a polyimide (PI) substrate and showed solvent resistance2– groups in the structure of tetra-amines (4A and 4A-3P) introduced several hydrophobic sites inside the hydrophilic polyamide active layer leading to the passage of both polar  and non-polar (n-hexane and toluene) solvents. Moreover, another variation in the chemistry of the newly developed polyamide active layer was also introduced as in the case of 4A both primary (–NH2) and secondary (–NH) amines were separated by ethylene –CH2–CH2– groups. In the case of 4A-3P, the two primary (–NH2) amino groups are separated by ethylene –CH2–CH2– and the two secondary amino (–NH) groups are separated by propylene –CH2–CH2–CH2– chain. This variation at the molecular level could potentially lead to different morphological and structural features leading to varied OSN performance. The fabricated membranes were extensively characterized by using a scanning electron microscope (SEM), attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, water contact angle (WCA), atomic force microscopy (AFM), energy dispersive X-ray (EDX) and elemental mapping. The fabricated membranes were used for OSN/SRNF applications by using both polar and non-polar solvents while different dyes were used as model solutes during filtration experiments.The current study was carried out by using the linear aliphatic amines 4A-3P and 4A on a crosslinked PAN support. The study was carried out through interfacial polymerization between either 4A-3P and TPC or 4A and TPC on crosslinked PAN support. In comparison to the previous studies where cyclic amines such as piperazine or aromatic amines such as meta-phenylenediamine (MPD) were used, we have used linear aliphatic amines 4A and 4A-3P crosslinked with an organic phase containing terephthaloyl chloride (TPC) as a cross-linker. The presence of multiple methylene –CHN,N′-Bis(2-aminoethyl)-1,3-propanediamine , N,N′-bis(3-aminopropyl)ethylenediamine , Triethylamine , Polyacrylonitrile , n-Hexane (≥ 99%), N,N′-dimethyl formamide , Polyethylene Terephthalate (PET) fabric, Methylene blue , Eriochrome black T , and Congo red  were all purchased from Sigma . Deionized (DI) water from the in-lab setup was used for all the experiments.Terephthaloyl chloride , 2–NH2) aqueous solution at 70 °C for 6 h. Then the crosslinked PAN support was thoroughly washed with an excess of DI water.The PAN dope solution was prepared by dissolving 12 g of perfectly dried PAN in 88 g of DMF. The solution was stirred at room temperature overnight, leading to a transparent solution of PAN. The PAN dope solution was allowed to stand until all of the air bubbles were completely removed. The PAN support was prepared by spreading an appropriate amount of PAN dope solution on a PET sheet affixed to a glass plate. Then the PAN was cast by using a custom-made Doctor’s blade (100 µm slit width) on PET support. Immediately after casting PAN, the support was dipped in a deionized water bath and allowed to stand, leading to phase inversion. Hence, PAN/PET ultrafiltration support was fabricated. The PAN support was crosslinked by dipping an appropriate piece of PAN/PET support in a 25% (v/v) hydrazine  −1, this can be attributed to the stretching vibration of the N–H bond of the amide linkage (–CO–NH) of the polyamide active layer of 4A-TPC@Crosslinked PAN and 4A-3P-TPC@crosslinked PAN. Similarly, in the case of crosslinked PAN, the 3600–3200 cm−1 broad peak can be attributed to the existence of the –N–H bond generated during crosslinking using hydrazine (NH2–NH2) as a crosslinking agent. As we move further, there is a short but relatively sharp peak located at 2900–2800 cm−1 in all of the FTIR spectra of all membranes including crosslinked PAN. This characteristic peak is due to –C–H stretching of the aliphatic backbones of the polyamide active layer due to constituent amines 4A, 4A-3P and PAN support. Furthermore, a very sharp and deep peak was visible at around 2200 cm−1 which is due to residual nitrile (–C≡N) groups in PAN. A relatively medium peak of crosslinked PAN can be seen in the region of 1700–1650 cm−1 which can be attributed to the stretching vibration of C=C/C=N bonds that originated during the crosslinking event of PAN with hydrazine. However, in the case of 4A-TPC@crosslinked PAN and 4A-3P-TPC@crosslinked PAN membranes, a doublet peak is shown in the region of 1700–1600 cm−1. In addition to C=C/C=N bonds of PAN, 4A-TPC@Crosslinked PAN and 4A-3P-TPC@Crosslinked PAN membranes have carbonyl functional group (> C=O) of the primary/secondary amide linkages of polyamide active layers. The doublet in the region of 1700–1600 cm−1 is attributed to the C=C/C=N and > C=O bonds of PAN and polyamide active layers. Therefore, the ATR-FTIR spectra of crosslinked PAN, 4A-TPC@Crosslinked PAN and 4A-3P-TPC@Crosslinked