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RationaleFactors associated with long-term sequelae emerging after the acute phase of COVID-19 (so called “long COVID”) are unclear. Here, we aimed to identify risk factors for the development of COVID-19 sequelae in a prospective cohort of subjects hospitalized for SARS-CoV-2 infection and followed up one year after discharge.MethodsA total of 324 subjects underwent a comprehensive and multidisciplinary evaluation one year after hospital discharge for COVID-19. A subgroup of 247/324 who consented to donate a blood sample were tested for a panel of circulating cytokines.ResultsIn 122 patients (37.8%) there was evidence of at least one persisting physical symptom. After correcting for comorbidities and COVID-19 severity, the risk of developing long COVID was lower in the 109 subjects admitted to the hospital in the third wave of the pandemic than in the 215 admitted during the first wave, (OR 0.69, 95%CI 0.51-0.93, p=0.01). Univariable analysis revealed female sex, diffusing capacity of the lungs for carbon monoxide (DLCO) value, body mass index, anxiety and depressive symptoms to be positively associated with COVID-19 sequelae at 1 year. Following logistic regression analysis, DLCO was the only independent predictor of residual symptoms (OR 0.98 CI 95% (0.96-0.99), p=0.01). In the subgroup of subjects with normal DLCO (> 80%), for whom residual lung damage was an unlikely explanation for long COVID, the presence of anxiety and depressive symptoms was significantly associated to persistent symptoms, together with increased levels of a set of pro-inflammatory cytokines: interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-2, IL-12, IL-1β, IL-17. In logistic regression analysis, depressive symptoms (p=0.02, OR 4.57 [1.21-17.21]) and IL-12 levels (p=0.03, OR 1.06 [1.00-1.11]) 1-year after hospital discharge were independently associated with persistence of symptoms.ConclusionsLong COVID appears mainly related to respiratory sequelae, prevalently observed during the first pandemic wave. Among patients with little or no residual lung damage, a cytokine pattern consistent with systemic inflammation is in place.

Abstract Many coronavirus disease 2019 (Covid-19) survivors show symptoms months after acute illness. The aim of this work is to describe the clinical evolution of Covid-19, one year after discharge. We performed a prospective cohort study on 238 patients previously hospitalized for Covid-19 pneumonia in 2020 who already underwent clinical follow-up 4 months post-Covid-19. 200 consented to participate to a 12-months clinical assessment, including: pulmonary function tests with diffusing lung capacity for carbon monoxide (DLCO); post-traumatic stress (PTS) symptoms evaluation by the Impact of Event Scale (IES); motor function evaluation (by Short Physical Performance Battery and 2 min walking test); chest Computed Tomography (CT). After 366 [363–369] days, 79 patients (39.5%) reported at least one symptom. A DLCO

Objectives: The usefulness of Virtual dissection tables (VDTs) as diagnostic tools is still poorly assessed.The purpose of this study was to evaluate their ability to improve the diagnostic accuracy of maxillofacial CT scans of patients presenting with Le Fort fractures. Methods: We retrospectively enrolled 10 trauma patients who had previously undergone maxillofacial CT scan. Five of these patients had been diagnosed with type I, II or III Le Fort fractures, while the other five had not revealed any evident maxillary bone fractures (control group). Four different reader groups were identified: staff radiologists, senior residents, junior residents, and students. Each group consisted of two readers who carried out a blinded double reading session. Readers evaluated CT scans on the radiological workstation first, and after they reviewed the VDT-generated 3D models (Anatomage Table, Anatomage Europe, Italy). We assessed: 1) Le Fort fracture grade, 2) confidence in diagnosis, 3) anatomic resolution, 4) 3D-model handling. Intra-reader agreement on Le Fort fracture grade was assessed using Cohen's. Qualitative parameters were determined using Likert scale. Results: Intra-reader agreement for Le Fort fracture grade according to Cohen's was above 90% in all readers. showed almost perfect agreement in 7 out of 8 readers and substantial agreement in 1 out of 8. Qualitative parameters indicated a substantial preference of the VDT over the radiological workstation in all readers. Conclusions: VDT represents a valuable tool for diagnosis and classification of complex maxillofacial injuries, regardless of whether the user is a student, a junior or senior resident, or a staff radiologist. Keywords: Imaging, Three-dimensional, Skull fractures, Facial injuries, Education, Medical, Tomography, X-ray computed, Virtual dissection table

Abstract Background Effective teamwork is crucial to providing safe and high-quality patient care, especially in acute care. Crew Resource Management (CRM) principles are often used for training teamwork in these situations, with escape rooms forming a promising new tool. However, little is known about escape room design characteristics and their effect on learning outcomes. We investigated the current status of design characteristics and their effect on learning outcomes for escape room-based CRM/teamwork training for acute care professionals. We also aimed to identify gaps in literature to guide further research. Methods Multiple databases were searched for studies describing the design and effect of escape rooms aimed training CRM/teamwork in acute care professionals and in situations that share characteristics. A standardized process was used for screening and selection. An evidence table that included study characteristics, design characteristics and effect of the escape room on learning outcomes was used to extract data. Learning outcomes were graded according to IPE expanded typology of Kirkpatrick’s levels of learning outcome and Medical Education Research Study Quality Instrument (MERSQI) scores were calculated to assess methodology. Results Fourteen studies were included. Common design characteristics were a team size of 4–6 participants, a 40-minute time limit, linear puzzle organization and use of briefing and structured debriefing. Information on alignment was only available in five studies and reporting on several other educational and escape room design characteristics was low. Twelve studies evaluated the effect of the escape room on teamwork: nine evaluated reaction (Kirkpatrick level 1; n = 9), two evaluated learning (Kirkpatrick level 2) and one evaluated both. Overall effect on teamwork was overtly positive, with little difference between studies. Together with a mean MERSQI score of 7.0, this precluded connecting specific design characteristics to the effect on learning outcomes. Conclusions There is insufficient evidence if and how design characteristics affect learning outcomes in escape rooms aimed at training CRM/teamwork in acute care professionals. Alignment of teamwork with learning goals is insufficiently reported. More complete reporting of escape rooms aimed at training CRM/teamwork in acute care professionals is needed, with a research focus on maximizing learning potential through design.

BackgroundHarmful alcohol consumption has been identified as a major contributor to disease, mortality, and social harm, accounting for 5.3% of worldwide deaths annually. In Denmark, an estimated 150,000 people suffer from alcohol use disorder (AUD), but a low proportion seek treatment due to person- and treatment-related barriers. Internet-based cognitive behavioral therapy (iCBT) has shown positive effects on the treatment gap, with patients reporting benefits such as increased knowledge and flexibility. However, there is a lack of research on blended cognitive behavioral therapy (bCBT), which combines face-to-face CBT (FtF CBT) and iCBT for AUD. ObjectiveThis study aims to investigate user experiences of bCBT. More specifically, it seeks to explore the advantages and disadvantages that users have experienced with bCBT for AUD, as well as their motivations for choosing this treatment format. MethodsA total of 30 patients who had participated in the Blend-A (Blending Internet Treatment into Conventional Face-to-Face Treatment for AUD) study and received the intervention were contacted and offered the opportunity to participate in semistructured individual telephone interviews. Of these, 12 patients consented to participate. Furthermore, an additional participant was approached at a municipal clinic and agreed to engage in an individual FtF interview. Thus, the final sample consisted of 13 patients. The interviews explored their background, experiences with digital technology, motivations for choosing internet-based treatment, and experiences with the program during AUD treatment. The interviews were audio-recorded and transcribed in full length and analyzed using thematic analysis. All data were anonymized and securely stored. ResultsWe found that users experienced several advantages of iCBT over a larger part of the treatment course, including increased anonymity and privacy. Most importantly, it offered flexibility, allowing patients to focus on their rehabilitation process at their own pace. Patients appreciated the availability of written text in the online program, finding it helpful for gaining knowledge and understanding of AUD and its impact on the individual with the condition. They emphasized how the assignments helped them fully engage in treatment by first acknowledging their problem with alcohol and then dedicating time to self-reflection before FtF sessions, allowing for more in-depth discussions with the therapist. They also appreciated the reminders, which motivated them to complete their assignments. ConclusionsOverall, patients perceived more benefits than disadvantages in using bCBT. Essentially, bCBT offers a form of assisted autonomy that cannot be fully achieved through iCBT or FtF CBT alone. It is only through their combination that patients can fully appreciate the benefits of the treatment, as they have time for self-reflection, with guidance from the therapist between FtF CBT sessions. Trial RegistrationClinicalTrials.gov NCT04535258; https://clinicaltrials.gov/ct2/show/NCT04535258

Abstract Background The application of lower limb traction during hip arthroscopy and femur fractures osteosynthesis is commonplace in orthopaedic surgeries. Traditional methods utilize a perineal post on a traction table, leading to soft tissue damage and nerve neuropraxia. A postless technique, using high-friction pads, has been considered as a potential damage-free alternative. However, whether these pads sufficiently prevent patient displacement remains unknown. Thus, this study systematically assesses the efficacy of commercial high-friction pads (PinkPad and CarePad) in restraining subject displacement, for progressively increasing traction loads and different Trendelenburg angles. Methods Three healthy male subjects were recruited and tested in supine and Trendelenburg positions (5° and 10°), using a customized boot-pulley system. Ten load disks (5 kg) were dropped at 15s intervals, increasing gradually the traction load up to 50 kg. Pelvis displacement along the traction direction was measured with a motion capture system. The displacement at 50 kg of traction load was analyzed and compared across various pads and bed inclinations. Response to varying traction loads was statistically assessed with a quadratic function model. Results Pelvis displacement at 50 kg traction load was below 60 mm for all conditions. Comparing PinkPad and CarePad, no significant differences in displacement were observed. Finally, similar displacements were observed for the supine and Trendelenburg positions. Conclusions Both PinkPad and CarePad exhibited nearly linear behavior under increasing traction loads, limiting displacement to 60 mm at most for 50 kg loads. Contrary to expectations, placing subjects in the Trendelenburg position did not increase adhesion.

Nowadays, the scientific community and industry are increasingly pressed to provide solutions for developing compact and highly-performing trace-gas sensors for several applications of crucial importance, such as environmental monitoring or medical diagnostics. In this context, this work describes a novel configuration, making use of a mid-IR spectrophone combining the compactness of a photo-acoustic setup, a non-conventional micro-electro-mechanical (MEMS) acousto-to-voltage transducer, and the sensitivity enhancement given by a cost-effective and easy-to-build dual-tube resonator configuration. In the optimal condition of sample pressure, the system developed in this work can achieve a minimum detection limit (MDL) equal to 0.34 ppb when averaging up to 10 s. Compared with previous literature of single-pass photoacoustic-based sensors for N2O, this corresponds to a significant improvement both for the achieved normalized noise equivalent absorption coefficient (NNEA) equal to 1.41 × 10−9 cm−1WHz−1/2, and for a Noise-Equivalent-Concentration (NEC) of 1 ppb obtained at 1 s of averaging time.

The achievable sensitivity level of photo-acoustic trace-gas sensors essentially depends on the performances of the acoustic transducer. In this work, the mechanical response of different silicon-based micro-electro-mechanical systems (MEMS) is characterized, aiming at investigating both their mechanical properties, namely the resonance frequency and the quality factor, and the minimum detection limit (MDL) achievable when they are exploited as an acoustic-to-voltage transducer in a trace-gas photoacoustic setup. For this purpose, a 4.56µm Continuous-Wave (CW) quantum cascade laser (QCL) is used to excite a strong N2O roto-vibrational transition with a line strength of 2.14 × 10−19 cm/molecule, and the detection of MEMS oscillations is performed via an interferometric readout. As a general trend, the minimum detection limit decreases when the resonance frequency investigated increases, achieving a value of 15 parts per billion with a 3 dB cut-off lock-in bandwidth equal to 100 mHz, around 10 kHz.

Abstract Photoacoustic dual-comb spectroscopy (DCS), converting spectral information in the optical frequency domain to the audio frequency domain via multi-heterodyne beating, enables background-free spectral measurements with high resolution and broad bandwidth. However, the detection sensitivity remains limited due to the low power of individual comb lines and the lack of broadband acoustic resonators. Here, we develop cavity-enhanced photoacoustic DCS, which overcomes these limitations by using a high-finesse optical cavity for the power amplification of dual-frequency combs and a broadband acoustic resonator with a flat-top frequency response. We demonstrate high-resolution spectroscopic measurements of trace amounts of C2H2, NH3 and CO in the entire telecommunications C-band. The method shows a minimum detection limit of 0.6 ppb C2H2 at the measurement time of 100 s, corresponding to the noise equivalent absorption coefficient of 7 × 10−10 cm−1. The proposed cavity-enhanced photoacoustic DCS may open new avenues for ultrasensitive, high-resolution, and multi-species gas detection with widespread applications.

Abstract Intratumoral heterogeneity impacts the success or failure of anti-cancer therapies. Here, we investigated the evolution and mechanistic heterogeneity in clonal populations of cell models for estrogen receptor positive breast cancer. To this end, we established barcoded models of luminal breast cancer and rendered them resistant to commonly applied first line endocrine therapies. By isolating single clones from the resistant cell pools and characterizing replicates of individual clones we observed inter- (between cell lines) and intra-tumor (between different clones from the same cell line) heterogeneity. Molecular characterization at RNA and phospho-proteomic levels revealed private clonal activation of the unfolded protein response and respective sensitivity to inhibition of the proteasome, and potentially shared sensitivities for repression of protein kinase C. Our in vitro findings are consistent with tumor-heterogeneity that is observed in breast cancer patients thus highlighting the need to uncover heterogeneity at an individual patient level and to adjust therapies accordingly.