PAN membranes have confirmed the presence of all the functional groups and bonds in their structure  analysis as shown in Fig. The elemental mapping analysis revealed a uniform distribution of all the elements throughout the entire membrane Fig. .Figure 72) are ethyl chains. This particular structure of 4A-3P allows flexibility of binding of TPC with the neighbouring 4A-3P chains. However, in the case of 4A amine, the secondary amino groups (–NH–) are separated by ethyl chains and primary amino groups (–NH2) are separated by propyl chains. As the secondary amino groups are close together the incorporation of TPC in between is not flexible and uniform . It was observed that the WCA of the Hydrazine Crosslinked PAN support was found to be 45.9° and hence the crosslinked PAN support was considerably hydrophilic. The hydrophilicity of crosslinked PAN support can be attributed to the contribution of hydrazine introducing amino groups in the support. Furthermore, the hydrophilicity of crosslinked PAN can also be due to partial hydrolysis of the PAN support. However, after the growth of the polyamide active layer on crosslinked PAN support, the membrane surface hydrophilicity decreased as the WCA increased (65.1°) in the case of 4A-TPC@Crosslinked PAN membrane and 59.9° for 4A-3P-TPC@Crosslinked PAN Fig. . This mia) and root mean square roughness (Rq) were found to increase in the following order: crosslinked PAN > 4A-TPC@Crosslinked PAN membrane > 4A-3P-TPC@Crosslinked PAN membrane  of 4A-3P-TPC@Crosslinked PAN membrane was higher (12.8 nm) than 4A-TPC@Crosslinked PAN membrane. The higher Ra values in the case of 4A-3P-TPC@Crosslinked PAN membrane were attributed to the presence of large valleys and deep ridges as seen in Fig. Another salient feature of membranes is their surface roughness which was measured by recording atomic force microscopy (AFM) images of the crosslinked PAN, 4A-TPC@Crosslinked PAN membrane and 4A-3P-TPC@Crosslinked PAN membrane. The membrane average roughness  showed the highest permeate flux, reaching 80 LMH, while isopropanol possessed the lowest permeate flux of 3 LMH and had the highest viscosity of 1.92 cP.The variation in permeate flux can also be explained by considering another factor, which is the viscosity of the solvent. It has been observed that as the viscosity of the solvent increases, the permeate flux decreases in an inverse pattern. The inverse relationship between viscosity and permeate flux can be seen in Fig. The separation potential of OSN/SRNF membranes was also studied by using different dyes such as CR, EBT, and MB as model solutes. The solution of each dye was prepared by dissolving an appropriate amount of the dye in methanol at a concentration of 10 ppm. The feed of each dye was loaded in the dead-end cell and filtration was carried out at 4 bar. The flux of both membranes remained constant for all of the tested dyes Fig. a,b. DuriFigure The OSN/SRNF performances of the current membranes have been compared with those of similar membranes from the literature as given in Table −2 h−1 as the pressure was increased from 4 to 10 bar. The 4A-3P-TPC@Crosslinked PAN membrane possessed n-hexane and toluene flux of 109.9 and 95.5 L m−2 h−1 respectively. The Congo red showed the highest rejection reaching 99.1% for 4A-TPC@Crosslinked PAN membrane and 98.8% for the 4A-3P-TPC@Crosslinked PAN membrane. In the case of Eriochrome Black T, the rejection stayed at 99.1% for 4A-TPC@Crosslinked PAN membrane while it was slightly reduced for 4A-3P-TPC@Crosslinked PAN membrane reaching 94.4%. Based on the rejection and flux data, the ethylene moeity between the two secondary amines led to a denser active layer compared to the propylene chain between the secondary amine groups of aliphatic amines.Interfacial polymerization has been successfully utilized for the fabrication of two thin film composite organic solvent nanofiltration/solvent resistant nanofiltration membranes. The structure of the polyamide active layers was tuned by slightly altering the chemistry of the reacting amines. Two different linear aliphatic amines, 4A with ethylene and 4A-3P with propylene, were used as aqueous amine solutions during IP on crosslinked PAN support. The resultant organic solvent nanofiltration/solvent resistant nanofiltration membranes 4A-TPC@Crosslinked PAN and 4A-3P-TPC@Crosslinked PAN membranes, were thoroughly characterized through scanning electron microscopy, water contact angle, energy disperse X-ray analysis, elemental mapping, attenuated total reflectance Fourier transform infrared spectrometry and atomic force microscopy. During organic solvent nanofiltration experiments, the 4A-TPC@Crosslinked PAN membrane showed an increase in permeate flux of n-hexane and toulene from 33.8 to 81.1 L mSupplementary Figures.