The escalating global emphasis on sustainability, coupled with stringent regulatory frameworks, has spurred the quest for environmentally viable alternatives to petroleum-derived materials. Within this context, the adhesives industry has been actively seeking renewable options and eco-friendly synthesis pathways. This study introduces geraniol, a monoterpenoid alcohol, in its unmodified form, as a key component in the production of waterborne pressure-sensitive adhesives (PSAs) based on acrylic latex through emulsion polymerization. Multiple formulations were developed at varying reaction times. The adhesives underwent comprehensive chemical characterization employing techniques such as Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Nuclear Magnetic Resonance (NMR), Gel Permeation Chromatography (GPC), and dynamic light scattering (DLS). The viscosities of the formulations were measured between 4000 and 5000 cP. Adhesion tests showed peel strength values of 0.52 N/mm on cardboard and 0.32 N/mm on painted steel for the geraniol-based formulations. The results demonstrate the potential for geraniol-based PSAs to offer a sustainable alternative to petroleum-derived adhesives, with promising thermal and adhesive properties.

Leucopterin (C6H5N5O3) is the white pigment in the wings of Pieris brassicae butterflies, and other butterflies; it can also be found in wasps and other insects. Its crystal structure and its tautomeric form in the solid state were hitherto unknown. Leucopterin turned out to be a variable hydrate, with 0.5 to about 0.1 molecules of water per leucopterin molecule. Under ambient conditions, the preferred state is the hemihydrate. Initially, all attempts to grow single crystals suitable for X-ray diffraction were to no avail. Attempts to determine the crystal structure by powder diffraction using the direct-space method failed, because the trials did not include the correct, but rare, space group P2/c. Attempts were made to solve the crystal structure by a global fit to the pair distribution function (PDF-Global-Fit), as described by Prill and co-workers [Schlesinger et al. (2021). J. Appl. Cryst. 54, 776–786]. The approach worked well, but the correct structure was not found, because again the correct space group was not included. Finally, tiny single crystals of the hemihydrate could be obtained, which allowed at least the determination of the crystal symmetry and the positions of the C, N and O atoms. The tautomeric state of the hemihydrate was assessed by multinuclear solid-state NMR spectroscopy. 15N CPMAS spectra showed the presence of one NH2 and three NH groups, and one unprotonated N atom, which agreed with the 1H MAS and 13C CPMAS spectra. Independently, the tautomeric state was investigated by lattice-energy minimizations with dispersion-corrected density functional theory (DFT-D) on 17 different possible tautomers, which also included the prediction of the corresponding 1H, 13C and 15N chemical shifts in the solid. All methods showed the presence of the 2-amino-3,5,8-H tautomer. The DFT-D calculations also confirmed the crystal structure. Heating of the hemihydrate results in a slow release of water between 130 and 250 °C, as shown by differential thermal analysis and thermogravimetry (DTA-TG). Temperature-dependent powder X-ray diffraction (PXRD) showed an irreversible continuous shift of the reflections upon heating, which reveals that leucopterin is a variable hydrate. This observation was also confirmed by PXRD of samples obtained under various synthetic and drying conditions. The crystal structure of a sample with about 0.2 molecules of water per leucopterin was solved by a fit with deviating lattice parameters (FIDEL), as described by Habermehl et al. [Acta Cryst. (2022), B78, 195–213]. A local fit, starting from the structure of the hemihydrate, as well as a global fit, starting from random structures, were performed, followed by Rietveld refinements. Despite dehydration, the space group remains P2/c. In both structures (hemihydrate and variable hydrate), the leucopterin molecules are connected by 2–4 hydrogen bonds into chains, which are connected by further hydrogen bonds to neighbouring chains. The molecular packing is very efficient. The density of leucopterin hemihydrate is as high as 1.909 kg dm−3, which is one of the highest densities for organic compounds consisting of C, H, N and O only. The high density might explain the good light-scattering and opacity properties of the wings of Pieris brassicae and other butterflies.

BackgroundThe use of digital technologies for health care has been the focus of social studies, which have concentrated on the digital divide between individuals who use technology and those who do not—with the latter often being considered as individuals with shortcomings. In Denmark, 91% of the population have computers and 97 out of 100 families have internet access, indicating that lack of access to technology is not the primary reason for nonuse. Although previous studies have primarily focused on participants' perspectives of using internet-based treatment for alcohol use disorder (AUD), no study has investigated individuals’ reasons to prefer face-to-face treatment over blended face-to-face and internet-based cognitive behavioral therapy (bCBT) for AUD among treatment-seeking populations. ObjectiveThe aim of this qualitative study was to investigate the nonuse of bCBT among patients with AUD. Specifically, this study aims to explore patients' reasons for choosing not to receive treatment via this format. MethodsThis study was conducted among Danish patients with AUD who were enrolled in the study “Blending internet treatment into conventional face-to-face treatment for alcohol use disorder (Blend-A)” but had not used bCBT. The participant group consisted of 11 patients with AUD: 3 women and 8 men. The age range of the participants was 29-78 years (mean 59 years). Individual semistructured interviews were conducted using cell phones to gather participants’ reasons for not choosing bCBT. The interviews were recorded, transcribed, and analyzed using thematic analysis. Five authors performed the analysis in 3 steps: (1) two authors read the transcripts and coded themes from their immediate impression of the material, (2) one author provided feedback, which was used to group overlapping themes together or create new themes that better reflected the content, and (3) the remaining two authors provided feedback on the analysis to improve its structure, readability, and relevance to the research aim. ResultsWe found that the participants had various reasons for choosing face-to-face treatment over bCBT; these reasons were more related to personal matters and lesser to digital health literacy. We identified 4 themes related to personal matters for choosing face-to-face treatment over bCBT: (1) patients’ need for attending sessions in person, (2) preference for verbal communication, (3) desire for immediate feedback, and (4) feeling more empowered and motivated with face-to-face sessions. ConclusionsThis study provides valuable insight into participants’ perspectives on blended therapy for AUD and highlights the importance of considering personal factors when designing digital health interventions. Our study indicates that most of the participants choose not to use bCBT for AUD because they perceive such treatment formats as impersonal. Instead, they prefer direct communication with the therapist, including the ability to express and comprehend facial expressions and body language. International Registered Report Identifier (IRRID)RR2-10.1186/s12888-021-03122-4

Hyperplexed in-situ targeted proteomics via antibody immunodetection (i.e., >15 markers) is changing how we classify cells and tissues. Differently from other high-dimensional single-cell assays (flow cytometry, single-cell RNA sequencing), the human eye is a necessary component in multiple procedural steps: image segmentation, signal thresholding, antibody validation, and iconographic rendering. Established methods complement the human image evaluation, but may carry undisclosed biases in such a new context, therefore we re-evaluate all the steps in hyperplexed proteomics. We found that the human eye can discriminate less than 64 out of 256 gray levels and has limitations in discriminating luminance levels in conventional histology images. Furthermore, only images containing visible signals are selected and eye-guided digital thresholding separates signal from noise. BRAQUE, a hyperplexed proteomic tool, can extract, in a marker-agnostic fashion, granular information from markers which have a very low signal-to-noise ratio and therefore are not visualized by traditional visual rendering. By analyzing a public human lymph node dataset, we also found unpredicted staining results by validated antibodies, which highlight the need to upgrade the definition of antibody specificity in hyperplexed immunostaining. Spatially hyperplexed methods upgrade and supplant traditional image-based analysis of tissue immunostaining, beyond the human eye contribution.