The search for highly efficient adsorbent materials remains a significant requirement in the field of adsorption for wastewater treatment. Computational study can highly contribute to the identification of efficient material. In this work, we propose a computational approach to study the adsorption of four cationic basic dyes, basic blue 26 (BB26), basic green 1 (BG1), basic yellow 2 (BY2), and basic red 1 (BR1), onto two models of graphene oxide as adsorbents. The main objectives of this study are the assessment of the adsorption capacity of the graphene oxide towards basic dyes and the evaluation of the environmental and temperature effects on the adsorption capacity. Quantum theory of atoms in molecules (QTAIM) analysis has been used to understand the interactions between the dyes and graphene oxides. In addition, adsorption free energies of the dyes onto graphene oxides are calculated in gas and solvent phases for temperatures varying from 200 to 400 K. As a result, the adsorption free energy varies linearly depending on the temperature, highlighting the importance of temperature effects in the adsorption processes. Furthermore, the results indicate that the environment (through the solvation) considerably affects the calculated adsorption free energies. Overall, the results show that the two models of graphene oxide used in this work are efficient for removing dyes from wastewater.We have optimized the complexes formed by the interaction of dyes with graphene oxides at the PW6B95-D3/def2-SVP level of theory. The SMD solvation model realizes the implicit solvation, and water is used as the solvent. Calculations are performed using the Gaussian 16 suite of program. QTAIM analysis is performed using the AIMAll program. Gibbs free energies as function of temperature are calculated using the TEMPO program.The online version contains supplementary material available at 10.1007/s00894-023-05761-8. Organic compounds, dyes, antioxidants, and pharmaceutical and personal care products are the primary pollutants that cause directly and indirectly damage and threaten human health. Emerging dyes are used in many sectors, such as textile sorting, printing, dyeing, and plastic production of plastics . HoweverPrevious work highlights the importance of the adsorption of basic dyes and provides avenues for developing new water treatment methods to eliminate emerging pollutants. Regti et al.  studied Using molecular dynamic simulations, the adsorption of dyes onto models of graphene oxide has been reported by several authors in the literature –18. Adsoa et al.  performea et al. .The exploration of the literature shows that few of the theoretical works have been reported. The search for efficient adsorbent materials remains a significant requirement in the field of adsorption for wastewater treatment. Most of the calculations in the literature are reported using electronic energy. It is necessary to use the Gibbs free energy to evaluate the adsorption process. The Gibbs free energy of adsorption considers the entropic and temperature effects on the adsorption. Despite some studies on implicit solvation, most research is carried out without considering the solvent effects on adsorption energy. In the present study, we studied the adsorption of four cationic basic dyes, BB26, BG1, BY2, and BR1, onto two models of graphene oxide as adsorbents. Calculations are performed in the gas and solvent phase using the PW6B95-D3  functionThis section starts with the presentation of the two models of graphene oxide used in this work  or even dyes of the same class, but which differ in their chemical structures. Graphene oxide (GO) has a structure similar to that of graphene. These two materials have a hexagonal carbon lattice, but the GO sheet is usually distorted where it is bound to oxygen groups . The resment}sp2 . The funment}sp2  and offementclass2pt{minimEA) and the ionization potential (IP) are calculated using Eqs. Chemical quantum molecular descriptors of the studied dyes have been calculated in this work to understand their reactivity. These descriptors are calculated using the frontier molecular orbitals HOMO  and LUMO . The energy gap values HOMO-LUMO (mentclass2pt{minimThe free energies of the complexes (dye + GO) at different temperatures are calculated using Fifen and coworkers’ TEMPO program , 25. TheIn this section, we comprehensively describe the computational approach used to study the adsorption of dyes  onto two models of graphene oxide as adsorbents. The adsorption is studied in both the gas phase and implicit solvent phase. Molecular structures of the dyes were built using the Avogadro . The theA QTAIM analysis is performed on the complexes to study the interactions between the dyes and the graphene oxides. The AIMAll program performs the QTAIM analysis .For the sake of the completeness of the study, the investigation started with calculating some DFT-based descriptors of the dyes to understand their reactivity. These calculations exploit the frontier molecular orbital energies. After calculating the descriptors, the structures of the complexes formed by the dyes and the two models of graphene oxide are optimized at the PW6B95-D3/def2-SVP level of theory. To understand the interaction between the dyes and the GO models, QTAIM analysis of the eight complexes is performed. Using the optimized structures of the complexes, the adsorption electronic energies and the adsorption free energies at room temperature are calculated. Finally, the effects of the temperature on the adsorption free energies of the complexes are assessed and presented.Molecular electronic descriptors and their calculated values are shown in Table The values of the electrophilicity index (mentclass2pt{minimacceptor . A stronument}ω) . The stamentclass2pt{minimTo calculate the adsorption energy, one needs the structures of the complexes formed by the combination of a dye and a GO model, in addition to the individual structures of the GO models and the dyes. Thus, we formed eight complexes by combining the GO models and the four dyes. After optimizations of the structures at the PW6B95-D3/def2-SVP level of theory, the located stable configurations are reported in Fig. To understand the interactions between the graphene oxide and the dyes, we performed a QTAIM analysis of the eight complexes. The structures reported in Fig.  bonding , 44. In  bonding –52. ThusAnalysis of Fig. Using the structures reported in Fig. For the first model of graphene oxide, the free energy values at room temperature are BB26  onto two models of graphene oxide at the PW6B95-D3/def2-SVP level of theory. We started by calculating some DFT-based descriptors of the dyes to predict their reactivities based on the frontier molecular orbital energies. Then, a QTAIM analysis has been performed. This allowed us to understand the interactions between the dyes and the graphene oxides. It has been found that the CHConformational search: The studied dyes have several conformers that could coexist in the solvent phase. A complete study considering the contribution of different conformers of the dyes would be closer to reality.Configurational search of the complex: The complex formed by the interaction of a dye with a graphene oxide model has several configurations with different relative energies. The global and local minima configurations should be considered for accuracy, weighted by their Boltzmann probabilities. It is important to state that this will be an expensive investigation necessary for accuracy.Environmental effects: In the current study, only implicit solvation has been considered to consider the environmental effects. A more accurate study including a few explicit water molecules would be welcome in the literature. Similar to the previous perspective, the current suggestion is foreseen to be an expensive procedure necessary for accuracy. Boltzmann weights should be used to consider the contribution of all possible configurations.This work lays a route for further theoretical investigations of graphene oxide as an adsorbent for emerging pollutants. As an introduction, this work has provided sufficient data to support the conclusion that graphene oxide can be a promising adsorbent for cationic dyes. Nevertheless, this work has limitations that need improvements in future studies. These limitations include the following:Supplementary file 1 (pdf 2976 KB)Supplementary file 2 (pdf 146 KB)Below is the link to the electronic supplementary material.