We investigate the possibility to apply quantum machine learning techniques for data analysis, with particular regard to an interesting use-case in high-energy physics. We propose an anomaly detection algorithm based on a parametrized quantum circuit. This algorithm was trained on a classical computer and tested with simulations as well as on real quantum hardware. Tests on NISQ devices were performed with IBM quantum computers. For the execution on quantum hardware, specific hardware-driven adaptations were devised and implemented. The quantum anomaly detection algorithm was able to detect simple anomalies such as different characters in handwritten digits as well as more complex structures such as anomalous patterns in the particle detectors produced by the decay products of long-lived particles produced at a collider experiment. For the high-energy physics application, the performance was estimated in simulation only, as the quantum circuit was not simple enough to be executed on the available quantum hardware platform. This work demonstrates that it is possible to perform anomaly detection with quantum algorithms; however, as an amplitude encoding of classical data is required for the task, due to the noise level in the available quantum hardware platform, the current implementation cannot outperform classic anomaly detection algorithms based on deep neural networks.

Chronic pain is an enormous public health concern, and its treatment is still an unmet medical need. Starting from data highlighting the promising effects of some nonsteroidal anti-inflammatory drugs in combination with gabapentin in pain treatment, we sought to combine ketoprofen lysine salt (KLS) and gabapentin to obtain an effective multimodal therapeutic approach for chronic pain. Using relevant in vitro models, we first demonstrated that KLS and gabapentin have supra-additive effects in modulating key pathways in neuropathic pain and gastric mucosal damage. To leverage these supra-additive effects, we then chemically combined the two drugs via co-crystallization to yield a new compound, a ternary drug-drug co-crystal of ketoprofen, lysine and gabapentin (KLS-GABA co-crystal). Physicochemical, biodistribution and pharmacokinetic studies showed that within the co-crystal, ketoprofen reaches an increased gastrointestinal solubility and permeability, as well as a higher systemic exposure in vivo compared to KLS alone or in combination with gabapentin, while both the constituent drugs have increased central nervous system permeation. These unique characteristics led to striking, synergistic anti-nociceptive and anti-inflammatory effects of KLS-GABA co-crystal, as well as significantly reduced spinal neuroinflammation, in translational inflammatory and neuropathic pain rat models, suggesting that the synergistic therapeutic effects of the constituent drugs are further boosted by the co-crystallization. Notably, while strengthening the therapeutic effects of ketoprofen, KLS-GABA co-crystal showed remarkable gastrointestinal tolerability in both inflammatory and chronic neuropathic pain rat models. In conclusion, these results allow us to propose KLS-GABA co-crystal as a new drug candidate with high potential clinical benefit–to–risk ratio for chronic pain treatment.

We present $\texttt{Qibolab}$, an open-source software library for quantum hardware control integrated with the $\texttt{Qibo}$ quantum computing middleware framework. $\texttt{Qibolab}$ provides the software layer required to automatically execute circuit-based algorithms on custom self-hosted quantum hardware platforms. We introduce a set of objects designed to provide programmatic access to quantum control through pulses-oriented drivers for instruments, transpilers and optimization algorithms. $\texttt{Qibolab}$ enables experimentalists and developers to delegate all complex aspects of hardware implementation to the library so they can standardize the deployment of quantum computing algorithms in a extensible hardware-agnostic way, using superconducting qubits as the first officially supported quantum technology. We first describe the status of all components of the library, then we show examples of control setup for superconducting qubits platforms. Finally, we present successful application results related to circuit-based algorithms.

Polyvinyl butyral (PVB) is widely used as an interlayer material in laminated glass applications, mainly in the automotive industry, but also for construction and photovoltaic applications. Post-consumed laminated glass is a waste that is mainly landfilled; nevertheless, it can be revalorized upon efficient separation and removal of adhered glass. PVB interlayers in laminated glass are always plasticized with a significant fraction in the 20–40% w/w range of plasticizer, and they are protected from the environment by two sheets of glass. In this work, the aim is to develop a thorough characterization strategy for PVB films. Neat reference PVB grades intended for interlayer use are compared with properly processed (delaminated) post-consumed PVB grades from the automotive and construction sectors. Methods are developed to open opportunities for recycling and reuse of the latter. The plasticizer content and chemical nature are determined by applying well-known analytical techniques, namely, FT-IR, TGA, NMR. The issue of potential aging during the life cycle of the original laminated material is also addressed through NMR. Based on the findings, a sensor capable of directly sorting PVB post-consumer materials will be developed and calibrated at a later stage.

IntroductionThis study investigates the implementation of a new, more automated screening procedure using the ItFits-toolkit in the online clinic, Internet Psychiatry (iPsych) (www.internetpsykiatrien.dk), delivering guided iCBT for mild to moderate anxiety and depressive disorders. The study focuses on how the therapists experienced the process.MethodsQualitative data were collected from semi-structured individual interviews with seven therapists from iPsych. The interviews were conducted using an interview guide with questions based on the Consolidated Framework for Implementation Research (CFIR). Quantitative data on the perceived level of normalization were collected from iPsych therapists, administrative staff, and off-site professionals in contact with the target demographic at 10-time points throughout the implementation.ResultsThe therapists experienced an improvement in the intake procedure. They reported having more relevant information about the patients to be used during the assessment and the treatment; they liked the new design better; there was a better alignment of expectations between patients and therapists; the patient group was generally a better fit for treatment after implementation; and more of the assessed patients were included in the program. The quantitative data support the interview data and describe a process of normalization that increases over time.DiscussionThe ItFits-toolkit appears to have been an effective mediator of the implementation process. The therapists were aided in the process of change, resulting in an enhanced ability to target the patients who can benefit from the treatment program, less expenditure of time on the wrong population, and more satisfied therapists.

Introduction: Spinal stability plays a crucial role in the success of the surgical treatment of lumbar vertebral metastasis and, in current practice, less invasive approaches such as short constructs have been considered. Concurrently, carbon fiber-reinforced (CFR) poly-ether-ether-ketone (PEEK) fixation devices are expanding in oncologic spinal surgery thanks to their radiotransparency and valid mechanical properties. This study attempts to provide an exhaustive biomechanical comparison of different CFR-PEEK surgical stabilizations through a highly reproducible experimental setup.Methods: A Sawbones biomimetic phantom (T12-S1) was tested in flexion, extension, lateral bending, and axial rotation. An hemisome lesion on L3 vertebral body was mimicked and different pedicle screw posterior fixations were realized with implants from CarboFix Orthopedics Ltd: a long construct involving two spinal levels above and below the lesion, and a short construct involving only the levels adjacent to L3, with and without the addition of a transverse rod-rod cross-link; to provide additional insights on its long-term applicability, the event of a pedicle screw loosening was also accounted.Results: Short construct reduced the overloading onset caused by long stabilization. Particularly, the segmental motion contribution less deviated from the physiologic pattern and also the long-chain stiffness was reduced with respect to the prevalent long construct. The use of the cross-link enhanced the short stabilization by making it significantly stiffer in lateral bending and axial rotation, and by limiting mobiliza-tion in case of pedicle screw loosening.Discussion: The present study proved in vitro the biomechanical benefits of cross-link augmentation in short CFR-PEEK fixation, demonstrating it to be a potential alternative to standard long fixation in the surgical management of lumbar metastasis.

In this study, experimental determination and computational prediction are combined to investigate the formation of a mixed amide-hydride solid solution for the CsNH2–CsH system in a wide compositional range. The experimentally obtained results strongly indicate that a complete amide-hydride solid solution Cs(NH2)xH1-x with a stable cubic structure is achievable when the molar fraction of amide (x) is lower than 0.9. These results validate and confirm our data computationally via first-principles calculations, including the simulations of infrared (IR) and nuclear magnetic resonance (NMR) spectra for structures of various compositions as well as the determination of the dipolar coupling constants. Both the computed vibrational frequencies and 1H chemical shifts of CsNH2 and CsH moieties in the Cs(NH2)xH1-x (x = 0.2, 0.5, 0.8, 1) solid solution structures agree with the experimental IR and 1H MAS NMR data of the mixed xCsNH2+(1-x)CsH samples, confirming the formation of the solid solutions. The closest interproton distance in the homogeneous Cs(NH2)0·5H0.5 solid solution is computed to be 3.67 Å, which is larger than that of the known Rb(NH2)0·5H0.5 solid solution (3.29 Å). This work's combination of theoretical research and experimentation provides a suitable framework for the structural analysis and property estimation of other M-N-H solid solutions.

Primary lymphomas of the central nervous system (PCNSL) are defined as diffuse large B-cell lymphomas (DLBCL) confined to the CNS. Here, the authors complete whole genome sequencing and RNA-seq to characterize 51 PCNSLs, and find common mutations in immune pathways and upregulated TERT expression and find distinct pathway differences between DLBCL and other primary CNS lymphomas.

Artificial intelligence and machine learning (AI/ML) are playing increasingly important roles, permeating the field of medical devices (MDs). This rapid progress has not yet been matched by the Health Technology Assessment (HTA) process, which still needs to define a common methodology for assessing AI/ML-based MDs. To collect existing evidence from the literature about the methods used to assess AI-based MDs, with a specific focus on those used for the management of heart failure (HF), the International Federation of Medical and Biological Engineering (IFMBE) conducted a scoping meta-review. This manuscript presents the results of this search, which covered the period from January 1974 to October 2022. After careful independent screening, 21 reviews, mainly conducted in North America and Europe, were retained and included. Among the findings were that deep learning is the most commonly utilised method and that electronic health records and registries are among the most prevalent sources of data for AI/ML algorithms. Out of the 21 included reviews, 19 focused on risk prediction and/or the early diagnosis of HF. Furthermore, 10 reviews provided evidence of the impact on the incidence/progression of HF, and 13 on the length of stay. From an HTA perspective, the main areas requiring improvement are the quality assessment of studies on AI/ML (included in 11 out of 21 reviews) and their data sources, as well as the definition of the criteria used to assess the selection of the most appropriate AI/ML algorithm.

We report on the development of a highly sensitive hydrogen sulfide (H2S) gas sensor exploiting the doubly resonant photoacoustic spectroscopy technique and using a near-infrared laser emitting at 1578.128 nm. By targeting the R(4) transition of H2S, we achieved a minimum detection limit of 10 part per billion in concentration and a normalized noise equivalent absorption coefficient of 8.9 × 10−12 W cm−1 Hz−1/2. A laser-cavity-molecule locking strategy is proposed to enhance the sensor stability for fast measurement when dealing with external disturbances. A comparison among the state-of-the-art H2S sensors using various spectroscopic techniques confirmed the record sensitivity achieved in this work.

Management control systems can receive adaptations and innovations in response to contingent variables external to organizations. The present study aims to verify if there are relations between the types of budget systems and the contingent factors that affect the industrial sector. The contingency variables: environment, structure, strategy, technological process and size were related to the budgetary taxonomy, the flexibility of changes in the budget and the budgeting process. Data collection was performed by questionnaire in 28 industries in Paraná. Data treatment involved relative frequency and canonical correlations in order to quantify the strength of the relationship between the study variables. The profile of the sample was predominantly of large companies and the food sector, which use the budget to direct resources, analyze performance and align with strategic planning. The types of flexible budget and by activity were predominant. The results of the canonical correlations allow to infer that the budgetary emphasis on operational plans is correlated to the decentralized organizational structure and repetitive processes, the budgetary emphasis on internal communication is related to the organization’s cost and size strategies, the continuous budget is related to operational plans and customized processes, and the flexible budget and zero-based process dimensions are related to legal aspects.

Abstract Background NG (nasogastric) tubes are used worldwide as a means to provide enteral nutrition. Testing the pH of tube aspirates prior to feeding is commonly used to verify tube location before feeding or medication. A pH at or lower than 5.5 was taken as evidence for stomach intubation. However, the existing standard pH strips lack sensitivity, especially in patients receiving feeding and antacids medication. We developed and validated a first-generation ester-impregnated pH strip test to improve the accuracy towards gastric placements in adult population receiving routine NG-tube feeding. The sensitivity was improved by its augmentation with the action of human gastric lipase (HGL), an enzyme specific to the stomach. Methods We carried out a multi-centred, prospective, two-gate diagnostic accuracy study on patients who require routine NG-tube feeding in 10 NHS hospitals comparing the sensitivity of the novel pH strip to the standard pH test, using either chest X-rays or, in its absence, clinical observation of the absence of adverse events as the reference standard. We also tested the novel pH strips in lung aspirates from patients undergoing oesophageal cancer surgeries using visual inspection as the reference standard. We simulated health economics using a decision analytic model and carried out adoption studies to understand its route to commercialisation. The primary end point is the sensitivity of novel and standard pH tests at the recommended pH cut-off of 5.5. Results A total of 6400 ester-impregnated pH strips were prepared based on an ISO13485 quality management system. A total of 376 gastric samples were collected from adult patients in 10 NHS hospitals who were receiving routine NG-tube feeding. The sensitivities of the standard and novel pH tests were respectively 49.2% (95% CI 44.1‑54.3%) and 70.2% (95% CI 65.6‑74.8%) under pH cut-off of 5.5 and the novel test has a lung specificity of 89.5% (95% CI 79.6%, 99.4%). Our simulation showed that using the novel test can potentially save 132 unnecessary chest X-rays per check per every 1000 eligible patients, or direct savings of £4034 to the NHS. Conclusions The novel pH test correctly identified significantly more patients with tubes located inside the stomach compared to the standard pH test used widely by the NHS. Trial registration http://www.isrctn.com/ISRCTN11170249 , Registered 21 June 2017—retrospectively registered

Uma situação real, como a limpeza da orla do lago Paranoá em Brasília, Brasil, concebeu um ambiente de ensino-aprendizagem, sustentado pelo método de aprendizagem baseada em projetos (PjBL), de modo a introduzir propostas de solução no âmbito dos Objetivos de Desenvolvimento Sustentável (ODS) na formação de estudantes de engenharia. Uma equipe de estudantes de Engenharia Mecânica, Mecatrônica e de Produção foi constituída para estudar o problema e desenvolver um sistema de coleta de resíduos flutuantes. O estudo envolveu uma pesquisa aplicada e resultou no projeto de controle de uma máquina para coleta de materiais em superfícies hídricas. Para validar o projeto de controle foi construído e testado um protótipo.