Research shows the benefits of music therapy for various mental health conditions, including depression, trauma, and schizophrenia. Music acts as a medium for processing emotions, trauma, and grief.Playing instruments can encourage emotional expression, socialization and exploration of various therapeutic themes .Group music therapy, measured by questionnaires and described in qualitative interviews, improved quality of life and self-esteem for people with severe mental illness (SMI).Group singing and song writing provide creative options for social connections. Music therapy should be considered as a component of holistic care for people with SMI. Jungup Lee, Thyer BA. May 2013Journal of Human Behaviour in the Social Environment 23(5):597-609Music therapy sessions are held in our hospital for people admitted to short-term hospitalization units and to psychosocial rehabilitation units. The goal of the sessions is to create a connection space, promote people’s confidence in their own resources for their recovery, and evoke valuable experiences and memories. Sometimes musicians from the community have been present in the sessions, contributing to overcoming the stigma towards mental illness.We describe self-assessment of people admitted to psychiatric units after attending music therapy sessions. People from brief hospitalization unit filled out a survey, after each session, voluntarily, about their emotional state at the beginning of the session and after it. People from rehabilitation units, voluntarily filled the SRS V.3.0. 2002-Miller. Duncan & Johnson escale.The SRS was designed for use by clinicians to assess the therapeutic alliance during therapy  3-12 12/14/04 3:53 PM Page 3).23 sessions took place for each unit. 39 patients from brief hospitalization, 22 women and 17 men, attended the sessions. 15 had a diagnosis of schizophrenia and related disorders, 13 were affective disorders, and 11 others diagnosis. All of them liked the participation either fully or partially. 76% men and 77% women felt better after, none of them reported to feel worse. 82% men and 86% women replied they would repeat the session.I felt heard, understood, and respected/ We worked on and talked about what I wanted to work on and talk about/ The therapist’s approach is a good fit for me) with an overall score of 9,62 over 10 .Patients from rehabilitation units were 7 women and 10 men. 14 had a schizophrenia related disorder and 3 had bipolar disorder. All items on the scale were scored above 9 over 10, (Music therapy sessions achieve benefits on an emotional level in any of the diagnoses, improving alliance with care teams, who value sessions as normalizing spaces, helping to overcome stigma.None Declared


As a unique ecosystem, Karst caves harbor an impressive diversity of specific fungi. However, the factors and mechanisms that shape fungal biodiversity in caves remain elusive. In this study, we explored the assembly patterns of fungal communities based on our previous research in eight representative Karst caves in Southwest China. Our results indicated that dispersal limitation plays a crucial role in shaping the overall fungal community as well as specific communities in rock, sediment, and water samples. However, “Undominated” processes contributed more than dispersal limitation in air samples. Interestingly, the dominant assembly processes varied between caves. Consistently, environmental selection had a minor impact on the assembly of fungal communities. Among the examined spatial and environmental variables, latitude, longitude, altitude, and temperature were found to significantly influence fungal communities irrespective of substrate type. These findings provide valuable insights into the ecological factors governing fungal community assembly in Karst caves. Understanding the assembly processes and mechanisms that shape community diversity, biogeography, succession, and function is a prominent topic of study in ecology, particularly in microbial ecology. However, most of these processes are still not well-understood or are highly controversial ,2,3,4. DCaves are unique ecosystems with distinct characters that differentiate them from outside environments, making them ideal conditions in which to test community assembly theories ,7. HowevBy collecting a large number of air, rock, sediment, and water samples from eight representative Karst caves in Southwest China, Zhang et al. systematically investigated the diversity, composition, and controlling factors of fungal communities in Karst caves using a high throughput sequencing method . In the Samples and molecular data used in this analysis were acquired from our previous study . In brieTotal genomic DNA was extracted using a FastDNA Spin Kit  according to the manufacturer’s instructions. The ITS1 rDNA region of each sample was amplified using the primer pair ITS1F/ITS2  with equRaw sequences were paired using FLASH (v1.2.11) , and theBray) were calculated using Rscript “bNTI_Local_Machine.r” written by Stegen et al. [Bray value was used to further resolve the pairwise comparisons that were assigned to stochastic processes [Bray < –0.95 and RCBray > 0.95 indicate a relative dominant influence of homogenizing dispersal and dispersal limitation, respectively, and RCBray values < 0.95 represent a crucial role for “Undominated” assembly, including weak selection, weak dispersal, diversification, and/or drift [p-value were calculated to explore the associations between βNTI values and changes in environmental variables in different samples. Meanwhile, Pearson’s correlation coefficients between fungal community Bray–Curtis similarities and geographic distance between samples were calculated to determine the spatial predictors of fungal community composition. The geographic distance (in km) between each sample, i.e., the straight-line distance between the sampling points, was calculated using the R package geosphere (v1.5) [To quantify the relative importance of stochastic and deterministic processes that drive fungal community assembly, beta nearest-taxon index (βNTI) and Bray–Curtis-based Raup–Crick   based on4+, N/NO3−, TP, and TS) variables together [A variation partition analysis (VPA) using distance-based redundancy analysis (db-RDA) was performed to determine the relative proportions of community variations that can be explained by spatial  and environmental  were clustered at a 97% similarity from 6,618,705 clean reads. Among the non-rare OTUs, 10,769 OTUs, accounting for 97.4% of the clustered reads, were assigned into the fungal kingdom . Before Bray indices were calculated to explore the relative importance of stochastic and deterministic processes in the assembly of the fungal community in caves  and water  communities, while temperature and altitude played more important roles in the rock  and sediment  communities (In the case of air samples, the fungal communities were significantly influenced by latitude, longitude, altitude, and temperature, while air humidity and sample distance from the entrance did not show significant effects a. Similamunities .Various fundamental biodiversity patterns have been observed in ecology ,37. HoweIn the current study, it was found that stochastic factors were the dominant drivers of fungal community assembly in Karst caves on a large scale. Stochastic processes have been recognized as controlling processes of microbial biodiversity in various studies ,38,39,40It is noteworthy that the importance of “Undominated” processes in the community assembly of air samples is greater than that of dispersal limitation c. There The dominant processes controlling community assembly in single caves were observed to be in contrast to our hypothesis. Dispersal limitation was found to be predominant in six caves, while homogeneous selection and “Undominated” processes were dominant in the remaining two caves. This contrast may be attributed to the specific structure and conditions present in each cave. For example, some caves are strongly zonal, while others consist of several large halls. Additionally, the influences of external communities, as well as animal and human activities, on fungal communities differ among caves. For instance, Zhang et al. found that fungal communities in Karst caves were greatly influenced by fungal communities in external environments due to airflow exchange ,45. MeanConsistent with the findings of Zhang et al. , our stuIn conclusion, our study provides a preliminary quantification of the assembly patterns of fungal communities in Karst caves, based on our previous investigation of fungal communities in eight caves in Southwest China. We found that dispersal limitation plays a crucial role in shaping both the overall fungal community and specific communities in rock, sediment, and water samples. However, “Undominated” processes have greater influence on the air fungal community compared to dispersal limitation. Moreover, the dominant processes differ between each cave. VPA analysis revealed that the environmental selection plays a minor role in the fungal community in caves. Among the spatial and environmental variables examined, latitude, longitude, altitude, and temperature significantly affect the fungal communities across all substrates. Overall, our study provides a valuable insight into the mechanisms and factors that control the assembly of fungal communities in Karst caves, which may contribute to further exploration and conservation efforts for microbial communities in these unique environments.


Using the fantastic features of the graphene/CaF2 multilayer, this article proposes an improvement sensor in the sensitivity (S), the figure of merit (FOM), and the quality factor (Q). The proposed sensor is based on the five-layers graphene/dielectric grating integrated with a Fabry–Perot cavity. By tuning graphene chemical potential (µc), due to the semi-metal features of graphene, the surface plasmon resonance (SPR) waves excited at the graphene/dielectric boundaries. Due to the vertical polarization of the source to the gratings and the symmetry of the electric field, both corners of the grating act as electric dipoles, and this causes the propagation of plasmonic waves on the graphene surface to propagate towards each other. Finally, it causes Fabry–Perot (FP) interference on the surface of graphene in the proposed structure's active medium (the area where the sample is located). In this article, using the inherent nature of FP interference and its S to the environment's refractive index (RI), by changing a minimal amount in the RI of the sample, the resonance wavelength (interferometer order) shifts sharply. The proposed design can detect and sense some cancers, such as Adrenal Gland Cancer, Blood Cancer, Breast Cancer I, Breast Cancer II, Cervical Cancer, and skin cancer precisely. By optimizing the structure, we can achieve an S as high as 9000 nm/RIU and a FOM of about 52.14 for the first resonance order (M1). Likewise, the remarkable S of 38,000 nm/RIU and the FOM of 81 have been obtained for the second mode (M2). In addition, the proposed label-free SPR sensor can detect changes in the concentration of various materials, including gases and biomolecules, hemoglobin, breast cancer, diabetes, leukemia, and most alloys, with an accuracy of 0.001. The proposed sensor can sense urine concentration with a maximum S of 8500 nm/RIU and cancers with high S in the 6000 nm/RIU range to 7000 nm/RIU. Also, four viruses, such as M13 bacteriophage, HIV type one, Herpes simplex type 1, and influenza, have been investigated, showing Maximum S (for second resonance mode of λR(M2) of 8000 nm/RIU (λR(M2) = 11.2 µm), 12,000 nm/RIU (λR(M2) = 10.73 µm), 38,000 nm/RIU (λR(M2) = 11.78 µm), and 12,000 nm/RIU (λR(M2) = 10.6 µm), respectively, and the obtained S for first resonance mode (λR(M1)) for mentioned viruses are 4740 nm/RIU (λR(M1) = 8.7 µm), 8010 nm/RIU (λR(M1) = 8.44 µm), 8100 nm/RIU (λR(M1) = 10.15 µm), and 9000 (λR(M1) = 8.36 µm), respectively.One of the primary