Digital twins (DTs) have been found useful in manufacturing, construction, and maintenance. Adapting DTs to serve cities, the question arises of what an urban digital twin should contain and how it should be orchestrated to serve a city’s dynamical ecosystem, along with how to enhance the efficiency of the city. We are aligning with the commonplace idea that the main advantage of using DTs is economical as, for example, DTs can improve the planning of activities thus saving money and time. But how can they be useful for a city? Instead of looking at the DTs as solutions in search of problems to be solved, we start from city needs. Our approach is two-fold. We start by briefly reviewing existing possibilities for meeting some specific needs, but keep the focus on identifying and attempting to close the gap between the needs arising from everyday city functions and the latest DT techniques useful for meeting those needs. DTs are technically different and serve different applications, yet they share a common identity and name, as well as several technical similarities. Adopting computer science terminology, we see a back-end city DT as the container of all information, while any single front-end, visualized or used either by humans or robots, offers a limited but meaningful representation of the DT for a specific application. Alas, there are multiple open questions regarding the realization and benefits of such back-end DT. Nevertheless, we discuss how the back-end DT (or any specific DT) could be updated autonomously from sensor data using artificial intelligence techniques, and how the front-ends could be used for large benefits to the entire city ecosystem.

A novel study on harmonic frequency combs emitted by quantum cascade lasers (QCLs) is presented here, demonstrating the presence of intensity correlations between twin modes characterizing the emission spectra. These originate from a four‐wave mixing process driven by the active medium's third‐order nonlinearity. The study of such correlations is essential for the engineering of a new generation of semiconductor devices with the potential of becoming integrated emitters of light with quantum properties, such as squeezing and entanglement. Starting from experimental results, the limits of state‐of‐the‐art technology are discussed as well as the possible methodologies that could lead to the detection of nonclassical phenomena, or alternatively improve the design of QCLs, in the compelling perspective of generating quantum correlations in mid‐infrared light.

Photoacoustic spectroscopy (PAS) based gas sensors with high sensitivity, wide dynamic range, low cost, and small footprint are desirable in energy, environment, safety, and public health. However, most works have focused on either acoustic resonator to enhance acoustic wave or optical resonator to enhance optical wave. Herein, we develop a gas sensor based on doubly resonant PAS in which the acoustic and optical waves are simultaneously enhanced using combined optical and acoustic resonators in a centimeter-long configuration. Not only the lower detection limit is enhanced by the double standing waves, but also the upper detection limit is expanded due to the short resonators. As an example, we developed a sensor by detecting acetylene (C2H2), achieving a noise equivalent absorption of 5.7 × 10−13 cm−1 and a dynamic range of eight orders. Compared to the state-of-the-art PAS gas sensors, the developed sensor achieves a record sensitivity and dynamic range.

The antimicrobial activity of the novel coordination polymers obtained by co-crystallizing the amino acids arginine or histidine, as both enantiopure L and racemic DL forms, with the salts Cu(NO3)2 and AgNO3 has been investigated to explore the effect of chirality in the cases of enantiopure and racemic forms. The compounds [Cu·AA·(NO3)2]CPs and [Ag·AA·NO3]CPs (AA = L-Arg, DL-Arg, L-His, DL-His) were prepared by mechanochemical, slurry, and solution methods and characterized by X-ray single-crystal and powder diffraction in the cases of the copper coordination polymers, and by powder diffraction and by solid-state NMR spectroscopy in the cases of the silver compounds. The two pairs of coordination polymers, [Cu·L-Arg·(NO3)2·H2O]CP and [Cu·DL-Arg·(NO3)2·H2O]CP, and [Cu·L-Hys·(NO3)2·H2O]CP and [Cu·DL-His·(NO3)2·H2O]CP, have been shown to be isostructural in spite of the different chirality of the amino acid ligands. A similar structural analogy could be established for the silver complexes on the basis of SSNMR. The activity against the bacterial pathogens Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus was assessed by carrying out disk diffusion assays on lysogeny agar media showing that, while there is no significant effect arising from the use of enantiopure or chiral amino acids, the coordination polymers exert an appreciable antimicrobial activity comparable, when not superior, to that of the metal salts alone.

Abstract Short chain chitooligosaccharides (COs) are chitin derivative molecules involved in plant-fungus signaling during arbuscular mycorrhizal (AM) interactions. In host plants, COs activate a symbiotic signalling pathway that regulates AM-related gene expression. Furthermore, exogenous CO application was shown to promote AM establishment, with a major interest for agricultural applications of AM fungi as biofertilizers. Currently, the main source of commercial COs is from the shrimp processing industry, but purification costs and environmental concerns limit the convenience of this approach. In an attempt to find a low cost and low impact alternative, this work aimed to isolate, characterize and test the bioactivity of COs from selected strains of phylogenetically distant filamentous fungi: Pleurotus ostreatus, Cunninghamella bertholletiae and Trichoderma viride. Our optimized protocol successfully isolated short chain COs from lyophilized fungal biomass. Fungal COs were more acetylated and displayed a higher biological activity compared to shrimp-derived COs, a feature that—alongside low production costs—opens promising perspectives for the large scale use of COs in agriculture.

A health technology assessment (HTA) is commonly defined as a multidisciplinary approach used to evaluate medical, social, economic, and ethical issues related to the use of a health technology in a systematic, transparent, unbiased, robust manner. To help inform HTA recommendations, the surveillance of social media platforms can provide important insights to the clinical community and to decision makers on the effectiveness and safety of the use of health technologies on a patient. A scoping review of the published literature was performed to gain some insight on the accuracy and automation of sentiment analysis (SA) used to assess public opinion on the use of health technologies. A literature search of major databases was conducted. The main search concepts were SA, social media, and patient perspective. Among the 1,776 unique citations identified, 12 studies that described the use of SA methods to evaluate public opinion on or experiences with the use of health technologies as posted on social media platforms were included. The SA methods used were either lexicon- or machine learning-based. Two studies focused on medical devices, three examined HPV vaccination, and the remaining studies targeted drug therapies. Due to the limitations and inherent differences among SA tools, the outcomes of these applications should be considered exploratory. The results of our study can initiate discussions on how the automation of algorithms to interpret public opinion of health technologies should be further developed to optimize the use of data available on social media.

The history of urban food forests (UFFs) dates back to ancient times, when civilizations incorporated edible species into wild forests to create an ecosystem as natural as and self-sufficient as possible. Since the second half of the 20th century, the practices of integrating edible plants into ornamental landscapes have spread throughout the world. Currently, UFFs must face a number of challenges similar to those encountered by urban forests: land tenure, governance, technical capacities, and pollution and global change issues, and must be addressed in order to identify the most suitable combination of productive, environmental, and socio-economic functions of UFF. The events on a global scale that occurred in the first decades of the 21st century are forcing those who live and work in urban environments to react quickly to address the upcoming challenges.