goals for the researchers is to create a high-quality sensor with a simple structure because of the urgent requirement to identify biomolecules at low concentrations to diagnose diseases and detect hazardous chemicals for health early on. Recently graphene has attracted much interest in the field of improved biosensors. Meanwhile, graphene with new materials such as CaF Because of this quick real-time detection, optical biosensors are also often used in medical applications2, environmental applications3, industrial applications4, etc. There are two primary approaches for using optical biosensors to find or sense biomolecules. Fluorescence is the foundation of the first detection approach, while label-free detection is the second. Of these two techniques, fluorescence-based detection employs biomolecular tags to find them. Although the Fluorescence approach is accurate, labeling all the samples makes it hard to use. On the other hand, this approach is expensive. Therefore, the second method has been widely used5.Recently, Optical biosensors have been the most efficient since they can detect biomolecules directly and instantly8. In contrast with the first approach, label-free techniques measure an inherent property of the query itself , thereby avoiding modifying interactors9. The successes of sensing technologies are determined mainly by their S, resolution, and detection limit. Dynamic range, real-time monitoring, multiplexing and HT capability, widespread applicability, and data handling are other key determining factors11.The label-free detection of biomolecules can be realized by the excitation of SPR in waveguides, photonic crystal fibers, and Bragg gratings12.In protein microarray experiments, signals can be detected by label-based or label-free strategies. Both approaches have their merits and demerits. Label-based detection methods require labeling query molecules with fluorescent dyes, radioisotopes, or epitope tags. Label-based detection is widely used in protein microarrays due to the expected availability of reagents and simple instrument requirements. However, these labeling strategies often alter the query molecule's surface characteristics and biological activities. Moreover, the labeling procedure is laborious and lengthy, limiting the number and types of query molecules that can be studied13. SPR technology detection in biosensors can also limit drug-serum interactions14. Using localized surface plasmon-based biosensors, which can detect biomolecules, facilitates the diagnosis of Alzheimer's disease15.Meanwhile, in many cancer situations, SPR sensors are helpful for drug discovery19, photodetectors21, sensors23, and Optical Tweezers26, graphene has been in the center of researchers' attention. This single-layer graphite allotrope known as graphene has unique optical and electrical features such as high carrier mobility, electrostatic doping, ultra-wide absorption spectrum27, easy fabrication while being compatible with well-established silicon technology28, and ultrafast charge carrier dynamics, which is originated from its 2D nature29. Nowadays, due to graphene's extraordinary optical and electrical characteristics, graphene-based SPR sensors are generating interest. It has been reported that graphene-based SPR sensors are suitable for biological applications with great features. Additionally, a graphene layer on the sensing medium results in superior conductivity and stable biomolecule absorption. The large carbon-based rings in biomolecules are the primary cause of a biomolecule's absorption by a graphene sheet30.In recent years, with the emergence of graphene and its applications in the electronics and photonics industry, such as optical modulatorsGraphene-based SPR sensors employ the shift in the graphene plasmon resonance wavelength to identify slight variations in the RI of the medium close to the graphene-based structure. Graphene-based sensors have made considerable advances in terms of sensing speed and structuring. Likewise, it can absorb bio and polar molecules well due to its high surface-to-volume ratio. Therefore, using graphene, electromagnetic waves could be coupled to the bound collective charge oscillations, forming localized SPR (LSPR).2 and graphene, has been reported31. The simulation results demonstrate multi-resonant modes suitable for ultrasensitive refractive index sensing. Also, a graphene-gold grating in the near-IR region has been proposed32, which performs well for detecting biomolecules and harmful gases for health. Absorption spectra of this structure indicate two resonance modes with S as high as 1100 nm/RIU and 1180 nm/RIU.Recently, prominent studies involving graphene grating structures have been reported. For instance, a graphene plasmonic grating ultrasensitive tunable terahertz sensor, which consists of SiO2 multilayer for detecting and sensing changes in the RI of samples (and thus the concentration) of gases, biomolecules, urine, and generally all materials with a refractive index between 1.000 and 1.800. Also, some cancers such as Adrenal Gland Cancer, Blood Cancer, Breast Cancer I, Breast Cancer II, Cervical Cancer, and skin cancer have been investigated precisely. This structure consists of five graphene layers separated by CaF2 layers and covers the grating structure's steps that form strong SPs in the mid-IR region. CaF2 has been used as a substrate material for graphene not only to increase the graphene plasmonic waves quality (due to zero imaginary part of permittivity in the wavelength range of interest) but also due to the high dielectric constant and its breakdown voltage, it causes to shift graphene chemical potential with very low gate voltage. Moreover, due to an ingenious method in which a polarized light source causes both edges of gratings to act as an electrical dipole, the excited plasmonic waves propagate toward each other and form an FP interference. This FP interferometer makes the primary mechanism of the proposed biosensor. Since FP interference is highly sensitive to its medium RI, the proposed design shows significant improvement in S, FOM, and Q. Additionally, research has been done on the potential sensing properties of various gas alloys and biomolecules. The proposed sensor can sense urine concentration with a maximum S of 8500 nm/RIU and cancers with high S in the 6000 nm/RIU range to 7000 nm/RIU. Also, four viruses, such as M13 bacteriophage, HIV type one, Herpes simplex type 1, and influenza, have been investigated, showing a Maximum S of 8000, 12,000, 38,000, and 12,000 nm/RIU, respectively.This paper proposes a structure and a novel method based on propagating plasmonic waves interferometer on graphene/CaF2 layers and cover the surface of gratings, which results in high electric field confinement. In addition, these gratings are created from CaF2, which is on the top of the gold substrate and serves as the gate voltage for adjusting the Fermi level of the graphene. In addition, to obtain realistic results, we rounded the grating corners in all simulations.A 3D view of the proposed sensor and its cross-section is shown in Fig. 26.This paper uses graphene as a 2D sheet with its surface conductivity. The surface conductivity of graphene can be separated into interband conductivity, which is the first term of Eq. , and intf is the Fermi energy, B is the Boltzmann constant, T = 300 K is the temperature, e is the elementary charge, ω is the angular frequency, and τ is the relaxation time, respectively. Here the intrinsic relaxation time is taken to be In Eq. , Ef is t2 layer and is taken 1 m2/Vs.,34. Figure The scattering rate is obtained by entclass1pt{minimaThe parameters shown in Fig. Most previous spp-based sensors consist of a prism substrate, a dielectric layer, novel metal film, liquid, and plasmon, which can only be excited by TM polarization (Kretschmann configuration) and have a large footprint after that, grating-based graphene sensors reached interests of researchers. Grating couplers have not been used in SPR sensors as widely as prism couplers. However, their compatibility with mass production and the prism's absence make grating-coupled SPR attractive for fabricating low-cost, compact-sensing devices.max is the change in the maximum wavelength of the absorption curve for a slight shift (Δn) in the RI of the material we want to measure, the figure of the merit (FOM) for the proposed sensor is calculated as Eq.  area is the optimum spectral range for biomolecule sensing since it doesn't result in photodamage. An optical sensor's detection accuracy will gradually increase if operated in the spectrum's infrared (IR) region since bio samples absorb considerably more in this region than in the visible area, which may also be connected to penetration depth towards the sample side.2), fluoride glass can meet the qualities mentioned earlier among other substrate glass materials for applications in the IR region. CaF2 with a low RI value can also provide superior error rejection (mainly angular) during mechanical setup. Consequently, CaF2 might be a suitable substrate for SPR-based IR applications35. Therefore, recently it has been shown that CaF2-based SPR sensor provides much better S than conventional dielectrics such as SiO2.A suitable substrate material should have good transparency, low refractive index (RI) discrepancy by varying the temperature, a big transmission window, and a high laser damage threshold in the Mid-IR spectral range. Like calcium fluoride 36:r is the dielectric function, and λ is the wavelength in μm.The approached experimental data of the permittivity of CaF2 a proper dielectric and spacer material for graphene in the wavelength of interest. Also, the mentioned features of CaF2 make it a very suitable substrate for graphene, preventing secondary effects and increasing graphene improvement.As shown in Fig. The optical analysis uses the FDTD method, and a normal incident with a linearly polarized source is employed to illuminate the structure. Its E-field is polarized perpendicularly to the gratings (in the x-direction). It is worth mentioning that the incident light that polarized parallel to the grating’s direction (in the y-direction) cannot activate the plasmon resonance because the structure entirely reflects it. The boundary conditions in the z-directions are Perfectly Matched Layers (PMLs), while the x and y directions are periodic.x37, SOx, and Cox38. In addition, since the number of blood illnesses and other forms of cancer continues to rise, there is a pressing need to detect origins and target tissues. For instance, some research has been conducted on the hemoglobin value of blood39 and the ability to see certain types of cancer, such as liver, blood, and breast, using an optical method. In this paper, we calculate the influence of the RI change of an analyte when it changes between 1 and 1.6, while the RI of the medium is assumed to be n = 1.33.One way to determine an analyte's concentration or perform a biophysical analysis is to evaluate the variation in the RI. Many biomolecules have refractive indices between 1.300 and 1.600, while the refractive index of most gases ranges from 1.000 to 1.600, such as NOFirst, we examine the effect of graphene layer number on proposed biosensor S. Figure In addition, the S of each case is written in the inset of Fig. As shown in Fig. 2 sandwich structure. As shown in Fig. Figure 2 layers. Therefore, we continue our simulation and calculations for a proposed biosensor with five graphene layers after this.Comparing Figs. We simulated wavelength-dependent absorption for various graphene Fermi levels, as shown in Fig. 2 is the most crucial gas (n = 1.0002) detected using the proposed sensor. Moreover, some biomolecules, such as MCF-7 (n = 1.401) and MDA-MB-231 (n = 1.399), can be used to diagnose breast cancer, and Jurkat biomolecule (n = 1.390), which is used to detect leukemia, respectively, are in this system identification region40 and can be easily detected by the proposed sensor.Figure