Abstract Coronavirus disease 2019 (COVID‐19) has transformed very quickly into a world pandemic with severe and unexpected consequences on human health. Concerted efforts to generate better diagnostic and prognostic tools have been ongoing. Research, thus far, has primarily focused on the virus itself or the direct immune response to it. Here, we propose extracellular vesicles (EVs) from serum liquid biopsies as a new and unique modality to unify diagnostic and prognostic tools for COVID‐19 analyses. EVs are a novel player in intercellular signalling particularly influencing immune responses. We herein show that innate and adaptive immune EVs profiling, together with SARS‐CoV‐2 Spike S1+ EVs provide a novel signature for SARS‐CoV‐2 infection. It also provides a unique ability to associate the co‐existence of viral and host cell signatures to monitor affected tissues and severity of the disease progression. And provide a phenotypic insight into COVID‐associated EVs.

Multidrug products enable more effective therapies and simpler administration regimens, provided that a stable formulation is prepared, with the desired composition. In this view, solid solutions have the advantage of combining the stability of a single crystalline phase with the potential of stoichiometry variation of a mixture. Here a drug–prodrug solid solution of cortisone and cortisol (hydrocortisone) is described. Despite the structural differences of the two components, the new phase is obtained both from solution and by supercritical CO2 assisted spray drying. In particular, to enter the solid solution, hydrocortisone must violate Etter's rules for hydrogen bonding. As a result, its dissolution rate is almost doubled.

O objetivo desta pesquisa foi a elaboração de um projeto de gestão do conhecimento em uma instituição de ensino superior. Buscou-se diagnosticar a realidade da gestão do conhecimento na IES pela aplicação do instrumento de Bukowitz e Williams (2002), bem como relacionar as ferramentas de gestão do conhecimento às características culturais da instituição. Trata-se de uma pesquisa intervencionista e quantitativa. Como resultado destaca-se os menores índices nos critérios de avaliação de novas formas de conhecimento e no descarte de conhecimento. A proposição foi de um projeto de gestão do conhecimento, composto de ferramentas tecnológicas -wikis, blogs e portais - e não tecnológicas - requisitos de capacidade futura, quadro de ação estratégica, métricas de mudança cultural, gestão de risco e seleção de processo. Palavras-chave: gestão do conhecimento; ferramentas de gestão do conhecimento; instituição de ensino superior.

Abstract Background Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of the mechanisms through which therapy resistance develops. Therefore, we aimed to identify methylation loci associated with endocrine therapy resistance. Methods We used genome-wide DNA methylation profiles of primary ER+/HER2- tumours from The Cancer Genome Atlas in combination with curated data on survival and treatment to predict development of endocrine resistance. Association of individual DNA methylation markers with survival was assessed using Cox proportional hazards models in a cohort of ER+/HER2- tumours (N = 552) and two sub-cohorts corresponding to the endocrine treatment (AI or TAM) that patients received (N = 210 and N = 172, respectively). We also identified multivariable methylation signatures associated with survival using Cox proportional hazards models with elastic net regularization. Individual markers and multivariable signatures were compared with DNA methylation profiles generated in a time course experiment using the T47D ER+ breast cancer cell line treated with tamoxifen or deprived from estrogen. Results We identified 134, 5 and 1 CpGs for which DNA methylation is significantly associated with survival in the ER+/HER2-, TAM and AI cohorts respectively. Multi-locus signatures consisted of 203, 36 and 178 CpGs and showed a large overlap with the corresponding single-locus signatures. The methylation signatures were associated with survival independently of tumour stage, age, AI treatment, and luminal status. The single-locus signature for the TAM cohort was conserved among the loci that were differentially methylated in endocrine-resistant T47D cells. Similarly, multi-locus signatures for the ER+/HER2- and AI cohorts were conserved in endocrine-resistant T47D cells. Also at the gene set level, several sets related to endocrine therapy and resistance were enriched in both survival and T47D signatures. Conclusions We identified individual and multivariable DNA methylation markers associated with therapy resistance independently of luminal status. Our results suggest that these markers identified from primary tumours prior to endocrine treatment are associated with development of endocrine resistance.

The dataset presented in this article contains information about marine Area-Based Management Tools (ABMTs) used to assess their contribution to the United Nations 2030 Sustainable Development Goals. Following the scope of the analysis, ABMTs were identified by scrutinizing international and regional legal sources related to ocean management in the fields of marine conservation, fisheries, deep sea bed mining, underwater natural and cultural heritage, environmental conservation, and marine spatial planning. Legal sources were screened to depict the following characteristics of individual ABMTs: i) management objectives; ii) authorities responsible for delivering such objectives; iii) the system of management and planning entailed in the ABMT including the zoning type; and iv) the specific spatial scope and domain each ABMT refer to in vertical depth and horizontal domain. Data were generated through an internal expert elicitation. Experts, initially trained in the data analysis and related protocol, contributed to the data production because of their specific knowledge and experience in ocean management. This dataset represents a unique source of information for advancing research about monitoring and assessment of the achievement of sustainable development goals that encompasses different types of ABMTs.

Single-cell biology has revolutionized the way we understand biological processes. In this paper, we provide a more tailored approach to clustering and analyzing spatial single-cell data coming from immunofluorescence imaging techniques. We propose Bayesian Reduction for Amplified Quantization in UMAP Embedding (BRAQUE) as an integrative novel approach, from data preprocessing to phenotype classification. BRAQUE starts with an innovative preprocessing, named Lognormal Shrinkage, which is able to enhance input fragmentation by fitting a lognormal mixture model and shrink each component towards its median, in order to help further the clustering step in finding more separated and clear clusters. Then, BRAQUE’s pipeline consists of a dimensionality reduction step performed using UMAP, and a clustering performed using HDBSCAN on UMAP embedding. In the end, clusters are assigned to a cell type by experts, using effects size measures to rank markers and identify characterizing markers (Tier 1), and possibly characterize markers (Tier 2). The number of total cell types in one lymph node detectable with these technologies is unknown and difficult to predict or estimate. Therefore, with BRAQUE, we achieved a higher granularity than other similar algorithms such as PhenoGraph, following the idea that merging similar clusters is easier than splitting unclear ones into clear subclusters.

When it comes to crystal structure determination, computational approaches such as Crystal Structure Prediction (CSP) have gained more and more attention since they offer some insight on how atoms and molecules are packed in the solid state, starting from only very basic information without diffraction data. Furthermore, it is well known that the coupling of CSP with solid-state NMR (SSNMR) greatly enhances the performance and the accuracy of the predictive method, leading to the so-called CSP-NMR crystallography (CSP-NMRX). In this paper, we present the successful application of CSP-NMRX to determine the crystal structure of three structural isomers of pyridine dicarboxylic acid, namely quinolinic, dipicolinic and dinicotinic acids, which can be in a zwitterionic form, or not, in the solid state. In a first step, mono- and bidimensional SSNMR spectra, i.e., 1H Magic-Angle Spinning (MAS), 13C and 15N Cross Polarisation Magic-Angle Spinning (CPMAS), 1H Double Quantum (DQ) MAS, 1H-13C HETeronuclear CORrelation (HETCOR), were used to determine the correct molecular structure (i.e., zwitterionic or not) and the local molecular arrangement; at the end, the RMSEs between experimental and computed 1H and 13C chemical shifts allowed the selection of the correct predicted structure for each system. Interestingly, while quinolinic and dipicolinic acids are zwitterionic and non-zwitterionic, respectively, in the solid state, dinicotinic acid exhibits in its crystal structure a “zwitterionic-non-zwitterionic continuum state” in which the proton is shared between the carboxylic moiety and the pyridinic nitrogen. Very refined SSNMR experiments were carried out, i.e., 14N-1H Phase-Modulated (PM) pulse and Rotational-Echo Saturation-Pulse Double-Resonance (RESPDOR), to provide an accurate N–H distance value confirming the hybrid nature of the molecule. The CSP-NMRX method showed a remarkable match between the selected structures and the experimental ones. The correct molecular input provided by SSNMR reduced the number of CSP calculations to be performed, leading to different predicted structures, while RMSEs provided an independent parameter with respect to the computed energy for the selection of the best candidate.