As evident from Fig. Figure Finally, Fig. 41. These results have been compared to other SPR-based sense methods, such as fiber optics, which can sense RI with an accuracy of Δn = 0.01 42, gold grating on SiO2, which is capable of detecting samples with an accuracy of Δn = 0.005 per RI unit43. In contrast, the proposed structure can sense refractive indices with a precision of less than 0.001.Additionally, the RI discrepancies between liver cancer cells (HCC = 1.347) and normal liver cells (NHCC = 1.345) are from the rank of 0.002, which can be identified using the suggested biosensor44. The refractive index of a patient with diabetes mellitus is relatively high. The mean refractive index of morning urine samples ranges from 1.336 ± 0.0019. In contrast, the refractive index of specific random samples is 1.335 ± 0.0017. As clear from Fig. Different glucose concentrations found in urine samples range in refractive index from 1.332 to 1.340Figure By looking precisely at Fig. Table Diabetes mellitus is a chronic metabolic condition that affects millions of people worldwide. This article examines the response of a graphene grating-based sensor to the refractive index of urine samples  to diagnose diabetes mellitus. Evanescent field interaction with the high glucose concentration, known as "hyperglycemia" (RI 1.347) sample over the proposed sensor, causes the refractive index to change. The proposed biosensor can also help detect low glucose levels (RI 1.2) and is named "hypoglycemia."Physically, a urine sample will change the surface tension, gravity, and refractive index due to the presence of glucose. Specific characteristics of label-free biosensing are their resistance to electromagnetic interference, compact design, the potential to integrate into the lab on a chip, etc. these sensors lead to significant developments in diagnosis, food safety management, pharmaceutical development, and monitoring of environmental hazards, and recently, it has become crucial to use a noninvasive glucose sensing method compared to the traditional blood pinpricking method. Also, some cancer such as Adrenal Gland Cancer, Blood Cancer, Breast Cancer I, Breast Cancer II, Cervical Cancer, and skin cancer have been investigated precisely.Figure µm to almost 6400 nm/RIU where the incident wavelength has been fixed to 14.05 µm. Also, the structure can sense Skin Cancer with a maximum S of nearly 6350 nm/RIU at 13.9 µm.Although the S fluctuation of the proposed structure concerning wavelength variations is insignificant for the diverse types of cancers shown in Table As evident from Fig. 51. Moreover, (MDA)-(MB)-231 and MCF-7 are classified as Types I and II of breast cancer, respectively. The S of each cancer can be defined as the shift in the absorption of the proposed structure when the refractive index changes from cancer RI to its normal cell RI. For example, the Jurkat cell or blood cancer has a refractive index of 1.39 with an 80% concentration, while its normal cell refractive index is 1.37653. Also, the refractive index of Cervical cancer with an 80% concentration is 1.392, as shown in Table 58. The refractive index of Adrenal Gland Cancer is 1.395 with an 80% concentration, and its normal cell owns a RI of 1.381 in the 30–70% concentration59. Also, Breast cancer I and type II own the normal cells with the RI of 1.385 and 1.38760. Finally, the RI of skin cancer  with an 80% concentration is 1.38, and its normal cell  RI with a concentration in the range of (30% to 70%) is 1.3661.The lists of refractive indices for the various cancer cells employed in this study are shown in Table 62. For example, the RI of the human immunodeficiency virus (HIV) is 1.5, which is entirely covered by the proposed structure. Table 63 inside a fluidic medium with its radius obtained from62.The capability of our proposed structure is not limited to these; the proposed sensor can identify and sense viruses inside the sample. The RI of different viruses is given in the previous literatureThe S of the proposed multilayer graphene sensor is compared in Table 2 gratings. The sensing medium is set between two grating structures. Modifying the structure made it possible to get the highest S, 8500 nm/RIU, and the FOM 52.14 for the first mode (mode 1) and the outstanding S, 10,000 nm/RIU, and the FOM 81 for the second mode (mode 2) for diabetes sensing. Our proposed method and structure can open a new door for integrated optical applications. Since most plasmonic-based sensors structure has a metallic shape to induce LPR in a metal–dielectric interface, our proposed sensor, by taking advantage of the semi-metal feature of graphene, can efficiently generate the plasmonic waves on the graphene surface, which finally, due to propagating the plasmonic waves on graphene surface in the opposite direction, the FP interference has happened which is the base mechanism of the sensing in the suggested biosensors. Also, it is evident that using metal on a graphene surface makes the fabrication process difficult and causes second-order effects. Since FP interference is highly sensitive to its medium RI, the proposed design shows significant improvement in S, FOM, and Q. Additionally, research has been done on the potential sensing properties of various gas alloys and biomolecules. The proposed sensor can sense urine concentration with a maximum S of 8500 nm/RIU and cancers with high S in the 6000 nm/RIU range to 7000 nm/RIU. Also, four viruses, such as M13 bacteriophage, HIV type one, Herpes simplex type 1, and influenza, have been investigated, showing Maximum S of 8000, 12,000, 38,000, and 12,000 nm/RIU, respectively.This study developed a high-performing RI sensor for sensing gas alloys, biomolecules, cancers, and viruses using the excitation of propagation SPs waves in multilayer graphene gratings. For better binding between gas alloys or biomolecules and cancers with a label-free SPR sensor to increase the performance of the proposed design, five graphene layers are embedded in the CaF