Este estudo analisa o efeito do capital intelectual sobre o desempenho financeiro de empresas do índice IBrX-50 da B3, bolsa de valores brasileira. Utilizaram-se os componentes do modelo VAIC™ (PULIC, 1998): o capital humano (HCE), capital estrutural (SCE) e a eficiência do capital empregado (CEE). O desempenho foi medido pelos indicadores financeiros ROA, ROE, ROS e o Valor de Mercado, medido pelo Q de Tobin. Trata-se de uma pesquisa quantitativa, descritiva, documental, com dados secundários de 2013 a 2017 coletados da Economática®. Quatro modelos econométricos foram estimados por regressão múltipla com dados em painel para testar as hipóteses. Os resultados indicam que todos os componentes afetam positivamente o ROA e o ROE; somente o CEE afeta o Valor de Mercado; o HCE afeta positiva, e o SCE negativamente o ROS. O estudo contribui com a análise empírica dos componentes do capital intelectual no contexto brasileiro.

Este estudo tem por procedimento um experimento cujo objetivo é verificar se a divulgação do Relato Integrado (RI) por uma organização influencia no julgamento e na tomada de decisão de investidores. Tendo como desenho experimental simples, a variável dependente consiste no julgamento e na tomada de decisão dos participantes, em uma escala de -5 a 5. A variável independente possui dois níveis, um com a utilização de um conjunto de relatórios contábeis tradicionais, e o outro acrescentando o RI. A amostra foi composta de discentes dos cursos de Ciências Contábeis, Administração e Ciências Econômicas de uma universidade pública do Paraná. A análise ocorreu por estatística descritiva e com o uso do Teste t. Com 269 resultados válidos, inferiu-se que o RI apresenta influência positiva sobre o julgamento e a tomada de decisão de investidores, o que contribui com a literatura por fornecer dados empíricos que corroboram os estudos de Atkins e Maroun (2015) e Cheng et al. (2015) e como contribuição prática fornece evidências de que o Relato Integrado gera valor para os investidores por intermédio das informações de sustentabilidade da organização. Por ser um estudo incipiente no Brasil, denota-se que limitações quanto aos resultados da técnica estatística são visualizadas, o que indicam oportunidades para a continuidade do trabalho e criação de um campo disciplinar em termos de pesquisas envolvendo RI e tomada de decisão.

This study aims at developing new multicomponent crystal forms of sulpiride, an antipsychotic drug. The main goal was to improve its solubility since it belongs to class IV of the BCS. Nine new adducts were obtained by combining the active pharmaceutical ingredient with acid coformers: a salt cocrystal and eight molecular salts. In addition, three novel co-drugs, of which two are molecular salts and one is a cocrystal, were also achieved. All samples were characterized in the solid state by complementary techniques (i.e., infrared spectroscopy, powder X-ray diffraction and solid-state NMR). For systems for which it was possible to obtain good-quality single crystals, the structure was solved by single crystal X-ray diffraction (SCXRD). SCXRD combined with solid-state NMR were used to evaluate the ionic or neutral character of the adducts. In vitro dissolution tests of the new crystal forms were performed and all the adducts display remarkable dissolution properties with respect to pure sulpiride.

The objective of this study was to suggest an alternative for managing the knowledge gained and resulting legacy from the application of the Problem Based Learning (PBL) method in a higher education context. The legacies of the PBL method are found to be more profound and diverse than those related to either the students' experience or the projects developed to solve real-world problems presented by external agents (the partners of the UnB Production Engineering course). The Production Engineering course has, since 2011, adopted the PBL method as an active learning methodology. Although each semester presents new opportunities in the process of consolidating this method, it’s been perceived that the many phases and results of this process are often utilized in real time only, contributing to the participating individuals exclusively as they occur. This is seen as a type of temporal result, seen only at a given "T" moment in the discipline’s lifecycle. Correspondingly, part of this knowledge is currently seen as perishable, since it is not possible to store it for future moments. In an attempt to extend this experience, starting in 2016 the University of Brasilia’s Production Engineering course has begun to develop an extension of PBL products by means of distinct events. The results haven been satisfactory, thus far involving 458 students and 7910 participants. As a legacy, it was possible to create a platform for the presentation of active learning methodologies and the exchange of experiences. Thus, the project presentations, once seen as distinct landmarks, became part of a legacy through a specific event, assisted and accessed as a course memory and a student’s digital portfolio.

Mesothelioma is a rare lethal tumor of dogs and humans involving cavities of the body. Dogs are considered a model for new drugs and therapeutic methods since they present spontaneous diseases similar to humans. Microfragmented adipose tissue (MFAT) uploaded by paclitaxel (PTX) is a drug delivery medium providing slow release of chemotherapic drugs. A dog affected by pleural, pericardial, and peritoneal mesothelioma was treated by 17 intracavitary ultrasound-guided injections of MFAT-PTX over 22 months. A long-lasting improvement of general conditions was observed, treatment was well-tolerated, and no toxicity or hypersensitivity was reported. Pharmacokinetic (PK) data indicated low drug localization in the circulatory system and a tendency to enter or remain in the extravascular compartments of the body. Indeed, low levels of free-circulating drugs for a short time produced low toxicity, whereas, a higher intracavitary PTX concentration can have major pharmacological efficacy. To our knowledge, this is the first time that mesothelioma has been treated using such a procedure, and this should be considered as a novel therapeutic approach. The low systemic absorption suggests the possible role of MFAT-PTX for loco-regional/intratumoral therapy also useful in other types of tumors, and further investigation is warranted.

Resumo Com base no pressuposto de que o direito à moradia é um princípio básico estabelecido em tratados internacionais e na própria Constituição brasileira, este ensaio tem três objetivos: situar historicamente a introdução deste princípio no contexto internacional e nacional; sua reelaboração a partir do conceito de adequação habitacional e a translação, no contexto brasileiro, da discussão sobre moradia adequada para moradia digna. Com este intuito, foram analisados documentos considerados centrais nesse debate, tendo como ponto de partida a Declaração de Direitos Humanos de 1948. Como método, a discussão está assentada na análise de documentos de domínio público e pautada na perspectiva da psicologia social discursiva. Como conclusão, consideramos que a translação de moradia adequada para moradia digna tem por base situar o direito à moradia como exercício de cidadania, com o uso de moradia digna para indicar que o que está em pauta é a possibilidade de ter uma vida digna.